FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Cheetham, CE Belluscio, L AF Cheetham, Claire E. Belluscio, Leonardo TI An Olfactory Critical Period SO SCIENCE LA English DT Editorial Material ID RESTORATION C1 [Cheetham, Claire E.; Belluscio, Leonardo] NINDS, Dev Neural Plast Sect, NIH, Bethesda, MD 20892 USA. RP Cheetham, CE (reprint author), NINDS, Dev Neural Plast Sect, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM belluscl@ninds.nih.gov RI Cheetham, Claire/A-2612-2017 OI Cheetham, Claire/0000-0002-4038-1501 NR 8 TC 3 Z9 3 U1 0 U2 10 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 APR 11 PY 2014 VL 344 IS 6180 BP 157 EP 158 DI 10.1126/science.1253136 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE6JD UT WOS:000334096300022 PM 24723600 ER PT J AU Camberg, JL Viola, MG Rea, L Hoskins, JR Wickner, S AF Camberg, Jodi L. Viola, Marissa G. Rea, Leslie Hoskins, Joel R. Wickner, Sue TI Location of Dual Sites in E. coli FtsZ Important for Degradation by ClpXP; One at the C-Terminus and One in the Disordered Linker SO PLOS ONE LA English DT Article ID BACTERIAL-CELL-DIVISION; CYTOSKELETAL PROTEIN FTSZ; ATP-DEPENDENT PROTEASES; P-BAD PROMOTER; ESCHERICHIA-COLI; CHAPERONE CLPX; BINDING DOMAIN; Z-RING; RECOGNITION; SUBSTRATE AB ClpXP is a two-component ATP-dependent protease that unfolds and degrades proteins bearing specific recognition signals. One substrate degraded by Escherichia coli ClpXP is FtsZ, an essential cell division protein. FtsZ forms polymers that assemble into a large ring-like structure, termed the Z-ring, during cell division at the site of constriction. The FtsZ monomer is composed of an N-terminal polymerization domain, an unstructured linker region and a C-terminal conserved region. To better understand substrate selection by ClpXP, we engineered FtsZ mutant proteins containing amino acid substitutions or deletions near the FtsZ C-terminus. We identified two discrete regions of FtsZ important for degradation of both FtsZ monomers and polymers by ClpXP in vitro. One region is located 30 residues away from the C-terminus in the unstructured linker region that connects the polymerization domain to the C-terminal region. The other region is near the FtsZ C-terminus and partially overlaps the recognition sites for several other FtsZ-interacting proteins, including MinC, ZipA and FtsA. Mutation of either region caused the protein to be more stable and mutation of both caused an additive effect, suggesting that both regions are important. We also observed that in vitro MinC inhibits degradation of FtsZ by ClpXP, suggesting that some of the same residues in the C-terminal site that are important for degradation by ClpXP are important for binding MinC. C1 [Camberg, Jodi L.; Rea, Leslie; Hoskins, Joel R.; Wickner, Sue] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Camberg, Jodi L.; Viola, Marissa G.] Univ Rhode Isl, Dept Cell & Mol Biol, Coll Environm & Life Sci, Kingston, RI 02881 USA. RP Camberg, JL (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM cambergj@mail.uri.edu; wickners@mail.nih.gov FU NIH National Cancer Institute, Center for Cancer Research [1ZIABC008710-35]; Rhode Island Foundation Medical Research Fund [20123829] FX This research was supported by the Intramural Research Program of the NIH National Cancer Institute, Center for Cancer Research (Award #1ZIABC008710-35) and the Rhode Island Foundation Medical Research Fund (Award # #20123829). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 13 Z9 13 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 APR 10 PY 2014 VL 9 IS 4 AR e94964 DI 10.1371/journal.pone.0094964 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI5LS UT WOS:000336909100147 PM 24722340 ER PT J AU Hauser, DN Dillman, AA Ding, JH Li, Y Cookson, MR AF Hauser, David N. Dillman, Allissa A. Ding, Jinhui Li, Yan Cookson, Mark R. TI Post-Translational Decrease in Respiratory Chain Proteins in the Polg Mutator Mouse Brain SO PLOS ONE LA English DT Article ID MITOCHONDRIAL-DNA MUTATIONS; POINT MUTATIONS; MTDNA DELETIONS; MICE; PHENOTYPES; EXPRESSION; DISEASE AB Mitochondrial DNA damage is thought to be a causal contributor to aging as mice with inactivating mutations in polymerase gamma (Polg) develop a progeroid phenotype. To further understand the molecular mechanisms underlying this phenotype, we used iTRAQ and RNA-Seq to determine differences in protein and mRNA abundance respectively in the brains of one year old Polg mutator mice compared to control animals. We found that mitochondrial respiratory chain proteins are specifically decreased in abundance in the brains of the mutator mice, including several nuclear encoded mitochondrial components. However, we found no evidence that the changes we observed in protein levels were the result of decreases in mRNA expression. These results show that there are post-translational effects associated with mutations in Polg. C1 [Hauser, David N.; Dillman, Allissa A.; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Hauser, David N.] Brown Univ, Dept Neurosci, Brown Univ Natl Inst Hlth Grad Partnership Progra, Providence, RI 02912 USA. [Dillman, Allissa A.] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. [Ding, Jinhui] NIA, Computat Biol Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Li, Yan] NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM Cookson@mail.nih.gov RI Hauser, David/I-4933-2012 OI Hauser, David/0000-0002-9500-5255 FU US National Institutes of Health, National Institute on Aging; US National Institutes of Health, National Institute of Neurological Disease and Stroke FX D.N.H., A. A. D., J.D., and M. R. C. are supported by the Intramural Research Program of the US National Institutes of Health, National Institute on Aging. Y.L. is supported by the Intramural Research Program of the US National Institutes of Health, National Institute of Neurological Disease and Stroke. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 20 TC 4 Z9 4 U1 0 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 APR 10 PY 2014 VL 9 IS 4 AR e94646 DI 10.1371/journal.pone.0094646 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI5LS UT WOS:000336909100114 PM 24722488 ER PT J AU Pitt, B Pfeffer, MA Assmann, SF Boineau, R Anand, IS Claggett, B Clausell, N Desai, AS Diaz, R Fleg, JL Gordeev, I Harty, B Heitner, JF Kenwood, CT Lewis, EF O'Meara, E Probstfield, JL Shaburishvili, T Shah, SJ Solomon, SD Sweitzer, NK Yang, S McKinlay, SM AF Pitt, Bertram Pfeffer, Marc A. Assmann, Susan F. Boineau, Robin Anand, Inder S. Claggett, Brian Clausell, Nadine Desai, Akshay S. Diaz, Rafael Fleg, Jerome L. Gordeev, Ivan Harty, Brian Heitner, John F. Kenwood, Christopher T. Lewis, Eldrin F. O'Meara, Eileen Probstfield, Jeffrey L. Shaburishvili, Tamaz Shah, Sanjiv J. Solomon, Scott D. Sweitzer, Nancy K. Yang, Song McKinlay, Sonja M. CA Topcat Investigators TI Spironolactone for Heart Failure with Preserved Ejection Fraction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; QUALITY-OF-LIFE; VENTRICULAR DYSFUNCTION; HYPERTENSIVE PATIENTS; TASK-FORCE; TRIAL; MORTALITY; OUTCOMES; CHARM AB BackgroundMineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. MethodsIn this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. ResultsWith a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 mol per liter) or higher, or dialysis. ConclusionsIn patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.) In this trial, 3445 patients with heart failure and a preserved ejection fraction were assigned to spironolactone or placebo. At a mean of 3.3 years, there was no significant difference in death from cardiovascular causes, aborted cardiac arrest, or hospitalization for heart failure. Many patients with heart failure have a normal or near-normal left ventricular ejection fraction.(1)-(4) Such patients share common signs and symptoms, as well as an impaired quality of life and a poor prognosis, with patients who have heart failure and a reduced ejection fraction.(5)-(8) However, the benefit of most medical therapies for heart failure is limited to those with a reduced ejection fraction, generally 40% or less.(1),(2),(9) The lack of favorable evidence from clinical-outcome trials involving patients with heart failure and a preserved left ventricular ejection fraction is reflected in current guidelines, which offer no specific ... C1 [Pitt, Bertram] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Pfeffer, Marc A.; Claggett, Brian; Desai, Akshay S.; Lewis, Eldrin F.; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Assmann, Susan F.; Harty, Brian; Kenwood, Christopher T.; McKinlay, Sonja M.] New England Res Inst, Watertown, MA USA. [Boineau, Robin; Fleg, Jerome L.; Yang, Song] NHLBI, Bethesda, MD 20892 USA. [Anand, Inder S.] Vet Affairs Med Ctr, Minneapolis, MN USA. [Anand, Inder S.] Univ Minnesota, Minneapolis, MN USA. [Clausell, Nadine] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Diaz, Rafael] Estudios Clin Latinoamer, Rosario, Santa Fe, Argentina. [Gordeev, Ivan] Pirogov Russian Natl Res Med Univ, Moscow, Russia. [Heitner, John F.] New York Methodist Hosp, Brooklyn, NY USA. [O'Meara, Eileen] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Probstfield, Jeffrey L.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Shaburishvili, Tamaz] Serv Clin, Tbilisi, Rep of Georgia. [Shah, Sanjiv J.] Northwestern Univ, Chicago, IL 60611 USA. [Sweitzer, Nancy K.] Univ Wisconsin, Madison, WI 53706 USA. RP Pfeffer, MA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM mpfeffer@rics.bwh.harvard.edu RI Clausell, Nadine /C-7813-2016; Ventura, Hector/A-7691-2011 OI Clausell, Nadine /0000-0003-4207-3809; FU National Heart, Lung, and Blood Institute, National Institutes of Health [HHSN268200425207C] FX Supported by a contract from the National Heart, Lung, and Blood Institute, National Institutes of Health (HHSN268200425207C). NR 38 TC 284 Z9 289 U1 4 U2 22 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 APR 10 PY 2014 VL 370 IS 15 BP 1383 EP 1392 DI 10.1056/NEJMoa1313731 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AE6IW UT WOS:000334095200006 PM 24716680 ER PT J AU McDermott, DH Liu, Q Velez, D Lopez, L Anaya-O'Brien, S Ulrick, J Kwatemaa, N Starling, J Fleisher, TA Priel, DAL Merideth, MA Giuntoli, RL Evbuomwan, MO Littel, P Marquesen, MM Hilligoss, D DeCastro, R Grimes, GJ Hwang, ST Pittaluga, S Calvo, KR Stratton, P Cowen, EW Kuhns, DB Malech, HL Murphy, PM AF McDermott, David H. Liu, Qian Velez, Daniel Lopez, Lizbeeth Anaya-O'Brien, Sandra Ulrick, Jean Kwatemaa, Nana Starling, Judy Fleisher, Thomas A. Priel, Debra A. Long Merideth, Melissa A. Giuntoli, Robert L. Evbuomwan, Moses O. Littel, Patricia Marquesen, Martha M. Hilligoss, Dianne DeCastro, Rosamma Grimes, George J. Hwang, Samuel T. Pittaluga, Stefania Calvo, Katherine R. Stratton, Pamela Cowen, Edward W. Kuhns, Douglas B. Malech, Harry L. Murphy, Philip M. TI A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor SO BLOOD LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; BONE-MARROW; IMMUNE-DEFICIENCY; PROGENITOR CELLS; MEMORY CD4(+); T-CELLS; MYELOKATHEXIS; HYPOGAMMAGLOBULINEMIA; DESENSITIZATION; INFECTIONS AB Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency disorder caused by gain-of-function mutations in the G protein-coupled chemokine receptor CXCR4. The CXCR4 antagonist plerixafor, which is approved by the US Food and Drug Administration (FDA) for stem cell mobilization in cancer and administered for that indication at 0.24 mg/kg, has been shown in short-term (1- to 2-week) phase 1 dose-escalation studies to correct neutropenia and other cytopenias in WHIM syndrome. However, long-term safety and long-termhematologic and clinical efficacy data are lacking. Here we report results from the first long-term clinical trial of plerixafor in any disease, in which 3 adults with WHIM syndrome self-injected 0.01 to 0.02 mg/kg (4% to 8% of the FDA-approved dose) subcutaneously twice daily for 6 months. Circulating leukocytes were durably increased throughout the trial in all patients, and this was associated with fewer infections and improvement in warts in combination with imiquimod; however, immunoglobulin levels and specific vaccine responses were not fully restored. No drug-associated side effects were observed. These results provide preliminary evidence for the safety and clinical efficacy of long-term, low-dose plerixafor in WHIM syndrome and support its continued study as mechanism-based therapy in this disease. The ClinicalTrials.gov identifier for this study is NCT00967785. C1 [McDermott, David H.; Liu, Qian; Velez, Daniel; Lopez, Lizbeeth; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Anaya-O'Brien, Sandra; Ulrick, Jean; Kwatemaa, Nana; Littel, Patricia; Marquesen, Martha M.; Hilligoss, Dianne; DeCastro, Rosamma; Malech, Harry L.] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA. [Starling, Judy; Grimes, George J.] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. [Fleisher, Thomas A.; Calvo, Katherine R.] NIH, Div Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Priel, Debra A. Long; Kuhns, Douglas B.] Clinical Serv Program Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. [Merideth, Melissa A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Giuntoli, Robert L.] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. [Evbuomwan, Moses O.; Pittaluga, Stefania] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hwang, Samuel T.] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. [Stratton, Pamela] NICHHD, Sect Pediat Endocrinol, NIH, Bethesda, MD 20892 USA. [Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP McDermott, DH (reprint author), NIAID, NIH, Bldg 10,Room 11N107, Bethesda, MD 20892 USA. EM dmcdermott@nih.gov OI Malech, Harry/0000-0001-5874-5775; McDermott, David/0000-0001-6978-0867; Calvo, Katherine/0000-0002-0771-4191 FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases; Office of Rare Diseases Research, National Institutes of Health; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases and the Office of Rare Diseases Research, National Institutes of Health and was funded in part with federal funds from the National Cancer Institute, National Institutes of Health under Contract No. HHSN261200800001E. Plerixafor was provided at no cost for the study by Genzyme/Sanofi. NR 36 TC 36 Z9 36 U1 0 U2 10 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 APR 10 PY 2014 VL 123 IS 15 BP 2308 EP 2316 DI 10.1182/blood-2013-09-527226 PG 9 WC Hematology SC Hematology GA AH1PQ UT WOS:000335893700009 PM 24523241 ER PT J AU Snyder, ML Love, SA Sorlie, PD Rosamond, WD Antini, C Metcalf, PA Hardy, S Suchindran, CM Shahar, E Heiss, G AF Snyder, Michelle L. Love, Shelly-Ann Sorlie, Paul D. Rosamond, Wayne D. Antini, Carmen Metcalf, Patricia A. Hardy, Shakia Suchindran, Chirayath M. Shahar, Eyal Heiss, Gerardo TI Redistribution of heart failure as the cause of death: the Atherosclerosis Risk in Communities Study SO POPULATION HEALTH METRICS LA English DT Article DE Cause of death; Coronary heart disease; Death certificates; Heart failure; Mortality; Vital statistics; Ill-defined causes of death ID PUBLIC-HEALTH UTILITY; CERTIFICATE DIAGNOSIS; DISEASE MORTALITY; UNITED-STATES; STATISTICS; VALIDATION; ACCURACY; VALIDITY; STROKE AB Background: Heart failure is sometimes incorrectly listed as the underlying cause of death (UCD) on death certificates, thus compromising the accuracy and comparability of mortality statistics. Statistical redistribution of the UCD has been used to examine the effect of misclassification of the UCD attributed to heart failure, but sex-and race-specific redistribution of deaths on coronary heart disease (CHD) mortality in the United States has not been examined. Methods: We used coarsened exact matching to infer the UCD of vital records with heart failure as the UCD from 1999 to 2010 for decedents 55 years old and older from states encompassing regions under surveillance by the Atherosclerosis Risk in Communities (ARIC) Study (Maryland, Minnesota, Mississippi, and North Carolina). Records with heart failure as the UCD were matched on decedent characteristics (five-year age groups, sex, race, education, year of death, and state) to records with heart failure listed among the multiple causes of death. Each heart failure death was then redistributed to plausible UCDs proportional to the frequency among matched records. Results: After redistribution the proportion of deaths increased for CHD, chronic obstructive pulmonary disease, diabetes, hypertensive heart disease, and cardiomyopathy, P < 0.001. The percent increase in CHD mortality after redistribution was the highest in Mississippi (12%) and lowest in Maryland (1.6%), with variations by year, race, and sex. Redistribution proportions for CHD were similar to CHD death classification by a panel of expert reviewers in the ARIC study. Conclusions: Redistribution of ill-defined UCD would improve the accuracy and comparability of mortality statistics used to allocate public health resources and monitor mortality trends. C1 [Snyder, Michelle L.; Love, Shelly-Ann; Rosamond, Wayne D.; Hardy, Shakia; Heiss, Gerardo] Univ N Carolina, Gillings Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA. [Sorlie, Paul D.] NHLBI, NIH, Bethesda, MD 20892 USA. [Antini, Carmen] Univ Chile, Sch Publ Hlth, Dept Epidemiol, Santiago 8380453, Chile. [Metcalf, Patricia A.] Univ Auckland, Dept Stat, Auckland 1142, New Zealand. [Suchindran, Chirayath M.] Univ N Carolina, Gillings Sch Publ Hlth, Dept Biostat, Chapel Hill, NC 27599 USA. [Shahar, Eyal] Univ Arizona, Div Epidemiol & Biostat, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85724 USA. RP Snyder, ML (reprint author), Univ N Carolina, Gillings Sch Publ Hlth, Dept Epidemiol, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA. EM mlmeyer@unc.edu FU NHLBI NIH HHS [T32 HL007055, N01 HC055018] NR 22 TC 4 Z9 5 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-7954 J9 POPUL HEALTH METR JI Popul. Health Metr. PD APR 10 PY 2014 VL 12 AR 10 DI 10.1186/1478-7954-12-10 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AH0FI UT WOS:000335794200001 PM 24716810 ER PT J AU Crawley, SW Shifrin, DA Grega-Larson, NE McConnell, RE Benesh, AE Mao, SL Zheng, YX Zheng, QY Nam, KT Millis, BA Kachar, B Tyska, MJ AF Crawley, Scott W. Shifrin, David A., Jr. Grega-Larson, Nathan E. McConnell, Russell E. Benesh, Andrew E. Mao, Suli Zheng, Yuxi Zheng, Qing Yin Nam, Ki Taek Millis, Bryan A. Kachar, Bechara Tyska, Matthew J. TI Intestinal Brush Border Assembly Driven by Protocadherin-Based Intermicrovillar Adhesion SO CELL LA English DT Article ID USHER-SYNDROME PROTEINS; SENSORY HAIR-CELLS; IN-VIVO; CADHERIN; LOCALIZATION; MECHANOTRANSDUCTION; ORGANIZATION; HARMONIN; DOMAIN; GENE AB Transporting epithelial cells build apical microvilli to increase membrane surface area and enhance absorptive capacity. The intestinal brush border provides an elaborate example with tightly packed microvilli that function in nutrient absorption and host defense. Although the brush border is essential for physiological homeostasis, its assembly is poorly understood. We found that brush border assembly is driven by the formation of Ca2+-dependent adhesion links between adjacent microvilli. Intermicrovillar links are composed of protocadherin-24 and mucin-like protocadherin, which target to microvillar tips and interact to form a trans-heterophilic complex. The cytoplasmic domains of microvillar protocadherins interact with the scaffolding protein, harmonin, and myosin-7b, which promote localization to microvillar tips. Finally, a mouse model of Usher syndrome lacking harmonin exhibits microvillar protocadherin mislocalization and severe defects in brush border morphology. These data reveal an adhesion-based mechanism for brush border assembly and illuminate the basis of intestinal pathology in patients with Usher syndrome. C1 [Crawley, Scott W.; Shifrin, David A., Jr.; Grega-Larson, Nathan E.; McConnell, Russell E.; Benesh, Andrew E.; Mao, Suli; Tyska, Matthew J.] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA. [Zheng, Yuxi; Zheng, Qing Yin] Case Western Reserve Univ, Dept Otolaryngol HNS, Cleveland, OH 44106 USA. [Nam, Ki Taek] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul 120752, South Korea. [Millis, Bryan A.; Kachar, Bechara] NIDCD, NIH, Bethesda, MD 20892 USA. RP Tyska, MJ (reprint author), Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA. EM matthew.tyska@vanderbilt.edu OI , /0000-0001-5063-8502 FU NIDCD; NIH; American Heart Association (AHA); AHA [12GRNT12050314]; VUMC Digestive Diseases Research Center [NIH P30DK058404]; Vanderbilt University IDEAS award; NIH [DC009246, DK075555, DK095811] FX The authors thank all members of the M.J.T. laboratory and the Vanderbilt Epithelial Biology Center for advice and support. Electron and light microscopy was performed in part through the use of the VUMC Cell Imaging Shared Resource. This work was supported by Intramural Programs of NIDCD, NIH (to B.K.), American Heart Association (AHA) predoctoral fellowships (to D.A.S. and R.E.M.), AHA postdoctoral fellowship (to S.W.C.), AHA grant-in-aid 12GRNT12050314 (to M.J.T.), the VUMC Digestive Diseases Research Center (NIH P30DK058404), a Vanderbilt University IDEAS award (to M.J.T.), and NIH DC009246 (to Q.Y.Z.), DK075555, and DK095811 (to M.J.T.). NR 50 TC 18 Z9 22 U1 2 U2 13 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 APR 10 PY 2014 VL 157 IS 2 BP 433 EP 446 DI 10.1016/j.cell.2014.01.067 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AE9DK UT WOS:000334304500016 PM 24725409 ER PT J AU Tsang, JS Schwartzberg, PL Kotliarov, Y Biancotto, A Xie, Z Germain, RN Wang, E Olnes, MJ Narayanan, M Golding, H Moir, S Dickler, HB Perl, S Cheung, F AF Tsang, John S. Schwartzberg, Pamela L. Kotliarov, Yuri Biancotto, Angelique Xie, Zhi Germain, Ronald N. Wang, Ena Olnes, Matthew J. Narayanan, Manikandan Golding, Hana Moir, Susan Dickler, Howard B. Perl, Shira Cheung, Foo CA Baylor HIPC Ctr CHI Consortium TI Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses SO CELL LA English DT Article ID PLASMA-CELL DIFFERENTIATION; UNFOLDED PROTEIN RESPONSE; H1N1 INFLUENZA VACCINE; YELLOW-FEVER VACCINE; SYSTEMS BIOLOGY; GENE-EXPRESSION; B-CELLS; SEASONAL INFLUENZA; ANTIBODY; IMMUNIZATION AB A major goal of systems biology is the development of models that accurately predict responses to perturbation. Constructing such models requires the collection of dense measurements of system states, yet transformation of data into predictive constructs remains a challenge. To begin to model human immunity, we analyzed immune parameters in depth both at baseline and in response to influenza vaccination. Peripheral blood mononuclear cell transcriptomes, serum titers, cell subpopulation frequencies, and B cell responses were assessed in 63 individuals before and after vaccination and were used to develop a systematic framework to dissect inter- and intra-individual variation and build predictive models of postvaccination antibody responses. Strikingly, independent of age and pre-existing antibody titers, accurate models could be constructed using pre-perturbation cell populations alone, which were validated using independent baseline time points. Most of the parameters contributing to prediction delineated temporally stable baseline differences across individuals, raising the prospect of immune monitoring before intervention. C1 [Tsang, John S.; Schwartzberg, Pamela L.; Kotliarov, Yuri; Biancotto, Angelique; Xie, Zhi; Germain, Ronald N.; Wang, Ena; Olnes, Matthew J.; Dickler, Howard B.; Perl, Shira; Cheung, Foo] NIH, Trans NIH Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA. [Tsang, John S.; Narayanan, Manikandan] NIAID, Lab Syst Biol, Syst Genom & Bioinformat Unit, NIH, Bethesda, MD 20892 USA. [Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Wang, Ena] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Olnes, Matthew J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Golding, Hana] US FDA, Lab Retrovirus Res, Bethesda, MD 20892 USA. [Moir, Susan] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Tsang, JS (reprint author), NIH, Trans NIH Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA. EM john.tsang@nih.gov; pams@nhgri.nih.gov RI Pos, Zoltan/C-3623-2014; Kotliarov, Yuri/B-6938-2017 OI Pos, Zoltan/0000-0002-2574-7616; FU NIAID; NCI; NHLBI; NIAMS; NICHD; NIDDK; NINDS; NIEHS; NEI; NHGRI FX We thank M. Connors, K. Subbarao, R. Seder, M. Roederer, D. Douek, J. Bennink, I. Fraser, J. Mandl, members of the Systems Genomics and Bioinformatics Unit (NIAID), and M. Eichelberger (FDA) for helpful advice and feedback; the staff of the NIH Clinical Center for outstanding clinical support; and NIAID's high-performance computing team for outstanding support. This work is funded by the Intramural Programs of NIAID, NCI, NHLBI, NIAMS, NICHD, NIDDK, NINDS, NIEHS, NEI, and NHGRI. NR 41 TC 76 Z9 76 U1 1 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD APR 10 PY 2014 VL 157 IS 2 BP 499 EP 513 DI 10.1016/j.cell.2014.03.031 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AE9DK UT WOS:000334304500021 PM 24725414 ER PT J AU Wu, YZ Antony, S Meitzler, JL Doroshow, JH AF Wu, Yongzhong Antony, Smitha Meitzler, Jennifer L. Doroshow, James H. TI Molecular mechanisms underlying chronic inflammation-associated cancers SO CANCER LETTERS LA English DT Review DE NADPH oxidase; Inflammation; Reactive oxygen; Cancer ID NF-KAPPA-B; OXYGEN SPECIES GENERATION; FAMILY NADPH OXIDASES; NECROSIS-FACTOR-ALPHA; INDUCIBLE FACTOR-I; FLAVIN DEHYDROGENASE INHIBITORS; HYDROGEN-PEROXIDE PRODUCTION; INTESTINAL EPITHELIAL-CELLS; PANCREATIC STELLATE CELLS; COLITIS-ASSOCIATED CANCER AB Although it is now accepted that chronic inflammation plays an essential role in tumorigenesis, the underlying molecular mechanisms linking inflammation and cancer remain to be fully explored. Inflammatory mediators present in the tumor microenvironment, including cytokines and growth factors, as well as reactive oxygen species (ROS) and reactive nitrogen species (RNS), have been implicated in the etiology of inflammation-associated cancers. Epithelial NADPH oxidase (Nox) family proteins, which generate ROS regulated by cytokines, are upregulated during chronic inflammation and cancer. ROS serve as effector molecules participating in host defense or as chemo-attractants recruiting leukocytes to wounds, thereby influencing the inflammatory reaction in damaged tissues. ROS can alter chromosomal DNA, leading to genomic instability, and may serve as signaling molecules that affect tumor cell proliferation, survival, metabolism, angiogenesis, and metastasis. Targeting Noxs and their downstream signaling components may be a promising approach to pre-empting inflammation-related malignancies. Published by Elsevier Ireland Ltd. C1 [Wu, Yongzhong; Antony, Smitha; Meitzler, Jennifer L.; Doroshow, James H.] NCI, Lab Mol Pharmacol, NIH, Bethesda, MD 20892 USA. [Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Doroshow, JH (reprint author), NIH, Div Canc Treatment & Diag, Bldg 31,Room 3A-44,31 Ctr Dr, Bethesda, MD 20892 USA. EM doroshoj@mail.nih.gov FU Center for Cancer Research; Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health FX This work was supported by federal funds from the Center for Cancer Research and the Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services. NR 152 TC 38 Z9 39 U1 1 U2 35 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD APR 10 PY 2014 VL 345 IS 2 SI SI BP 164 EP 173 DI 10.1016/j.canlet.2013.08.014 PG 10 WC Oncology SC Oncology GA AE5AK UT WOS:000334000000005 PM 23988267 ER PT J AU Oh, SW Harris, JA Ng, L Winslow, B Cain, N Mihalas, S Wang, QX Lau, C Kuan, L Henry, AM Mortrud, MT Ouellette, B Nguyen, TN Sorensen, SA Slaughterbeck, CR Wakeman, W Li, Y Feng, D Ho, A Nicholas, E Hirokawa, KE Bohn, P Joines, KM Peng, HC Hawrylycz, MJ Phillips, JW Hohmann, JG Wohnoutka, P Koch, C Bernard, A Dang, C Jones, AR Zeng, HK Gerfen, CR AF Oh, Seung Wook Harris, Julie A. Ng, Lydia Winslow, Brent Cain, Nicholas Mihalas, Stefan Wang, Quanxin Lau, Chris Kuan, Leonard Henry, Alex M. Mortrud, Marty T. Ouellette, Benjamin Nguyen, Thuc Nghi Sorensen, Staci A. Slaughterbeck, Clifford R. Wakeman, Wayne Li, Yang Feng, David Ho, Anh Nicholas, Eric Hirokawa, Karla E. Bohn, Phillip Joines, Kevin M. Peng, Hanchuan Hawrylycz, Michael J. Phillips, John W. Hohmann, John G. Wohnoutka, Paul Koch, Christof Bernard, Amy Dang, Chinh Jones, Allan R. Zeng, Hongkui Gerfen, Charles R. TI A mesoscale connectome of the mouse brain SO NATURE LA English DT Article ID MEDIAL PREFRONTAL CORTEX; PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; PARAFASCICULAR THALAMIC NUCLEUS; RAT VISUAL-CORTEX; THALAMOCORTICAL PROJECTIONS; EFFERENT PROJECTIONS; BARREL CORTEX; CORTICOTHALAMIC PROJECTIONS; CORTICAL PROJECTIONS; AFFERENT CONNECTIONS AB Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease. C1 [Oh, Seung Wook; Harris, Julie A.; Ng, Lydia; Winslow, Brent; Cain, Nicholas; Mihalas, Stefan; Wang, Quanxin; Lau, Chris; Kuan, Leonard; Henry, Alex M.; Mortrud, Marty T.; Ouellette, Benjamin; Nguyen, Thuc Nghi; Sorensen, Staci A.; Slaughterbeck, Clifford R.; Wakeman, Wayne; Li, Yang; Feng, David; Ho, Anh; Nicholas, Eric; Hirokawa, Karla E.; Bohn, Phillip; Joines, Kevin M.; Peng, Hanchuan; Hawrylycz, Michael J.; Phillips, John W.; Hohmann, John G.; Wohnoutka, Paul; Koch, Christof; Bernard, Amy; Dang, Chinh; Jones, Allan R.; Zeng, Hongkui] Allen Inst Brain Sci, Seattle, WA 98103 USA. [Gerfen, Charles R.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Zeng, HK (reprint author), Allen Inst Brain Sci, Seattle, WA 98103 USA. OI Nguyen, Thuc Nghi/0000-0002-6466-5883; Koch, Christof/0000-0001-6482-8067 FU Allen Institute for Brain Science FX We wish to thank the Allen Mouse Brain Connectivity Atlas Advisory Council members, D. Anderson, E. M. Callaway, K. Svoboda, J. L. R. Rubenstein, C. B. Saper and M. P. Stryker for their insightful advice. We thank T. Ragan for providing invaluable support and advice in the development and customization of the TissueCyte 1000 systems. We are grateful for the technical support of the many staff members in the Allen Institute who are not part of the authorship of this paper. This work was funded by the Allen Institute for Brain Science. The authors wish to thank the Allen Institute founders, P. G. Allen and J. Allen, for their vision, encouragement and support. NR 127 TC 306 Z9 309 U1 7 U2 108 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 APR 10 PY 2014 VL 508 IS 7495 BP 207 EP + DI 10.1038/nature13186 PG 28 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4UK UT WOS:000333979900037 PM 24695228 ER PT J AU Worobey, M Han, GZ Rambaut, A AF Worobey, Michael Han, Guan-Zhu Rambaut, Andrew TI A synchronized global sweep of the internal genes of modern avian influenza virus SO NATURE LA English DT Article ID EQUINE INFLUENZA; A VIRUSES; MAXIMUM-LIKELIHOOD; MOLECULAR CLOCKS; EVOLUTION; SEQUENCES; SWINE; DATES; DNA; RECOMBINATION AB Zoonotic infectious diseases such as influenza continue to pose a grave threat to human health(1). However, the factors that mediate the emergence of RNA viruses such as influenza A virus (IAV) are still incompletely understood(2,3). Phylogenetic inference is crucial to reconstructing the origins and tracing the flow of IAV within and between hosts(3-8). Here we show that explicitly allowing IAV host lineages to have independent rates of molecular evolution is necessary for reliable phylogenetic inference of IAV and that methods that do not do so, including 'relaxed' molecular clock models(9), can be positively misleading. A phylogenomic analysis using a host-specific local clock model recovers extremely consistent evolutionary histories across all genomic segments and demonstrates that the equine H7N7 lineage is a sister clade to strains from birds-as well as those from humans, swine and the equine H3N8 lineage-sharing an ancestor with them in the mid to late 1800s. Moreover, major western and eastern hemisphere avian influenza lineages inferred for each gene coalesce in the late 1800s. On the basis of these phylogenies and the synchrony of these key nodes, we infer that the internal genes of avian influenza virus (AIV) underwent a global selective sweep beginning in the late 1800s, a process that continued throughout the twentieth century and up to the present. The resulting western hemispheric AIV lineage subsequently contributed most of the genomic segments to the 1918 pandemic virus and, independently, the 1963 equine H3N8 panzootic lineage. This approach provides a clear resolution of evolutionary patterns and processes in IAV, including the flow of viral genes and genomes within and between host lineages. C1 [Worobey, Michael; Han, Guan-Zhu] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA. [Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland. [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Worobey, M (reprint author), Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA. EM worobey@email.arizona.edu; a.rambaut@ed.ac.uk RI Han, Guan-Zhu/A-6818-2011; OI Rambaut, Andrew/0000-0003-4337-3707 FU David and Lucile Packard Foundation; Wellcome Trust [092807]; European Union [278433-PREDEMICS]; European Research Council [260864]; National Institutes of Health/National Institute of Allergy and Infectious Diseases [R01AI084691] FX We thank J. Barnes, S. Meno, M. Shaw, R. Donis, S. Krauss, K. Friedman, R. Webster, Y. Muramoto and Y. Kawaoka for assistance in locating and sequencing A/equine/Detroit/3/1964(H7N7), A/chicken/Japan/1925(H7N7) and A/duck/Manitoba/1953(H10N7); M. Sanderson for comments on the HSLC model; S. Zohari for discussions of the NS1/2 A and B lineages; and M. Nachman, Y. Kawaoka, T. Watts, J. Cox, and D. Gill for comments. This work was supported by grants from the David and Lucile Packard Foundation to M. W., and the Wellcome Trust (grant no. 092807) to A. R. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 278433-PREDEMICS and European Research Council grant agreement no. 260864. The methodological approach was developed in part with support from a grant from the National Institutes of Health/National Institute of Allergy and Infectious Diseases. (R01AI084691). NR 44 TC 55 Z9 56 U1 8 U2 68 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 APR 10 PY 2014 VL 508 IS 7495 BP 254 EP + DI 10.1038/nature13016 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4UK UT WOS:000333979900046 PM 24531761 ER PT J AU Duyvestyn, JM Taylor, SJ Dagger, SA Orandle, M Morse, HC Thien, CBF Langdon, WY AF Duyvestyn, Johanna M. Taylor, Samuel J. Dagger, Samantha A. Orandle, Marlene Morse, Herbert C., III Thien, Christine B. F. Langdon, Wallace Y. TI Dasatinib Targets B-Lineage Cells but Does Not Provide an Effective Therapy for Myeloproliferative Disease in c-Cbl RING Finger Mutant Mice SO PLOS ONE LA English DT Article ID JUVENILE MYELOMONOCYTIC LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACQUIRED UNIPARENTAL DISOMY; HEMATOPOIETIC STEM-CELLS; SRC-FAMILY KINASES; LYN-DEFICIENT MICE; INHIBITOR DASATINIB; AUTOIMMUNE-DISEASE; MYELOID NEOPLASMS; TYROSINE KINASES AB This study aimed to determine whether the multi-kinase inhibitor dasatinib would provide an effective therapy for myeloproliferative diseases (MPDs) involving c-Cbl mutations. These mutations, which occur in the RING finger and linker domains, abolish the ability of c-Cbl to function as an E3 ubiquitin ligase and downregulate activated protein tyrosine kinases. Here we analyzed the effects of dasatinib in a c-Cbl RING finger mutant mouse that develops an MPD with a phenotype similar to the human MPDs. The mice are characterized by enhanced tyrosine kinase signaling resulting in an expansion of hematopoietic stem cells, multipotent progenitors and cells within the myeloid lineage. Since c-Cbl is a negative regulator of c-Kit and Src signaling we reasoned that dasatinib, which targets these kinases, would be an effective therapy. Furthermore, two recent studies showed dasatinib to be effective in inhibiting the in vitro growth of cells from leukemia patients with c-Cbl RING finger and linker domain mutations. Surprisingly we found that dasatinib did not provide an effective therapy for c-Cbl RING finger mutant mice since it did not suppress any of the hematopoietic lineages that promote MPD development. Thus we conclude that dasatinib may not be an appropriate therapy for leukemia patients with c-Cbl mutations. We did however find that dasatinib caused a marked reduction of pre-B cells and immature B cells which correlated with a loss of Src activity. This study is therefore the first to provide a detailed characterization of in vivo effects of dasatinib in a hematopoietic disorder that is driven by protein tyrosine kinases other than BCR-ABL. C1 [Duyvestyn, Johanna M.; Taylor, Samuel J.; Dagger, Samantha A.; Thien, Christine B. F.; Langdon, Wallace Y.] Univ Western Australia, Sch Pathol & Lab Med, Crawley, WA, Australia. [Orandle, Marlene] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, NIH, Rockville, MD USA. [Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD USA. RP Langdon, WY (reprint author), Univ Western Australia, Sch Pathol & Lab Med, Crawley, WA, Australia. EM wally.langdon@uwa.edu.au OI Morse, Herbert/0000-0002-9331-3705; Taylor, Samuel/0000-0002-9468-8752 FU National Health and Medical Research Council [572516, 634414]; Cancer Council of WA; Medical and the Health Research Infrastructure Fund; Intramural Research Program of the NIH FX This work was supported by National Health and Medical Research Council Project Grants 572516 and 634414, the Cancer Council of WA, and the Medical and the Health Research Infrastructure Fund, and in part by the Intramural Research Program of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 5 Z9 5 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 APR 9 PY 2014 VL 9 IS 4 DI 10.1371/journal.pone.0094717 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE9PC UT WOS:000334339000138 ER PT J AU Wang, Z Anderson, FA Ward, M Bhattacharyya, T AF Wang, Zhong Anderson, Frederick A., Jr. Ward, Michael Bhattacharyya, Timothy TI Surgical Site Infections and Other Postoperative Complications following Prophylactic Anticoagulation in Total Joint Arthroplasty SO PLOS ONE LA English DT Article ID TOTAL KNEE ARTHROPLASTY; VENOUS THROMBOEMBOLISM PROPHYLAXIS; MOLECULAR-WEIGHT HEPARIN; PRIMARY TOTAL HIP; UNITED-STATES; RISK-FACTORS; REPLACEMENT; THROMBOPROPHYLAXIS; OUTCOMES AB Background: Anticoagulants reduce the risk of venous thromboembolism (VTE) after total joint replacement. However, concern remains that pharmacologic VTE prophylaxis can lead to bleeding, which may impact on postoperative complications such as infections and reoperations. Methods and Findings: From the Global Orthopedic Registry (GLORY), we reviewed 3,755 patients in US who elected for primary total hip or knee arthroplasty, received either warfarin or low molecular weight heparin ( LMWH) as VTE prophylactics, and had up-to-90-day follow-up after discharge. We compared incidence rates of VTE, infections and other complications between LMWH and warfarin groups, and used multivariate analyses with propensity score weighting to generate the odds ratio (OR). Patients receiving LMWH tended to be older and higher in the American Society of Anesthesiologists grade scores. In contrast, warfarin was used more frequently for hip arthroplasty with longer duration among patients with more pre-existing comorbidity (all P<0.02). A weight variable was created with propensity score to account for differences in covariate distributions. Propensity score-weighted analyses showed no differences in VTE complications. However, compared to warfarin, LMWH was associated with significantly higher rates of bleeding (6.2% vs. 2.1%; OR = 3.82, 95% confidence interval [CI], 2.64 to 5.52), blood transfusion (29.4% vs. 22.0%; OR = 1.75, 95% CI, 1.51 to 2.04), reoperations (2.4% vs. 1.3%; OR = 1.77, 95% CI, 1.07 to 2.93) and infections (1.6% vs. 0.6%; OR = 2.79, 95% CI, 1.42 to 5.45). Similar results were obtained from compliant uses of warfarin (26%) and LMWH (62%) according to clinical guidelines. While surgical site infections were mostly superficial, current study was underpowered to compare incidence rates of deep infections (<1.0%). Conclusions: Surgical site infections and reoperations in 3 months following primary total joint arthroplasty may be associated with anticoagulant use that exhibited higher bleeding risk. Long-term complications and deep wound infections remain to be studied. C1 [Wang, Zhong; Ward, Michael; Bhattacharyya, Timothy] NIAMSD, Clin Trials & Outcomes Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Anderson, Frederick A., Jr.] Univ Massachusetts, Sch Med, Ctr Outcomes Res, Worcester, MA USA. RP Wang, Z (reprint author), NIAMSD, Clin Trials & Outcomes Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. EM john.wang@nih.gov FU Intramural Research Program of NIAMS at NIH FX This study was supported by the Intramural Research Program of NIAMS at NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 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 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2014 VL 9 IS 4 AR e91755 DI 10.1371/journal.pone.0091755 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE9PC UT WOS:000334339000012 PM 24717837 ER PT J AU Randow, F Youle, RJ AF Randow, Felix Youle, Richard J. TI Self and Nonself: How Autophagy Targets Mitochondria and Bacteria SO CELL HOST & MICROBE LA English DT Review ID DEPOLARIZED MITOCHONDRIA; ANTIBACTERIAL AUTOPHAGY; DAMAGED MITOCHONDRIA; DOPAMINERGIC-NEURONS; PINK1-PARKIN PATHWAY; SELECTIVE AUTOPHAGY; PARKIN RECRUITMENT; ERYTHROID-CELLS; RECEPTOR NDP52; LIGASE PARKIN AB Autophagy is an evolutionarily conserved pathway that transports cytoplasmic components for degradation into lysosomes. Selective autophagy can capture physically large objects, including cell-invading pathogens and damaged or superfluous organelles. Selectivity is achieved by cargo receptors that detect substrate-associated "eat-me" signals. In this Review, we discuss basic principles of selective autophagy and compare the "eat-me" signals and cargo receptors that mediate autophagy of bacteria and bacteria-derived endosymbionts-i.e., mitochondria. C1 [Randow, Felix] MRC, Mol Biol Lab, Div Prot & Nucle Acid Chem, Cambridge CB2 0QH, England. [Randow, Felix] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 0QQ, England. [Youle, Richard J.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Randow, F (reprint author), MRC, Mol Biol Lab, Div Prot & Nucle Acid Chem, Francis Crick Ave, Cambridge CB2 0QH, England. EM randow@mrc-lmb.cam.ac.uk; youler@ninds.nih.gov FU MRC [U105170648]; National Institute of Neurological Disorders and Stroke intramural program FX We apologize to all colleagues whose work could not be cited due to space limitations. Work in the authors' laboratories was supported by the MRC (U105170648, FR) and the National Institute of Neurological Disorders and Stroke intramural program (to R.Y.). We thank members of our laboratories for invaluable discussions. NR 90 TC 62 Z9 63 U1 4 U2 26 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 EI 1934-6069 J9 CELL HOST MICROBE JI Cell Host Microbe PD APR 9 PY 2014 VL 15 IS 4 BP 404 EP 412 DI 10.1016/j.chom.2014.03.012 PG 9 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AE8VL UT WOS:000334280900005 PM 24721569 ER PT J AU He, S Wang, YX Petralia, RS Brenowitz, SD AF He, Shan Wang, Ya-Xian Petralia, Ronald S. Brenowitz, Stephan D. TI Cholinergic Modulation of Large-Conductance Calcium-Activated Potassium Channels Regulates Synaptic Strength and Spine Calcium in Cartwheel Cells of the Dorsal Cochlear Nucleus SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; DENDRITIC SPINES; GLUTAMATE RECEPTORS; ACETYLTRANSFERASE ACTIVITY; RAT HIPPOCAMPUS; NERVOUS-SYSTEM; MOUSE-BRAIN; SK CHANNELS; NEURONS; SYNAPSES AB Acetylcholine is a neuromodulatory transmitter that controls synaptic plasticity and sensory processing in many brain regions. The dorsal cochlear nucleus (DCN) is an auditory brainstem nucleus that integrates auditory signals from the cochlea with multisensory inputs from several brainstem nuclei and receives prominent cholinergic projections. In the auditory periphery, cholinergic modulation serves a neuroprotective function, reducing cochlear output under high sound levels. However, the role of cholinergic signaling in the DCN is less understood. Here we examine postsynaptic mechanisms of cholinergic modulation at glutamatergic synapses formed by parallel fiber axons onto cartwheel cells (CWCs) in the apical DCN circuit from mouse brainstem slice using calcium (Ca) imaging combined with two-photon laser glutamate uncaging onto CWC spines. Activation of muscarinic acetylcholine receptors (mAChRs) significantly increased the amplitude of both uncaging-evoked EPSPs (uEPSPs) and spine Ca transients. Our results demonstrate that mAChRs in CWC spines act by suppressing large-conductance calcium-activated potassium (BK) channels, and this effect is mediated through the cAMP/protein kinase A signaling pathway. Blocking BK channels relieves voltage-dependent magnesium block of NMDA receptors, thereby enhancing uEPSPs and spine Ca transients. Finally, wedemonstrate thatmAChRactivation inhibits L-type Ca channels and thus may contribute to the suppression of BK channels by mAChRs. In summary, we demonstrate a novel role for BK channels in regulating glutamatergic transmission and show that this mechanism is under modulatory control of mAChRs. C1 [He, Shan; Brenowitz, Stephan D.] Natl Inst Deafness & Other Commun Disorders, Sect Synapt Transmiss, NIH, Bethesda, MD 20892 USA. [Wang, Ya-Xian; Petralia, Ronald S.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. RP Brenowitz, SD (reprint author), Howard Hughes Med Inst, Janelia Farm Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA. EM brenowitzs@janelia.hhmi.org FU National Institute on Deafness; Communication Disorders Intramural Research Program FX This work was supported by the National Institute on Deafness and Other Communication Disorders Intramural Research Program. We thank Drs. Miloslav Sedlacek and Noah Roy for helpful comments on this manuscript. NR 60 TC 6 Z9 6 U1 0 U2 3 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 APR 9 PY 2014 VL 34 IS 15 BP 5261 EP 5272 DI 10.1523/JNEUROSCI.3728-13.2014 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AE9RX UT WOS:000334347700019 PM 24719104 ER PT J AU Eapen, ZJ Lauer, MS Temple, RJ AF Eapen, Zubin J. Lauer, Michael S. Temple, Robert J. TI The Imperative of Overcoming Barriers to the Conduct of Large, Simple Trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Eapen, Zubin J.] Duke Clin Res Inst, Durham, NC 27715 USA. [Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Temple, Robert J.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Eapen, ZJ (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM zubin.eapen@duke.edu FU FDA HHS [U19FD003800] NR 5 TC 28 Z9 29 U1 0 U2 6 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 APR 9 PY 2014 VL 311 IS 14 BP 1397 EP 1398 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AE4EP UT WOS:000333935000012 PM 24715072 ER PT J AU Gliwa, C Pearson, SD AF Gliwa, Catherine Pearson, Steven D. TI Evidentiary Rationales for the Choosing Wisely Top 5 Lists SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Gliwa, Catherine; Pearson, Steven D.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Pearson, SD (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM pearsonsd@cc.nih.gov FU Intramural NIH HHS NR 2 TC 13 Z9 13 U1 0 U2 1 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 APR 9 PY 2014 VL 311 IS 14 BP 1443 EP 1444 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AE4EP UT WOS:000333935000022 PM 24715077 ER PT J AU Cheung, HH Liu, XZ Canterel-Thouennon, L Li, L Edmonson, C Rennert, OM AF Cheung, Hoi-Hung Liu, Xiaozhuo Canterel-Thouennon, Lucile Li, Lu Edmonson, Catherine Rennert, Owen M. TI Telomerase Protects Werner Syndrome Lineage-Specific Stem Cells from Premature Aging SO STEM CELL REPORTS LA English DT Article ID SELF-RENEWAL; IN-VIVO; WRN; SENESCENCE; MICE; TRF2; DIFFERENTIATION; INSTABILITY; GENERATION; MUTATIONS AB Werner syndrome (WS) patients exhibit premature aging predominantly in mesenchyme-derived tissues, but not in neural lineages, a consequence of telomere dysfunction and accelerated senescence. The cause of this lineage-specific aging remains unknown. Here, we document that reprogramming of WS fibroblasts to pluripotency elongated telomere length and prevented telomere dysfunction. To obtain mechanistic insight into the origin of tissue-specific aging, we differentiated iPSCs to mesenchymal stem cells (MSCs) and neural stem/progenitor cells (NPCs). We observed recurrence of premature senescence associated with accelerated telomere attrition and defective synthesis of the lagging strand telomeres in MSCs, but not in NPCs. We postulate this ''aging'' discrepancy is regulated by telomerase. Expression of hTERT or p53 knockdown ameliorated the accelerated aging phenotypein MSC, whereas inhibition of telomerase sensitized NPCs to DNA damage. Our findings unveil a role for telomerase in the protection of accelerated aging in a specific lineage of stem cells. C1 [Cheung, Hoi-Hung; Liu, Xiaozhuo; Canterel-Thouennon, Lucile; Edmonson, Catherine; Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Genom, NIH, Bethesda, MD 20892 USA. [Cheung, Hoi-Hung; Liu, Xiaozhuo; Li, Lu] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. RP Cheung, HH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Genom, NIH, Bethesda, MD 20892 USA. EM cheunghh@cuhk.edu.hk; rennerto@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank Dr. Bob Weinberg for providing the pBABE-hygro-hTERT retroviral vector. This research was supported by an intramural research grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 52 TC 23 Z9 24 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2213-6711 J9 STEM CELL REP JI Stem Cell Rep. PD APR 8 PY 2014 VL 2 IS 4 BP 534 EP 546 DI 10.1016/j.stemcr.2014.02.006 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AI1XP UT WOS:000336648800012 PM 24749076 ER PT J AU Moran, AE Forouzanfar, MH Roth, GA Mensah, GA Ezzati, M Murray, CJL Naghavi, M AF Moran, Andrew E. Forouzanfar, Mohammad H. Roth, Gregory A. Mensah, George A. Ezzati, Majid Murray, Christopher J. L. Naghavi, Mohsen TI Temporal Trends in Ischemic Heart Disease Mortality in 21 World Regions, 1980 to 2010 The Global Burden of Disease 2010 Study SO CIRCULATION LA English DT Article DE epidemiology; mortality; myocardial ischemia; trends; world health ID MONICA PROJECT POPULATIONS; CARDIOVASCULAR-DISEASE; RISK-FACTORS; DEVELOPING-COUNTRIES; SYSTEMATIC ANALYSIS; EVENT RATES; DEATH; STATISTICS; TRANSITION; DECLINE AB Background Ischemic heart disease (IHD) is the leading cause of death worldwide. The Global Burden of Diseases, Risk Factors and Injuries 2010 Study estimated global and regional IHD mortality from 1980 to 2010. Methods and Results Sources for IHD mortality estimates were country-level surveillance, verbal autopsy, and vital registration data. Regional income, metabolic and nutritional risk factors, and other covariates were estimated from surveys and a systematic review. An estimation and validation process led to an ensemble model of IHD mortality for 21 world regions. Globally, age-standardized IHD mortality has declined since the 1980s, and high-income regions (especially Australasia, Western Europe, and North America) experienced the most remarkable declines. Age-standardized IHD mortality increased in former Soviet Union countries and South Asia in the 1990s and attenuated after 2000. In 2010, Eastern Europe and Central Asia had the highest age-standardized IHD mortality rates. More IHD deaths occurred in South Asia in 2010 than in any other region. On average, IHD deaths in South Asia, North Africa and the Middle East, and sub-Saharan Africa occurred at younger ages in comparison with most other regions. Conclusions In most world regions, particularly in high-income regions, age-standardized IHD mortality rates have declined significantly since 1980. High age-standardized IHD mortality in Eastern Europe, Central Asia, and South Asia point to the need to prevent and control established risk factors in those regions and to research the unique behavioral and environmental determinants of higher IHD mortality. C1 [Moran, Andrew E.] Columbia Univ, Med Ctr, Dept Med, Div Gen Med, New York, NY 10032 USA. [Forouzanfar, Mohammad H.; Roth, Gregory A.; Murray, Christopher J. L.; Naghavi, Mohsen] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Roth, Gregory A.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA. [Mensah, George A.] NHLBI, CTRIS, NIH, Bethesda, MD 20892 USA. [Ezzati, Majid] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, London, England. [Ezzati, Majid] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England. RP Moran, AE (reprint author), Columbia Univ, Div Gen Med, Presbyterian Hosp East Room 105,622 West 168th St, New York, NY 10032 USA. EM aem35@cumc.columbia.edu FU Bill and Melinda Gates Foundation; American Heart Association; US National Heart, Lung, and Blood Institute [K08 HL089675-01A1]; Columbia University Irving Scholarship FX This research was supported by the Bill and Melinda Gates Foundation, an American Heart Association Postdoctoral Fellowship to Dr Roth, and US National Heart, Lung, and Blood Institute award K08 HL089675-01A1, and a Columbia University Irving Scholarship to Dr Moran. NR 26 TC 89 Z9 93 U1 7 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD APR 8 PY 2014 VL 129 IS 14 BP 1483 EP 1492 DI 10.1161/CIRCULATIONAHA.113.004042 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AG4DQ UT WOS:000335369900008 PM 24573352 ER PT J AU Moran, AE Forouzanfar, MH Roth, GA Mensah, GA Ezzati, M Flaxman, A Murray, CJL Naghavi, M AF Moran, Andrew E. Forouzanfar, Mohammad H. Roth, Gregory A. Mensah, George A. Ezzati, Majid Flaxman, Abraham Murray, Christopher J. L. Naghavi, Mohsen TI The Global Burden of Ischemic Heart Disease in 1990 and 2010 SO CIRCULATION LA English DT Article DE angina pectoris; epidemiology; heart failure; myocardial infarction; myocardial ischemia; trends; world health ID CORONARY MICROVASCULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; CHEST-PAIN; SYSTEMATIC ANALYSIS; MAGNETIC-RESONANCE; ROSE QUESTIONNAIRE; CARDIAC TROPONIN; WOMEN; COUNTRIES; ANGINA AB Background Ischemic heart disease (IHD) burden consists of years of life lost from IHD deaths and years of disability lived with 3 nonfatal IHD sequelae: nonfatal acute myocardial infarction, angina pectoris, and ischemic heart failure. Our aim was to estimate the global and regional burden of IHD in 1990 and 2010. Methods and Results Global and regional estimates of acute myocardial infarction incidence and angina and heart failure prevalence by age, sex, and world region in 1990 and 2010 were estimated based on data from a systematic review and nonlinear mixed-effects meta-regression methods. Age-standardized acute myocardial infarction incidence and angina prevalence decreased globally between 1990 and 2010; ischemic heart failure prevalence increased slightly. The global burden of IHD increased by 29 million disability-adjusted life-years (29% increase) between 1990 and 2010. About 32.4% of the growth in global IHD disability-adjusted life-years between 1990 and 2010 was attributable to aging of the world population, 22.1% was attributable to population growth, and total disability-adjusted life-years were attenuated by a 25.3% decrease in per capita IHD burden (decreased rate). The number of people living with nonfatal IHD increased more than the number of IHD deaths since 1990, but >90% of IHD disability-adjusted life-years in 2010 were attributable to IHD deaths. Conclusions Globally, age-standardized acute myocardial infarction incidence and angina prevalence have decreased, and ischemic heart failure prevalence has increased since 1990. Despite decreased age-standardized fatal and nonfatal IHD in most regions since 1990, population growth and aging led to a higher global burden of IHD in 2010. C1 [Moran, Andrew E.] Columbia Univ, Med Ctr, Dept Med, Div Gen Med, New York, NY 10032 USA. [Forouzanfar, Mohammad H.; Roth, Gregory A.; Flaxman, Abraham; Murray, Christopher J. L.; Naghavi, Mohsen] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Roth, Gregory A.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA. [Mensah, George A.] NHLBI, CTRIS, NIH, Bethesda, MD 20892 USA. [Ezzati, Majid] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, London, England. [Ezzati, Majid] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England. RP Moran, AE (reprint author), Columbia Univ, Div Gen Med, Presbyterian Hosp East Room 105,622 West 168th St, New York, NY 10032 USA. EM aem35@cumc.columbia.edu FU Bill and Melinda Gates Foundation; American Heart Association; US National Heart, Lung, and Blood Institute [K08 HL089675-01A1]; Columbia University Irving Scholarship FX This research was supported by the Bill and Melinda Gates Foundation, an American Heart Association Postdoctoral Fellowship to Dr Roth, and US National Heart, Lung, and Blood Institute award K08 HL089675-01A1, and a Columbia University Irving Scholarship to Dr Moran. NR 29 TC 97 Z9 102 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD APR 8 PY 2014 VL 129 IS 14 BP 1493 EP 1501 DI 10.1161/CIRCULATIONAHA.113.004046 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AG4DQ UT WOS:000335369900009 PM 24573351 ER PT J AU Chretien, JP George, D Shaman, J Chitale, RA McKenzie, FE AF Chretien, Jean-Paul George, Dylan Shaman, Jeffrey Chitale, Rohit A. McKenzie, F. Ellis TI Influenza Forecasting in Human Populations: A Scoping Review SO PLOS ONE LA English DT Review ID TIME-SERIES MODEL; PANDEMIC INFLUENZA; INFECTIOUS-DISEASE; EPIDEMIC MODELS; PREDICTION; SURVEILLANCE; STRATEGIES; A/H1N1PDM; OUTBREAKS; ILLNESS AB Forecasts of influenza activity in human populations could help guide key preparedness tasks. We conducted a scoping review to characterize these methodological approaches and identify research gaps. Adapting the PRISMA methodology for systematic reviews, we searched PubMed, CINAHL, Project Euclid, and Cochrane Database of Systematic Reviews for publications in English since January 1, 2000 using the terms '' influenza AND (forecast* OR predict*)'', excluding studies that did not validate forecasts against independent data or incorporate influenza-related surveillance data from the season or pandemic for which the forecasts were applied. We included 35 publications describing population-based (N = 27), medical facility-based (N = 4), and regional or global pandemic spread (N = 4) forecasts. They included areas of North America (N = 15), Europe (N = 14), and/or Asia-Pacific region (N = 4), or had global scope (N = 3). Forecasting models were statistical (N = 18) or epidemiological (N = 17). Five studies used data assimilation methods to update forecasts with new surveillance data. Models used virological (N = 14), syndromic (N = 13), meteorological (N = 6), internet search query (N = 4), and/or other surveillance data as inputs. Forecasting outcomes and validation metrics varied widely. Two studies compared distinct modeling approaches using common data, 2 assessed model calibration, and 1 systematically incorporated expert input. Of the 17 studies using epidemiological models, 8 included sensitivity analysis. This review suggests need for use of good practices in influenza forecasting (e. g., sensitivity analysis); direct comparisons of diverse approaches; assessment of model calibration; integration of subjective expert input; operational research in pilot, real-world applications; and improved mutual understanding among modelers and public health officials. C1 [Chretien, Jean-Paul; Chitale, Rohit A.] Armed Forces Hlth Surveillance Ctr, Div Integrated Biosurveillance, Silver Spring, MD USA. [George, Dylan] Dept Hlth & Human Serv, Biomed Adv Res & Dev Author, Div Analyt Decis Support, Washington, DC USA. [Shaman, Jeffrey] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA. [McKenzie, F. Ellis] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Chretien, JP (reprint author), Armed Forces Hlth Surveillance Ctr, Div Integrated Biosurveillance, Silver Spring, MD USA. EM jean.chretien.mil@mail.mil OI Chretien, Jean-Paul/0000-0001-8143-6823 FU US NIH [GM100467]; NIH Models of Infectious Disease Agent Study program [1U54GM088558]; NIEHS Center [ES009089]; RAPIDD program of the Science and Technology Directorate, US Department of Homeland Security; Fogarty International Center, National Institutes of Health FX Funding for JS was provided by US NIH grant GM100467 and the NIH Models of Infectious Disease Agent Study program through cooperative agreement 1U54GM088558, as well as NIEHS Center grant ES009089 and the RAPIDD program of the Science and Technology Directorate, US Department of Homeland Security, and Fogarty International Center, 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 51 TC 18 Z9 18 U1 2 U2 23 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 APR 8 PY 2014 VL 9 IS 4 AR e94130 DI 10.1371/journal.pone.0094130 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE7FA UT WOS:000334160900090 PM 24714027 ER PT J AU Hyland, PL Hu, N Rotunno, M Su, H Wang, CY Wang, LM Pfeiffer, RM Gherman, B Giffen, C Dykes, C Dawsey, SM Abnet, CC Johnson, KM Acosta, RD Young, PE Cash, BD Taylor, PR AF Hyland, Paula L. Hu, Nan Rotunno, Melissa Su, Hua Wang, Chaoyu Wang, Lemin Pfeiffer, Ruth M. Gherman, Barbara Giffen, Carol Dykes, Cathy Dawsey, Sanford M. Abnet, Christian C. Johnson, Kathryn M. Acosta, Ruben D. Young, Patrick E. Cash, Brooks D. Taylor, Philip R. TI Global Changes in Gene Expression of Barrett's Esophagus Compared to Normal Squamous Esophagus and Gastric Cardia Tissues SO PLOS ONE LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; TRANSCRIPTION FACTORS; INCREASING INCIDENCE; CDX-2 EXPRESSION; CANCER INCIDENCE; ADENOCARCINOMA; RISK; METAPLASIA; EPITHELIUM; DIFFERENTIATION AB Background: Barrett's esophagus (BE) is a metaplastic precursor lesion of esophageal adenocarcinoma (EA), the most rapidly increasing cancer in western societies. While the prevalence of BE is increasing, the vast majority of EA occurs in patients with undiagnosed BE. Thus, we sought to identify genes that are altered in BE compared to the normal mucosa of the esophagus, and which may be potential biomarkers for the development or diagnosis of BE. Design: We performed gene expression analysis using HG-U133A Affymetrix chips on fresh frozen tissue samples of Barrett's metaplasia and matched normal mucosa from squamous esophagus (NE) and gastric cardia (NC) in 40 BE patients. Results: Using a cut off of 2-fold and P, 1.12E-06 (0.05 with Bonferroni correction), we identified 1324 differentially expressed genes comparing BE vs NE and 649 differentially-expressed genes comparing BE vs NC. Except for individual genes such as the SOXs and PROM1 that were dysregulated only in BE vs NE, we found a subset of genes (n = 205) whose expression was significantly altered in both BE vs NE and BE vs NC. These genes were overrepresented in different pathways, including TGF-beta and Notch. Conclusion: Our findings provide additional data on the global transcriptome in BE tissues compared to matched NE and NC tissues which should promote further understanding of the functions and regulatory mechanisms of genes involved in BE development, as well as insight into novel genes that may be useful as potential biomarkers for the diagnosis of BE in the future. C1 [Hyland, Paula L.; Hu, Nan; Rotunno, Melissa; Su, Hua; Wang, Chaoyu; Wang, Lemin; Pfeiffer, Ruth M.; Dawsey, Sanford M.; Abnet, Christian C.; Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Hyland, Paula L.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Gherman, Barbara] Westat Corp, Rockville, MD USA. [Giffen, Carol] Informat Management Serv Inc, Silver Spring, MD USA. [Dykes, Cathy; Johnson, Kathryn M.; Acosta, Ruben D.; Young, Patrick E.; Cash, Brooks D.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. RP Hyland, PL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM hylandpl@mail.nih.gov RI Abnet, Christian/C-4111-2015 OI Abnet, Christian/0000-0002-3008-7843 FU National Institutes of Health, National Cancer Institute; Division of Cancer Epidemiology and Genetics; Cancer Prevention Fellowship Program, Division of Cancer Prevention, NCI; Health and Social Care (HSC), Northern Ireland, UK FX This research was supported by Intramural Research Program of the National Institutes of Health, National Cancer Institute, the Division of Cancer Epidemiology and Genetics, the Cancer Prevention Fellowship Program, Division of Cancer Prevention, NCI (to P. L. H); and Health and Social Care (HSC), Northern Ireland, UK (to P. L. H). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 5 Z9 6 U1 0 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 APR 8 PY 2014 VL 9 IS 4 AR e93219 DI 10.1371/journal.pone.0093219 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE7FA UT WOS:000334160900018 PM 24714516 ER PT J AU Shao, J Choe, V Cheng, HL Tsai, YC Weissman, AM Luo, SW Rao, H AF Shao, Jia Choe, Vitnary Cheng, Haili Tsai, Yien Che Weissman, Allan M. Luo, Shiwen Rao, Hai TI Ubiquitin Ligase gp78 Targets Unglycosylated Prion Protein PrP for Ubiquitylation and Degradation SO PLOS ONE LA English DT Article ID PROTEASOME SYSTEM; ENDOPLASMIC-RETICULUM; MISFOLDED PRP; DISEASES; CYTOSOL; DYSFUNCTION; INHIBITION; PATHWAY AB Prion protein PrP is a central player in several devastating neurodegenerative disorders, including mad cow disease and Creutzfeltd-Jacob disease. Conformational alteration of PrP into an aggregation-prone infectious form PrPSc can trigger pathogenic events. How levels of PrP are regulated is poorly understood. Human PrP is known to be degraded by the proteasome, but the specific proteolytic pathway responsible for PrP destruction remains elusive. Here, we demonstrate that the ubiquitin ligase gp78, known for its role in protein quality control, is critical for unglycosylated PrP ubiquitylation and degradation. Furthermore, C-terminal sequences of PrP protein are crucial for its ubiquitylation and degradation. Our study reveals the first ubiquitin ligase specifically involved in prion protein PrP degradation and PrP sequences crucial for its turnover. Our data may lead to a new avenue to control PrP level and pathogenesis. C1 [Shao, Jia; Luo, Shiwen] Nanchang Univ, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China. [Choe, Vitnary; Cheng, Haili; Rao, Hai] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Tsai, Yien Che; Weissman, Allan M.] NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. RP Luo, SW (reprint author), Nanchang Univ, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China. EM shiwenluo@ncu.edu.cn; raoh@uthscsa.edu OI Tsai, Yien Che/0000-0001-9624-1092 FU NIH [GM 078085]; Welch Foundation [AQ-1747]; Department of Defense [W911NF-11-10466]; NSFC [81060095]; 973 Program of China [2010CB535001]; 555 Program of Jiangxi; Center for Cancer Research, National Cancer Institute, NIH FX HR and SL are supported by the NIH (GM 078085), the Welch Foundation (AQ-1747), and the Department of Defense (W911NF-11-10466), NSFC (81060095), 973 Program of China (2010CB535001) and 555 Program of Jiangxi. AMW is supported by the Center for Cancer Research, National Cancer Institute, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 4 Z9 4 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 8 PY 2014 VL 9 IS 4 AR e92290 DI 10.1371/journal.pone.0092290 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE7FA UT WOS:000334160900004 PM 24714645 ER PT J AU Kozakov, D Li, KY Hall, DR Beglov, D Zheng, JF Vakili, P Schueler-Furman, O Paschalidis, IC Clore, GM Vajda, S AF Kozakov, Dima Li, Keyong Hall, David R. Beglov, Dmitri Zheng, Jiefu Vakili, Pirooz Schueler-Furman, Ora Paschalidis, Ioannis Ch Clore, G. Marius Vajda, Sandor TI Encounter complexes and dimensionality reduction in protein-protein association SO ELIFE LA English DT Article ID PARAMAGNETIC RELAXATION ENHANCEMENT; PHOSPHORYL TRANSFER COMPLEX; FREE-ENERGY LANDSCAPE; N-TERMINAL DOMAIN; ENZYME-I; DOCKING; VISUALIZATION; RECOGNITION; MECHANISM; BINDING AB An outstanding challenge has been to understand the mechanism whereby proteins associate. We report here the results of exhaustively sampling the conformational space in protein-protein association using a physics-based energy function. The agreement between experimental intermolecular paramagnetic relaxation enhancement (PRE) data and the PRE profiles calculated from the docked structures shows that the method captures both specific and non-specific encounter complexes. To explore the energy landscape in the vicinity of the native structure, the nonlinear manifold describing the relative orientation of two solid bodies is projected onto a Euclidean space in which the shape of low energy regions is studied by principal component analysis. Results show that the energy surface is canyon-like, with a smooth funnel within a two dimensional subspace capturing over 75% of the total motion. Thus, proteins tend to associate along preferred pathways, similar to sliding of a protein along DNA in the process of protein-DNA recognition. C1 [Kozakov, Dima; Hall, David R.; Beglov, Dmitri; Vajda, Sandor] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Li, Keyong; Zheng, Jiefu; Paschalidis, Ioannis Ch] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. [Li, Keyong; Vakili, Pirooz; Paschalidis, Ioannis Ch] Boston Univ, Div Syst Engn, Boston, MA 02215 USA. [Vakili, Pirooz] Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. [Schueler-Furman, Ora] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Microbiol & Mol Genet, IL-91010 Jerusalem, Israel. [Clore, G. Marius] Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD USA. [Vajda, Sandor] Boston Univ, Dept Chem, Boston, MA 02215 USA. RP Kozakov, D (reprint author), Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. EM midas@bu.edu; yannisp@bu.edu; mariusc@intra.niddk.nih.gov; vajda@bu.edu RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU National Institutes of Health [GM93147, GM61867]; National Institutes of Health Intramural program of NIDDK; National Science Foundation [DBI1147082]; US Israel Binational Science Foundation [2009418]; Russian Ministry of Education and Science [14.A18.21.1973] FX National Institutes of Health GM93147 Dima Kozakov, Ioannis Ch Paschalidis; National Institutes of Health GM61867 Sandor Vajda; National Institutes of Health Intramural program of NIDDK G Marius Clore; National Science Foundation DBI1147082 Dima Kozakov, Sandor Vajda; US Israel Binational Science Foundation 2009418 Dima Kozakov, Ora Schueler-Furman; Russian Ministry of Education and Science 14.A18.21.1973 Dima Kozakov NR 52 TC 12 Z9 12 U1 1 U2 17 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD APR 8 PY 2014 VL 3 AR e01370 DI 10.7554/eLife.01370 PG 21 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AE9TA UT WOS:000334351700001 PM 24714491 ER PT J AU Nguyen, DP Lin, SC AF Nguyen, David P. Lin, Shih-Chieh TI A frontal cortex event-related potential driven by the basal forebrain SO ELIFE LA English DT Article ID DEEP BRAIN-STIMULATION; PREFRONTAL CORTEX; SELECTIVE ATTENTION; NUCLEUS BASALIS; NEURONS; RAT; PROJECTIONS; SYSTEMS; TASK; ELECTROPHYSIOLOGY AB Event-related potentials (ERPs) are widely used in both healthy and neuropsychiatric conditions as physiological indices of cognitive functions. Contrary to the common belief that cognitive ERPs are generated by local activity within the cerebral cortex, here we show that an attention-related ERP in the frontal cortex is correlated with, and likely generated by, subcortical inputs from the basal forebrain (BF). In rats performing an auditory oddball task, both the amplitude and timing of the frontal ERP were coupled with BF neuronal activity in single trials. The local field potentials (LFPs) associated with the frontal ERP, concentrated in deep cortical layers corresponding to the zone of BF input, were similarly coupled with BF activity and consistently triggered by BF electrical stimulation within 5-10 msec. These results highlight the important and previously unrecognized role of long-range subcortical inputs from the BF in the generation of cognitive ERPs. C1 [Nguyen, David P.; 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 National Institutes of Health; Brain & Behavior Research Foundation (NARSAD) FX National Institutes of Health David P Nguyen, Shih-Chieh Lin; Brain & Behavior Research Foundation (NARSAD) Young Investigator Award Shih-Chieh Lin NR 52 TC 15 Z9 15 U1 0 U2 6 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD APR 8 PY 2014 VL 3 AR e02148 DI 10.7554/eLife.02148 PG 17 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AE9TA UT WOS:000334351700007 PM 24714497 ER PT J AU Sojka, DK Plougastel-Douglas, B Yang, LP Pak-Wittel, MA Artyomov, MN Ivanova, Y Zhong, C Chase, JM Rothman, PB Yu, J Riley, JK Zhu, JF Tian, ZG Yokoyama, WM AF Sojka, Dorothy K. Plougastel-Douglas, Beatrice Yang, Liping Pak-Wittel, Melissa A. Artyomov, Maxim N. Ivanova, Yulia Zhong, Chao Chase, Julie M. Rothman, Paul B. Yu, Jenny Riley, Joan K. Zhu, Jinfang Tian, Zhigang Yokoyama, Wayne M. TI Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells SO ELIFE LA English DT Article ID INNATE LYMPHOID-CELLS; METRIAL GLAND-CELLS; RECEPTOR-GAMMA CHAIN; MEMORY T-CELLS; HEMATOPOIETIC STEM; MICE LACKING; RAT-LIVER; EXPRESSION; MOUSE; MATURATION AB Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis and transcription factor-deficient mice to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells. Taken together with analysis of trNK cells in other tissues, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. C1 [Sojka, Dorothy K.; Plougastel-Douglas, Beatrice; Yang, Liping; Pak-Wittel, Melissa A.; Chase, Julie M.; Yu, Jenny; Yokoyama, Wayne M.] Washington Univ, Sch Med, Div Rheumatol, St Louis, MO 63130 USA. [Artyomov, Maxim N.; Ivanova, Yulia] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Zhong, Chao; Zhu, Jinfang] NIAID, Mol & Cellular Immunoregulat Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Rothman, Paul B.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Riley, Joan K.] Washington Univ, Sch Med, Div Obstet & Gynecol, St Louis, MO USA. [Tian, Zhigang] Univ Sci & Technol China, Sch Life Sci, Dept Immunol, Hefei 230026, Peoples R China. [Tian, Zhigang] Hefei Natl Lab Phys Sci Microscale, Hefei, Peoples R China. [Yokoyama, Wayne M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. RP Yokoyama, WM (reprint author), Washington Univ, Sch Med, Div Rheumatol, St Louis, MO 63130 USA. EM yokoyama@dom.wustl.edu RI Zhu, Jinfang/B-7574-2012; Tian, Zhigang/J-3512-2013 FU Howard Hughes Medical Institute; National Institutes of Health [1R01AI106561, 2R01AI033903, P30AR048335, T32 CA009547]; National Institutes of Health FX Howard Hughes Medical Institute Wayne M Yokoyama; National Institutes of Health 1R01AI106561 Wayne M Yokoyama; National Institutes of Health 2R01AI033903 Wayne M Yokoyama; National Institutes of Health Jinfang Zhu; National Institutes of Health P30AR048335 Wayne M Yokoyama; National Institutes of Health T32 CA009547 Dorothy K Sojka NR 65 TC 112 Z9 115 U1 7 U2 22 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD APR 8 PY 2014 VL 3 AR e01659 DI 10.7554/eLife.01659 PG 21 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AE9TA UT WOS:000334351700002 PM 24714492 ER PT J AU Rezlescu, C Barton, JJS Pitcher, D Duchaine, B AF Rezlescu, Constantin Barton, Jason J. S. Pitcher, David Duchaine, Bradley TI Normal acquisition of expertise with greebles in two cases of acquired prosopagnosia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FUSIFORM FACE AREA; OBJECT RECOGNITION; OCCIPITOTEMPORAL CORTEX; VISUAL EXPERTISE; PERCEPTION; MECHANISMS; NEUROPSYCHOLOGY; SPECIFICITY; SELECTIVITY; COMPETITION AB Face recognition is generally thought to rely on different neurocognitive mechanisms than most types of objects, but the specificity of these mechanisms is debated. One account suggests the mechanisms are specific to upright faces, whereas the expertise view proposes the mechanisms operate on objects of high within-class similarity with which an observer has become proficient at rapid individuation. Much of the evidence cited in support of the expertise view comes from laboratory-based training experiments involving computer-generated objects called greebles that are designed to place face-like demands on recognition mechanisms. A fundamental prediction of the expertise hypothesis is that recognition deficits with faces will be accompanied by deficits with objects of expertise. Here we present two cases of acquired prosopagnosia, Herschel and Florence, who violate this prediction: Both show normal performance in a standard greeble training procedure, along with severe deficits on a matched face training procedure. Herschel and Florence also meet several response time criteria that advocates of the expertise view suggest signal successful acquisition of greeble expertise. Furthermore, Herschel's results show that greeble learning can occur without normal functioning of the right fusiform face area, an area proposed to mediate greeble expertise. The marked dissociation between face and greeble expertise undermines greeble-based claims challenging face-specificity and indicates face recognition mechanisms are not necessary for object recognition after laboratorybased training. C1 [Rezlescu, Constantin] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Rezlescu, Constantin] UCL, Dept Cognit Perceptual & Brain Sci, London WC1H 0AP, England. [Barton, Jason J. S.] Univ British Columbia, Div Neurol, Dept Med, Vancouver, BC V5Z 3N9, Canada. [Barton, Jason J. S.] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 3N9, Canada. [Pitcher, David] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Duchaine, Bradley] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. RP Rezlescu, C (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM rezlescu@gmail.com RI Barton, Jason/A-6362-2012; Rezlescu, Constantin/C-3314-2012 OI Rezlescu, Constantin/0000-0001-8960-6305 FU AXA Research Fund; Bogue Research Fellowship; Hitchcock Foundation FX We thank Florence and Herschel for the generous contribution of their time and effort. This research was partly supported by AXA Research Fund, a Bogue Research Fellowship (to C. R.), and a Hitchcock Foundation grant (to B. D.). NR 54 TC 12 Z9 12 U1 9 U2 33 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 APR 8 PY 2014 VL 111 IS 14 BP 5123 EP 5128 DI 10.1073/pnas.1317125111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4VU UT WOS:000333985200031 PM 24706834 ER PT J AU Wang, F Wang, Z Hida, N Kiesewetter, DO Ma, Y Yang, K Rong, PF Liang, JM Tian, J Niu, G Chen, XY AF Wang, Fu Wang, Zhe Hida, Naoki Kiesewetter, Dale O. Ma, Ying Yang, Kai Rong, Pengfei Liang, Jimin Tian, Jie Niu, Gang Chen, Xiaoyuan TI A cyclic HSV1-TK reporter for real-time PET imaging of apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE reporter probe; positron-emission tomography ID PROTEIN-PROTEIN INTERACTIONS; POSITRON-EMISSION-TOMOGRAPHY; PROGRAMMED CELL-DEATH; SIMPLEX-VIRUS TYPE-1; IN-VIVO; THYMIDINE KINASE; LIVING SUBJECTS; ANNEXIN-V; CANCER; GENE AB The coordination of cell proliferation and programmed death (apoptosis) is essential for normal physiology, and imbalance in these two opposing processes is implicated in various diseases. Objective and quantitative noninvasive imaging of apoptosis would significantly facilitate rapid screening as well as validation of therapeutic chemicals. Herein, we molecularly engineered an apoptosis switch-on PET-based cyclic herpes simplex virus type 1-thymidine kinase reporter (cTK266) containing a caspase-3 recognition domain as the switch. Translation of the reporter and protein splicing in healthy mammalian cells produce an inactive cyclic chimera. Upon apoptosis, caspase-3-specific cleavage of the circular product occurs, resulting in the restoration of the thymidine kinase activity, which can be detected in living cells and animals by noninvasive PET imaging. Our results showed the high sensitivity of this reporter in dynamic and quantitative imaging of apoptosis in living subjects. This reporter could be applied as a valuable tool for high-throughput functional screening of proapoptotic and antiapoptotic compounds in preclinical models in drug development, and monitoring the destination of therapeutic cells in clinical settings. C1 [Wang, Fu; Liang, Jimin; Tian, Jie] Xidian Univ, Sch Life Sci & Technol, Xian 710071, Shaanxi, Peoples R China. [Wang, Fu; Wang, Zhe; Hida, Naoki; Kiesewetter, Dale O.; Ma, Ying; Yang, Kai; Rong, Pengfei; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Tian, J (reprint author), Xidian Univ, Sch Life Sci & Technol, Xian 710071, Shaanxi, Peoples R China. EM jaytian99@gmail.com; gang.niu@nih.gov; shawn.chen@nih.gov RI Tian, Jie/H-1190-2011; Tian, Jie/M-5675-2013; Liang, Jimin/B-5394-2014; Song, Jiangdian/L-6992-2016; OI Tian, Jie/0000-0003-0498-0432; Song, Jiangdian/0000-0002-3355-9930; Wang, Fu/0000-0001-9222-0833 FU National Basic Research and Development Program of China (973 Program) [2011CB707702, 2013CB733802, 2014CB744503]; National Natural Science Foundation of China [81301214, 81090272, 81227901, 81371596]; Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX This work was supported by the National Basic Research and Development Program of China (973 Program) (2011CB707702, 2013CB733802, and 2014CB744503), National Natural Science Foundation of China (81301214, 81090272, 81227901, and 81371596), and the Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 45 TC 12 Z9 13 U1 1 U2 30 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 APR 8 PY 2014 VL 111 IS 14 BP 5165 EP 5170 DI 10.1073/pnas.1321374111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4VU UT WOS:000333985200038 PM 24706884 ER PT J AU Lu, JH Yu, YD Zhu, I Cheng, YF Sun, PD AF Lu, Jinghua Yu, Yadong Zhu, Iowis Cheng, Yifan Sun, Peter D. TI Structural mechanism of serum amyloid A-mediated inflammatory amyloidosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE heparan sulfate binding site; HDL binding site ID HIGH-DENSITY-LIPOPROTEIN; ACUTE-PHASE REACTANT; FIBRIL FORMATION; RHEUMATOID-ARTHRITIS; RECEPTOR-BINDING; PROTEINS; HEXAMER; AGGREGATION; PROTEASES; OLIGOMER AB Serum amyloid A (SAA) represents an evolutionarily conserved family of inflammatory acute-phase proteins. It is also a major constituent of secondary amyloidosis. To understand its function and structural transition to amyloid, we determined a structure of human SAA1.1 in two crystal forms, representing a prototypic member of the family. Native SAA1.1 exists as a hexamer, with subunits displaying a unique four-helix bundle fold stabilized by its long C-terminal tail. Structure-based mutational studies revealed two positive-charge clusters, near the center and apex of the hexamer, that are involved in SAA association with heparin. The binding of high-density lipoprotein involves only the apex region of SAA and can be inhibited by heparin. Peptide amyloid formation assays identified the N-terminal helices 1 and 3 as amyloidogenic peptides of SAA1.1. Both peptides are secluded in the hexameric structure of SAA1.1, suggesting that the native SAA is nonpathogenic. Furthermore, dissociation of the SAA hexamer appears insufficient to initiate amyloidogenic transition, and proteolytic cleavage or removal of the C-terminal tail of SAA resulted in formation of various-sized structural aggregates containing similar to 5-nm regular repeating protofibril-like units. The combined structural and functional studies provide mechanistic insights into the pathogenic contribution of glycosaminoglycan in SAA1.1-mediated AA amyloid formation. C1 [Lu, Jinghua; Zhu, Iowis; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Yu, Yadong; Cheng, Yifan] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM psun@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Dr. Terry W. Du Clos for providing SAA1-containing human serum and Kiyoshi Egami for performing EM imaging on the helix 1 and 3 peptide samples. We thank the shared Biomedical Engineering and Physical Science Resource at the National Institutes of Health for help with the ultracentrifugation assays. This research was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 38 TC 29 Z9 30 U1 1 U2 23 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 APR 8 PY 2014 VL 111 IS 14 BP 5189 EP 5194 DI 10.1073/pnas.1322357111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4VU UT WOS:000333985200042 PM 24706838 ER PT J AU Wuttke, R Hofmann, H Nettels, D Borgia, MB Mittal, J Best, RB Schuler, B AF Wuttke, Rene Hofmann, Hagen Nettels, Daniel Borgia, Madeleine B. Mittal, Jeetain Best, Robert B. Schuler, Benjamin TI Temperature-dependent solvation modulates the dimensions of disordered proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Sanchez theory; ABSINTH; HIV integrase; cold shock protein; prothymosin alpha ID SINGLE-MOLECULE SPECTROSCOPY; COIL-GLOBULE TRANSITION; N-TERMINAL DOMAIN; HYDROPHOBIC HYDRATION; UNFOLDED PROTEINS; INTERNAL-FRICTION; COLD DENATURATION; AQUEOUS-SOLUTIONS; INDUCED COLLAPSE; SOLVENT WATER AB For disordered proteins, the dimensions of the chain are an important property that is sensitive to environmental conditions. We have used single-molecule Forster resonance energy transfer to probe the temperature-induced chain collapse of five unfolded or intrinsically disordered proteins. Because this behavior is sensitive to the details of intrachain and chain-solvent interactions, the collapse allows us to probe the physical interactions governing the dimensions of disordered proteins. We find that each of the proteins undergoes a collapse with increasing temperature, with the most hydrophobic one, lambda-repressor, undergoing a reexpansion at the highest temperatures. Although such a collapse might be expected due to the temperature dependence of the classical "hydrophobic effect," remarkably we find that the largest collapse occurs for the most hydrophilic, charged sequences. Using a combination of theory and simulation, we show that this result can be rationalized in terms of the temperature-dependent solvation free energies of the constituent amino acids, with the solvation properties of the most hydrophilic residues playing a large part in determining the collapse. C1 [Wuttke, Rene; Hofmann, Hagen; Nettels, Daniel; Borgia, Madeleine B.; Schuler, Benjamin] Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland. [Mittal, Jeetain] Lehigh Univ, Dept Chem Engn, Bethlehem, PA 18015 USA. [Best, Robert B.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Best, RB (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM robertbe@helix.nih.gov; schuler@bioc.uzh.ch RI Schuler, Benjamin/E-7342-2011; Hofmann, Hagen/L-5735-2013; Best, Robert/H-7588-2016 OI Schuler, Benjamin/0000-0002-5970-4251; Best, Robert/0000-0002-7893-3543 FU Swiss National Science Foundation; Swiss National Center of Competence in Research for Structural Biology; European Research Council; National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health; National Science Foundation [CBET-1120399, MCB-120014] FX We thank Andrea Soranno for discussion, Brigitte Buchli for labeled CspM34, Andreas Vitalis for helpful advice on the use of the CAMPARI code, and Rohit Pappu and Andreas Vitalis for discussions on solvation free energies. This work was supported by the Swiss National Science Foundation (B. S.), the Swiss National Center of Competence in Research for Structural Biology (B. S.), a Starting Investigator grant of the European Research Council (to B. S.), the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health (R. B. B.), and National Science Foundation Grant CBET-1120399 (to J. M.). This study used the high-performance computing capabilities of the Biowulf cluster at the National Institutes of Health (R. B. B.) and the Extreme Science and Engineering Discovery Environment, which is supported by National Science Foundation Grant MCB-120014 (to J.M.). NR 78 TC 44 Z9 44 U1 6 U2 57 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 APR 8 PY 2014 VL 111 IS 14 BP 5213 EP 5218 DI 10.1073/pnas.1313006111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4VU UT WOS:000333985200046 PM 24706910 ER PT J AU Ingaramo, M York, AG Wawrzusin, P Milberg, O Hong, A Weigert, R Shroff, H Patterson, GH AF Ingaramo, Maria York, Andrew G. Wawrzusin, Peter Milberg, Oleg Hong, Amy Weigert, Roberto Shroff, Hari Patterson, George H. TI Two-photon excitation improves multifocal structured illumination microscopy in thick scattering tissue SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE multiphoton; superresolution ID MICROLENS-ARRAY SCANNER; MULTIPHOTON MICROSCOPY; FLUORESCENCE MICROSCOPY; DIFFRACTION-LIMIT; RESOLUTION LIMIT; PINHOLE; LIVE; BREAKING; SINGLE AB Multifocal structured illumination microscopy (MSIM) provides a twofold resolution enhancement beyond the diffraction limit at sample depths up to 50 mu m, but scattered and out-of-focus light in thick samples degrades MSIM performance. Here we implement MSIM with a microlens array to enable efficient two-photon excitation. Two-photon MSIM gives resolution-doubled images with better sectioning and contrast in thick scattering samples such as Caenorhabditis elegans embryos, Drosophila melanogaster larval salivary glands, and mouse liver tissue. C1 [Ingaramo, Maria; York, Andrew G.; Wawrzusin, Peter; Shroff, Hari; Patterson, George H.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. [Milberg, Oleg; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [Hong, Amy] NHLBI, NIH, Bethesda, MD 20892 USA. RP Patterson, GH (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. EM pattersg@mail.nih.gov RI Shroff, Hari/E-7247-2016 OI Shroff, Hari/0000-0003-3613-8215 FU National Institutes of Health; National Institute of Biomedical Imaging and Bioengineering; National Institute of Dental and Craniofacial Research; National Heart, Lung, and Blood Institute FX This work was supported by the Intramural Research Programs of the National Institutes of Health including the National Institute of Biomedical Imaging and Bioengineering; the National Institute of Dental and Craniofacial Research; and the National Heart, Lung, and Blood Institute. NR 30 TC 18 Z9 18 U1 3 U2 22 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 8 PY 2014 VL 111 IS 14 BP 5254 EP 5259 DI 10.1073/pnas.1314447111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4VU UT WOS:000333985200053 PM 24706872 ER PT J AU Rudebeck, PH Putnam, PT Daniels, TE Yang, TM Mitz, AR Rhodes, SEV Murray, EA AF Rudebeck, Peter H. Putnam, Philip T. Daniels, Teresa E. Yang, Tianming Mitz, Andrew R. Rhodes, Sarah E. V. Murray, Elisabeth A. TI A role for primate subgenual cingulate cortex in sustaining autonomic arousal SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Area 25; infralimbic; pupil size; anticipatory arousal ID VENTROMEDIAL PREFRONTAL CORTEX; MEDIAL FRONTAL-CORTEX; CONDITIONED EMOTIONAL RESPONSES; INFRALIMBIC CORTEX; MOOD DISORDERS; LESIONS; DEPRESSION; EXTINCTION; BEHAVIOR; AMYGDALA AB The subgenual anterior cingulate cortex (subgenual ACC) plays an important role in regulating emotion, and degeneration in this area correlates with depressed mood and anhedonia. Despite this understanding, it remains unknown how this part of the prefrontal cortex causally contributes to emotion, especially positive emotions. Using Pavlovian conditioning procedures in macaque monkeys, we examined the contribution of the subgenual ACC to autonomic arousal associated with positive emotional events. After such conditioning, autonomic arousal increases in response to cues that predict rewards, and monkeys maintain this heightened state of arousal during an interval before reward delivery. Here we show that although monkeys with lesions of the subgenual ACC show the initial, cue-evoked arousal, they fail to sustain a high level of arousal until the anticipated reward is delivered. Control procedures showed that this impairment did not result from differences in autonomic responses to reward delivery alone, an inability to learn the association between cues and rewards, or to alterations in the light reflex. Our data indicate that the subgenual ACC may contribute to positive affect by sustaining arousal in anticipation of positive emotional events. A failure to maintain positive affect for expected pleasurable events could provide insight into the pathophysiology of psychological disorders in which negative emotions dominate a patient's affective experience. C1 [Rudebeck, Peter H.; Putnam, Philip T.; Daniels, Teresa E.; Yang, Tianming; Mitz, Andrew R.; Rhodes, Sarah E. V.; Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Rudebeck, PH (reprint author), Icahn Sch Med Mt Sinai, New York, NY 10029 USA. EM peter.rudebeck@mssm.edu RI Yang, Tianming/D-3582-2014; OI Yang, Tianming/0000-0001-6976-9246; Rudebeck, Peter/0000-0002-1411-7555; Murray, Elisabeth/0000-0003-1450-1642 FU National Institute of Mental Health FX We thank Vincent Costa, Bruno Averbeck, and Steven Wise for advice on analyses and comments on an earlier version of the manuscript. We also thank Yogita Chudasama for assistance with surgery and John Kakareka, Randal Pursely, and Tom Pohida for their assistance in processing physiological signals. This work was supported by the Intramural Research Program of the National Institute of Mental Health. NR 40 TC 15 Z9 15 U1 4 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 8 PY 2014 VL 111 IS 14 BP 5391 EP 5396 DI 10.1073/pnas.1317695111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4VU UT WOS:000333985200076 PM 24706828 ER PT J AU Rojas, M Gingras, AC Dever, TE AF Rojas, Margarito Gingras, Anne-Claude Dever, Thomas E. TI Protein phosphatase PP1/GLC7 interaction domain in yeast eIF2 gamma bypasses targeting subunit requirement for eIF2 alpha dephosphorylation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INITIATION-FACTOR 2; TRANSFER-RNA BINDING; TRANSLATION INITIATION; SACCHAROMYCES-CEREVISIAE; ALPHA-SUBUNIT; REGULATORY SUBUNIT; STRUCTURAL BASIS; KINASE GCN2; GLYCOGEN ACCUMULATION; FUNCTIONAL-ANALYSIS AB Whereas the protein kinases GCN2, HRI, PKR, and PERK specifically phosphorylate eukaryotic translation initiation factor 2 (eIF2 alpha) on Ser51 to regulate global and gene-specific mRNA translation, eIF2 alpha is dephosphorylated by the broadly acting serine/threonine protein phosphatase 1 (PP1). In mammalian cells, the regulatory subunits GADD34 and CReP target PP1 to dephosphorylate eIF2 alpha; however, as there are no homologs of these targeting subunits in yeast, it is unclear how GLC7, the functional homolog of PP1 in yeast, is recruited to dephosphorylate eIF2 alpha. Here, we show that a novel N-terminal extension on yeast eIF2 gamma contains a PP1-binding motif (KKVAF) that enables eIF2 gamma to pull down GLC7 and target it to dephosphorylate eIF2 alpha. Truncation or point mutations designed to eliminate the KKVAF motif in eIF2 gamma impair eIF2 alpha dephosphorylation in vivo and in vitro and enhance expression of GCN4. Replacement of the N terminus of eIF2 gamma with the GLC7-binding domain from GAC1 or fusion of heterologous dimerization domains to eIF2 gamma and GLC7, respectively, maintained eIF2 alpha phosphorylation at basal levels. Taken together, these results indicate that, in contrast to the paradigm of distinct PP1-targeting or regulatory subunits, the unique N terminus of yeast eIF2 gamma functions in cis to target GLC7 to dephosphorylate eIF2 alpha. C1 [Rojas, Margarito; Dever, Thomas E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Gingras, Anne-Claude] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Ctr Syst Biol, Toronto, ON M5G 1X5, Canada. [Gingras, Anne-Claude] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. RP Dever, TE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM tdever@nih.gov RI Gingras, Anne-Claude/E-9982-2010; OI Gingras, Anne-Claude/0000-0002-6090-4437; Dever, Thomas/0000-0001-7120-9678 FU US National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank Kelly Tatchell for providing reagents and advice for purifying GLC7. We also thank Chune Cao, Meghna Thakur, Byung-Sik Shin, and Jason Murray for technical support and A. Hinnebusch and members of the T. E. D. and Hinnebusch laboratories for helpful discussions. This work was supported, in part, by the Intramural Research Program of the US National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (to T.E.D.) NR 64 TC 7 Z9 7 U1 0 U2 10 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 APR 8 PY 2014 VL 111 IS 14 BP E1344 EP E1353 DI 10.1073/pnas.1400129111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4VU UT WOS:000333985200007 PM 24706853 ER PT J AU Liu, YX Kot, A Drakopoulos, F Yao, CJ Fedorov, A Enquobahrie, A Clatz, O Chrisochoides, NP AF Liu, Yixun Kot, Andriy Drakopoulos, Fotis Yao, Chengjun Fedorov, Andriy Enquobahrie, Andinet Clatz, Olivier Chrisochoides, Nikos P. TI An ITK implementation of a physics-based non-rigid registration method for brain deformation in image-guided neurosurgery SO FRONTIERS IN NEUROINFORMATICS LA English DT Article DE image-guided neurosurgery; non-rigid registration; block matching; finite element; ITK; GPU ID INTRAOPERATIVE MRI AB As part of the ITK v4 project efforts, we have developed ITK filters for physics-based non-rigid registration (PBNRR), which satisfies the following requirements: account for tissue properties in the registration, improve accuracy compared to rigid registration, and reduce execution time using GPU and multi-core accelerators. The implementation has three main components: (1) Feature Point Selection, (2) Block Matching (mapped to both multi-core and GPU processors), and (3) a Robust Finite Element Solver. The use of multi-core and GPU accelerators in ITK v4 provides substantial performance improvements. For example, for the non-rigid registration of brain MRIs, the performance of the block matching filter on average is about 10 times faster when 12 hyperthreaded multi-cores are used and about 83 times faster when the NVIDIA Tesla GPU is used in Dell Workstation. C1 [Liu, Yixun; Kot, Andriy; Drakopoulos, Fotis; Fedorov, Andriy; Chrisochoides, Nikos P.] Old Dominion Univ, CRTC Lab, Norfolk, VA 23529 USA. [Liu, Yixun; Kot, Andriy; Drakopoulos, Fotis; Fedorov, Andriy; Chrisochoides, Nikos P.] Old Dominion Univ, Norfolk, VA 23529 USA. [Liu, Yixun] NIH, Bethesda, MD 20892 USA. [Yao, Chengjun] Huashan Hosp, Dept Neurosurg, Shanghai, Peoples R China. [Fedorov, Andriy] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Enquobahrie, Andinet] Kitware Inc, Clifton Pk, NY USA. [Clatz, Olivier] INRIA Sophia Antipolis, Asclepios Res Lab, Sophia Antipolis, France. RP Liu, YX (reprint author), Old Dominion Univ, CRTC Lab, E&CS Bldg,4700 Elkhorn AveSuite 3300, Norfolk, VA 23529 USA. EM nikos@cs.odu.edu FU ARRA funds for the ITK-v4 implementation [NLM A2D2 201000586P]; NSF [CCF-1139864, CCF-1136538, CSI-1136536]; John Simon Guggenheim Foundation; Richard T. Cheng Endowment; WM FX This work is funded mainly by the ARRA funds for the ITK-v4 implementation with grant number: NLM A2D2 201000586P. In addition, this work is supported in part by NSF grants: CCF-1139864, CCF-1136538, and CSI-1136536 and by the John Simon Guggenheim Foundation and the Richard T. Cheng Endowment. We would like to thank Luis Ibanez, Matt McCormick, and Arnaud Gelas for their help on ITK coding style. Also, we would like to thank the image-to-mesh conversion team at CRTC, especially Panos Foteinos for providing the Finite Element Meshes for the evaluation of the software and Dr. Michele Audette at ODU for bringing this opportunity to our attention while he was at Kitware. The staff of W&M at Grants Office have been extremely helpful with the transition of this grant from W&M to ODU. We also want to thank Miss Caitlin Reed for her proofreading of this paper. And last but not least, Dr. Terry Yoo and his staff at NLM, for his constant support and understanding to accommodate us with all shorts of issues created due to our transition to ODU. NR 18 TC 2 Z9 2 U1 2 U2 8 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5196 J9 FRONT NEUROINFORM JI Front. Neuroinformatics PD APR 7 PY 2014 VL 8 AR 33 DI 10.3389/fninf.2014.00033 PG 10 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA AZ3DL UT WOS:000348107800001 PM 24778613 ER PT J AU Little, MH Brown, D Humphreys, BD McMahon, AP Miner, JH Sands, JM Weisz, OA Mullins, C Hoshizaki, D AF Little, Melissa H. Brown, Dennis Humphreys, Benjamin D. McMahon, Andrew P. Miner, Jeffrey H. Sands, Jeff M. Weisz, Ora A. Mullins, Chris Hoshizaki, Deborah CA KRND TI Defining Kidney Biology to Understand Renal Disease SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article AB The Kidney Research National Dialogue represents a novel effort by the National Institute of Diabetes and Digestive and Kidney Diseases to solicit and prioritize research objectives from the renal research and clinical communities. The present commentary highlights selected scientific opportunities specific to the study of renal development, physiology, and cell biology. Describing such fundamental kidney biology serves as a necessary foundation for translational and clinical studies that will advance disease care and prevention. It is intended that these objectives foster and focus scientific efforts in these areas in the coming decade and beyond. C1 [Little, Melissa H.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. [Brown, Dennis] Harvard Univ, Massachussetts Gen Hosp, Ctr Syst Biol, Boston, MA 02115 USA. [Brown, Dennis] Harvard Univ, Massachussetts Gen Hosp, Program Membrane Biol, Boston, MA 02115 USA. [Brown, Dennis] Harvard Univ, Massachussetts Gen Hosp, Div Nephrol, Boston, MA 02115 USA. [Humphreys, Benjamin D.] Harvard Univ, Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [McMahon, Andrew P.] Univ So Calif, Los Angeles, CA USA. [Miner, Jeffrey H.] Washington Univ, Sch Med, Div Renal, St Louis, MO 63110 USA. [Sands, Jeff M.] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Sands, Jeff M.] Emory Univ, Sch Med, Dept Physiol, Atlanta, GA 30322 USA. [Weisz, Ora A.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Mullins, Chris; Hoshizaki, Deborah] NIDDK, NIH, Bethesda, MD 20892 USA. RP Hoshizaki, D (reprint author), NIDDK, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM DKHOSH@NIH.GOV RI Little, Melissa/A-6170-2010 OI Little, Melissa/0000-0003-0380-2263 FU Evotec FX B.D.H. is funded by a grant from Evotec with the goal of discovering new therapeutic targets to treat acute kidney disease and CKD. A.P.M. is in collaboration around kidney disease with Evotec, for which the laboratory of A.P.M. receives research support from Evotec. NR 1 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR 7 PY 2014 VL 9 IS 4 BP 809 EP 811 DI 10.2215/CJN.10851013 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA AE2XM UT WOS:000333836600026 PM 24370769 ER PT J AU Mehrotra, R Agarwal, A Bargman, JM Himmelfarb, J Johansen, KL Watnick, S Work, J McBryde, K Flessner, M Kimmel, PL AF Mehrotra, Rajnish Agarwal, Anil Bargman, Joanne M. Himmelfarb, Jonathan Johansen, Kirsten L. Watnick, Suzanne Work, Jack McBryde, Kevin Flessner, Michael Kimmel, Paul L. CA KRND TI Dialysis Therapies: A National Dialogue SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article AB The National Institute of Diabetes, Digestive, and Kidney Diseases-supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives that would improve our understanding of kidney function and disease. Kidney Research National Dialogue participants identified the need to improve outcomes in ESRD by decreasing mortality and morbidity and enhancing quality of life as high priority areas in kidney research. To reach these goals, we must identify retained toxins in kidney disease, accelerate technologic advances in dialysate composition and devices to remove these toxins, advance vascular access, and identify measures that decrease the burden of disease in maintenance dialysis patients. Together, these research objectives provide a path forward for improving patient-centered outcomes in ESRD. C1 [Mehrotra, Rajnish; Himmelfarb, Jonathan] Univ Washington, Dept Med, Div Nephrol, Kidney Res Inst, Seattle, WA 98195 USA. [Agarwal, Anil] Ohio State Univ, Columbus, OH 43210 USA. [Bargman, Joanne M.] Univ Hlth Network, Toronto, ON, Canada. [Johansen, Kirsten L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Watnick, Suzanne] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Work, Jack] Emory Univ, Atlanta, GA 30322 USA. [McBryde, Kevin; Flessner, Michael; Kimmel, Paul L.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Flessner, M (reprint author), NIDDK, Div Kidney & Urol, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM mike.flessner@nih.gov NR 2 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR 7 PY 2014 VL 9 IS 4 BP 812 EP 814 DI 10.2215/CJN.12601213 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA AE2XM UT WOS:000333836600027 PM 24458085 ER PT J AU Kaskel, F Batlle, D Beddhu, S Daugirdas, J Feldman, H Ferris, M Fine, L Freedman, BI Kimmel, PL Flessner, MF Star, RA AF Kaskel, Frederick Batlle, Daniel Beddhu, Srinivasan Daugirdas, John Feldman, Harold Ferris, Maria Fine, Lawrence Freedman, Barry I. Kimmel, Paul L. Flessner, Michael F. Star, Robert A. CA KRND TI Improving CKD Therapies and Care: A National Dialogue SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE CKD; pediatric; adolescent; diet; hypertension AB The Kidney Research National Dialogue, supported by the National Institute of Diabetes and Digestive and Kidney Diseases, asked the research and clinical communities to formulate and prioritize research objectives that would improve our understanding of kidney function and diseases. This commentary outlines the high-priority research objectives for CKD. The goal of these research objectives is to enhance knowledge to improve outcomes in people with CKD. Basic and translational research, longitudinal observations, and epidemiologic studies can each point to targets for intervention. Future interventions must be informed by data from well designed, large representative observational studies that include collection of genetic and phenotypic data as well as biospecimens. Interaction of genetic and environmental factors must be part of the analysis, including the influence of diet, comorbid conditions, and medication. The focus should be not only on slowing or preventing progression of CKD, but also on regression of disease to the greatest extent possible. C1 [Flessner, Michael F.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Flessner, MF (reprint author), NIDDK, Div Kidney Urol & Hematol Dis, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM flessnermf@niddk.nih.gov FU Takeda; AbbVie FX S.D. reports that he has received research funding from Takeda and AbbVie and served as a consultant to AbbVie. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR 7 PY 2014 VL 9 IS 4 BP 815 EP 817 DI 10.2215/CJN.12631213 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA AE2XM UT WOS:000333836600028 PM 24509296 ER PT J AU Baez, A Majdalani, N Shiloach, J AF Baez, Antonino Majdalani, Nadim Shiloach, Joseph TI Production of recombinant protein by a novel oxygen-induced system in Escherichia coli SO MICROBIAL CELL FACTORIES LA English DT Article DE soxS promoter; Protein oxidation; GFP oxidation; High cell density; Carbonyl groups ID INDUCIBLE EXPRESSION SYSTEM; SUPEROXIDE DISMUTASE; PHAGE-LAMBDA; STRESS; BACTERIA; PROMOTERS; YIELD; SOXRS AB Background: The SoxRS regulon of E. coli is activated in response to elevated dissolved oxygen concentration likely to protect the bacteria from possible oxygen damage. The soxS expression can be increased up to 16 fold, making it a possible candidate for recombinant protein expression. Compared with the existing induction approaches, oxygen induction is advantageous because it does not involve addition or depletion of growth factors or nutrients, addition of chemical inducers or temperature changes that can affect growth and metabolism of the producing bacteria. It also does not affect the composition of the growth medium simplifying the recovery and purification processes. Results: The soxS promoter was cloned into the commercial pGFPmut3.1 plasmid creating pAB49, an expression vector that can be induced by increasing oxygen concentration. The efficiency and the regulatory properties of the soxS promoter were characterized by measuring the GFP expression when the culture dissolved oxygen concentration was increased from 30% to 300% air saturation. The expression level of recombinant GFP was proportional to the oxygen concentration, demonstrating that pAB49 is a controllable expression vector. A possible harmful effect of elevated oxygen concentration on the recombinant product was found to be negligible by determining the protein-carbonyl content and its specific fluorescence. By performing high density growth in modified LB medium, the cells were induced by increasing the oxygen concentration. After 3 hours at 300% air saturation, GFP fluorescence reached 109000 FU (494 mg of GFP/L), representing 3.4% of total protein, and the cell concentration reached 29.1 g/L (DW). Conclusions: Induction of recombinant protein expression by increasing the dissolved oxygen concentration was found to be a simple and efficient alternative expression strategy that excludes the use of chemical, nutrient or thermal inducers that have a potential negative effect on cell growth or the product recovery. C1 [Baez, Antonino; Shiloach, Joseph] Natl Inst Diabet & Digest & Kidney Dis, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. [Majdalani, Nadim] NCI, NIH, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. EM yossi@nih.gov FU Intramural program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX Funding was provided by the intramural program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. The authors would like to thank Mrs. D. Livnat for critical editorial assistance. NR 23 TC 6 Z9 6 U1 0 U2 25 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2859 J9 MICROB CELL FACT JI Microb. Cell. Fact. PD APR 7 PY 2014 VL 13 AR 50 DI 10.1186/1475-2859-13-50 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AF4XT UT WOS:000334718600001 PM 24708849 ER PT J AU Feigin, VL Forouzanfar, MH Krishnamurthi, R Mensah, GA AF Feigin, Valery L. Forouzanfar, Mohammad H. Krishnamurthi, Rita Mensah, George A. TI Global burden of stroke: an underestimate Reply SO LANCET LA English DT Letter C1 [Feigin, Valery L.; Krishnamurthi, Rita] Auckland Univ Technol Univ, Sch Publ Hlth & Psychosocial Studies, Natl Inst Stroke & Appl Neurosci, Sch Rehabil & Occupat Studies,Fac Hlth & Environm, Auckland 1142, New Zealand. [Forouzanfar, Mohammad H.] Univ Washington, Dept Global Hlth, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA. RP Feigin, VL (reprint author), Auckland Univ Technol Univ, Sch Publ Hlth & Psychosocial Studies, Natl Inst Stroke & Appl Neurosci, Sch Rehabil & Occupat Studies,Fac Hlth & Environm, Auckland 1142, New Zealand. EM valery.feigin@aut.ac.nz NR 5 TC 4 Z9 4 U1 1 U2 3 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 APR 5 PY 2014 VL 383 IS 9924 BP 1205 EP 1206 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AE6LO UT WOS:000334104600016 PM 24703556 ER PT J AU Salpea, P Stratakis, CA AF Salpea, Paraskevi Stratakis, Constantine A. TI Carney complex and McCune Albright syndrome: An overview of clinical manifestations and human molecular genetics SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Review DE Carney complex; PRKAR1A; McCune-Albright; GNAS; Endocrine neoplasia ID NODULAR ADRENOCORTICAL DISEASE; SECRETING PITUITARY-TUMORS; HUMAN SOMATOTROPH ADENOMAS; GROWTH-HORMONE EXCESS; STIMULATORY G-PROTEIN; C-FOS PROTOONCOGENE; FIBROUS DYSPLASIA; REGULATORY SUBUNIT; ADRENAL-HYPERPLASIA; PRKAR1A MUTATION AB Endocrine neoplasia syndromes feature a wide spectrum of benign and malignant tumors of endocrine and non-endocrine organs associated with other clinical manifestations. This study outlines the main clinical features, genetic basis, and molecular mechanisms behind two multiple endocrine neoplasia syndromes that share quite a bit of similarities, but one can be inherited whereas the other is always sporadic, Carney complex (CNC) and McCune-Albright (MAS), respectively. Spotty skin pigmentation, cardiac and other myxomas, and different types of endocrine tumors and other characterize Carney complex, which is caused largely by inactivating Protein kinase A, regulatory subunit, type I, Alpha (PRMR1A) gene mutations. The main features of McCune-Albright are fibrous dysplasia of bone (FD), cafe-au-lait macules and precocious puberty; the disease is caused by activating mutations in the Guanine Nucleotide-binding protein, Alpha-stimulating activity polypeptide (GNAS) gene which are always somatic. We review the clinical manifestations of the two syndromes and provide an update on their molecular genetics. Published by Elsevier Ireland Ltd. C1 Natl Inst Child Hlth & Human Dev NICHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH, Bethesda, MD 20892 USA. Natl Inst Child Hlth & Human Dev NICHD, Pediat Endocrinol Interinst Training Program, Eunice Kennedy Shriver, NIH, Bethesda, MD 20892 USA. RP Salpea, P (reprint author), NICHD, SEGEN, PDEGEN, NIH,NIH Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3330,MSC1103, Bethesda, MD 20892 USA. EM salpeapa@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 92 TC 29 Z9 30 U1 4 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD APR 5 PY 2014 VL 386 IS 1-2 SI SI BP 85 EP 91 DI 10.1016/j.mce.2013.08.022 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA AE5EA UT WOS:000334009400008 PM 24012779 ER PT J AU King, KS Pacak, K AF King, Kathryn S. Pacak, Karel TI Familial pheochromocytomas and paragangliomas SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Review DE Pheochromocytoma; Paraganglioma; VHL; MEN2; NF1; SDHA ID VONHIPPEL-LINDAU DISEASE; CARNEY-STRATAKIS-SYNDROME; MEDULLARY-THYROID CANCER; HYPOXIA-INDUCIBLE FACTOR; SDHD GENE-MUTATIONS; GERMLINE MUTATIONS; SUCCINATE-DEHYDROGENASE; SPORADIC PHEOCHROMOCYTOMA; FUNCTIONAL PARAGANGLIOMA; MOLECULAR-GENETICS AB Pheochromocytomas and paragangliomas are neural crest cell tumors of the adrenal medulla and para-sympathetic/sympathetic ganglia, respectively, that are often associated with catecholamine production. Genetic research over the years has led to our current understanding of the association 13 susceptibility genes with the development of these tumors. Most of the susceptibility genes are now associated with specific clinical presentations, biochemical makeup, tumor location, and associated neoplasms. Recent scientific advances have highlighted the role of somatic mutations in the development of pheochromocytoma/paraganglioma as well as the usefulness of immunohistochemistry in triaging genetic testing. We can now approach genetic testing in pheochromocytoma/paraganglioma patients in a very organized scientific way allowing for the reduction of both the financial and emotional burden on the patient. The discovery of genetic predispositions to the development of pheochromocytoma/paraganglioma not only facilitates better understanding of these tumors but will also lead to improved diagnosis and treatment of this disease. (C) 2014 Published by Elsevier Ireland Ltd. C1 [King, Kathryn S.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, Program Reprod & Adult Endocrinol, NIH, Bldg 10,CRC,1 East,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU NIH, NICHD FX This research was supported, in part, by the Intramural Research Program of the NIH, NICHD. NR 97 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD APR 5 PY 2014 VL 386 IS 1-2 SI SI BP 92 EP 100 DI 10.1016/j.mce.2013.07.032 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA AE5EA UT WOS:000334009400009 PM 23933153 ER PT J AU Kosmidis, S Missirlis, F Botellea, JA Schneuwly, S Rouault, TA Skoulakis, EMC AF Kosmidis, Stylianos Missirlis, Fanis Botellea, Jose A. Schneuwly, Stephan Rouault, Tracey A. Skoulakis, Efthimios M. C. TI Behavioral decline and premature lethality upon pan-neuronal ferritin overexpression in Drosophila infected with a virulent form of Wolbachia SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE metal; symbiosis; rickettsia; popcorn; wMel; insect; immunity; aging ID IRON-ABSORPTION; MELANOGASTER; HOST; STRAIN; MODEL; DEGENERATION; TEMPERATURE; METABOLISM; INSIGHTS; WMELPOP AB Iron is required for organismal growth. Therefore, limiting iron availability may be a key part of the host's innate immune response to various pathogens, for example, in Drosophila infected with Zygomycetes. One way the host can transiently reduce iron bioavailability is by ferritin overexpression. To study the effects of neuronal-specific ferritin overexpression on survival and neurodegeneration we generated flies simultaneously over-expressing transgenes for both ferritin subunits in all neurons. We used two independent recombinant chromosomes bearing UAS-Fer1HCH, UAS-Fer2LCH transgenes and obtained qualitatively different levels of late-onset behavioral and lifespan declines. We subsequently discovered that one parental strain had been infected with a virulent form of the bacterial endosymbiont Wolbachia, causing widespread neuronal apoptosis and premature death. This phenotype was exacerbated by ferritin overexpression and was curable by antibiotic treatment. Neuronal ferritin overexpression in uninfected flies did not cause evident neurodegeneration but resulted in a late-onset behavioral decline, as previously reported for ferritin overexpression in glia. The results suggest that ferritin overexpression in the central nervous system of flies is tolerated well in young individuals with adverse manifestations appearing only late in life or under unrelated pathophysiological conditions. C1 [Kosmidis, Stylianos; Skoulakis, Efthimios M. C.] Biomed Sci Res Ctr Alexander Fleming, Neurosci Div, Vari, Greece. [Kosmidis, Stylianos] Columbia Univ, Dept Neurosci, New York, NY USA. [Missirlis, Fanis; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, NIH, Bethesda, MD USA. [Missirlis, Fanis] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Fisiol Biofis & Neurociencias, Mexico City 07360, DF, Mexico. [Botellea, Jose A.; Schneuwly, Stephan] Univ Regensburg, Inst Zool, D-93053 Regensburg, Germany. RP Missirlis, F (reprint author), Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Fisiol Biofis & Neurociencias, Ave Inst Politecn Nacl 2508, Mexico City 07360, DF, Mexico. EM fanis@fisio.cinvestav.mx RI Missirlis, Fanis/C-1137-2011 OI Missirlis, Fanis/0000-0003-0467-8444 FU Intramural Program of the Eunice Kennedy Shrivel-National Institute of Child Health and Human Development in the USA; CONACYT project in Mexico [179835] FX This research was supported by the Intramural Program of the Eunice Kennedy Shrivel-National Institute of Child Health and Human Development in the USA and the CONACYT project 179835 in Mexico. We thank Kostas Bourtzis for providing Wolbachia infected flies and advice for detecting the bacteria. NR 34 TC 7 Z9 7 U1 1 U2 7 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-9812 J9 FRONT PHARMACOL JI Front. Pharmacol. PD APR 4 PY 2014 VL 5 AR 66 DI 10.3389/fphar.2014.00066 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AX6ZE UT WOS:000347065700001 PM 24772084 ER PT J AU Rogers, NM Seeger, F Garcin, ED Roberts, DD Isenberg, JS AF Rogers, Natasha M. Seeger, Franziska Garcin, Elsa D. Roberts, David D. Isenberg, Jeffrey S. TI Regulation of soluble guanylate cyclase by matricellular thrombospondins: implications for blood flow SO FRONTIERS IN PHYSIOLOGY LA English DT Review DE soluble guanylate cyclase; cyclic guanosine monophosphate; thrombospondin-1; CD47; nitric oxide; cardiovascular disease; ROS ID NITRIC-OXIDE SYNTHASE; VASCULAR SMOOTH-MUSCLE; H-NOX DOMAIN; ISCHEMIA-REPERFUSION INJURY; PULMONARY ARTERIAL-HYPERTENSION; INTEGRIN-ASSOCIATED PROTEIN; T-CELL-ACTIVATION; HYDROGEN-SULFIDE; ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE AB Nitric oxide (NO) maintains cardiovascular health by activating soluble guanylate cyclase (sGC) to increase cellular cGMP levels. Cardiovascular disease is characterized by decreased NO-sGC-cGMP signaling. Pharmacological activators and stimulators of sGC are being actively pursued as therapies for acute heart failure and pulmonary hypertension. Here we review molecular mechanisms that modulate sGC activity while emphasizing a novel biochemical pathway in which binding of the matricellular protein thrombospondin-1 (TSP1) to the cell surface receptor CD47 causes inhibition of sGC. We discuss the therapeutic implications of this pathway for blood flow, tissue perfusion, and cell survival under physiologic and disease conditions. C1 [Rogers, Natasha M.; Isenberg, Jeffrey S.] Univ Pittsburgh, Sch Med, Dept Med, Vasc Med Inst, Pittsburgh, PA 15261 USA. [Seeger, Franziska; Garcin, Elsa D.] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21228 USA. [Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Isenberg, Jeffrey S.] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15261 USA. RP Isenberg, JS (reprint author), Univ Pittsburgh, Sch Med, BST, Room E1258,200 Lothrop St, Pittsburgh, PA 15261 USA. EM jsi5@pitt.edu RI Roberts, David/A-9699-2008; Garcin, Elsa/C-1556-2013 OI Roberts, David/0000-0002-2481-2981; Garcin, Elsa/0000-0003-0501-8421 FU NIH [R01HL-108954, 1R01HL112914-01A1]; American Heart Association [11BGIA7210001, 10SDG2600345, 13PRE17000045, 13POST14520003]; Intramural Research Program of the NIH/NCI; Institute for Transfusion Medicine; Hemophilia Center of Western Pennsylvania; Vascular Medicine Institute FX This work was supported by NIH grants R01HL-108954 and 1R01HL112914-01A1 and American Heart Association grants 11BGIA7210001 (Jeffrey S. Isenberg) 10SDG2600345 (Elsa D. Garcin), 13PRE17000045 (Franziska Seeger) and 13POST14520003 (Natasha M. Rogers) and by the Intramural Research Program of the NIH/NCI (David D. Roberts). This work was further supported by the Institute for Transfusion Medicine, the Hemophilia Center of Western Pennsylvania and the Vascular Medicine Institute (Jeffrey S. Isenberg). NR 206 TC 5 Z9 5 U1 1 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PD APR 4 PY 2014 VL 5 AR 134 DI 10.3389/fphys.2014.00134 PG 14 WC Physiology SC Physiology GA AX6LA UT WOS:000347032600002 PM 24772092 ER PT J AU Zare, H Khodursky, A Sartorelli, V AF Zare, Hossein Khodursky, Arkady Sartorelli, Vittorio TI An evolutionarily biased distribution of miRNA sites toward regulatory genes with high promoter-driven intrinsic transcriptional noise SO BMC EVOLUTIONARY BIOLOGY LA English DT Article DE microRNAs; Transcriptional noise; Nucleosome occupancy; Evolution ID CONSERVED NONCODING ELEMENTS; MICRORNA TARGETS; CELL-PROLIFERATION; FEEDBACK LOOP; ALU ELEMENTS; EXPRESSION; IMPACT; DIFFERENTIATION; ROBUSTNESS; DROSOPHILA AB Background: miRNAs are a major class of regulators of gene expression in metazoans. By targeting cognate mRNAs, miRNAs are involved in regulating most, if not all, biological processes in different cell and tissue types. To better understand how this regulatory potential is allocated among different target gene sets, we carried out a detailed and systematic analysis of miRNA target sites distribution in the mouse genome. Results: We used predicted conserved and non-conserved sites for 779 miRNAs in 3' UTR of 18440 genes downloaded from TargetScan website. Our analysis reveals that 3' UTRs of genes encoding regulatory proteins harbor significantly greater number of miRNA sites than those of non-regulatory, housekeeping and structural, genes. Analysis of miRNA sites for orthologous 3' UTR's in 10 other species indicates that the regulatory genes were maintaining or accruing miRNA sites while non-regulatory genes gradually shed them in the course of evolution. Furthermore, we observed that 3' UTR of genes with higher gene expression variability driven by their promoter sequence content are targeted by many more distinct miRNAs compared to genes with low transcriptional noise. Conclusions: Based on our results we envision a model, which we dubbed "selective inclusion", whereby non-regulatory genes with low transcription noise and stable expression profile lost their sites, while regulatory genes which endure higher transcription noise retained and gained new sites. This adaptation is consistent with the requirements that regulatory genes need to be tightly controlled in order to have precise and optimum protein level to properly function. C1 [Zare, Hossein; Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. [Khodursky, Arkady] Univ Minnesota, Inst Biotechnol, Dept Biochem Mol Biol & Biophys, St Paul, MN 55108 USA. RP Zare, H (reprint author), NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM hzare@mail.nih.gov; sartorev@mail.nih.gov FU Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH) FX This work was supported by Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH). NR 49 TC 1 Z9 1 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD APR 4 PY 2014 VL 14 AR 74 DI 10.1186/1471-2148-14-74 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA AI3MY UT WOS:000336766900001 PM 24707827 ER PT J AU Bansal, S Leu, AN Gonzalez, FJ Guengerich, FP Chowdhury, AR Anandatheerthavarada, HK Avadhani, NG AF Bansal, Seema Leu, Adrian N. Gonzalez, Frank J. Guengerich, F. Peter Chowdhury, Anindya Roy Anandatheerthavarada, Hindupur K. Avadhani, Narayan G. TI Mitochondrial Targeting of Cytochrome P450 (CYP) 1B1 and Its Role in Polycyclic Aromatic Hydrocarbon- induced Mitochondrial Dysfunction* SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Carcinogenesis; Cytochrome P450; DNA Damage; Membrane Proteins; Mitochondria; Mitochondrial DNA ID KNOCKOUT MOUSE LINES; PROTEIN-KINASE-A; ENDOPLASMIC-RETICULUM; BETA-NAPHTHOFLAVONE; DRUG-METABOLISM; MEDIATED PHOSPHORYLATION; CATALYTIC-PROPERTIES; CHIMERIC SIGNALS; OXIDATIVE STRESS; P4501B1 VARIANTS AB Background: Cytochrome P450 (CYP) 1B1 activates diverse polycyclic aromatic hydrocarbons (PAH) to reactive species. Results: Processing by a cytosolic Ser protease activates a mitochondrial (mt) targeting signal of CYP1B1. Conclusion: Mitochondrial CYP1B1 plays a role in PAH-induced mtDNA damage and mitochondrial dysfunction. Significance: PAH-induced mitochondrial dysfunction may be important in tissue injury and inflammation. We report that polycyclic aromatic hydrocarbon (PAH)-inducible CYP1B1 is targeted to mitochondria by sequence-specific cleavage at the N terminus by a cytosolic Ser protease (polyserase 1) to activate the cryptic internal signal. Site-directed mutagenesis, COS-7 cell transfection, and in vitro import studies in isolated mitochondria showed that a positively charged domain at residues 41-48 of human CYP1B1 is part of the mitochondrial (mt) import signal. Ala scanning mutations showed that the Ser protease cleavage site resides between residues 37 and 41 of human CYP1B1. Benzo[a]pyrene (BaP) treatment induced oxidative stress, mitochondrial respiratory defects, and mtDNA damage that was attenuated by a CYP1B1-specific inhibitor, 2,3,4,5-tetramethoxystilbene. In support, the mitochondrial CYP1B1 supported by mitochondrial ferredoxin (adrenodoxin) and ferredoxin reductase showed high aryl hydrocarbon hydroxylase activity. Administration of benzo[a]pyrene or 2,3,7,8-tetrachlorodibenzodioxin induced similar mitochondrial functional abnormalities and oxidative stress in the lungs of wild-type mice and Cyp1a1/1a2-null mice, but the effects were markedly blunted in Cyp1b1-null mice. These results confirm a role for CYP1B1 in inducing PAH-mediated mitochondrial dysfunction. The role of mitochondrial CYP1B1 was assessed using A549 lung epithelial cells stably expressing shRNA against NADPH-cytochrome P450 oxidoreductase or mitochondrial adrenodoxin. Our results not only show conservation of the endoprotease cleavage mechanism for mitochondrial import of family 1 CYPs but also reveal a direct role for mitochondrial CYP1B1 in PAH-mediated oxidative and chemical damage to mitochondria. C1 [Bansal, Seema; Leu, Adrian N.; Chowdhury, Anindya Roy; Anandatheerthavarada, Hindupur K.; Avadhani, Narayan G.] Univ Penn, Dept Anim Biol, Philadelphia, PA 19104 USA. [Bansal, Seema; Leu, Adrian N.; Chowdhury, Anindya Roy; Anandatheerthavarada, Hindupur K.; Avadhani, Narayan G.] Univ Penn, Sch Vet Med, Mari Lowe Ctr Comparat Oncol, Philadelphia, PA 19104 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Guengerich, F. Peter] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. [Guengerich, F. Peter] Vanderbilt Univ, Sch Med, Ctr Mol Toxicol, Nashville, TN 37232 USA. RP Avadhani, NG (reprint author), Univ Penn, Dept Anim Biol, Philadelphia, PA 19104 USA. EM Narayan@vet.upenn.edu FU National Institutes of Health [R01 GM34883, R37 CA090426]; Harret Ellison Woodward Trust FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 GM34883 (to N. G. A.) and Grant R37 CA090426 (to F. P. G.). This work was also supported by the Harret Ellison Woodward Trust (to N. G. A). NR 66 TC 12 Z9 13 U1 3 U2 23 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 APR 4 PY 2014 VL 289 IS 14 BP 9936 EP 9951 DI 10.1074/jbc.M113.525659 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AE2MK UT WOS:000333807000043 PM 24497629 ER PT J AU Emery, AC Eiden, MV Eiden, LE AF Emery, Andrew C. Eiden, Maribeth V. Eiden, Lee E. TI Separate Cyclic AMP Sensors for Neuritogenesis, Growth Arrest, and Survival of Neuroendocrine Cells* SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cyclic AMP (cAMP); ERK; Guanine Nucleotide Exchange Factor (GEF); p38 MAPK; Protein Kinase A (PKA); Epac; NCS; Rapgef2 ID CYCLASE-ACTIVATING POLYPEPTIDE; DEPENDENT PROTEIN-KINASE; PC12 CELLS; ADENYLATE-CYCLASE; NEURITE OUTGROWTH; NEURONAL DIFFERENTIATION; SIGNALING PATHWAY; FARNESYLTHIOSALICYLIC ACID; NEUROTROPHIN RECEPTOR; SUSTAINED ACTIVATION AB Background: Three cAMP sensors (PKA, Epac1/2, and NCS/Rapgef2) coexist in neuroendocrine cells. Their roles in differentiation require elucidation. Results: Epac2, PKA, and NCS/Rapgef2 independently gate signaling for growth arrest, cell survival, and neuritogenesis after GPCR-G(s) engagement in PC12 cells. Conclusion: Parallel, insulated pathways effect cAMP-dependent neuroendocrine cell differentiation. Significance: Assays for parcellated cAMP signaling in neuroendocrine cells have a broad application for CNS drug discovery. Dividing neuroendocrine cells differentiate into a neuronal-like phenotype in response to ligands activating G protein-coupled receptors, leading to the elevation of the second messenger cAMP. Growth factors that act at receptor tyrosine kinases, such as nerve growth factor, also cause differentiation. We report here that two aspects of cAMP-induced differentiation, neurite extension and growth arrest, are dissociable at the level of the sensors conveying the cAMP signal in PC12 and NS-1 cells. Following cAMP elevation, neuritogenic cyclic AMP sensor/Rapgef2 is activated for signaling to ERK to mediate neuritogenesis, whereas Epac2 is activated for signaling to the MAP kinase p38 to mediate growth arrest. Neither action of cAMP requires transactivation of TrkA, the receptor for NGF. In fact, the differentiating effects of NGF do not require activation of any of the cAMP sensors protein kinase A, Epac, or neuritogenic cyclic AMP sensor/Rapgef2 but, rather, depend on ERK and p38 activation via completely independent signaling pathways. Hence, cAMP- and NGF-dependent signaling for differentiation are also completely insulated from each other. Cyclic AMP and NGF also protect NS-1 cells from serum withdrawal-induced cell death, again by two wholly separate signaling mechanisms, PKA-dependent for cAMP and PKA-independent for NGF. C1 [Emery, Andrew C.; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Intramural Res Program, Bethesda, MD 20892 USA. [Eiden, Maribeth V.] NIMH, Sect Directed Gene Transfer, Lab Cellular & Mol Regulat, Intramural Res Program, Bethesda, MD 20892 USA. RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Intramural Res Program, 9000 Rockville Pike,Bldg 49,Rm 5A38, Bethesda, MD 20892 USA. EM eidenl@mail.nih.gov OI Emery, Andrew/0000-0002-6760-2570; Eiden, Lee/0000-0001-7524-944X FU National Institute of Mental Health Intramural Research Program [1ZIAMH002386, 1ZIAMH002592] FX This work was supported, in whole or in part, by National Institute of Mental Health Intramural Research Program Projects 1ZIAMH002386 (to L. E. E.) and 1ZIAMH002592 (to M. V. E.). NR 58 TC 7 Z9 7 U1 0 U2 6 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 APR 4 PY 2014 VL 289 IS 14 BP 10126 EP 10139 DI 10.1074/jbc.M113.529321 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AE2MK UT WOS:000333807000059 PM 24567337 ER PT J AU Joe, MK Kwon, HS Cojocaru, R Tomarev, SI AF Joe, Myung Kuk Kwon, Heung Sun Cojocaru, Radu Tomarev, Stanislav I. TI Myocilin Regulates Cell Proliferation and Survival SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Apoptosis; Cell Growth; Cell Proliferation; Cell Signaling; ERK; Mesenchymal Stem Cells ID OPEN-ANGLE GLAUCOMA; TRABECULAR MESHWORK CELLS; MESENCHYMAL STEM-CELLS; GENE-EXPRESSION; PROTEIN COMPLEX; GASTRIC-CANCER; KINASE KINASE; NON-SECRETION; TUMOR-GROWTH; ER STRESS AB Background: The physiological function(s) of myocilin, a glaucoma-associated protein, is poorly understood. Results: Myocilin enhances cell proliferation and survival together with the activation of the ERK signaling pathway. Myocilin-deficient mesenchymal stem cells demonstrate reduced proliferation and survival. Conclusion: Myocilin participates in the regulation of cell growth and survival. Significance: This study provides new insight into the role of myocilin in ocular and non-ocular tissues. Myocilin, a causative gene for open angle glaucoma, encodes a secreted glycoprotein with poorly understood functions. To gain insight into its functions, we produced a stably transfected HEK293 cell line expressing myocilin under an inducible promoter and compared gene expression profiles between myocilin-expressing and vector control cell lines by a microarray analysis. A significant fraction of differentially expressed genes in myocilin-expressing cells was associated with cell growth and cell death, suggesting that myocilin may have a role in the regulation of cell growth and survival. Increased proliferation of myocilin-expressing cells was demonstrated by the WST-1 proliferation assay, direct cell counting, and immunostaining with antibodies against Ki-67, a cellular proliferation marker. Myocilin-containing conditioned medium also increased proliferation of unmodified HEK293 cells. Myocilin-expressing cells were more resistant to serum starvation-induced apoptosis than control cells. TUNEL-positive apoptotic cells were dramatically decreased, and two apoptotic marker proteins, cleaved caspase 7 and cleaved poly(ADP-ribose) polymerase, were significantly reduced in myocilin-expressing cells as compared with control cells under apoptotic conditions. In addition, myocilin-deficient mesenchymal stem cells exhibited reduced proliferation and enhanced susceptibility to serum starvation-induced apoptosis as compared with wild-type mesenchymal stem cells. Phosphorylation of ERK1/2 and its upstream kinases, c-Raf and MEK, was increased in myocilin-expressing cells compared with control cells. Elevated phosphorylation of ERK1/2 was also observed in the trabecular meshwork of transgenic mice expressing 6-fold higher levels of myocilin when compared with their wild-type littermates. These results suggest that myocilin promotes cell proliferation and resistance to apoptosis via the ERK1/2 MAPK signaling pathway. C1 [Tomarev, Stanislav I.] NEI, SRGCB, LRCMB, NIH, Bethesda, MD 20892 USA. [Cojocaru, Radu] Elsevier Life Sci Solut, Rockville, MD 20852 USA. RP Tomarev, SI (reprint author), NEI, SRGCB, LRCMB, NIH, Bldg 6,Rm 212,6 Ctr Dr, Bethesda, MD 20892 USA. EM tomarevs@nei.nih.gov FU National Institutes of Health, NEI, Intramural Research Program FX This work was supported, in whole or in part, by the National Institutes of Health, NEI, Intramural Research Program. NR 76 TC 7 Z9 7 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 4 PY 2014 VL 289 IS 14 BP 10155 EP 10167 DI 10.1074/jbc.M113.547091 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AE2MK UT WOS:000333807000061 PM 24563482 ER PT J AU Askari, AA Thomson, S Edin, ML Lih, FB Zeldin, DC Bishop-Bailey, D AF Askari, Ara A. Thomson, Scott Edin, Matthew L. Lih, Fred B. Zeldin, Darryl C. Bishop-Bailey, David TI Basal and inducible anti-inflammatory epoxygenase activity in endothelial cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Endothelial; TNF alpha; Epoxygenase; Soluble epoxide hydrolase ID SOLUBLE EPOXIDE HYDROLASE; ACID METABOLISM; CYTOCHROME-P450; INHIBITION; PATHWAYS; EPOXYEICOSANOIDS; ACTIVATION; EXPRESSION; HEALTH; MICE AB The roles of CYP lipid-metabolizing pathways in endothelial cells are poorly understood. Human endothelial cells expressed CYP2J2 and soluble epoxide hydrolase (sEH) mRNA and protein. The TLR-4 agonist LPS (1 mu g/ml; 24 h) induced CYP2J2 but not sEH mRNA and protein. LC-MS/MS analysis of the stable commonly used human endothelial cell line EA.Hy926 showed active epoxygenase and epoxide hydrolase activity: with arachidonic acid (stable epoxide products 5,6-DHET, and 14,15-DHET), linoleic acid (9,10-EPOME and 12,13-EPOME and their stable epoxide hydrolase products 9,10-DHOME and 12,13-DHOME), docosahexaenoic acid (stable epoxide hydrolase product 19,20-DiHDPA) and eicosapentaenoic acid (stable epoxide hydrolase product 17,18-DHET) being formed. Inhibition of epoxygenases using either SKF525A or MS-PPOH induced TNF alpha release, but did not affect LPS, IL-1 beta, or phorbol-12-myristate-13-acetate (PMA)-induced TNF alpha release. In contrast, inhibition of soluble epoxide hydrolase by AUDA or TPPU inhibited basal, LPS, IL-1 beta, and PMA induced TNF alpha . release, and LPS-induced NF kappa B p65 nuclear translocation. In conclusion, human endothelial cells contain a TLR-4 regulated epoxygenase CYP2J2 and metabolize linoleic acid > eicosapentaenoic acid > arachidonic acid > docosahexaenoic acid to products with anti-inflammatory activity. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Askari, Ara A.] Queen Mary Univ, London, England. [Thomson, Scott; Bishop-Bailey, David] Univ London Royal Vet Coll, London, England. [Edin, Matthew L.; Lih, Fred B.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Bishop-Bailey, D (reprint author), Univ London Royal Vet Coll, London, England. EM dbishopbailey@rvc.ac.uk OI Edin, Matthew/0000-0002-7042-500X FU British Heart Foundation, United Kingdom [PG/11/39/28890]; National Institutes of Health, NIEHS FX This work was funded by grants from the British Heart Foundation, United Kingdom (PG/11/39/28890), and the Intramural Research Programs of the National Institutes of Health, NIEHS (D.C.Z.). NR 30 TC 13 Z9 14 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 4 PY 2014 VL 446 IS 2 BP 633 EP 637 DI 10.1016/j.bbrc.2014.03.020 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AF7NU UT WOS:000334902600035 PM 24631907 ER PT J AU Christensen, LB Woods, TA Carmody, AB Caughey, B Peterson, KE AF Christensen, Leah B. Woods, Tyson A. Carmody, Aaron B. Caughey, Byron Peterson, Karin E. TI Age-related differences in neuroinflammatory responses associated with a distinct profile of regulatory markers on neonatal microglia SO JOURNAL OF NEUROINFLAMMATION LA English DT Article ID HUMAN NK CELLS; BRAIN-DEVELOPMENT; PROTEIN-ALPHA; EARLY-LIFE; LIPOPOLYSACCHARIDE; ASTROCYTES; INFECTION; SCHIZOPHRENIA; ACTIVATION; EXPRESSION AB Background: The perinatal period is one in which the mammalian brain is particularly vulnerable to immune-mediated damage. Early inflammation in the central nervous system (CNS) is linked with long-term impairment in learning and behavior, necessitating a better understanding of mediators of neuroinflammation. We therefore directly examined how age affected neuroinflammatory responses to pathogenic stimuli. Methods: In mice, susceptibility to neurological damage changes dramatically during the first few weeks of life. Accordingly, we compared neuroinflammatory responses to pathogen associated molecular patterns (PAMPs) of neonatal (two day-old) and weanling (21 day-old) mice. Mice were inoculated intracerebrally with PAMPs and the cellular and molecular changes in the neuroinflammatory response were examined. Results: Of the 12 cytokines detected in the CNS following toll-like receptor 4 (TLR4) stimulation, ten were significantly higher in neonates compared with weanling mice. A similar pattern of increased cytokines in neonates was also observed with TLR9 stimulation. Analysis of cellular responses indicated a difference in microglial activation markers in the CNS of neonatal mice and increased expression of proteins known to modulate cellular activation including CD11a, F4/80 and CD172a. We also identified a new marker on microglia, SLAMF7, which was expressed at higher levels in neonates compared with weanlings. Conclusions: A unique neuroinflammatory profile, including higher expression of several proinflammatory cytokines and differential expression of microglial markers, was observed in brain tissue from neonates following TLR stimulation. This increased neuroinflammatory response to PAMPs may explain why the developing brain is particularly sensitive to infection and why infection or stress during this time can lead to long-term damage in the CNS. C1 [Christensen, Leah B.; Woods, Tyson A.; Carmody, Aaron B.; Caughey, Byron; Peterson, Karin E.] Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Peterson, KE (reprint author), Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. EM petersonka@niaid.nih.gov RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 FU Intramural Research program of the National Institute of Allergy and Infectious Disease FX The authors would like to thank Bruce Chesebro, Sue Priola, Katherine Taylor and Clayton Winkler for review of the manuscript and helpful suggestions. The authors would also like to thank Lara Myers for her helpful suggestions on flow cytometry. This work was funded by the Intramural Research program of the National Institute of Allergy and Infectious Disease. NR 54 TC 4 Z9 4 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD APR 4 PY 2014 VL 11 AR 70 DI 10.1186/1742-2094-11-70 PG 13 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA AF8GE UT WOS:000334952900001 PM 24708744 ER PT J AU Kagaayi, J Gray, RH Whalen, C Fu, PF Neuhauser, D McGrath, JW Sewankambo, NK Serwadda, D Kigozi, G Nalugoda, F Reynolds, SJ Wawer, MJ Singer, ME AF Kagaayi, Joseph Gray, Ronald H. Whalen, Christopher Fu, Pingfu Neuhauser, Duncan McGrath, Janet W. Sewankambo, Nelson K. Serwadda, David Kigozi, Godfrey Nalugoda, Fred Reynolds, Steven J. Wawer, Maria J. Singer, Mendel E. TI Indices to Measure Risk of HIV Acquisition in Rakai, Uganda SO PLOS ONE LA English DT Article ID MALE CIRCUMCISION; COST-EFFECTIVENESS; PREEXPOSURE PROPHYLAXIS; AIDS-PREVENTION; COMMUNITY TRIAL; UNITED-STATES; RURAL UGANDA; ALCOHOL-USE; INFECTION; WOMEN AB Introduction: Targeting most-at-risk individuals with HIV preventive interventions is cost-effective. We developed gender-specific indices to measure risk of HIV among sexually active individuals in Rakai, Uganda. Methods: We used multivariable Cox proportional hazards models to estimate time-to-HIV infection associated with candidate predictors. Reduced models were determined using backward selection procedures with Akaike's information criterion (AIC) as the stopping rule. Model discrimination was determined using Harrell's concordance index (c index). Model calibration was determined graphically. Nomograms were used to present the final prediction models. Results: We used samples of 7,497 women and 5,783 men. 342 new infections occurred among females (incidence 1.11/100 person years,) and 225 among the males (incidence 1.00/100 person years). The final model for men included age, education, circumcision status, number of sexual partners, genital ulcer disease symptoms, alcohol use before sex, partner in high risk employment, community type, being unaware of a partner's HIV status and community HIV prevalence. The Model's optimism-corrected c index was 69.1 percent (95% CI = 0.66, 0.73). The final women's model included age, marital status, education, number of sex partners, new sex partner, alcohol consumption by self or partner before sex, concurrent sexual partners, being employed in a high-risk occupation, having genital ulcer disease symptoms, community HIV prevalence, and perceiving oneself or partner to be exposed to HIV. The models optimism-corrected c index was 0.67 (95% CI = 0.64, 0.70). Both models were well calibrated. Conclusion: These indices were discriminative and well calibrated. This provides proof-of-concept that population-based HIV risk indices can be developed. Further research to validate these indices for other populations is needed. C1 [Kagaayi, Joseph] Rakai Hlth Sci Program, Entebbe, Uganda. [Kagaayi, Joseph; Fu, Pingfu; Neuhauser, Duncan; Kigozi, Godfrey; Nalugoda, Fred; Singer, Mendel E.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Gray, Ronald H.; Wawer, Maria J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [McGrath, Janet W.] Case Western Reserve Univ, Dept Anthropol, Cleveland, OH 44106 USA. [Whalen, Christopher] Univ Georgia, Dept Epidemiol & Biostat, Athens, GA 30602 USA. [Sewankambo, Nelson K.; Serwadda, David] Makerere Univ, Coll Hlth Sci, Kampala, Uganda. [Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Reynolds, Steven J.] Johns Hopkins Sch Med, Baltimore, MD USA. RP Kagaayi, J (reprint author), Rakai Hlth Sci Program, Entebbe, Uganda. EM jxk597@case.edu OI Sewankambo, Nelson/0000-0001-9362-053X FU National Institute of Child Health and Human Development of the National Institutes of Health [RO1HD050180]; National Institutes of Health [U01AI075115]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX The study was supported by National Institute of Child Health and Human Development of the National Institutes of Health; grant number RO1HD050180; and National Institutes of Health; grant number U01AI075115; and in part (SJR) by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, 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 40 TC 5 Z9 5 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 APR 4 PY 2014 VL 9 IS 4 AR e92015 DI 10.1371/journal.pone.0092015 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE6MJ UT WOS:000334107500012 PM 24704778 ER PT J AU Lefevre, CE Wilson, VAD Morton, FB Brosnan, SF Paukner, A Bates, TC AF Lefevre, Carmen Emilia Wilson, Vanessa A. D. Morton, F. Blake Brosnan, Sarah F. Paukner, Annika Bates, Timothy C. TI Facial Width-To-Height Ratio Relates to Alpha Status and Assertive Personality in Capuchin Monkeys SO PLOS ONE LA English DT Article ID SEX-DIFFERENCES; AGGRESSIVE-BEHAVIOR; HOCKEY PLAYERS; BODY-WEIGHT; COMPETITION; DIMORPHISM; PRIMATES; CEBUS; FACES; CUES AB Social dominance hierarchies play a pivotal role in shaping the behaviour of many species, and sex differences within these hierarchies often exist. To date, however, few physical markers of dominance have been identified. Such markers would be valuable in terms of understanding the etiology of dominant behaviour and changes in social hierarchies over time. Animals may also use such traits to evaluate the potential dominance of others relative to themselves (i.e. a physical "cue"). Facial width-to-height ratio (fWHR), for example, has been suggested as a cue to dominance in humans, with links to both dominant behaviour and the perception of dominance in other individuals. Whether this association is present in nonhuman animals is currently not known. Therefore, here we examine within-species links between fWHR and dominant behaviour in 64 brown capuchin monkeys (Sapajus spp.) aged between 2 and 40 years. fWHR was positively associated with alpha status and with a dimensional rating of assertive personality in both males and females. Moreover, fWHR showed significant sexual dimorphism in adults but not juveniles, suggesting a developmental change may occur during puberty. In a sub-sample, sex differences were mediated by weight, suggesting fWHR dimorphism does not exceed what would be expected by differences in body weight. This is the first report of an association between face shape and behaviour in a nonhuman species. Results are discussed in terms of the role that face-behaviour associations might play within capuchin societies, and the possible selective forces that might have led to the evolution of fWHR-dominance associations in humans. C1 [Lefevre, Carmen Emilia] Univ Leeds, Sch Business, Ctr Decis Res, Leeds, W Yorkshire, England. [Wilson, Vanessa A. D.; Bates, Timothy C.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Wilson, Vanessa A. D.; Morton, F. Blake] Scottish Primate Res Grp, Edinburgh, Midlothian, Scotland. [Morton, F. Blake] Univ Stirling, Sch Nat Sci, Behav & Evolut Res Grp, Stirling FK9 4LA, Scotland. [Brosnan, Sarah F.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Brosnan, Sarah F.] Georgia State Univ, Language Res Ctr, Atlanta, GA 30303 USA. [Paukner, Annika] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Dept Hlth & Human Serv, Poolesville, MD USA. RP Lefevre, CE (reprint author), Univ Leeds, Sch Business, Ctr Decis Res, Leeds, W Yorkshire, England. EM carmenlefevre@me.com; tim.bates@ed.ac.uk OI Bates, Timothy/0000-0002-1153-9007 FU Intramural NIH HHS [Z99 HD999999] NR 48 TC 9 Z9 9 U1 2 U2 29 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 APR 4 PY 2014 VL 9 IS 4 AR e93369 DI 10.1371/journal.pone.0093369 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE6MJ UT WOS:000334107500033 PM 24705247 ER PT J AU Salamoun, J Anderson, S Burnett, JC Gussio, R Wipf, P AF Salamoun, Joseph Anderson, Shelby Burnett, James C. Gussio, Rick Wipf, Peter TI Synthesis of Heterocyclic Triads by Pd-Catalyzed Cross-Couplings and Evaluation of Their Cell-Specific Toxicity Profile SO ORGANIC LETTERS LA English DT Article ID CANCER CELLS; IN-VIVO; THIOPHENE; EFFICIENT; APOPTOSIS; OXAZOLE; RITA; P53; REGIOSELECTIVITY; IDENTIFICATION AB Two complementary approaches for the preparation of linked 5-membered heterocycles were developed. The Pd-catalyzed Suzuki-Miyaura cross-coupling with halogenated furan, thiophene, and selenophene led to higher overall yields, but C,H-bond activation was a more efficient strategy for the coupling at C(2) of oxazoles. Potency and selectivity of the final hydroxymethyl products in renal (A498), lung (NCI-H226), kidney (CAKI-1), and breast (MDA-MB-468, MCF7) carcinoma cell lines were determined. C1 [Salamoun, Joseph; Anderson, Shelby; Wipf, Peter] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. [Burnett, James C.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Computat Drug Dev Grp, Frederick, MD 21702 USA. [Gussio, Rick] Frederick Natl Lab Canc Res, Dev Therapeut Program, Computat Drug Dev Grp, Frederick, MD 21702 USA. RP Wipf, P (reprint author), Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. EM pwipf@pitt.edu FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project was funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. We thank Dr. Erin Skoda (University of Pittsburgh) for valuable contributions to the synthesis of lob and 11b and Dr. Chris Rosenker (University of Pittsburgh) for scaling up 4a and exploring the cross-coupling of 4a and 5a. NR 38 TC 3 Z9 3 U1 1 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 EI 1523-7052 J9 ORG LETT JI Org. Lett. PD APR 4 PY 2014 VL 16 IS 7 BP 2034 EP 2037 DI 10.1021/ol500620m PG 4 WC Chemistry, Organic SC Chemistry GA AE5GU UT WOS:000334016600052 PM 24641272 ER PT J AU Fauci, AS Marovich, MA Dieffenbach, CW Hunter, E Buchbinder, SP AF Fauci, Anthony S. Marovich, Mary A. Dieffenbach, Carl W. Hunter, Eric Buchbinder, Susan P. TI Immune Activation with HIV Vaccines SO SCIENCE LA English DT Editorial Material ID T-CELLS; EFFICACY TRIAL; DOUBLE-BLIND; STEP; ACQUISITION; INFECTION; AIDSVAX; ALVAC; RISK; TIME C1 [Fauci, Anthony S.; Marovich, Mary A.; Dieffenbach, Carl W.] NIAID, Bethesda, MD 20892 USA. [Hunter, Eric] Emory Univ, Dept Pathol & Lab Med, Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Buchbinder, Susan P.] Univ Calif San Francisco, Dept Med, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. RP Fauci, AS (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000390-25, Z01 AI000677-15]; NCRR NIH HHS [P51 RR000165]; NIAID NIH HHS [U19 AI096187, UM1 AI068614]; NIH HHS [P51 OD011132] NR 19 TC 31 Z9 31 U1 2 U2 17 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD APR 4 PY 2014 VL 344 IS 6179 BP 49 EP 51 DI 10.1126/science.1250672 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE1RD UT WOS:000333746100046 PM 24700849 ER PT J AU Li, FY Chaigne-Delalande, B Su, HL Uzel, G Matthews, H Lenardo, MJ AF Li, Feng-Yen Chaigne-Delalande, Benjamin Su, Helen Uzel, Gulbu Matthews, Helen Lenardo, Michael J. TI XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus SO BLOOD LA English DT Article ID LINKED LYMPHOPROLIFERATIVE DISEASE; INFECTION; CELLS; NK; CYTOTOXICITY; ACTIVATION; NKG2D AB Epstein-Barr virus (EBV) is an oncogenic gammaherpesvirus that infects and persists in 95% of adults worldwide and has the potential to cause fatal disease, especially lymphoma, in immunocompromised hosts. Primary immunodeficiencies (PIDs) that predispose to EBV-associated malignancies have provided novel insights into the molecular mechanisms of immune defense against EBV. We have recently characterized a novel PID now named "X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia" (XMEN) disease characterized by loss-of-function mutations in the gene encoding magnesium transporter 1 (MAGT1), chronic high-level EBV with increased EBV-infected B cells, and heightened susceptibility to EBV-associated lymphomas. The genetic etiology of XMEN disease has revealed an unexpected quantitative role for intracellular free magnesium in immune functions and has led to novel diagnostic and therapeutic strategies. Here, we review the clinical presentation, genetic mutation spectrum, molecular mechanisms of pathogenesis, and diagnostic and therapeutic considerations for this previously unrecognized disease. C1 [Li, Feng-Yen; Chaigne-Delalande, Benjamin; Matthews, Helen; Lenardo, Michael J.] NIAID, Mol Dev Immune Syst Sect, Lymphocyte Mol Genet Unit, Immunol Lab,NIH, Bethesda, MD 20892 USA. [Li, Feng-Yen] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Su, Helen] NIAID, Immunol Dis Unit, Lab Host Def, NIH, Bethesda, MD 20892 USA. [Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), Immunol Lab, 10 Ctr Dr,Bldg 10,Room 11D14, Bethesda, MD 20892 USA. EM lenardo@nih.gov RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH [ZO1AI001187-01]; Office of Disease Prevention, NIH FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH (ZO1AI001187-01) and by co-funding through the Office of Disease Prevention, NIH. NR 16 TC 32 Z9 33 U1 0 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 APR 3 PY 2014 VL 123 IS 14 BP 2148 EP 2152 DI 10.1182/blood-2013-11-538686 PG 5 WC Hematology SC Hematology GA AH1OE UT WOS:000335889600009 PM 24550228 ER PT J AU Isasi, R Andrews, PW Baltz, JM Bredenoord, AL Burton, P Chiu, IM Hull, SC Jung, JW Kurtz, A Lomax, G Ludwig, T McDonald, M Morris, C Ng, HH Rooke, H Sharma, A Stacey, GN Williams, C Zeng, FY Knoppers, BM AF Isasi, Rosario Andrews, Peter W. Baltz, Jay M. Bredenoord, Annelien L. Burton, Paul Chiu, Ing-Ming Hull, Sara Chandros Jung, Ji-Won Kurtz, Andreas Lomax, Geoffrey Ludwig, Tenneille McDonald, Michael Morris, Clive Ng, Huck Hui Rooke, Heather Sharma, Alka Stacey, Glyn N. Williams, Clare Zeng, Fanyi Knoppers, Bartha Maria TI Identifiability and Privacy in Pluripotent Stem Cell Research SO CELL STEM CELL LA English DT Editorial Material AB Data sharing is an essential element of research; however, recent scientific and social developments have challenged conventional methods for protecting privacy. Here we provide guidance for determining data sharing thresholds for human pluripotent stem cell research aimed at a wide range of stakeholders, including research consortia, biorepositories, policy-makers, and funders. C1 [Isasi, Rosario; Knoppers, Bartha Maria] McGill Univ, Dept Human Genet, Ctr Genom & Policy, Fac Med, Montreal, PQ H3A 0G1, Canada. [Andrews, Peter W.] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England. [Baltz, Jay M.] Univ Ottawa, Ottawa Hosp Res Inst, Ottawa, ON K1H 8L6, Canada. [Baltz, Jay M.] Univ Ottawa, Dept Obstet & Gynecol, Fac Med, Ottawa, ON K1H 8L6, Canada. [Bredenoord, Annelien L.] Univ Med Ctr Utrecht, Dept Med Eth, Julius Ctr, NL-3584 CX Utrecht, Netherlands. [Burton, Paul] Univ Bristol, Sch Social & Community Med, Bristol BS8 1TH, Avon, England. [Chiu, Ing-Ming] Natl Hlth Res Inst, ICSM, Jhunan 35053, Miaoli, Taiwan. [Hull, Sara Chandros] NIH, NHGRI Bioeth Core, Bethesda, MD 20892 USA. [Jung, Ji-Won] Natl Inst Hlth, Ctr Biomed Sci, Div Intractable Dis, Chungcheongbuk Do 363951, South Korea. [Jung, Ji-Won] Korea Ctr Dis Control & Prevent, Chungcheongbuk Do 363951, South Korea. [Kurtz, Andreas] Berlin Brandenburg Ctr Regenerat Therapies, D-13353 Berlin, Germany. [Lomax, Geoffrey] Calif Inst Regenerat Med, San Francisco, CA 94107 USA. [Ludwig, Tenneille] WiCell Res Inst, Madison, WI 53726 USA. [McDonald, Michael] Univ British Columbia, Sch Populat & Publ Hlth, W Maurice Young Ctr Appl Eth, Vancouver, BC V6T 1Z2, Canada. [Morris, Clive] Natl Hlth & Med Res Council, Canberra, ACT 2601, Australia. [Ng, Huck Hui] ASTAR, Genome Inst Singapore, Singapore 138672, Singapore. [Rooke, Heather] Int Soc Stem Cell Res, Skokie, IL 60077 USA. [Sharma, Alka] Govt India, Minist Sci & Technol, Dept Biotechnol, Med Biotechnol Div, New Delhi 110003, India. [Stacey, Glyn N.] Natl Inst Biol Stand & Controls, S Mimms UB8 3PH, Herts, England. [Williams, Clare] Brunel Univ, Sch Social Sci, Dept Sociol & Commun, Uxbridge UB8 3PH, Middx, England. [Zeng, Fanyi] Shanghai Stem Cell Inst, Shanghai Inst Med Genet, Shanghai 200025, Peoples R China. RP Isasi, R (reprint author), McGill Univ, Dept Human Genet, Ctr Genom & Policy, Fac Med, Montreal, PQ H3A 0G1, Canada. EM rosario.isasi@mcgill.ca RI Ng, Huck Hui/A-1135-2009; Chiu, Ing-Ming/B-1534-2008; OI Williams, Clare/0000-0001-6315-5534; Morris, Clive/0000-0003-1392-7959 FU Intramural NIH HHS [Z99 HG999999]; Medical Research Council [G1001045, MR/L01324X/1]; Wellcome Trust [086034] NR 10 TC 12 Z9 12 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD APR 3 PY 2014 VL 14 IS 4 BP 427 EP 430 DI 10.1016/j.stem.2014.03.014 PG 4 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AF5PW UT WOS:000334766400007 PM 24702994 ER PT J AU Kim, S Kim, N Presson, AP Metzger, ME Bonifacino, AC Sehl, M Chow, SA Crooks, GM Dunbar, CE An, DS Donahue, RE Chen, ISY AF Kim, Sanggu Kim, Namshin Presson, Angela P. Metzger, Mark E. Bonifacino, Aylin C. Sehl, Mary Chow, Samson A. Crooks, Gay M. Dunbar, Cynthia E. An, Dong Sung Donahue, Robert E. Chen, Irvin S. Y. TI Dynamics of HSPC Repopulation in Nonhuman Primates Revealed by a Decade-Long Clonal-Tracking Study SO CELL STEM CELL LA English DT Article ID HEMATOPOIETIC STEM-CELL; SCID-X1 GENE-THERAPY; IN-VIVO; LENTIVIRAL VECTOR; SELF-RENEWAL; RETROVIRAL INTEGRATION; HIGH-THROUGHPUT; HETEROGENEITY; DIFFERENTIATION; RECONSTITUTION AB In mice, clonal tracking of hematopoietic stem cells (HSCs) has revealed variations in repopulation characteristics. However, it is unclear whether similar properties apply in primates. Here, we examined this issue through tracking of thousands of hematopoietic stem and progenitor cells (HSPCs) in rhesus macaques for up to 12 years. Approximately half of the clones analyzed contributed to long-term repopulation (over 3-10 years), arising in sequential groups and likely representing self-renewing HSCs. The remainder contributed primarily for the first year. The long-lived clones could be further subdivided into functional groups contributing primarily to myeloid, lymphoid, or both myeloid and lymphoid lineages. Over time, the 4%-10% of clones with robust dual lineage contribution predominated in repopulation. HSPCs expressing a CCR5 shRNA transgene behaved similarly to controls. Our study therefore documents HSPC behavior in a clinically relevant model over a long time frame and provides a substantial system-level data set that is a reference point for future work. C1 [Kim, Sanggu; Chen, Irvin S. Y.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Chow, Samson A.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Presson, Angela P.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. [Sehl, Mary; Chen, Irvin S. Y.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Sehl, Mary] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90095 USA. [Kim, Sanggu; Presson, Angela P.; Chow, Samson A.; An, Dong Sung; Chen, Irvin S. Y.] Univ Calif Los Angeles, UCLA AIDS Inst, Los Angeles, CA 90095 USA. [An, Dong Sung] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. [Crooks, Gay M.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Kim, Namshin] Korea Res Inst Biosci & Biotechnol, Korean Bioinformat Ctr, Taejon 305806, South Korea. [Metzger, Mark E.; Bonifacino, Aylin C.; Dunbar, Cynthia E.; Donahue, Robert E.] NHLBI, Hematol Branch, NIH, Rockville, MD 20850 USA. RP Chen, ISY (reprint author), Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. EM syuchen@mednet.ucla.edu FU NIH, Hematology Branch, National Heart, Lung and Blood Institute; NIH [AI055281-06A2, CA68859, P01 HL073104, K99 HL116234]; California Institute of Regenerative Medicine [DR1-01431]; UCLA AIDS Institute/Center for AIDS Research [AI28697]; Korean NRF [2011-0030049]; Next-Gen BioGreen21 [PJ008019, PJ008068]; Calimmune, Inc. FX We thank the animal support and veterinary staff of both 5 Research Court and the Division of Veterinary Resources for maintaining these nonhuman primates for all these years; Keyvan Keyvanfar of the Hematology Branch and Ann Williams of the Core Flow Cytometry Laboratory, NHLBI, for performing cell sorting; and the UCLA Genotyping and Sequencing Core for performing DNA sequencing. This work was supported in part by the intramural program of the NIH, Hematology Branch, National Heart, Lung and Blood Institute; NIH grants AI055281-06A2 (I.S.Y.C.), CA68859 (S. A. C.), P01 HL073104 (G. M. C.), and K99 HL116234 (S. K.); the California Institute of Regenerative Medicine DR1-01431 (I.S.Y.C.); The UCLA AIDS Institute/Center for AIDS Research AI28697; and Korean NRF grants (2011-0030049) and Next-Gen BioGreen21 (PJ008019 & PJ008068). I.S.Y.C. is a founder of Calimmune, Inc., a company developing genetic therapies for HIV disease. NR 46 TC 19 Z9 19 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD APR 3 PY 2014 VL 14 IS 4 BP 473 EP 485 DI 10.1016/j.stem.2013.12.012 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AF5PW UT WOS:000334766400011 PM 24702996 ER PT J AU Wu, CF Li, B Lu, R Koelle, SJ Yang, YQ Jares, A Krouse, AE Metzger, M Liang, F Lore, K Wu, CO Donahue, RE Chen, ISY Weissman, I Dunbar, CE AF Wu, Chuanfeng Li, Brian Lu, Rong Koelle, Samson J. Yang, Yanqin Jares, Alexander Krouse, Alan E. Metzger, Mark Liang, Frank Lore, Karin Wu, Colin O. Donahue, Robert E. Chen, Irvin S. Y. Weissman, Irving Dunbar, Cynthia E. TI Clonal Tracking of Rhesus Macaque Hematopoiesis Highlights a Distinct Lineage Origin for Natural Killer Cells SO CELL STEM CELL LA English DT Article ID COMMON LYMPHOID PROGENITORS; MOUSE BONE-MARROW; HUMAN CORD BLOOD; STEM-CELLS; GENE-THERAPY; IN-VIVO; LENTIVIRAL VECTOR; NONHUMAN-PRIMATES; RETROVIRAL VECTORS; INTEGRATION SITES AB Analysis of hematopoietic stem cell function in nonhuman primates provides insights that are relevant for human biology and therapeutic strategies. In this study, we applied quantitative genetic barcoding to track the clonal output of transplanted autologous rhesus macaque hematopoietic stem and progenitor cells over a time period of up to 9.5 months. We found that unilineage short-term progenitors reconstituted myeloid and lymphoid lineages at 1 month but were supplanted over time by multilineage clones, initially myeloid restricted, then myeloid-B clones, and then stable myeloid-B-T multilineage, long-term repopulating clones. Surprisingly, reconstitution of the natural killer (NK) cell lineage, and particularly the major CD16(+)/CD56(-) peripheral blood NK compartment, showed limited clonal overlap with T, B, or myeloid lineages, and therefore appears to be ontologically distinct. Thus, in addition to providing insights into clonal behavior over time, our analysis suggests an unexpected paradigm for the relationship between NK cells and other hematopoietic lineages in primates. C1 [Wu, Chuanfeng; Li, Brian; Koelle, Samson J.; Jares, Alexander; Krouse, Alan E.; Metzger, Mark; Donahue, Robert E.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Lu, Rong; Weissman, Irving] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Palo Alto, CA 94305 USA. [Yang, Yanqin] NHLBI, DNA Sequencing & Genom Core, NIH, Bethesda, MD 20892 USA. [Liang, Frank; Lore, Karin] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Chen, Irvin S. Y.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA AIDS Inst, Los Angeles, CA 90095 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov RI Wu, Chuanfeng/A-1109-2016; OI /0000-0001-7321-776X FU Division of Intramural Research of the NHLBI [NIH-UO1-HL099999, NIH-K99-HL11304, CIRM-TG2-01159] FX We thank Naoya Uchida for the chi HIV packaging system, Danny Douek for helpful comments, and Ann Williams (NHLBI FACS Core) and Jun Zhu (DNA Sequencing and Genomics Core) for technical assistance. This research was supported by the Division of Intramural Research of the NHLBI (grants NIH-UO1-HL099999 to I. W., NIH-K99-HL11304 to R. L., and CIRM-TG2-01159 to R.L.). NR 67 TC 29 Z9 30 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD APR 3 PY 2014 VL 14 IS 4 BP 486 EP 499 DI 10.1016/j.stem.2014.01.020 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AF5PW UT WOS:000334766400012 PM 24702997 ER PT J AU Soeiro-de-Souza, MG Gold, PW Brunoni, AR de Sousa, RT Zanetti, MV Carvalho, AF Gattaz, WF Machado-Vieira, R Teixeira, AL AF Soeiro-de-Souza, Marcio Gerhardt Gold, Philip W. Brunoni, Andre R. de Sousa, Rafael T. Zanetti, Marcus V. Carvalho, Andre F. Gattaz, Wagner Farid Machado-Vieira, Rodrigo Teixeira, Antonio Lucio TI Lithium Decreases Plasma Adiponectin Levels in Bipolar Depression SO NEUROSCIENCE LETTERS LA English DT Article DE Lithium; Adiponectin; Bipolar; Disorder; Depression; Metabolic; Treatment ID CARDIOVASCULAR-DISEASE; MOOD DISORDERS; WEIGHT-GAIN; OBESITY; LEPTIN; RESISTIN; SCHIZOPHRENIA; INFLAMMATION; ADIPOKINES AB Lithium, a first line treatment for bipolar disorder (BD), has been associated with significant weight gain, but the mechanisms underlying this phenomenon are still unclear. It has been suggested that changes in production/release of adipokines - molecules secreted by adipose tissue presenting anti-inflammatory (adiponectin) and pro-inflammatory (leptin, resistin) properties - might be implicated. Adiponectin, resistin and leptin were assessed in 25 acutely depressed BD individuals (88% medication-free and 68% treatment-naive) at baseline and after 6 weeks of lithium therapy, and in 23 healthy controls matched by age. The 21-item Hamilton Depression Rating Scale was used to assess depression severity. Levels of adiponectin significantly decreased after lithium monotherapy, while the levels of resistin and leptin remained stable after the follow-up period. Adipokine levels during depressive episodes in BD did not differ compared to controls. Pretreatment levels of leptin were higher in remitters and changes in resistin levels were negatively correlated to improvement of depressive symptoms with lithium. Our findings shed light in this pathophysiological process, which might be associated with metabolic syndrome, inflammation and other medical comorbidities in BD. Published by Elsevier Ireland Ltd. C1 [Soeiro-de-Souza, Marcio Gerhardt] Univ Sao Paulo, Dept & Inst Psychiat, Mood Disorders Unit GRUDA, BR-05508 Sao Paulo, Brazil. [Gold, Philip W.; Machado-Vieira, Rodrigo] NIMH, NIH, Bethesda, MD 20892 USA. [Brunoni, Andre R.] Univ Sao Paulo, Serv Interdisciplinary Neuromodulat, Interdisciplinary Ctr Appl Neuromodulat, Dept & Inst Psychiat,Univ Hosp, Ribeirao Preto, Brazil. [de Sousa, Rafael T.; Zanetti, Marcus V.; Gattaz, Wagner Farid; Machado-Vieira, Rodrigo] Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci, BR-05508 Sao Paulo, Brazil. [Zanetti, Marcus V.; Gattaz, Wagner Farid; Machado-Vieira, Rodrigo] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Ribeirao Preto, Brazil. [Carvalho, Andre F.] Univ Fed Ceara, Fac Med, Psychiat Res Grp, Fortaleza, Ceara, Brazil. [Teixeira, Antonio Lucio] Univ Minas Gerais UFMG, Div Neurol, Neuropsychiat Branch, Belo Horizonte, MG, Brazil. RP Machado-Vieira, R (reprint author), Sch Med, Inst & Dept Psychiat, Rua Ovidio Pires de Campos 785, BR-01060970 Sao Paulo, Brazil. EM marciogss@gmail.com; machadovieirar@gmail.com RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Gattaz, Wagner/C-4456-2012; Brunoni, Andre/H-8394-2012; Soeiro-de-Souza, Marcio/J-9430-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Brunoni, Andre/0000-0002-6310-3571; Soeiro-de-Souza, Marcio/0000-0002-9293-3128 FU Sao Paulo Research Foundation (FAPESP, Brazil) [2009/14891-9]; CNPq; Fapemig FX This study was sponsored by Sao Paulo Research Foundation (FAPESP, Brazil) (2009/14891-9), CNPq, and Fapemig. NR 31 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 3 PY 2014 VL 564 BP 111 EP 114 DI 10.1016/j.neulet.2014.02.005 PG 4 WC Neurosciences SC Neurosciences & Neurology GA AF8SK UT WOS:000334985700022 PM 24525248 ER PT J AU Artis, ML Huestis, DL Lehmann, T AF Artis, Monica L. Huestis, Diana L. Lehmann, Tovi TI The effects of oviposition-site deprivation on longevity and bloodfeeding rate in Anopheles gambiae SO PARASITES & VECTORS LA English DT Article DE Aestivation; African malaria mosquito; Dry season; Drought; Vectorial capacity ID FORCED EGG-RETENTION; FEMALE BODY-SIZE; DRY SEASON; VECTORIAL CAPACITY; DIPTERA-CULICIDAE; METABOLIC-RATE; SAHEL; INFECTION; MOSQUITO; REPRODUCTION AB Background: The African malaria mosquito, Anopheles gambiae, needs surface water in order to lay their eggs. In many parts of Africa, there are dry periods varying from days to months in length when suitable larval sites are not available and female mosquitoes experience oviposition-site deprivation (OSD). Previous studies have shown that egg-laying and egg-hatching rates were reduced due to OSD. Here, we assessed its effect on longevity and bloodfeeding rate of Anopheles gambiae. We predicted that OSD will increase mosquito longevity and the aptitude of mosquitoes to take additional blood meals; importantly, these changes will increase its vectorial capacity. Methods: To measure the effect of OSD, four treatments were utilized: two oviposition-deprived groups, one of which was bloodfed once (OBOD) and one that was bloodfed weekly (MBOD); a non-oviposition-deprived, weekly bloodfed control group (MBC); and a blood-deprived age-control group (BD). Mortality was assessed daily and bloodfeeding rate was measured at weekly intervals. Results: Under OSD, survival of female A. gambiae was reduced by 10-20%, reflecting reduction of the MBOD and OBOD groups from the MBC group, respectively. Likewise, bloodfeeding response during three weeks of OSD was reduced but the reduction varied as a function of time from the last blood meal. Conclusions: These results indicate that OSD is expected to reduce A. gambiae vectorial capacity and that OSD alone does not act as cue used by female mosquitoes to switch into a dormant state of extended survivorship with reproductive quiescence. C1 [Artis, Monica L.; Huestis, Diana L.; Lehmann, Tovi] NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Lehmann, T (reprint author), NIH, Lab Malaria & Vector Res, Bldg 10, Bethesda, MD 20892 USA. EM tlehmann@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; NIAID INRO Fellowship Program FX The authors thank A. Laughinghouse and K. Lee for insectary support and B. St. Laurent and K. Dieter, and 2 anonymous reviewers for their helpful comments on prior versions of this manuscript. This study was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. M. Artis was supported in part by the NIAID INRO Fellowship Program. NR 29 TC 5 Z9 5 U1 3 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 APR 3 PY 2014 VL 7 DI 10.1186/1756-3305-7-163 PG 6 WC Parasitology SC Parasitology GA AF9WH UT WOS:000335064900003 PM 24708656 ER PT J AU Giubellino, A Shankavaram, U Bullova, P Schovanek, J Zhang, YQ Shen, M Patel, N Elkahloun, A Lee, MJ Trepel, J Ferrer, M Pacak, K AF Giubellino, Alessio Shankavaram, Uma Bullova, Petra Schovanek, Jan Zhang, Yaqin Shen, Min Patel, Nikita Elkahloun, Abdel Lee, Min-Jung Trepel, Jane Ferrer, Marc Pacak, Karel TI High-Throughput Screening for the Identification of New Therapeutic Options for Metastatic Pheochromocytoma and Paraganglioma SO PLOS ONE LA English DT Article ID MALIGNANT PHEOCHROMOCYTOMA; COMBINATION; MUTATIONS; GENETICS; MAX; INHIBITORS; UPDATE; MODELS; CANCER; MYC AB Drug repurposing or repositioning is an important part of drug discovery that has been growing in the last few years for the development of therapeutic options in oncology. We applied this paradigm in a screening of a library of about 3,800 compounds (including FDA-approved drugs and pharmacologically active compounds) employing a model of metastatic pheochromocytoma, the most common tumor of the adrenal medulla in children and adults. The collection of approved drugs was screened in quantitative mode, testing the compounds in compound-titration series (dose-response curves). Analysis of the dose-response screening data facilitated the selection of 50 molecules with potential bioactivity in pheochromocytoma cells. These drugs were classified based on molecular/cellular targets and signaling pathways affected, and selected drugs were further validated in a proliferation assay and by flow cytometric cell death analysis. Using meta-analysis information from molecular targets of the top drugs identified by our screening with gene expression data from human and murine microarrays, we identified potential drugs to be used as single drugs or in combination. An example of a combination with a synergistic effect is presented. Our study exemplifies a promising model to identify potential drugs from a group of clinically approved compounds that can more rapidly be implemented into clinical trials in patients with metastatic pheochromocytoma or paraganglioma. C1 [Giubellino, Alessio; Bullova, Petra; Schovanek, Jan; Patel, Nikita; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Zhang, Yaqin; Shen, Min; Ferrer, Marc] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Elkahloun, Abdel] NHGRI, NIH, Bethesda, MD 20892 USA. [Lee, Min-Jung; Trepel, Jane] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Shankavaram, Uma] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Bullova, Petra] Slovak Acad Sci, Inst Virol, Dept Mol Med, Bratislava, Slovakia. [Schovanek, Jan] Univ Hosp Olomouc, Dept Internal Med Nephrol Rheumatol & Endocrinol, Olomouc, Czech Republic. RP Giubellino, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. EM giubella@mail.nih.gov; karel@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health FX This work was supported by the Intramural Research funding of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 4 Z9 4 U1 0 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 APR 3 PY 2014 VL 9 IS 4 AR e90458 DI 10.1371/journal.pone.0090458 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE6LR UT WOS:000334105000010 PM 24699253 ER PT J AU Nguitragool, W Rayavara, K Desai, SA AF Nguitragool, Wang Rayavara, Kempaiah Desai, Sanjay A. TI Proteolysis at a Specific Extracellular Residue Implicates Integral Membrane CLAG3 in Malaria Parasite Nutrient Channels SO PLOS ONE LA English DT Article ID SURFACE ANION CHANNEL; FALCIPARUM-INFECTED ERYTHROCYTES; RED-BLOOD-CELLS; PLASMODIUM-FALCIPARUM; HOST ERYTHROCYTE; MULTIGENE FAMILY; PLASMA-MEMBRANE; SODIUM-CHANNEL; RHOPH COMPLEX; PROTEINS AB The plasmodial surface anion channel mediates uptake of nutrients and other solutes into erythrocytes infected with malaria parasites. The clag3 genes of P. falciparum determine this channel's activity in human malaria, but how the encoded proteins contribute to transport is unknown. Here, we used proteases to examine the channel's composition and function. While proteases with distinct specificities all cleaved within an extracellular domain of CLAG3, they produced differing degrees of transport inhibition. Chymotrypsin-induced inhibition depended on parasite genotype, with channels induced by the HB3 parasite affected to a greater extent than those of the Dd2 clone. Inheritance of functional proteolysis in the HB3xDd2 genetic cross, DNA transfection, and gene silencing experiments all pointed to the clag3 genes, providing independent evidence for a role of these genes. Protease protection assays with a Dd2-specific inhibitor and site-directed mutagenesis revealed that a variant L1115F residue on a CLAG3 extracellular loop contributes to inhibitor binding and accounts for differences in functional proteolysis. These findings indicate that surface-exposed CLAG3 is the relevant pool of this protein for channel function. They also suggest structural models for how exposed CLAG3 domains contribute to pore formation and parasite nutrient uptake. C1 [Nguitragool, Wang; Rayavara, Kempaiah; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Nguitragool, W (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM wang.ngu@mahidol.ac.th; sdesai@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 14 Z9 14 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 APR 3 PY 2014 VL 9 IS 4 AR e93759 DI 10.1371/journal.pone.0093759 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE6LR UT WOS:000334105000101 PM 24699906 ER PT J AU Segal, L Katz, LS Shapira, H Sandbank, J Geras-Raaka, E Gershengorn, MC Oron, Y AF Segal, Liora Katz, Liora S. Shapira, Hagit Sandbank, Judith Geras-Raaka, Elizabeth Gershengorn, Marvin C. Oron, Yoram TI PAR-3 Knockdown Enhances Adhesion Rate of PANC-1 Cells via Increased Expression of Integrin alpha v and E-Cadherin SO PLOS ONE LA English DT Article ID THROMBIN RECEPTOR EXPRESSION; CANCER INVASION; PANCREATIC-CANCER AB The balance between the adhesion of cancer cells to extracellular matrix and their migratory potential, as well as their proteolytic activity, are important parameters that determine cancer cells invasiveness and metastasis. Since thrombin has been implicated in cancer progression, we studied the role(s) of thrombin-activated receptors in the adhesion process. We stably knocked down proteinase-activated receptors (PARs) -1, or -3 in human pancreatic adenocarcinoma PANC-1 cells. PANC-1 cells exhibit rapid adhesion to cell culture treated plastic and much faster kinetics of adhesion to Matrigel coated surface. Knockdown of PAR-1 had no effect on cells' adhesiveness, while PAR-3 knockdowns (KDs) exhibited much faster adhesion kinetics. PAR-3 KDs also exhibited slower in vitro wound closure than vector-control and PAR-1 KD cells. To study the molecular mechanism(s) of PAR-3 KD cells' enhanced rate of adhesion, we assayed the expression of the molecules that mediate cell-surface and cell-cell adhesion. ITG alpha v, as well as ITG alpha 6 and ITG alpha 10 mRNAs, were greatly enriched (>40-fold) in a rapidly-adhering sub-population of PAR-3 KD cells. The whole population of both PAR-1 and -3 KDs exhibited enhanced expression of a number of integrins (ITGs) mRNAs. However, ITGav mRNA and protein expression was increased in PAR-3 KD and markedly decreased in PAR-1 KD. PAR-3 KD cells also expressed more E-cadherin mRNA and protein. The enhanced adhesion kinetics of PAR-3 KDs was almost fully inhibited by calcium chelation, or by a HAV-motive decapeptide that affects E-cadherin intermolecular interactions. We propose that the enhanced rate of adhesion of PAR-3 KDs results from enhanced expression of E-cadherin, leading to a greater adhesion of free-floating cells to cells rapidly bound to the surface via their integrins, and particularly ITGav. C1 [Segal, Liora; Oron, Yoram] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, Ramat Aviv, Israel. [Katz, Liora S.; Geras-Raaka, Elizabeth; Gershengorn, Marvin C.] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA. [Shapira, Hagit] Inst Pathol, Cent Lab, Rehovot, Israel. [Sandbank, Judith] Assaf Harofe Hosp, Inst Pathol, Ramat Aviv, Israel. [Sandbank, Judith] Tel Aviv Univ, Sackler Fac Med, Dept Pathol, Ramat Aviv, Israel. RP Oron, Y (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, Ramat Aviv, Israel. EM medfair@post.tau.ac.il FU Andy Lebach Chair of Clinical Pharmacology and Toxicology, Tel Aviv University, YO incumbent FX Supported in part by the Andy Lebach Chair of Clinical Pharmacology and Toxicology, Tel Aviv University, YO incumbent. No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 20 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 APR 3 PY 2014 VL 9 IS 4 AR e93879 DI 10.1371/journal.pone.0093879 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE6LR UT WOS:000334105000117 PM 24699825 ER PT J AU Xiao, YM Esser, L Zhou, F Li, C Zhou, YH Yu, CA Qin, ZH Xia, D AF Xiao, Yu-Mei Esser, Lothar Zhou, Fei Li, Chang Zhou, Yi-Hui Yu, Chang-An Qin, Zhao-Hai Xia, Di TI Studies on Inhibition of Respiratory Cytochrome bc(1) Complex by the Fungicide Pyrimorph Suggest a Novel Inhibitory Mechanism SO PLOS ONE LA English DT Article ID IRON-SULFUR PROTEIN; X-RAY-STRUCTURE; RHODOBACTER-SPHAEROIDES; ELECTRON-TRANSFER; MITOCHONDRIAL RESPIRATION; SACCHAROMYCES-CEREVISIAE; OXIDATION SITE; SUBUNIT-IV; YEAST; MODE AB The respiratory chain cytochrome bc(1) complex (cyt bc(1)) is a major target of numerous antibiotics and fungicides. All cyt bc(1) inhibitors act on either the ubiquinol oxidation (Q(P)) or ubiquinone reduction (Q(N)) site. The primary cause of resistance to bc(1) inhibitors is target site mutations, creating a need for novel agents that act on alternative sites within the cyt bc(1) to overcome resistance. Pyrimorph, a synthetic fungicide, inhibits the growth of a broad range of plant pathogenic fungi, though little is known concerning its mechanism of action. In this study, using isolated mitochondria from pathogenic fungus Phytophthora capsici, we show that pyrimorph blocks mitochondrial electron transport by affecting the function of cyt bc(1). Indeed, pyrimorph inhibits the activities of both purified 11-subunit mitochondrial and 4-subunit bacterial bc(1) with IC50 values of 85.0 mu M and 69.2 mu M, respectively, indicating that it targets the essential subunits of cyt bc(1) complexes. Using an array of biochemical and spectral methods, we show that pyrimorph acts on an area near the Q(P) site and falls into the category of a mixed-type, noncompetitive inhibitor with respect to the substrate ubiquinol. In silico molecular docking of pyrimorph to cyt b from mammalian and bacterial sources also suggests that pyrimorph binds in the vicinity of the quinol oxidation site. C1 [Xiao, Yu-Mei; Li, Chang; Zhou, Yi-Hui; Qin, Zhao-Hai] China Agr Univ, Dept Appl Chem, Beijing 100094, Peoples R China. [Xiao, Yu-Mei; Esser, Lothar; Zhou, Fei; Zhou, Yi-Hui; Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Yu, Chang-An] Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. RP Qin, ZH (reprint author), China Agr Univ, Dept Appl Chem, Beijing 100094, Peoples R China. EM qinzhaohai@263.net; xiad@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; National Basic Research Science Foundation of China [2010CB126100] FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by a grant from the National Basic Research Science Foundation of China (2010CB126100) to ZQ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 6 Z9 6 U1 2 U2 33 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 APR 3 PY 2014 VL 9 IS 4 AR e93765 DI 10.1371/journal.pone.0093765 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE6LR UT WOS:000334105000104 PM 24699450 ER PT J AU Phillips, J Wendler, D AF Phillips, John Wendler, David TI Which Alternatives Should Investigators Disclose to Research Subjects? SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Phillips, John; Wendler, David] NIH, Ctr Clin, Bethesda, MD USA. RP Wendler, D (reprint author), Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD APR 3 PY 2014 VL 14 IS 4 BP 54 EP 55 DI 10.1080/15265161.2014.889954 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA AE8QQ UT WOS:000334266800024 PM 24730499 ER PT J AU Lee, M Dworkin, AM Gildea, D Trivedi, NS Moorhead, GB Crawford, NPS AF Lee, M. Dworkin, A. M. Gildea, D. Trivedi, N. S. Moorhead, G. B. Crawford, N. P. S. CA NISC Comparative Sequencing Progra TI RRP1B is a metastasis modifier that regulates the expression of alternative mRNA isoforms through interactions with SRSF1 SO ONCOGENE LA English DT Article DE Metastasis; RRP1B; germline modifiers; RNA-seq; alternative splicing; breast cancer ID SPLICE-SITE SELECTION; BREAST-CANCER; PROTEINS; MOUSE; TUMOR; SEQ; IDENTIFICATION; SIGNATURE; SEQUENCE; PATTERNS AB RRP1B (ribosomal RNA processing 1 homolog B) was first identified as a metastasis susceptibility gene in breast cancer through its ability to modulate gene expression in a manner that can be used to accurately predict prognosis in breast cancer. However, the mechanism(s) by which RRP1B modulates gene expression is currently unclear. Many RRP1B binding candidates are involved in alternative splicing, a mechanism of gene expression regulation that is increasingly recognized to be involved in cancer progression and metastasis. One such target is SRSF1 (serine/arginine-rich splicing factor 1) (SF2/ASF, splicing factor 2/alternative splicing factor), an essential splicing regulator that also functions as an oncoprotein. Earlier studies demonstrated that splicing and transcription occur concurrently and are coupled processes. Given that RRP1B regulates transcriptional activity, we hypothesized that RRP1B also regulates the expression of alternative mRNA isoforms through its interaction with SRSF1. Interaction between RRP1B and SRSF1 was verified by coimmunoprecipitation and coimmunofluorescence. Treatment of cells with transcriptional inhibitors significantly increased this interaction, demonstrating that the association of these two proteins is transcriptionally regulated. To assess the role of RRP1B in the regulation of alternative isoform expression, RNA-sequencing data were generated from control and Rrp1b-knockdown cells. Knockdown of Rrp1b induced a significant change in isoform expression in over 600 genes compared with control cell lines. This was verified by quantitative reverse-transcription PCR using isoform-specific primers. Pathway enrichment analyses identified cell cycle and checkpoint regulation to be those most affected by Rrp1b knockdown. These data suggest that RRP1B suppresses metastatic progression by altering the transcriptome through its interaction with splicing regulators such as SRSF1. C1 [Lee, M.; Dworkin, A. M.; Crawford, N. P. S.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Gildea, D.; Trivedi, N. S.; NISC Comparative Sequencing Progra] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Moorhead, G. B.] Univ Calgary, Dept Biol Sci, Calgary, AB, Canada. RP Crawford, NPS (reprint author), NHGRI, Canc Genet Branch, NIH, MSC 8000,50 South Dr,Bldg 50,Room 5154, 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. We thank Stephen Wincovitch and Sujata Bupp for technical assistance, and Drs Kent Hunter, Tom Misteli and Larry Brody for critical review of the manuscript. NR 47 TC 11 Z9 11 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD APR 3 PY 2014 VL 33 IS 14 BP 1818 EP 1827 DI 10.1038/onc.2013.133 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AE9RE UT WOS:000334345500008 PM 23604122 ER PT J AU Hakami, R Etemadi, A Kamangar, F Pourshams, A Mohtadinia, J Firoozi, MS Birkett, N Boffetta, P Dawsey, SM Malekzadeh, R AF Hakami, Roya Etemadi, Arash Kamangar, Farin Pourshams, Akram Mohtadinia, Javad Firoozi, Mehdi Saberi Birkett, Nicholas Boffetta, Paolo Dawsey, Sanford M. Malekzadeh, Reza TI Cooking Methods and Esophageal Squamous Cell Carcinoma in High-Risk Areas of Iran SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID FISH FRIED OIL; AROMATIC-HYDROCARBON RESIDUES; GRILLED RED MEAT; HETEROCYCLIC AMINES; DIETARY-INTAKE; WELL-DONE; CANCER; POPULATION; EXPOSURE; BENZO(A)PYRENE AB Cooking methods have been implicated in the etiology of gastrointestinal cancers, reflecting exposure to potential carcinogens as results of cooking. We used a validated food frequency questionnaire and a pretested cooking method questionnaire in 3 groups: 40 esophageal squamous cell carcinoma (ESCC) cases from a high-risk area in northeast of Iran, 40 healthy subjects from the same high-risk area, and 40 healthy subjects from a low-risk area in Southern Iran. We compared the frequency of boiling, grilling, and frying, and the frying score among these 3 groups. We also calculated "frying index" by multiplying the frequency of each fried food item by its frying score. Mean frying to boiling ratios were 18.2:1, 12.8:1, and 2.6:1 for cases, high-risk controls, and low-risk controls, respectively (P < 0.01). Reuse of cooking oil for frying was reported in 37.5% of the ESCC cases, 25% of high-risk controls, and 7.5% of low-risk controls (P < 0.001). Frying index was higher in the high-risk than in the low-risk controls (P < 0.001) and in cases than in the high-risk controls (P < 0.05) after adjusting for smoking, opium use, rural residence, education, and ethnicity. High-temperature cooking and frying may be associated with increased risk of ESCC in high-risk areas. C1 [Hakami, Roya; Etemadi, Arash; Kamangar, Farin; Pourshams, Akram; Firoozi, Mehdi Saberi; Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran. [Etemadi, Arash; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA. [Mohtadinia, Javad] Tabriz Univ Med Sci, Sch Hlth & Nutr, Tabriz, Iran. [Firoozi, Mehdi Saberi] Shiraz Univ Med Sci, Gastroenterohepatol Res Ctr, Shiraz, Iran. [Birkett, Nicholas] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Mt Sinai Sch Med, Inst Transit Epidemiol, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. RP Etemadi, A (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. EM arash.etemadi@nih.gov RI Etemadi, Arash/C-1386-2016; OI Etemadi, Arash/0000-0002-3458-1072; Malekzadeh, Reza/0000-0003-1043-3814 FU Tabriz University of Medical Science; Digestive Disease Research Center of Tehran University of Medical Science, Iran; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health FX This study was supported by funds from Tabriz University of Medical Science and Digestive Disease Research Center of Tehran University of Medical Science, Iran. It was also supported in part by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. We thank Dr. Yoosefi in Shiraz and Ms. Mohammadi and Ms. Goglani in Gonbad for their collaboration in this study. NR 32 TC 3 Z9 3 U1 0 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0163-5581 EI 1532-7914 J9 NUTR CANCER JI Nutr. Cancer PD APR 3 PY 2014 VL 66 IS 3 BP 500 EP 505 DI 10.1080/01635581.2013.779384 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA AE6AZ UT WOS:000334072000019 PM 24033341 ER PT J AU Liu, Y Li, X Aryee, MJ Ekstrom, TJ Padyukov, L Klareskog, L Vandiver, A Moore, AZ Tanaka, T Ferrucci, L Fallin, MD Feinberg, AP AF Liu, Yun Li, Xin Aryee, Martin J. Ekstrom, Tomas J. Padyukov, Leonid Klareskog, Lars Vandiver, Amy Moore, Ann Zenobia Tanaka, Toshiko Ferrucci, Luigi Fallin, M. Daniele Feinberg, Andrew P. TI GeMes, Clusters of DNA Methylation under Genetic Control, Can Inform Genetic and Epigenetic Analysis of Disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID EPIGENOME-WIDE ASSOCIATION; HUMAN GENOME; LOCI; EPIDEMIOLOGY; POPULATION; CONSORTIUM; PATTERNS; SMOKING; CELL AB Epigenetic marks such as DNA methylation have generated great interest in the study of human disease. However, studies of DNA methylation have not established population-epigenetics principles to guide design, efficient statistics, or interpretation. Here, we show that the clustering of correlated DNA methylation at CpGs was similar to that of linkage-disequilibrium (LD) correlation in genetic SNP variation but for much shorter distances. Some clustering of methylated CpGs appeared to be genetically driven. Further, a set of correlated methylated CpGs related to a single SNP-based LD block was not always physically contiguous-segments of uncorrelated methylation as long as 300 kb could be interspersed in the cluster. Thus, we denoted these sets of correlated CpGs as GeMes, defined as potentially noncontiguous methylation clusters under the control of one or more methylation quantitative trait loci. This type of correlated methylation structure has implications for both biological functions of DNA methylation and for the design, analysis, and interpretation of epigenome-wide association studies. C1 [Liu, Yun; Li, Xin; Aryee, Martin J.; Vandiver, Amy; Fallin, M. Daniele; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. [Liu, Yun; Li, Xin; Vandiver, Amy; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Aryee, Martin J.] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02114 USA. [Aryee, Martin J.] Harvard Univ, Sch Med, Charlestown, MA 02114 USA. [Ekstrom, Tomas J.; Padyukov, Leonid; Klareskog, Lars] Karolinska Inst, Ctr Mol Med, S-17176 Stockholm, Sweden. [Ekstrom, Tomas J.; Padyukov, Leonid; Klareskog, Lars] Univ Hosp, S-17176 Stockholm, Sweden. [Ekstrom, Tomas J.] Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden. [Padyukov, Leonid; Klareskog, Lars] Karolinska Inst, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden. [Moore, Ann Zenobia; Tanaka, Toshiko; Ferrucci, Luigi] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Fallin, M. Daniele] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Deparment Mental Hlth, Baltimore, MD 21205 USA. RP Fallin, MD (reprint author), Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. EM dfallin@jhsph.edu; afeinberg@jhu.edu OI Klareskog, Lars/0000-0001-9601-6186; Padyukov, Leonid/0000-0003-2950-5670 FU National Institutes of Health (NIH) [HG003233, AG042187]; Swedish AFA Insurance grants; Swedish Strategic Research Foundation; European Research Council; Intramural Research Program of the NIH National Institute on Aging; MedStar Research Institute FX We thank Rafael Irizarry for the idea of using 450K array replicates to estimate and describe between-CpG correlations across the genome. This work was supported by National Institutes of Health (NIH) grants HG003233 (A.P.F) and AG042187 (to A.P.F. and M.D.F.), by Swedish AFA Insurance grants to T.J.E., and by grants to L.K. from the Swedish Strategic Research Foundation and European Research Council. The Baltimore Longitudinal Study of Aging was supported in part by the Intramural Research Program of the NIH National Institute on Aging. A portion of that support was through a research-and-development contract with MedStar Research Institute. NR 44 TC 38 Z9 38 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR 3 PY 2014 VL 94 IS 4 BP 485 EP 495 DI 10.1016/j.ajhg.2014.02.011 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AE1XC UT WOS:000333765300001 PM 24656863 ER PT J AU Hyman, SE AF Hyman, Steven E. TI PERSPECTIVE Revealing molecular secrets SO NATURE LA English DT Editorial Material ID SCHIZOPHRENIA; MUTATIONS C1 [Hyman, Steven E.] Broad Inst Harvard & Massachusetts Inst Technol, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA. [Hyman, Steven E.] US Natl Inst Mental Hlth, Bethesda, MD USA. RP Hyman, SE (reprint author), Broad Inst Harvard & Massachusetts Inst Technol, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA. EM seh@harvard.edu NR 7 TC 4 Z9 4 U1 1 U2 7 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 APR 3 PY 2014 VL 508 IS 7494 BP S20 EP S20 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AD9UL UT WOS:000333609900014 PM 24695333 ER PT J AU De La Garza, R Galloway, GP Newton, TF Mendelson, J Haile, CN Dib, E Hawkins, RY Chen, CYA Mahoney, JJ Mojsiak, J Lao, G Anderson, A Kahn, R AF De La Garza, R., II Galloway, G. P. Newton, T. F. Mendelson, J. Haile, C. N. Dib, E. Hawkins, R. Y. Chen, C. -Y. A. Mahoney, J. J., III Mojsiak, J. Lao, G. Anderson, A. Kahn, R. TI Assessment of safety, cardiovascular and subjective effects after intravenous cocaine and lofexidine SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Article DE Addiction; Cocaine; Lofexidine; Norepinepherine; Treatment ID DOPAMINE-BETA-HYDROXYLASE; INDUCED REINSTATEMENT; ALPHA-1-ADRENERGIC RECEPTORS; CONTROLLED-TRIAL; BLOOD-PRESSURE; D-AMPHETAMINE; DOUBLE-BLIND; NOREPINEPHRINE; SEEKING; STRESS AB The primary objective of this study was to determine the safety of lofexidine, an alpha 2 receptor agonist, alone and concurrent with cocaine in non-treatment seeking cocaine-dependent or cocaine-abusing participants. After screening, eligible participants received double-blind, randomized infusions of saline and 20 mg of cocaine on Day 1, and saline and 40 mg of cocaine on Day 2. Subjects were randomized and started receiving daily administration of placebo (N = 4) or lofexidine on Day 3 and continued on this schedule until Day 7. Two dosing regimens for lofexedinewere investigated: 0.8 QID (N = 3) and 0.2 mg QID (N = 11). On Days 6 and 7, subjects received double-blind infusions of saline and 20 mg of cocaine on Day 6, and saline and 40 mg of cocaine on Day 7. The data reveal a notable incidence of hemodynamic-related AEs over the course of the study. Two of the three participants at the 0.8 mg dose level discontinued, and five of 11 participants at the 0.2 mg dose level were withdrawn (or voluntarily discontinued) after hemodynamic AEs. Subjective effects and cardiovascular data were derived from all participants who were eligible to receive infusions (i.e., did not meet stopping criteria) on Days 6 and 7 (6 received lofexidine 0.2 mg, QID and 4 received placebo, QID). As expected, cocaine significantly increased heart rate and blood pressure, as well as several positive subjective effects. There was a trend for lofexidine to decrease cocaine-induced cardiovascular changes and cocaine-induced ratings for "any drug effect", "good effects", and "desire cocaine", but sample size issues limit the conclusions that can be drawn. Despite the trends to reduce cocaine-induced subjective effects, cardiovascular AEs may limit future utility of lofexidine as a treatment for this population. (C) 2013 Elsevier Inc. All rights reserved. C1 [De La Garza, R., II; Newton, T. F.; Haile, C. N.; Hawkins, R. Y.; Mahoney, J. J., III] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Galloway, G. P.; Mendelson, J.; Dib, E.; Chen, C. -Y. A.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Mojsiak, J.; Lao, G.; Anderson, A.; Kahn, R.] NIDA, NIH, Bethesda, MD 20892 USA. RP De La Garza, R (reprint author), Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, 1977 Butler Blvd,Ste E4-163, Houston, TX 77030 USA. EM rg12@bcm.edu RI De La Garza, Richard/B-2489-2014; Mahoney, James/I-2753-2014; OI De La Garza, Richard/0000-0003-1943-4469; Mahoney, James/0000-0003-0824-1776; Haile, Colin/0000-0001-8293-7291; newton, thomas/0000-0002-3198-5901 FU National Institutes on Drug Abuse; NIH-funded GCRC resources at BCM [RR 00188]; National Center for Research Resources; National Center for Advancing Translational Sciences; NIH, through UCSF-CTSI [UL1 RR024131]; MEDVAMC, Houston, TX FX Funding for this study was derived from a contract to R. De La Garza and G. Galloway from the National Institutes on Drug Abuse, and also included use of NIH-funded GCRC resources at BCM (RR 00188). This publication was supported in part by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH, through UCSF-CTSI Grant Number UL1 RR024131. Part of this work was conducted at, and supported by, the MEDVAMC, Houston, TX. NR 40 TC 3 Z9 3 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD APR 3 PY 2014 VL 50 BP 44 EP 52 DI 10.1016/j.pnpbp.2013.11.013 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 302AQ UT WOS:000330574000006 PM 24316175 ER PT J AU Shu, YP Liang, Y Liang, ZJ Zhao, XY Zhu, XH Feng, WL Liang, JM Ito, Y AF Shu, Yaping Liang, Yong Liang, Zhenjie Zhao, Xiaoyun Zhu, Xiaohua Feng, Wanlian Liang, Jianmei Ito, Yoichiro TI STUDIES ON A SIMPLE AND EFFICIENT METHOD FOR LARGE-SCALE PREPARATION OF GENKWANIN FROM DAPHNE GENKWA SIEB. ET ZUCC. USING NORMAL-PHASE FLASH CHROMATOGRAPHY SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Daphne genkwa Sieb; et Zucc; genkwanin; normal-phase flash chromatography; preparative separation; selection of solvent system; thin layer chromatography ID FLOWER BUDS; FLAVONOIDS; EXTRACTS; PLANT; CELLS AB Genkwanin, a flavonoid that has anti-oxidant and antitumor activities, was isolated and purified from flowers of Daphne genkwa Sieb. et Zucc. in a large-scale by normal-phase flash chromatography (NPFC). Dried flower buds were extracted with methanol at room temperature and concentrated. The residues were suspended in water and first extracted with petroleum ether and then chloroform. Genkwanin was concentrated in the chloroform and insoluble fractions. Under the target-guidance of thin layer chromatography (TLC) as well as solubility experiments, a solvent system composed of cyclohexane-acetone (22:3, v/v) was selected. At a flow rate of 30mL/min, the insoluble and chloroform fractions were separated to yield 1.5g and 1.35g of genkwanin with high purities of 98.3% and 98.6% by HPLC analysis, respectively. The chemical structure of the compound was identified by ESI-MS and NMR. Results of the present study indicated that NPFC was a large preparative-scale, speedy, and simple process separation technology, and it was feasible to find the appropriate proportion of solvent system by transformation from TLC condition. C1 [Shu, Yaping; Liang, Yong; Liang, Zhenjie; Zhao, Xiaoyun; Zhu, Xiaohua; Feng, Wanlian] S China Normal Univ, Sch Chem & Environm, Inst Analyt Chem, Guangzhou, Guangdong, Peoples R China. [Liang, Jianmei] Shangqiu Med Coll, Dept Med Technol, Shangqiu, Peoples R China. [Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 23 TC 0 Z9 0 U1 3 U2 19 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 EI 1520-572X J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PD APR 3 PY 2014 VL 37 IS 6 BP 773 EP 785 DI 10.1080/10826076.2012.749501 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 285WE UT WOS:000329424900001 PM 24489458 ER PT J AU Guha, R Medina-Franco, JL AF Guha, Rajarshi Medina-Franco, Jose L. TI On the validity versus utility of activity landscapes: are all activity cliffs statistically significant? SO JOURNAL OF CHEMINFORMATICS LA English DT Article DE Consensus models; Structure-activity relationships; Significant activity cliffs; Structure Activity Landscape Index ID CONSENSUS-ACTIVITY-CLIFFS; DATA-FUSION; SIMILARITY; TARGETS; ANTIPROTOZOAL; INDEX; 2D AB Background: Most work on the topic of activity landscapes has focused on their quantitative description and visual representation, with the aim of aiding navigation of SAR. Recent developments have addressed applications such as quantifying the proportion of activity cliffs, investigating the predictive abilities of activity landscape methods and so on. However, all these publications have worked under the assumption that the activity landscape models are "real" (i.e., statistically significant). Results: The current study addresses for the first time, in a quantitative manner, the significance of a landscape or individual cliffs in the landscape. In particular, we question whether the activity landscape derived from observed (experimental) activity data is different from a randomly generated landscape. To address this we used the SALI measure with six different data sets tested against one or more molecular targets. We also assessed the significance of the landscapes for single and multiple representations. Conclusions: We find that non-random landscapes are data set and molecular representation dependent. For the data sets and representations used in this work, our results suggest that not all representations lead to non-random landscapes. This indicates that not all molecular representations should be used to a) interpret the SAR and b) combined to generate consensus models. Our results suggest that significance testing of activity landscape models and in particular, activity cliffs, is key, prior to the use of such models. C1 [Guha, Rajarshi] NIH, Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Medina-Franco, Jose L.] Univ Nacl Autonoma Mexico, Inst Quim, Mexico City 04510, DF, Mexico. RP Guha, R (reprint author), NIH, Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM guhar@mail.nih.gov FU Molecular Libraries Initiative (National Institutes of Health) [U54 MH084681]; PAPIIT [IA200413] FX We thank the lab of Dr. Rafael Castillo for providing the chemical structures of the published BZD set used in this work. R.G. was supported by the Molecular Libraries Initiative (National Institutes of Health grant U54 MH084681). JL.M-F thanks PAPIIT grant IA200413. NR 34 TC 4 Z9 4 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-2946 J9 J CHEMINFORMATICS JI J. Cheminformatics PD APR 2 PY 2014 VL 6 AR 11 DI 10.1186/1758-2946-6-11 PG 9 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA AG7NU UT WOS:000335605600001 PM 24694189 ER PT J AU Cahoon, EK Inskip, PD Gridley, G Brenner, AV AF Cahoon, E. K. Inskip, P. D. Gridley, G. Brenner, A. V. TI Immune-related conditions and subsequent risk of brain cancer in a cohort of 4.5 million male US veterans SO BRITISH JOURNAL OF CANCER LA English DT Article DE brain cancer; glioma; allergy; atopy; autoimmune disease; inflammatory conditions; diabetes ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GLIOMA RISK; DIABETES-MELLITUS; ADULT GLIOMA; AUTOIMMUNE-DISEASES; ALLERGIC CONDITIONS; ANTIHISTAMINE USE; IMMUNOGLOBULIN-E; MEDICATION USE; UNITED-STATES AB Background: Case-control studies have reported an inverse association between self-reported history of allergy and risk of glioma, but cohort data are limited. Our objectives were to evaluate the associations of major groups of medically diagnosed immune-related conditions (allergy/atopy, autoimmune disease, diabetes, infectious/inflammatory disease) and to explore associations with specific conditions in relation to subsequent diagnosis of brain cancer in a large cohort study. Methods: We used hospital discharge records for a cohort of 4.5 million male US veterans, of whom 4383 developed primary brain cancer. Rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using time-dependent Poisson regression. Results: We found a significant trend of decreasing RRs for brain cancer with longer duration of allergy/atopy (P 0.02), but not for other conditions studied. Rate ratios of brain cancer for allergy/atopy and diabetes with duration of 10 or more years were 0.60 (95% CI: 0.43, 0.83) and 0.75 (95% CI: 0.62, 0.93), respectively. Several associations with specific conditions were found, but these did not withstand correction for multiple comparisons. Conclusions: This study lends some support to an inverse association between allergy/atopy and diabetes of long duration and brain cancer risk, but prospective studies with biological samples are needed to uncover the underlying biological mechanisms. C1 [Cahoon, E. K.; Inskip, P. D.; Gridley, G.; Brenner, A. V.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20850 USA. RP Cahoon, EK (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20850 USA. EM cahoonek@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute; US Public Health Service of the Department of Health and Human Services FX This study was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and the US Public Health Service of the Department of Health and Human Services. NR 65 TC 6 Z9 6 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD APR 2 PY 2014 VL 110 IS 7 BP 1825 EP 1833 DI 10.1038/bjc.2014.97 PG 9 WC Oncology SC Oncology GA AF1TD UT WOS:000334495700019 PM 24595001 ER PT J AU Hooker, GW King, L VanHusen, L Graves, K Peshkin, BN Isaacs, C Taylor, KL Poggi, E Schwartz, MD AF Hooker, Gillian W. King, Lesley VanHusen, Lauren Graves, Kristi Peshkin, Beth N. Isaacs, Claudine Taylor, Kathryn L. Poggi, Elizabeth Schwartz, Marc D. TI Long-term satisfaction and quality of life following risk reducing surgery in BRCA1/2 mutation carriers SO HEREDITARY CANCER IN CLINICAL PRACTICE LA English DT Article DE BRCA1/2; Decision making; Satisfaction; Quality of life ID CONTRALATERAL PROPHYLACTIC MASTECTOMY; BREAST-CANCER SURVIVORS; OVARIAN-CANCER; SALPINGO-OOPHORECTOMY; PATIENT SATISFACTION; DECISION-MAKING; WOMEN; PREDICTORS; OUTCOMES; RECONSTRUCTION AB Background: As BRCA1/2 testing becomes more routine, questions remain about long-term satisfaction and quality of life following testing. Previously, we described long term distress and risk management outcomes among women with BRCA1/2 mutations. This study addresses positive psychological outcomes in BRCA1/2 carriers, describing decision satisfaction and quality of life in the years following testing. Methods: We evaluated satisfaction with testing and management decisions among 144 BRCA1/2 carriers. Prior to genetic testing, we assessed family history, sociodemographics and distress. At a mean of 5.3 years post-testing, we assessed management decisions, satisfaction with decisions and, among women with cancer, quality of life. Results: Overall, satisfaction with decision making was high. Women who had risk reducing mastectomy or oophorectomy were more satisfied with management decisions. Participants who obtained a risk reducing oophorectomy were more satisfied with their genetic testing decision. Among affected carriers, high pretest anxiety was associated with poorer quality of life and having had risk reducing mastectomy prior to testing was associated with better quality of life. The negative impact of pre-test anxiety was diminished among women who had mastectomies before testing. Conclusions: BRCA1/2 carriers are satisfied with their testing and risk management decisions and report good quality of life years after testing. Having risk reducing surgery predicts increased satisfaction and improved quality of life. C1 [VanHusen, Lauren; Graves, Kristi; Peshkin, Beth N.; Poggi, Elizabeth; Schwartz, Marc D.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Jess & Mildred Fisher Ctr Familial Canc Res, Dept Oncol, Washington, DC 20057 USA. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Jess & Mildred Fisher Ctr Familial Canc Res, Dept Med & Oncol, Washington, DC 20057 USA. [Hooker, Gillian W.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD USA. [King, Lesley] Univ Washington, Sch Med, Washington, DC USA. [Taylor, Kathryn L.] Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. RP Schwartz, MD (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Jess & Mildred Fisher Ctr Familial Canc Res, Dept Oncol, Washington, DC 20057 USA. EM schwartm@georgetown.edu FU NCI NIH HHS [P30 CA051008] NR 36 TC 4 Z9 4 U1 3 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1731-2302 EI 1897-4287 J9 HERED CANCER CLIN PR JI Hered. Cancer Clin. Pract. PD APR 2 PY 2014 VL 12 AR 9 DI 10.1186/1897-4287-12-9 PG 8 WC Oncology SC Oncology GA AF1HQ UT WOS:000334465400001 PM 24690515 ER PT J AU Morita, Y Callicott, JH Testa, LR Mighdoll, MI Dickinson, D Chen, Q Tao, R Lipska, BK Kolachana, B Law, AJ Ye, TZ Straub, RE Weinberger, DR Kleinman, JE Hyde, TM AF Morita, Yukitaka Callicott, Joseph H. Testa, Lauren R. Mighdoll, Michelle I. Dickinson, Dwight Chen, Qiang Tao, Ran Lipska, Barbara K. Kolachana, Bhaskar Law, Amanda J. Ye, Tianzhang Straub, Richard E. Weinberger, Daniel R. Kleinman, Joel E. Hyde, Thomas M. TI Characteristics of the Cation Cotransporter NKCC1 in Human Brain: Alternate Transcripts, Expression in Development, and Potential Relationships to Brain Function and Schizophrenia SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GABA; mRNA; neurotransmitter; NKCC1; schizophrenia; transcripts ID DORSOLATERAL PREFRONTAL CORTEX; K-CL COTRANSPORTER; CHLORIDE COTRANSPORTER; GENE-EXPRESSION; NERVOUS-SYSTEM; EXCITATORY ACTIONS; SPLICE VARIANTS; WORKING-MEMORY; RELATIVE RISK; GABA AB Early in development, GABA, aninhibitory neurotransmitter in adults, is excitatory. NKCC1(SLC12A2) encodes one of two cation chloride cotransporters mediating the conversion of GABA from excitatory to inhibitory. Using 3' and 5' RACE and PCR, we verified previously characterized alternative transcripts of NKCC1a (1-27) and NKCC1b (1-27(Delta 21)), identified new NKCC1 transcripts, and explored their expression patterns during human prefrontal cortical development. A novel ultra-short transcript (1-2a) was expressed preferentially in the fetus. Expression of NKCC1b and 1-2a were decreased in schizophrenia compared with controls (NKCC1b: 0.8-fold decrease, p = 0.013; 1-2a: 0.8-fold decrease, p = 0.006). Furthermore, the expression of NKCC1b was associated with NKCC1 polymorphism rs3087889. The minor allele at rs3087889, associated with reduced NKCC1b expression( homozygous for major allele: N = 37; homozygous for minor allele: N = 15; 1.5-fold decrease; p<0.01), was also associated with a modest increase in schizophrenia risk in a case-control sample (controls: N = 435; cases: N = 397, OR = 1.5). This same allele was then found associated with cognitive (n = 369) and fMRI (n = 313) intermediate phenotypes associated with schizophrenia-working memory(Cohen's d = 0.35), global cognition org(d = 0.18), and prefrontal inefficiency (d = 0.36) as measured by BOLD fMRI during a working memory task. Together, these preclinical and clinical results suggest that variation in NKCC1 may increase risk for schizophrenia via alterations of mRNA expression at the molecular level and impairment of optimal prefrontal function at the macro or systems level. C1 [Morita, Yukitaka; Callicott, Joseph H.; Testa, Lauren R.; Dickinson, Dwight; Chen, Qiang; Tao, Ran; Lipska, Barbara K.; Kolachana, Bhaskar; Law, Amanda J.; Ye, Tianzhang; Straub, Richard E.; Weinberger, Daniel R.; Kleinman, Joel E.; Hyde, Thomas M.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Div Intramural Res Programs,NIH, Bethesda, MD 20892 USA. [Morita, Yukitaka] Hiroshima City Hosp, Dept Psychiat, Hiroshima 7308518, Japan. [Mighdoll, Michelle I.; Chen, Qiang; Tao, Ran; Ye, Tianzhang; Straub, Richard E.; Weinberger, Daniel R.; Kleinman, Joel E.; Hyde, Thomas M.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Law, Amanda J.] Univ Colorado, Sch Med, Dept Psychiat, Neurodev & Neuropsychiat Genet Lab, Aurora, CO 80045 USA. [Law, Amanda J.] Univ Colorado, Sch Med, Dept Cell & Dev Biol, Neurodev & Neuropsychiat Genet Lab, Aurora, CO 80045 USA. [Weinberger, Daniel R.; Hyde, Thomas M.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Weinberger, Daniel R.; Hyde, Thomas M.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. RP Hyde, TM (reprint author), Lieber Inst Brain Dev, 855 North Wolfe St,Suite 300, Baltimore, MD 21205 USA. EM Thomas.Hyde@LIBD.org RI Callicott, Joseph/C-9102-2009; Lipska, Barbara/E-4569-2017; OI Callicott, Joseph/0000-0003-1298-3334; Law, Amanda/0000-0002-2574-1564 NR 57 TC 18 Z9 18 U1 0 U2 18 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 APR 2 PY 2014 VL 34 IS 14 BP 4929 EP 4940 DI 10.1523/JNEUROSCI.1423-13.2014 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AE6CL UT WOS:000334076000018 PM 24695712 ER PT J AU Zhang, L Chen, WZ Iyer, LM Hu, J Wang, G Fu, Y Yu, M Dai, Q Aravind, L He, C AF Zhang, Liang Chen, Weizhong Iyer, Lakshminarayan M. Hu, Jennifer Wang, Gloria Fu, Ye Yu, Miao Dai, Qing Aravind, L. He, Chuan TI A TET Homologue Protein from Coprinopsis cinerea (CcTET) That Biochemically Converts 5-Methylcytosine to 5-Hydroxymethylcytosine, 5-Formylcytosine, and 5-Carboxylcytosine SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DNA METHYLATION; COMPLEX MODIFICATIONS; MAMMALIAN DNA; THYMINE DNA; DEMETHYLATION; GENOME; GLYCOSYLASE; OXIDATION; REVEALS; DEMETER AB DNA methylation (5-methylcytosine, 5mC) plays critical biological functions in mammals and plants as a vital epigenetic marker. The Ten-Eleven translocation dioxygenases (TET1, 2, and 3) have been found to oxidize 5mC to 5-hydroxymethylcytosine (5hmC) and then to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in mammalian cells. We report herein three mushroom TET homologues from Coprinopsis cinerea that can mediate 5mC oxidation. Specifically, one homologue (CCIG_05589, CcTET) shows similar activity to its mammalian TET homologues. Biochemically, CcTET actively converts 5mC to 5hmC, SIC, and 5caC under natural conditions (pH 7.0). Interestingly, CcTET also converts the majority of 5mC to SIC under slightly acidic (pH 5.8) and neutral conditions. Kinetics analyses of the oxidation by CcTET under neutral conditions indicate that conversion of 5mC to 5hmC and 5hmC to SIC are faster than that of 5fC to 5caC, respectively. Our results provide an example of a TET homologue in a non-mammalian organism that exhibits full 5mC-to-5caC oxidation activity and a slight preference to producing SIC. The preferential accumulation of SIC in the in vitro oxidation reactions under both neutral and acidic conditions may have biological implications for 5mC oxidation in fungi species. C1 [Zhang, Liang; Hu, Jennifer; Wang, Gloria; Fu, Ye; Yu, Miao; Dai, Qing; He, Chuan] Univ Chicago, Dept Chem, Chicago, IL 60637 USA. [Zhang, Liang; Hu, Jennifer; Wang, Gloria; Fu, Ye; Yu, Miao; Dai, Qing; He, Chuan] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA. [Chen, Weizhong] Univ Sci & Technol China, Dept Chem Phys, Hefei 230026, Anhui, Peoples R China. [Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP He, C (reprint author), Univ Chicago, Dept Chem, 5735 S Ellis Ave, Chicago, IL 60637 USA. EM chuanhe@uchicago.edu RI Zhang, Liang/F-8064-2013 FU National Institutes of Health [HG006827, GM071440]; DHHS, National Library of Medicine, NIH, USA FX This work is supported by National Institutes of Health HG006827, GM071440 (C.H.) and the intramural research grant of the DHHS, National Library of Medicine, NIH, USA (LA. and L.M.I.). We thank S. F. Reichard for editing the manuscript. NR 45 TC 13 Z9 13 U1 1 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 2 PY 2014 VL 136 IS 13 BP 4801 EP 4804 DI 10.1021/ja500979k PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA AE4JE UT WOS:000333947900002 PM 24655109 ER PT J AU Doyle, SL Ozaki, E Brennan, K Humphries, MM Mulfaul, K Keaney, J Kenna, PF Maminishkis, A Kiang, AS Saunders, SP Hams, E Lavelle, EC Gardiner, C Fallon, PG Adamson, P Humphries, P Campbell, M AF Doyle, Sarah L. Ozaki, Ema Brennan, Kiva Humphries, Marian M. Mulfaul, Kelly Keaney, James Kenna, Paul F. Maminishkis, Arvydas Kiang, Anna-Sophia Saunders, Sean P. Hams, Emily Lavelle, Ed C. Gardiner, Clair Fallon, Padraic G. Adamson, Peter Humphries, Peter Campbell, Matthew TI IL-18 Attenuates Experimental Choroidal Neovascularization as a Potential Therapy for Wet Age-Related Macular Degeneration SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; NLRP3 INFLAMMASOME ACTIVATION; AUTOPHAGY; CELLS; RECOGNITION; BEVACIZUMAB; SB-485232; CANCER AB Age-related macular degeneration (AMD) is the most common form of central retinal blindness globally. Distinct processes of the innate immune system, specifically activation of the NLRP3 inflammasome, have been shown to play a central role in the development of both "dry" and neovascular ("wet") forms of the disease. We show that the inflammatory cytokine interleukin-18 (IL-18) can regulate choroidal neovascularization formation in mice. We observed that exogenous administration of mature recombinant IL-18 has no effect on retinal pigment epithelial (RPE) cell viability, but that overexpression of pro-IL-18 or pro-IL-1 beta alone can cause RPE cell swelling and subsequent atrophy, a process that can be inhibited by the promotion of autophagy. A direct comparison of local and systemic administration of mature recombinant IL-18 with current anti-VEGF (vascular endothelial growth factor)-based therapeutic strategies shows that IL-18 treatment works effectively alone and more effectively in combination with anti-VEGF therapy and represents a novel therapeutic strategy for the treatment of wet AMD. C1 [Doyle, Sarah L.; Mulfaul, Kelly] Univ Dublin Trinity Coll, Sch Med, Dept Clin Med, Dublin 2, Ireland. [Doyle, Sarah L.; Mulfaul, Kelly] Our Ladys Childrens Hosp, Natl Childrens Res Ctr, Dublin 12, Ireland. [Ozaki, Ema; Humphries, Marian M.; Keaney, James; Kenna, Paul F.; Kiang, Anna-Sophia; Humphries, Peter; Campbell, Matthew] Univ Dublin Trinity Coll, Smurfit Inst Genet, Ocular Genet Unit, Dublin 2, Ireland. [Brennan, Kiva; Lavelle, Ed C.; Gardiner, Clair] Univ Dublin Trinity Coll, Sch Biochem & Immunol, Immunol Res Ctr, Trinity Biomed Sci Inst, Dublin 2, Ireland. [Kenna, Paul F.] Royal Victorian Eye & Ear Hosp, Res Fdn, Dublin 2, Ireland. [Maminishkis, Arvydas] NEI, NIH, Bethesda, MD 20892 USA. [Saunders, Sean P.; Hams, Emily; Fallon, Padraic G.] Univ Dublin Trinity Coll, Sch Med, Trinity Biomed Sci Inst, Dublin 2, Ireland. [Adamson, Peter] GlaxoSmithKline, Ophthiris Discovery Performance Unit, Stevenage SG1 2NY, Herts, England. RP Doyle, SL (reprint author), Univ Dublin Trinity Coll, Sch Med, Dept Clin Med, Dublin 2, Ireland. EM sarah.doyle@tcd.ie; matthew.campbell@tcd.ie RI Doyle, Sarah/C-1453-2014; OI Doyle, Sarah/0000-0002-6294-9380; Fallon, Padraic/0000-0002-8401-7293; Saunders, Sean/0000-0003-1689-3598; Lavelle, Ed/0000-0002-3167-1080; Hams, Emily/0000-0002-9745-3246 FU Enterprise Ireland; GSK; Science Foundation Ireland (SFI) [12/YI/B2614]; BrightFocus Foundation; SFI; Health Research Board of Ireland; Irish Research Council for Science Engineering and Technology; United States Department of Defense (Telemedicine and Advanced Technology Research Center); European Research Council FX Funding: Enterprise Ireland, GSK, Science Foundation Ireland (SFI) (12/YI/B2614), and BrightFocus Foundation. The Ocular Genetics Unit at TCD is supported by SFI, the Health Research Board of Ireland, Irish Research Council for Science Engineering and Technology, the United States Department of Defense (Telemedicine and Advanced Technology Research Center), and the European Research Council. NR 28 TC 14 Z9 15 U1 1 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 2 PY 2014 VL 6 IS 230 AR 230ra44 DI 10.1126/scitranslmed.3007616 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AE3UX UT WOS:000333905000002 PM 24695684 ER PT J AU Elmore, JG Kramer, BS AF Elmore, Joann G. Kramer, Barnett S. TI Breast Cancer Screening Toward Informed Decisions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID COMPUTER-AIDED DETECTION; MAMMOGRAPHY; RISK C1 [Elmore, Joann G.] Univ Washington, Sch Med, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. [Kramer, Barnett S.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Elmore, JG (reprint author), Univ Washington, Sch Med, Harborview Med Ctr, Dept Med, 325 Ninth St,POB 359780, Seattle, WA 98104 USA. EM jelmore@uw.edu NR 13 TC 10 Z9 10 U1 0 U2 6 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 APR 2 PY 2014 VL 311 IS 13 BP 1298 EP 1299 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AE0HU UT WOS:000333645400012 PM 24691605 ER PT J AU Ying, TL Ju, TW Wang, YP Prabakaran, P Dimitrov, DS AF Ying, Tianlei Ju, Tina W. Wang, Yanping Prabakaran, Ponraj Dimitrov, Dimiter S. TI Interactions of IgG1 CH2 and CH3 domains with FcRn SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE FcRn; antibody fragments; CH2 domain; CH3 domain; small-size ID INCREASED-STABILITY; MOLECULAR-DYNAMICS; CONSTANT DOMAINS; RECEPTOR; THERAPEUTICS; BINDING; PROTEIN; DESIGN; COMPLEX AB Antibody fragments are emerging as promising biopharmaceuticals because of their relatively small-size and other unique properties. However, when compared to full-size antibodies, most of the current antibody fragments of VH or VL display greatly reduced half-lives. A promising approach to overcome this problem is through the development of novel antibody fragments based on IgG Fc region, which contributes to the long half-life of IgG through its unique pH-dependent association with the neonatal Fc receptor (FcRn). The IgG Fc region comprises two CH2 and two CH3 domains. In this report, we present a comparative study of the FcRn binding capability of the CH2 and CH3 domains. The stability and aggregation resistance of these domains were also investigated and compared. We found that monomeric CH2 and CH3 domains exhibited the pH-dependent FcRn binding while the dimeric forms of CH2 and CH3 domains did not. Although all of these domains had high serum stability, they had aggregation tendencies as measured by dynamic light scattering. By providing a better understanding of the structure activity relationship of the Fc fragment, these results guide further approaches to generate novel Fc-based small-size antibody fragments that possess pH-dependent FcRn binding capability, desired in vivo half-lives, and other favorable biophysical properties for their druggability. C1 [Ying, Tianlei; Ju, Tina W.; Wang, Yanping; Prabakaran, Ponraj; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA. [Wang, Yanping; Prabakaran, Ponraj] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD USA. RP Ying, TL (reprint author), NCI, Prot Interact Grp, Canc & Inflammat Program, NIH, Bldg 567,Room 185, Frederick, MD 21702 USA. EM yingt@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; Federal funds from the NIH, National Cancer Institute [NO1-CO-12400, HHSN261200800001E] FX We thank Dr. Sergey G. Tarasov and Marzena A. Dyba of the Biophysics Resource in the Structural Biophysics Laboratory, NCIFrederick for helpful discussions and technical support. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by Federal funds from the NIH, National Cancer Institute, under contract numbers NO1-CO-12400 and HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 24 TC 1 Z9 1 U1 0 U2 4 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD APR 2 PY 2014 VL 5 DI 10.3389/fimmu.2014.00146 PG 7 WC Immunology SC Immunology GA CH6FH UT WOS:000354131300003 ER PT J AU Hangartner, TN Short, DF Gilsanz, V Kalkwarf, HJ Lappe, JM Oberfield, S Shepherd, JA Zemel, BS Winer, K AF Hangartner, T. N. Short, D. F. Gilsanz, V. Kalkwarf, H. J. Lappe, J. M. Oberfield, S. Shepherd, J. A. Zemel, B. S. Winer, K. TI INCLUSION OF ANTHROPOMETRIC PARAMETERS IN THE CREATION OF REFERENCE CURVES FOR PEDIATRIC BONE MINERAL DENSITY AND BONE MINERAL CONTENT: IMPACT ON CLASSIFICATION OF BELOW-NORMAL INDIVIDUALS SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases CY APR 02-05, 2014 CL Seville, SPAIN SP WCO, IOF, ESCEO C1 [Hangartner, T. N.; Short, D. F.] Wright State Univ, Dayton, OH 45435 USA. [Gilsanz, V.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Kalkwarf, H. J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Lappe, J. M.] Creighton Univ, Omaha, NE 68178 USA. [Oberfield, S.] Columbia Univ, New York, NY USA. [Shepherd, J. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Zemel, B. S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Winer, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD APR PY 2014 VL 25 SU 2 MA P131 BP S173 EP S173 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CA1AT UT WOS:000348645700140 ER PT J AU Smith, SJ Hughes, SH AF Smith, Steven J. Hughes, Stephen H. TI Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Immunology; Issue 86; HIV; cytotoxicity; infectivity; luciferase; drug resistance; integrase; reverse transcriptase ID IMMUNODEFICIENCY-VIRUS TYPE-1; STRAND TRANSFER; ANTIRETROVIRAL THERAPY; DRUG SUSCEPTIBILITY; INITIAL TREATMENT; INFECTED PATIENTS; DNA INTEGRATION; IN-VIVO; RALTEGRAVIR; RESISTANCE AB Although a number of anti HIV drugs have been approved, there are still problems with toxicity and drug resistance. This demonstrates a need to identify new compounds that can inhibit infection by the common drug resistant HIV-1 strains with minimal toxicity. Here we describe an efficient assay that can be used to rapidly determine the cellular cytotoxicity and efficacy of a compound against WT and mutant viral strains. The desired target cell line is seeded in a 96-well plate and, after a 24 hr incubation, serially dilutions of the compounds to be tested are added. No further manipulations are necessary for cellular cytotoxicity assays; for anti HIV assays a predetermined amount of either a WT or drug resistant HIV-1 vector that expresses luciferase is added to the cells. Cytotoxicity is measured by using an ATP dependent luminescence assay and the impact of the compounds on infectivity is measured by determining the amount of luciferase in the presence or the absence of the putative inhibitors. This screening assay takes 4 days to complete and multiple compounds can be screened in parallel. Compounds are screened in triplicate and the data are normalized to the infectivity/ATP levels in absence of target compounds. This technique provides a quick and accurate measurement of the efficacy and toxicity of potential anti HIV compounds. C1 [Smith, Steven J.; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Bethesda, MD 20892 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, Bethesda, MD 20892 USA. EM hughesst@mail.nih.gov FU Intramural Research Program of the NCI FX This research was supported by the Intramural Research Program of the NCI. NR 38 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2014 IS 86 AR e51400 DI 10.3791/51400 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA0LK UT WOS:000348609000056 ER PT J AU Abeliovich, H Zarei, M Rigbolt, K Youle, R AF Abeliovich, Hagai Zarei, Mostafa Rigbolt, Kristoffer Youle, Richard TI A role for mitochondrial dynamics in the segregation of mitochondrial matrix proteins during stationary phase mitophagy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Abeliovich, Hagai] Hebrew Univ Jerusalem, IL-76100 Rehovot, Israel. [Youle, Richard] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. [Zarei, Mostafa; Rigbolt, Kristoffer] Univ Freiburg, Ctr Biol Signaling Studies, D-79106 Freiburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 557.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701393 ER PT J AU Andrews, K Palachuvattil, J Dang, P Gusev, P Savarala, S Pehrsson, P Harnly, J Dwyer, J Betz, J Saldanha, L Bailey, R Costello, R Gahche, J Hardy, C Emenaker, N AF Andrews, K. Palachuvattil, J. Dang, P. Gusev, P. Savarala, S. Pehrsson, P. Harnly, J. Dwyer, J. Betz, J. Saldanha, L. Bailey, R. Costello, R. Gahche, J. Hardy, C. Emenaker, N. TI Botanical initiative for the Dietary Supplement Ingredient Database: green tea pilot study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Gahche, J.] NHANES CDC NCHS, Hyattsville, MD USA. [Hardy, C.] CFSAN FDA, College Pk, MD USA. [Emenaker, N.] NCI NIH, Bethesda, MD USA. [Dwyer, J.; Betz, J.; Saldanha, L.; Bailey, R.; Costello, R.] ODS NIH, Bethesda, MD USA. [Harnly, J.] BHNRC FCMDL USDA ARS, Beltsville, MD USA. [Andrews, K.; Palachuvattil, J.; Dang, P.; Gusev, P.; Savarala, S.; Pehrsson, P.] BHNRC NDL USDA ARS, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 245.7 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700274 ER PT J AU Bailey, R Fakhouri, T Park, Y Dwyer, J Thomas, P Dodd, K Gahche, J Miller, P Sempos, C Murray, D AF Bailey, Regan Fakhouri, Tala Park, Yikyung Dwyer, Johanna Thomas, Paul Dodd, Kevin Gahche, Jaime Miller, Paige Sempos, Christopher Murray, David TI Multivitamin-mineral use and cardiovascular disease mortality in the US SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Miller, Paige] Exponent, Chicago, IL USA. [Fakhouri, Tala; Gahche, Jaime] Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Bailey, Regan; Park, Yikyung; Dwyer, Johanna; Thomas, Paul; Dodd, Kevin; Sempos, Christopher; Murray, David] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 370.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701019 ER PT J AU Bailey, R Looker, A Gahche, J Mills, J Weaver, C AF Bailey, Regan Looker, Anne Gahche, Jaime Mills, James Weaver, Connie TI Homocysteine and bone mineral density in older females in the United States SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Looker, Anne; Gahche, Jaime] Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Bailey, Regan; Mills, James] NIH, Bethesda, MD 20892 USA. [Weaver, Connie] Purdue Univ, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 257.5 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700330 ER PT J AU Byun, J Gardner, K AF Byun, Jung Gardner, Kevin TI p300 Is a preferred client protein for nuclear chaperones SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Byun, Jung; Gardner, Kevin] NCI, Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 800.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704339 ER PT J AU Byun, J Gardner, K AF Byun, Jung Gardner, Kevin TI A CtBP-miRNA network links metabolism with the acquisition of stem cell traits and drug resistance SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Byun, Jung; Gardner, Kevin] NCI, Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 59.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646702040 ER PT J AU Dahal, R Bala, PA Sharma, B Cha, J Cao, JJ Boateng, C Lever, J Newman, A Foster, J Henry, L Vaughan, R AF Dahal, Rejwi Bala, Pramod Akula Sharma, Babita Cha, Joo Cao, Jianjing Boateng, Comfort Lever, John Newman, Amy Foster, James Henry, L. Vaughan, Roxanne TI Identification of the attachment site for the cocaine analog [I-125]JHC 2-48 on the dopamine transporter SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Cha, Joo; Cao, Jianjing; Boateng, Comfort; Newman, Amy] NIDA IRP, Med Chem Sect, Baltimore, MD USA. [Lever, John] Univ Missouri, Columbia, MO USA. [Lever, John] Truman VA, Columbia, MO USA. [Dahal, Rejwi; Bala, Pramod Akula; Sharma, Babita; Foster, James; Henry, L.; Vaughan, Roxanne] Univ N Dakota, Grand Forks, ND 58201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 803.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704364 ER PT J AU Dashti, H Smith, C Tanaka, T Ordovas, J AF Dashti, Hassan Smith, Caren Tanaka, Toshiko Ordovas, Jose TI Interactions between circadian gene variants and fatty acid intake for metabolic syndrome risk: a meta-analysis from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Dashti, Hassan; Smith, Caren; Ordovas, Jose] Tufts Univ, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Tanaka, Toshiko] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 373.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701028 ER PT J AU Dencker, D Gould, R Bubser, M Bridges, T Wood, M Duggan, M Wood, M Fink-Jensen, A Wess, J Conn, P Jones, C AF Dencker, Ditte Gould, Robert Bubser, Michael Bridges, Thomas Wood, Michael Duggan, Mark Wood, Michael Fink-Jensen, Anders Wess, Juergen Conn, P. Jones, Carrie TI M4 muscarinic acetylcholine receptor modulation of associative learning and behavioral flexibility in a novel touchscreen cognitive assessment SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Wood, Michael; Conn, P.; Jones, Carrie] Vanderbilt Univ, Med Ctr, Dept Chem, Nashville, TN USA. [Gould, Robert; Bubser, Michael; Bridges, Thomas; Wood, Michael; Conn, P.; Jones, Carrie] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Gould, Robert; Bubser, Michael; Bridges, Thomas; Wood, Michael; Conn, P.; Jones, Carrie] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN USA. [Wess, Juergen] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Dencker, Ditte; Fink-Jensen, Anders] Univ Copenhagen, Lab Neuropsychiat, Inst Neurosci & Pharmacol, Copenhagen, Denmark. [Dencker, Ditte; Fink-Jensen, Anders] Univ Copenhagen, Psychiat Ctr Copenhagen, Copenhagen, Denmark. [Duggan, Mark; Wood, Michael] AstraZeneca, Neurosci Innovat Med, Cambridge, MA USA. [Bridges, Thomas; Wood, Michael; Conn, P.; Jones, Carrie] Vanderbilt Specialized Chem Ctr Probe Dev, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 845.8 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705150 ER PT J AU Dodd, K Nicastro, H AF Dodd, Kevin Nicastro, Holly TI Comparison of NHANES 2007-2010 methodologies for assessing dietary supplement use, part I SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Nicastro, Holly] NCI, Canc Prevent Div, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Dodd, Kevin] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 245.4 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700271 ER PT J AU Emery, A Eiden, M Mustafa, T Eiden, L AF Emery, Andrew Eiden, Maribeth Mustafa, Tomris Eiden, Lee TI GPCR-Gs-mediated cyclic AMP signaling for neuritogenesis, growth arrest, and cell survival is parcellated among the cAMP sensors NCS/Rapgef2, Epac, and PKA SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Emery, Andrew; Eiden, Maribeth; Mustafa, Tomris; Eiden, Lee] NIMH IRP, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 843.7 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705130 ER PT J AU Garcia-Cazarin, M Wambogo, E Regan, K Davis, C AF Garcia-Cazarin, Mary Wambogo, Edwina Regan, Karen Davis, Cindy TI Dietary supplement research portfolio at the National Institutes of Health (NIH) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Regan, Karen] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. [Garcia-Cazarin, Mary; Wambogo, Edwina; Regan, Karen; Davis, Cindy] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 809.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704406 ER PT J AU Gottesman, M AF Gottesman, Michael TI Exploring the complexity of multidrug resistance in cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Gottesman, Michael] NCI, Lab Cell Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 91.1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705179 ER PT J AU Gould, R Nedelcovych, M Dencker, D Melancon, B Stauffer, S Wood, M Wess, J Xiang, ZX Lindsley, C Conn, P Jones, C AF Gould, Robert Nedelcovych, Michael Dencker, Ditte Melancon, Bruce Stauffer, Shaun Wood, Michael Wess, Jurgen Xiang, Zixiu Lindsley, Craig Conn, P. Jones, Carrie TI Influence of M-1 muscarinic acetylcholine receptor activation on arousal and cognitive performance using electroencephalography and novel touchscreen cognition assessment SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Wess, Jurgen] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD USA. [Dencker, Ditte] Ctr Psychiat, Lab Neuropsychiat, Copenhagen, Denmark. [Stauffer, Shaun; Wood, Michael; Lindsley, Craig] Vanderbilt Univ, Dept Chem, Nashville, TN USA. [Gould, Robert; Nedelcovych, Michael; Melancon, Bruce; Stauffer, Shaun; Wood, Michael; Xiang, Zixiu; Lindsley, Craig; Conn, P.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA. [Gould, Robert; Nedelcovych, Michael; Melancon, Bruce; Stauffer, Shaun; Wood, Michael; Xiang, Zixiu; Lindsley, Craig; Conn, P.; Jones, Carrie] Vanderbilt Univ, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37235 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 845.5 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705147 ER PT J AU Grannan, M Bubser, M Bridges, T Gould, R Thorbek, DD Daniels, J Noetzel, M Niswender, C Duggan, M Brandon, N Dunlop, J Wood, M Wess, J Wood, M Lindsley, C Conn, P Jones, C AF Grannan, Michael Bubser, Michael Bridges, Thomas Gould, Robert Thorbek, Ditte Dencker Daniels, J. Noetzel, Meredith Niswender, Colleen Duggan, Mark Brandon, Nicholas Dunlop, John Wood, Michael Wess, Jurgen Wood, Michael Lindsley, Craig Conn, P. Jones, Carrie TI Effects of the M4 muscarinic receptor positive allosteric modulator VU0467154 on cognition and pyramidal cell firing properties in layer V of the mPFC SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Duggan, Mark; Brandon, Nicholas; Dunlop, John; Wood, Michael] AstraZeneca, Neurosci Innovat Med, Cambridge, MA USA. [Thorbek, Ditte Dencker] Copenhagen Univ Hosp, Psychiat Ctr Copenhagen, Lab Neuropsychiat, Copenhagen, Denmark. [Wess, Jurgen] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Grannan, Michael; Bubser, Michael; Bridges, Thomas; Gould, Robert; Daniels, J.; Noetzel, Meredith; Niswender, Colleen; Wood, Michael; Lindsley, Craig; Conn, P.; Jones, Carrie] Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN USA. [Bridges, Thomas; Daniels, J.; Noetzel, Meredith; Niswender, Colleen; Wood, Michael; Lindsley, Craig; Conn, P.; Jones, Carrie] Vanderbilt Specialized Chem Ctr Probe Dev MLPCN, Nashville, TN USA. [Grannan, Michael; Bubser, Michael; Bridges, Thomas; Gould, Robert; Daniels, J.; Noetzel, Meredith; Niswender, Colleen; Wood, Michael; Lindsley, Craig; Conn, P.; Jones, Carrie] Vanderbilt Univ, Nashville, TN 37235 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 845.9 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705151 ER PT J AU Gusev, P Andrews, K Palachuvattil, J Dang, P Roseland, J Holden, J Savarala, S Pehrsson, P Dwyer, J Betz, J Saldanha, L Bailey, R Costello, R Gahche, J Hardy, C Emenaker, N Douglass, L AF Gusev, P. Andrews, K. Palachuvattil, J. Dang, P. Roseland, J. Holden, J. Savarala, S. Pehrsson, P. Dwyer, J. Betz, J. Saldanha, L. Bailey, R. Costello, R. Gahche, J. Hardy, C. Emenaker, N. Douglass, L. TI Over-the-counter prenatal multivitamin/mineral products: chemical analysis for the Dietary Supplement Ingredient Database SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Gahche, J.] CDC, NHANES, NCHS, Hyattsville, MD USA. [Douglass, L.] Consulting Statistician, Longmont, CO USA. [Hardy, C.] FDA, CFSAN, College Pk, MD USA. [Emenaker, N.] NCI, NIH, Bethesda, MD 20892 USA. [Dwyer, J.; Betz, J.; Saldanha, L.; Bailey, R.; Costello, R.] NIH, ODS, Bethesda, MD 20892 USA. [Gusev, P.; Andrews, K.; Palachuvattil, J.; Dang, P.; Roseland, J.; Holden, J.; Savarala, S.; Pehrsson, P.] ARS, BHNRC, NDL, USDA, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 809.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704408 ER PT J AU Hurley, J Stanley, R Ragusa, M AF Hurley, James Stanley, Robin Ragusa, Michael TI The beginning of the end: how the Atg1 scaffold nucleates autophagosome biogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Stanley, Robin; Ragusa, Michael] NIDDK, NIH, Bethesda, MD 20892 USA. [Hurley, James] Univ Calif Berkeley, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 237.2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700263 ER PT J AU Hutsell, B Banks, M Negus, S Rice, K AF Hutsell, Blake Banks, Matthew Negus, Steve Rice, Kenner TI Effects of the kappa opioid antagonist nor-binaltorphimine on cocaine vs. food choice and extended-access cocaine intake in rhesus monkeys SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Rice, Kenner] NIAAA, Chem Biol Branch, Bethesda, MD USA. [Rice, Kenner] NIDA, Bethesda, MD 20892 USA. [Hutsell, Blake; Banks, Matthew; Negus, Steve] Virginia Commonwealth Univ, Richmond, VA USA. RI Banks, Matthew/K-4429-2014 OI Banks, Matthew/0000-0003-4949-5246 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 658.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646702471 ER PT J AU Jameson, JB Kantz, A Jadhav, A Simeonov, A Maloney, D Holman, T AF Jameson, J. Brian, II Kantz, Auric Jadhav, Ajit Simeonov, Anton Maloney, David Holman, Ted TI Discovery and characterization of potent and selective inhibitors to human epithelial 15-lipoxygenase-2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Jadhav, Ajit; Simeonov, Anton; Maloney, David] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Jameson, J. Brian, II; Kantz, Auric; Holman, Ted] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 582.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701494 ER PT J AU John, W Green, H Newman, A Nader, M AF John, William Green, Heather Newman, Amy Nader, Michael TI Effects of selective dopamine D3 receptor compounds in nonhuman primate models of cocaine and methamphetamine abuse SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Newman, Amy] NIDA IRP, Med Chem Sect, Baltimore, MD USA. [John, William; Green, Heather; Nader, Michael] Wake Forest Sch Med, Winston Salem, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 661.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646703004 ER PT J AU Jovic, M Kim, YJ Toth, B Tuymetova, G Tsiomenko, A Balla, T AF Jovic, Marko Kim, Yeun Ju Toth, Balazs Tuymetova, Galina Tsiomenko, Arnold Balla, Tamas TI A novel protein family controls trafficking and metabolism of glycosphingolipids SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Jovic, Marko; Kim, Yeun Ju; Toth, Balazs; Tuymetova, Galina; Tsiomenko, Arnold; Balla, Tamas] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 606.9 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646702120 ER PT J AU Justinova, Z Mascia, P Secci, M Redhi, G Piomelli, D Goldberg, S AF Justinova, Zuzana Mascia, Paola Secci, Maria Redhi, Godfrey Piomelli, Daniele Goldberg, Steven TI The FAAH inhibitor PF-04457845 has THC-like rewarding and reinstatement effects in squirrel monkeys and increases dopamine levels in the nucleus accumbens shell in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Justinova, Zuzana; Mascia, Paola; Secci, Maria; Redhi, Godfrey; Goldberg, Steven] NIDA, IRP, NIH, DHHS, Baltimore, MD USA. [Piomelli, Daniele] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 838.6 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705087 ER PT J AU Lahiri, S Chao, J Tavassoli, S Wong, A Young, B Loewen, C Prinz, W AF Lahiri, Sujoy Chao, Jesse Tavassoli, Shabnam Wong, Andrew Young, Barry Loewen, Christopher Prinz, William TI A conserved ER-membrane complex facilitates phospholipid exchange between the ER and mitochondria SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Lahiri, Sujoy; Prinz, William] NIDDKD, Bethesda, MD USA. [Chao, Jesse; Tavassoli, Shabnam; Wong, Andrew; Young, Barry; Loewen, Christopher] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 758.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704155 ER PT J AU Lazo-Fernandez, Y Aguilera, G Beierwaltes, W Verlander, J Kim, Y Pacak, K Plotsky, P Wall, S AF Lazo-Fernandez, Yoskaly Aguilera, Greti Beierwaltes, William Verlander, Jill Kim, Young Pacak, Karel Plotsky, Paul Wall, Susan TI Pendrin localizes to the adrenal medulla where it modulates catecholamine release SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Lazo-Fernandez, Yoskaly; Kim, Young; Plotsky, Paul; Wall, Susan] Emory Univ, Sch Med, Atlanta, GA USA. [Beierwaltes, William] Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA. [Aguilera, Greti; Pacak, Karel] NICHD, NIH, Bethesda, MD USA. [Verlander, Jill] Univ Florida, Div Nephrol Hypertens & Transplantat, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 701.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646703308 ER PT J AU Le, K Li, CC Moss, J Vaughan, M AF Le, Kang Li, Chun-Chun Moss, Joel Vaughan, Martha TI Arf guanine nucleotide-exchange factors BIG1 and BIG2 regulate beta-catenin signaling via direct interaction and cAMP/PKA pathway SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Le, Kang; Li, Chun-Chun; Moss, Joel; Vaughan, Martha] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 604.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646702096 ER PT J AU Lee, SM Zhang, Y Tsuchiya, H Smalling, R Jetten, A Wang, L AF Lee, Sang Min Zhang, Yuxia Tsuchiya, Hiroyuki Smalling, Rana Jetten, Anton Wang, Li TI Circadian clock control of hepatic metabolism via nuclear receptor SHP SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Jetten, Anton] NIH, Div Intramural Res, Res Triangle Pk, NC USA. [Lee, Sang Min; Zhang, Yuxia; Tsuchiya, Hiroyuki; Smalling, Rana; Wang, Li] Univ Utah, Sch Med, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 579.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701473 ER PT J AU Lee, SH Gu, LY Yang, W Li, GM AF Lee, Sanghee Gu, Liya Yang, Wei Li, Guo-Min TI Mechanism of mismatch-provoked excision in a defined mismatch repair system SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Yang, Wei] NIDDK, NIH, Bethesda, MD USA. [Lee, Sanghee; Li, Guo-Min] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY USA. [Lee, Sanghee; Gu, Liya; Li, Guo-Min] Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 735.14 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704048 ER PT J AU Martin-Biggers, J Beluska, K Tursi, M Quick, V Byrd-Bredbenner, C AF Martin-Biggers, Jennifer Beluska, Katrina Tursi, Mary Quick, Virginia Byrd-Bredbenner, Carol TI Magazine headline themes/emotions that motivate mothers to read nutrition education materials SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Quick, Virginia] NICHHD, Bethesda, MD 20892 USA. [Martin-Biggers, Jennifer; Beluska, Katrina; Tursi, Mary; Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 262.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700354 ER PT J AU Muhie, S Yang, RT Hammamieh, R Jett, M AF Muhie, Seid Yang, Ruoting Hammamieh, Rasha Jett, Marti TI Gene expression alterations in patients with post-traumatic stress disorder SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Muhie, Seid; Yang, Ruoting] NCI, Adv Biomed Comp Ctr, Frederick, MD 21701 USA. [Muhie, Seid; Hammamieh, Rasha; Jett, Marti] USACHER, Integrat Syst Biol Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 776.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704230 ER PT J AU Muhie, S Srinivasan, S Gautam, A Chakraborty, N Hammamieh, R Jett, M AF Muhie, Seid Srinivasan, Seshamalini Gautam, Aarti Chakraborty, Nabarun Hammamieh, Rasha Jett, Marti TI Time-course analysis of gene expression in a mouse model simulating aspects of human post-traumatic stress disorder SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Muhie, Seid] NCI, Adv Biomed Computat Ctr, Frederick, MD 21701 USA. [Muhie, Seid; Srinivasan, Seshamalini; Gautam, Aarti; Chakraborty, Nabarun; Hammamieh, Rasha; Jett, Marti] USACHER, Integrat Syst Biol Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 776.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704231 ER PT J AU Murphy, R Reinders, I Garcia, M Eiriksdottir, G Launer, L Benediktsson, R Jonsson, P Gudnason, V Harris, T AF Murphy, Rachel Reinders, Ilse Garcia, Melissa Eiriksdottir, Gudny Launer, Lenore Benediktsson, Rafn Jonsson, Palmi Gudnason, Vilmundur Harris, Tamara TI New insight into the obesity paradox among older adults with diabetes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Eiriksdottir, Gudny; Gudnason, Vilmundur] IHA Res Inst, Kopavogur, Iceland. [Jonsson, Palmi] Landspitali Natl Univ Hosp, Reykjavik, Iceland. [Murphy, Rachel; Reinders, Ilse; Garcia, Melissa; Launer, Lenore; Harris, Tamara] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Benediktsson, Rafn] Univ Iceland, Reykjavik, Iceland. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 391.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701111 ER PT J AU Naydenov, N Feygin, A Conti, M Adelstein, R Ivanov, A AF Naydenov, Nayden Feygin, Alex Conti, Mary Adelstein, Robert Ivanov, Andrei TI Intestinal epithelium specific knockout of nonmuscle myosin II A disrupts epithelial barrier and exaggerates experimental colitis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Conti, Mary; Adelstein, Robert] NHLBI, Bethesda, MD 20892 USA. [Naydenov, Nayden; Feygin, Alex; Ivanov, Andrei] Virginia Commonwealth Univ, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 60.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646702085 ER PT J AU Neunuebel, M Chen, Y Backlund, P Machner, M AF Neunuebel, Maria Chen, Yang Backlund, Peter Machner, Matthias TI Pathogen-mediated regulation of small GTPases SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Neunuebel, Maria; Backlund, Peter; Machner, Matthias] NICHD, Cell Biol & Metab Program, Bethesda, MD USA. [Chen, Yang] Sch Life Sci, Beijing, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 739.9 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704084 ER PT J AU Nicastro, H Dodd, K AF Nicastro, Holly Dodd, Kevin TI Comparison of NHANES 2007-2010 methodologies for assessing dietary supplement use, part II SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Nicastro, Holly] NCI, Canc Prevent Div, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Dodd, Kevin] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 245.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700270 ER PT J AU Nonaka, R Iesaki, T de Vega, S Yamada, Y Arikawa-Hirasawa, E AF Nonaka, Risa Iesaki, Takafumi de Vega, Susana Yamada, Yoshihiko Arikawa-Hirasawa, Eri TI The role of the extracellular matrix protein Perlecan in the arterial wall SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Iesaki, Takafumi] Juntendo Univ, Fac Med, Dept Physiol, Tokyo, Japan. [Nonaka, Risa; de Vega, Susana; Arikawa-Hirasawa, Eri] Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Tokyo, Japan. [Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 546.10 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701341 ER PT J AU Parker, A Gottesman, S AF Parker, Ashley Gottesman, Susan TI Small RNA regulation of a multidrug efflux pump SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Parker, Ashley; Gottesman, Susan] NIH, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 750.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704114 ER PT J AU Quick, V Nansel, T Liu, D Lipsky, L Due, P Iannotti, R AF Quick, Virginia Nansel, Tonja Liu, Danping Lipsky, Leah Due, Pernille Iannotti, Ronald TI Body image and weight control in youth: 9-year international trends from 24 countries SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Quick, Virginia; Nansel, Tonja; Liu, Danping; Lipsky, Leah] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Iannotti, Ronald] Univ Massachusettes Boston, Boston, MA USA. [Due, Pernille] Univ Southern Denmark, Natl Inst Publ Hlth, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 811.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704432 ER PT J AU Quick, V Byrd-Bredbenner, C AF Quick, Virginia Byrd-Bredbenner, Carol TI Disordered eating behaviors and attitudes of females with cystic fibrosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Quick, Virginia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, New Brunswick, NJ 08903 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 628.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646702263 ER PT J AU Raghavan, R Raiten, D AF Raghavan, Ramkripa Raiten, Daniel TI Biomarkers of Nutrition for Development (BOND): the Query-Based System presenting a new interactive resource for the community SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Raghavan, Ramkripa; Raiten, Daniel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 630.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646702276 ER PT J AU Saldanha, L Dwyer, J Bailen, R Andrews, K Bailey, R Betz, J Burt, V Chang, F Costello, R Emenaker, N Gahche, J Harnly, J Hardy, C Pehrsson, P AF Saldanha, L. Dwyer, J. Bailen, R. Andrews, K. Bailey, R. Betz, J. Burt, V. Chang, F. Costello, R. Emenaker, N. Gahche, J. Harnly, J. Hardy, C. Pehrsson, P. TI When a dietary supplement product name says "energy", what's in the bottle? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Andrews, K.; Harnly, J.; Pehrsson, P.] USDA ARS, Beltsville, MD USA. [Hardy, C.] US FDA, CFSAN, College Pk, MD USA. [Emenaker, N.] NCI, NIH, Rockville, MD USA. [Burt, V.; Gahche, J.] CDC, NHANES, Hyattsville, MD USA. [Chang, F.] Natl Lib Med, NIH, Bethesda, MD USA. [Saldanha, L.; Dwyer, J.; Bailen, R.; Bailey, R.; Betz, J.; Costello, R.] NIH, ODS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 634.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646702298 ER PT J AU Santos, J Gutterman, D Beyer, A AF Santos, Janine Gutterman, David Beyer, Andreas TI Mitochondrial telomerase regulates flow mediated dilation by suppressing mitochondrial derived free radical production SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Santos, Janine] NIEHS, NIH, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Gutterman, David; Beyer, Andreas] Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 664.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646703016 ER PT J AU Schap, T Thompson, F Dodd, K Potischman, N George, S Coleman, L Gahche, J Alexander, G Groesbeck, M Kahle, L Kushi, L Clancy, H Sundaram, M Kirkpatrick, S Dixit-Joshi, S Zimmerman, T Douglass, D Mittl, B Bailey, R Subar, A AF Schap, TusaRebecca Thompson, Frances Dodd, Kevin Potischman, Nancy George, Stephanie Coleman, Laura Gahche, Jaime Alexander, Gwen Groesbeck, Michelle Kahle, Lisa Kushi, Lawrence Clancy, Heather Sundaram, Maria Kirkpatrick, Sharon Dixit-Joshi, Sujata Zimmerman, Thea Douglass, Deirdre Mittl, Beth Bailey, Regan Subar, Amy TI Comparison of dietary supplement intake reporting between the Automated Self-Administered 24-Hour Recall (ASA24) and Automated Multiple Pass Method (AMPM) recalls SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Coleman, Laura] Abbott Nutr, Columbus, OH USA. [Gahche, Jaime] Ctr Dis Control & Prevent, Hyattsville, MD USA. [Alexander, Gwen; Groesbeck, Michelle] Henry Ford Hlth Syst, Detroit, MI USA. [Kahle, Lisa] InformationManagement Syst, Silver Spring, MD USA. [Kushi, Lawrence; Clancy, Heather] Kaiser Permanente No Calif, Oakland, CA USA. [Sundaram, Maria] Marshfield Clin Res Fdn, Marshfield, WI USA. [Schap, TusaRebecca; Thompson, Frances; Dodd, Kevin; Potischman, Nancy; George, Stephanie; Subar, Amy] NCI, Rockville, MD USA. [Bailey, Regan] Off Dietary Supplements, Rockville, MD USA. [Kirkpatrick, Sharon] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. [Dixit-Joshi, Sujata; Zimmerman, Thea; Douglass, Deirdre; Mittl, Beth] WESTAT Corp, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 245.2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700269 ER PT J AU Sebastian, R Goldman, J Enns, CW Martin, C Steinfeldt, L Dwyer, J Moshfegh, A Milner, J AF Sebastian, Rhonda Goldman, Joseph Enns, Cecilia Wilkinson Martin, Carrie Steinfeldt, Lois Dwyer, Johanna Moshfegh, Alanna Milner, John TI Food sources of flavonoids for adults in the United States: What We Eat in America, NHANES 2007-2008 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Sebastian, Rhonda; Goldman, Joseph; Enns, Cecilia Wilkinson; Martin, Carrie; Steinfeldt, Lois; Moshfegh, Alanna; Milner, John] ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA. [Dwyer, Johanna] NIH, Off Dietary Supplements, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 369.5 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700489 ER PT J AU Sebastian, R Goldman, J Enns, CW Martin, C Steinfeldt, L Dwyer, J Moshfegh, A Milner, J AF Sebastian, Rhonda Goldman, Joseph Enns, Cecilia Wilkinson Martin, Carrie Steinfeldt, Lois Dwyer, Johanna Moshfegh, Alanna Milner, John TI Flavonoid intakes by adults in the United States: What We Eat in America, NHANES 2007-2008 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Sebastian, Rhonda; Goldman, Joseph; Enns, Cecilia Wilkinson; Martin, Carrie; Steinfeldt, Lois; Moshfegh, Alanna; Milner, John] ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA. [Dwyer, Johanna] NIH, Off Dietary Supplements, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 245.5 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700272 ER PT J AU Subramanian, N Natarajan, K Clatworthy, M Wang, Z Germain, R AF Subramanian, Naeha Natarajan, Kannan Clatworthy, Menna Wang, Ze Germain, Ronald TI Mitochondria play a central role in NLRP3 inflammasome activation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Clatworthy, Menna] Inst Med Res, Lab Syst Biol, Lymphocyte Biol Sect, Bethesda, MD USA. [Subramanian, Naeha] Inst Syst Biol, Seattle, WA USA. [Clatworthy, Menna] NIAID, NIH, Cambridge, England. [Natarajan, Kannan] NIAID, Immunol Lab, Mol Biol Sect, NIH, Bethesda, MD 20892 USA. [Wang, Ze; Germain, Ronald] NIAID, Lab Syst Biol, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 349.1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700445 ER PT J AU Tasevska, N Midthune, D Tinker, L Neuhouser, M Beasley, J Van Horn, L Lampe, J Potischman, N Prentice, R Kipnis, V AF Tasevska, Natasha Midthune, Douglas Tinker, Lesley Neuhouser, Marian Beasley, Jeannette Van Horn, Linda Lampe, Johanna Potischman, Nancy Prentice, Ross Kipnis, Victor TI Performance of Food Frequency Questionnaire, 4-d food record and 24-h dietary recall to measure total sugars (TS) against the urinary TS biomarker in postmenopausal women SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Beasley, Jeannette] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Tasevska, Natasha] Arizona State Univ, Phoenix, AZ USA. [Tinker, Lesley; Neuhouser, Marian; Lampe, Johanna; Prentice, Ross] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Tasevska, Natasha; Midthune, Douglas; Potischman, Nancy; Kipnis, Victor] NCI, Bethesda, MD 20892 USA. [Van Horn, Linda] Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 36.4 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700471 ER PT J AU Tauseef, M Sukriti, S Ramaswamy, S Dietrich, A Birnbaumer, L Malik, A Mehta, D AF Tauseef, Mohammad Sukriti, Sukriti Ramaswamy, Suresh Dietrich, Alexander Birnbaumer, Lutz Malik, Asrar Mehta, Dolly TI Deletion of transient receptor potential canonical channel 1 prevents pulmonary vascular hyper-permeability and edema formation secondary to cAMP activation of SPHK1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Birnbaumer, Lutz] NIEHS, Res Triangle Pk, NC 27709 USA. [Tauseef, Mohammad; Sukriti, Sukriti; Ramaswamy, Suresh; Malik, Asrar; Mehta, Dolly] Univ Illinois, Chicago, IL USA. [Dietrich, Alexander] Walther Straub Inst Pharmacol & Toxicol, Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 847.4 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705162 ER PT J AU Van Itallie, C Tietgens, A Aponte, A Fredriksson, K Fanning, A Gucek, M Anderson, J AF Van Itallie, Christina Tietgens, Amber Aponte, Angel Fredriksson, Karin Fanning, Alan Gucek, Marjan Anderson, James TI Biotin ligase tagging identifies E-cadherin protein neighbors, including lipoma preferred partner, which modulates epithelial cell-cell and cell-substrate adhesion SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Van Itallie, Christina; Tietgens, Amber; Aponte, Angel; Fredriksson, Karin; Gucek, Marjan] NHLBI, NIH, Bethesda, MD 20892 USA. [Anderson, James] NHLBI, OD Natl Inst Hlth, Bethesda, MD 20892 USA. [Fanning, Alan] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 694.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646703253 ER PT J AU Wang, CY Carriquiry, A Chen, TC Loria, C Pfeiffer, C Liu, K Sempos, C Perrine, C Swanson, C Cogswell, M AF Wang, Chia-Yih Carriquiry, Alicia Chen, Te-Ching Loria, Catherine Pfeiffer, Christine Liu, Kiang Sempos, Christopher Perrine, Cria Swanson, Christine Cogswell, Mary TI Estimating distributions of usual 24-hour sodium excretion from timed-spot urines in adults 18-39 years SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Pfeiffer, Christine; Perrine, Cria; Cogswell, Mary] CDC, Atlanta, GA 30333 USA. [Wang, Chia-Yih; Chen, Te-Ching] CDC, Hyattsville, MD USA. [Carriquiry, Alicia] Iowa State Univ, Ames, IA USA. [Loria, Catherine; Sempos, Christopher; Swanson, Christine] NIH, Bethesda, MD 20892 USA. [Liu, Kiang] Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 632.11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646702284 ER PT J AU Wang, P Martin, W AF Wang, Ping Martin, William TI Transmigration of M1 and M 2 macrophages in pulmonary vessels following intratracheal bleomycin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Wang, Ping] NICHD, Lab Lung Injury & Repair, NIH, Rockville, MD USA. [Martin, William] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 834.7 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705060 ER PT J AU Wankhade, U Wiese, M Kulkarni, A Rane, S AF Wankhade, Umesh Wiese, Mohmmad Kulkarni, Ashok Rane, Sushil TI Adipose-tissue specific deletion of TGF-beta receptor 1 kinase protects mice from diet-induced obesity and diabetes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Kulkarni, Ashok] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Wankhade, Umesh; Wiese, Mohmmad; Rane, Sushil] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 577.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701465 ER PT J AU Wilson, S AF Wilson, Samuel TI Understanding base lesion DNA repair SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Wilson, Samuel] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 477.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701197 ER PT J AU Bi, HC Pan, YZ Gonzalez, F Yu, AM AF Bi, Huichang Pan, Yu-Zhuo Gonzalez, Frank Yu, Aiming TI Metabolomics reveals 1-methylnicotinamide and nicotinamide N-methyltransferase as crucial biomarkers in microRNA-1291-altered pancreatic carcinoma cell metabolism SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bi, Huichang; Gonzalez, Frank] NCI, NIH, Bethesda, MD 20892 USA. [Bi, Huichang] Sun Yat Sen Univ, Guangzhou 510275, Guangdong, Peoples R China. [Pan, Yu-Zhuo] SUNY Buffalo, Buffalo, NY 14260 USA. [Yu, Aiming] Univ Calif Davis, Sacramento, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1147.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651002081 ER PT J AU Byrd, A O'Brien, X Johnson, C Zarember, K Sampaio, E Laforce-Nesbitt, S Bliss, J Newburger, P Holland, S Reichner, J AF Byrd, Angel O'Brien, Xian Johnson, Courtney Zarember, Kol Sampaio, Elizabeth Laforce-Nesbitt, Sonia Bliss, Joseph Newburger, Peter Holland, Steven Reichner, Jonathan TI Assessment of NETosis in patients with primary immunodeficiencies: evidence for a ROS-independent pathway SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Byrd, Angel; O'Brien, Xian; Johnson, Courtney; Bliss, Joseph; Reichner, Jonathan] Brown Univ, Rhode Isl Hosp, Dept Surg, Div Surg Res, Providence, RI 02903 USA. [Sampaio, Elizabeth; Holland, Steven] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Zarember, Kol; Holland, Steven] NIH, Lab Host Def, Bethesda, MD 20892 USA. [Newburger, Peter] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01605 USA. [Byrd, Angel; Johnson, Courtney; Bliss, Joseph; Reichner, Jonathan] Warren Alpert Med Sch, Providence, RI USA. [Byrd, Angel; Johnson, Courtney; Bliss, Joseph; Reichner, Jonathan] Grad Program Pathobiol, Providence, RI USA. [Byrd, Angel; Laforce-Nesbitt, Sonia; Bliss, Joseph] Brown Univ, Women & Infants Hosp Rhode Island, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1046.6 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000319 ER PT J AU Byrd-Bredbenner, C Quick, V White, A Shoff, S Lohse, B Horacek, T Kattlemann, K Phillips, B Hoerr, S Greene, G AF Byrd-Bredbenner, Carol Quick, Virginia White, Adrienne Shoff, Suzanne Lohse, Barbara Horacek, Tanya Kattlemann, Kendra Phillips, Beatrice Hoerr, Sharon Greene, Geoffrey TI Concordance of self-report and measured height and weight of college students SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hoerr, Sharon] Michigan State Univ, Lansing, MI USA. [Quick, Virginia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Lohse, Barbara] Penn State Univ, University Pk, PA 16802 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, New Brunswick, NJ 08903 USA. [Kattlemann, Kendra] S Dakota State Univ, Brookings, SD 57007 USA. [Horacek, Tanya] Syracuse Univ, Syracuse, NY USA. [Phillips, Beatrice] Tuskegee Univ, Tuskegee, AL 36088 USA. [White, Adrienne] Univ Maine, Orono, ME USA. [Greene, Geoffrey] Univ Rhode Isl, Kingston, RI 02881 USA. [Shoff, Suzanne] Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1031.9 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000215 ER PT J AU Chou, CL Hageman, D Knepper, M AF Chou, Chung-Lin Hageman, Daniel Knepper, Mark TI Aquaporin-2 interactome in rat inner medullary collecting duct SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Chou, Chung-Lin; Hageman, Daniel; Knepper, Mark] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1137.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651002002 ER PT J AU Claxton, J Sandoval, P Lee, JW Hoffert, J Knepper, M AF Claxton, J'Neka Sandoval, Pablo Lee, Jae Wook Hoffert, Jason Knepper, Mark TI Identifying transcriptional targets of vasopressin using combined ChIP-seq and RNA-seq analysis of mpkCCD cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Claxton, J'Neka; Sandoval, Pablo; Lee, Jae Wook; Hoffert, Jason; Knepper, Mark] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1181.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651002353 ER PT J AU Davis, A Richter, A Becker, S Moyer, J Sandouk, A Skinner, J Taubenberger, J AF Davis, Anne Richter, Anke Becker, Steven Moyer, Jenna Sandouk, Aline Skinner, Jeff Taubenberger, Jeffery TI Characterizing and diminishing autofluorescence in formalin-fixed paraffin-embedded human respiratory tissue SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Richter, Anke] Grad Sch Int Studies, Def Resources Management Inst, Naval Postgrad Sch, Monterey, CA USA. [Skinner, Jeff] NIAID, Bethesda, MD 20892 USA. [Davis, Anne; Moyer, Jenna; Sandouk, Aline; Taubenberger, Jeffery] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. [Becker, Steven] NIH, Off Director, Bethesda, MD 20892 USA. [Davis, Anne] N Carolina State Univ, Coll Vet Med, Raleigh, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA LB482 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651004422 ER PT J AU DuMond, J Kumar, R Ramkissoon, K Izumi, Y Thompson, B Burg, M Ferraris, J AF DuMond, Jenna Kumar, Raj Ramkissoon, Kevin Izumi, Yuichiro Thompson, Brad Burg, Maurice Ferraris, Joan TI An intrinsically disordered region of the transcription factor, NFAT5, becomes more ordered with an increase in osmolality SO FASEB JOURNAL LA English DT Meeting Abstract C1 [DuMond, Jenna; Ramkissoon, Kevin; Izumi, Yuichiro; Burg, Maurice; Ferraris, Joan] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Kumar, Raj] Commonwealth Med Coll, Dept Basic Sci, Scranton, PA USA. [Thompson, Brad] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1182.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651002363 ER PT J AU Fisher, J Vincent, S Wannas, P Wess, J AF Fisher, John Vincent, Sandra Wannas, Paul Wess, Jurgen TI Loss of M2 and M3 muscarinic receptor function in double mutant mice eliminates ovalbumin-induced airway hyperresponsiveness SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wess, Jurgen] NIDDK, Bethesda, MD 20892 USA. [Fisher, John; Vincent, Sandra; Wannas, Paul] Queens Univ, Kingston, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 870.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651003066 ER PT J AU Hamilton, K Lundsmith, E Hahn, C Noubissi, F Spiegelman, V Rustgi, A AF Hamilton, Kathryn Lundsmith, Emma Hahn, Christopher Noubissi, Felicite Spiegelman, Vladimir Rustgi, Anil TI IMP1 loss promotes enhanced recovery from acute colitis SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hamilton, Kathryn; Lundsmith, Emma; Hahn, Christopher; Rustgi, Anil] NIDDK, Intestinal Stem Cell Consortium, NIAID, Duarte, CA USA. [Hamilton, Kathryn; Lundsmith, Emma; Hahn, Christopher; Rustgi, Anil] Univ Penn, Philadelphia, PA 19104 USA. [Noubissi, Felicite; Spiegelman, Vladimir] Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 899.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651003269 ER PT J AU Hammond, G Machner, M Balla, T AF Hammond, Gerry Machner, Matthias Balla, Tamas TI Phosphatidylinositol-4-phosphate synthesis and turnover spans multiple membrane compartments SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hammond, Gerry; Machner, Matthias; Balla, Tamas] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 999.2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651004208 ER PT J AU Hardison, R Wu, WS Morrissey, C Keller, C Mishra, T Pimkin, M Blobel, G Weiss, M Bodine, D AF Hardison, Ross Wu, Weisheng Morrissey, Christapher Keller, Cheryl Mishra, Tejaswini Pimkin, Maxim Blobel, Gerd Weiss, Mitchell Bodine, David TI Dynamic shifts in transcription factor occupancy drive reprogramming of gene expression during hematopoietic differentiation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bodine, David] NHGRI, NIH, Bethesda, MD 20892 USA. [Hardison, Ross; Morrissey, Christapher; Keller, Cheryl; Mishra, Tejaswini] Penn State Univ, University Pk, PA 16802 USA. [Pimkin, Maxim; Blobel, Gerd; Weiss, Mitchell] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Wu, Weisheng] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA LB181 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651004274 ER PT J AU Hiranita, T Kopajtic, T Mesangeau, C Narayanan, S McCurdy, C Katz, J AF Hiranita, Takato Kopajtic, Theresa Mesangeau, Christopher Narayanan, Sanju McCurdy, Christopher Katz, Jonathan TI The dopamine uptake inhibitor, WIN 35,428, has sigma2 receptor agonist effects that contribute to its self-administration SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hiranita, Takato; Kopajtic, Theresa; Katz, Jonathan] NIH, Baltimore, MD USA. [Mesangeau, Christopher; Narayanan, Sanju; McCurdy, Christopher] Univ Mississippi, Sch Pharm, University, MS 38677 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 848.10 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651002396 ER PT J AU Huang, I Kireeva, M Irvin, J Gotte, D Schafer, B Strathern, J Kashlev, M AF Huang, Ingold Kireeva, Maria Irvin, Jordan Gotte, Deanna Schafer, Brenda Strathern, Jeffrey Kashlev, Mikhail TI Multiple mechanisms for transcription fidelity maintenance in vivo SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Huang, Ingold; Kireeva, Maria; Irvin, Jordan; Gotte, Deanna; Schafer, Brenda; Strathern, Jeffrey; Kashlev, Mikhail] NCI, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 939.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651003483 ER PT J AU Huang, J Liu, SO Bellani, M Ling, C Wang, YS Wang, WD Seidman, M AF Huang, Jing Liu, Shuo Bellani, Marina Ling, Chen Wang, Yinsheng Wang, Weidong Seidman, Michael TI Fanconi anemia protein FANCM promotes replication traverse of DNA interstrand crosslinks SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Ling, Chen; Wang, Weidong] NIA, LG, NIH, Baltimore, MD 21224 USA. [Huang, Jing; Bellani, Marina; Seidman, Michael] NIA, LMG, NIH, Baltimore, MD 21224 USA. [Liu, Shuo; Wang, Yinsheng] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA LB128 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651004225 ER PT J AU Hwang, G Chou, CL Hoffert, J Knepper, M AF Hwang, Gloria Chou, Chung-Lin Hoffert, Jason Knepper, Mark TI Identification of protein kinases that phosphorylate the urea channel protein UT-A1 SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hwang, Gloria; Chou, Chung-Lin; Hoffert, Jason; Knepper, Mark] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1137.11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651001500 ER PT J AU Izumi, Y Burg, M Ferraris, J AF Izumi, Yuichiro Burg, Maurice Ferraris, Joan TI 14-3-3-beta and -epsilon Contribute to nuclear factor of activated T-cells 5 (NFAT5) activity by regulating NFAT5 protein expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Izumi, Yuichiro; Burg, Maurice; Ferraris, Joan] NHLBI, SBC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 895.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651003246 ER PT J AU Lundsmith, E Hamilton, K Noubissi, F Hahn, C Spiegelman, V Rustgi, A AF Lundsmith, Emma Hamilton, Kathryn Noubissi, Felicite Hahn, Christopher Spiegelman, Vladimir Rustgi, Anil TI IMP1 loss in intestinal epithelial cells promotes altered Paneth cell morphology and autophagy defects SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Lundsmith, Emma; Hamilton, Kathryn; Hahn, Christopher; Rustgi, Anil] NIDDKD, NIH, Bethesda, MD USA. [Lundsmith, Emma; Hamilton, Kathryn; Hahn, Christopher; Rustgi, Anil] Univ Penn, Dept Med, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Noubissi, Felicite; Spiegelman, Vladimir] Univ Wisconsin, Sch Med, Dept Dermatol, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 899.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651003268 ER PT J AU Lyons, C AF Lyons, Cassandra TI Direct detection of green fluorescent protein in histological preparations of recombinant vaccinia virus in mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Lyons, Cassandra] NIAID, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1050.9 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000356 ER PT J AU Mann, J Li, N Laky, K Fraser, I Nita-Lazar, A AF Mann, Jessica Li, Ning Laky, Karen Fraser, Iain Nita-Lazar, Aleksandra TI Investigating the role of protein O-fucosyltransferase 1 in Toll-like receptor signaling SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Laky, Karen] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Mann, Jessica; Li, Ning; Fraser, Iain; Nita-Lazar, Aleksandra] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1004.6 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000030 ER PT J AU Popelka, J Quick, V Murray, P Olfert, M AF Popelka, Jessie Quick, Virginia Murray, Pamela Olfert, Melissa TI The use of technology in eating disorder treatment programs SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Quick, Virginia] Natl Inst Hlth, Bethesda, MD USA. [Popelka, Jessie; Olfert, Melissa] W Virginia Univ, Morgantown, WV 26506 USA. [Murray, Pamela] W Virginia Univ, Sch Med Pediat, Morgantown, WV 26506 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1020.4 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000132 ER PT J AU Potischman, N Zimmerman, T Douglass, D Dixit-Joshi, S Kirkpatrick, S Subar, A McNutt, S Coleman, L Alexander, G Kushi, L Thompson, F AF Potischman, Nancy Zimmerman, Thea Douglass, Deirdre Dixit-Joshi, Sujata Kirkpatrick, Sharon Subar, Amy McNutt, Suzanne Coleman, Laura Alexander, Gwen Kushi, Lawrence Thompson, Frances TI Influence of editing free text responses on nutrient and food group estimates from the Automated Self-Administered 24-hour dietary recall SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Coleman, Laura] Abbott Nutr, Columbus, OH USA. [Alexander, Gwen] Henry Ford Hlth Syst, Detroit, MI USA. [Kushi, Lawrence] Kaiser Permanente No Calif, Oakland, CA USA. [Potischman, Nancy; Subar, Amy; Thompson, Frances] NCI, Bethesda, MD 20892 USA. [Kirkpatrick, Sharon] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. [Zimmerman, Thea; Douglass, Deirdre; Dixit-Joshi, Sujata; McNutt, Suzanne] WESTAT Corp, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1022.7 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000151 ER PT J AU Ramessar, K Xiong, C Krumpe, L Buckheit, R Wilson, J McMahon, J O'Keefe, B AF Ramessar, Koreen Xiong, Chang Krumpe, Lauren Buckheit, Robert Wilson, Jennifer McMahon, James O'Keefe, Barry TI Isolation and characterization of a novel class of potent anti-HIV proteins from an Australian soft coral SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Buckheit, Robert] ImQuest BioSci, Frederick, MD USA. [Ramessar, Koreen; Xiong, Chang; Krumpe, Lauren; Wilson, Jennifer; McMahon, James; O'Keefe, Barry] NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 975.6 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651004122 ER PT J AU Ramkissoon, K DuMond, J Izumi, Y Williams, C Gucek, M Wang, GH Burg, M Ferraris, J AF Ramkissoon, Kevin DuMond, Jenna Izumi, Yuichiro Williams, Chester Gucek, Marjan Wang, Guanghui Burg, Maurice Ferraris, Joan TI In-cell cross-linking and identification of the nuclear actor of activated T-cells 5 protein interactome using the mass spectrometry-cleavable covalent crosslinker DC4 SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Ramkissoon, Kevin; DuMond, Jenna; Izumi, Yuichiro; Williams, Chester; Gucek, Marjan; Wang, Guanghui; Burg, Maurice; Ferraris, Joan] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1182.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651002362 ER PT J AU Talbot, J Geffert, L Wolters, N Amos, M Dallman, E Munro, C Tolle, E Larkey, J Tanda, G Katz, J Indarte, M Madura, J Surratt, C AF Talbot, Jeffery Geffert, Laura Wolters, Nicholas Amos, Mary Dallman, Elizabeth Munro, Caitlin Tolle, Erica Larkey, Jessica Tanda, Gianluigi Katz, Jonathan Indarte, Martin Madura, Jeffry Surratt, Christopher TI A novel triple reuptake inhibitor with rapid antidepressant properties identified by virtual screening SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Madura, Jeffry] Duquesne Univ, Pittsburgh, PA 15219 USA. [Geffert, Laura; Indarte, Martin; Surratt, Christopher] Duquesne Univ, Coll Pharm, Pittsburgh, PA 15219 USA. [Tanda, Gianluigi; Katz, Jonathan] NIDA, Intramural Res Program, Baltimore, MD USA. [Wolters, Nicholas; Amos, Mary; Dallman, Elizabeth; Munro, Caitlin; Tolle, Erica; Larkey, Jessica] Ohio No Univ, Coll Pharm, Ada, OH 45810 USA. [Talbot, Jeffery] Roseman Univ Hlth Sci, Henderson, NV USA. RI Tanda, Gianluigi/B-3318-2009 OI Tanda, Gianluigi/0000-0001-9526-9878 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1144.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651002057 ER PT J AU Underhill, S Thiels, E Amara, S AF Underhill, Suzanne Thiels, Edda Amara, Susan TI The mechanism of amphetamine-mediated trafficking of the dopamine transporter SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Underhill, Suzanne; Amara, Susan] NIMH, NIH, Bethesda, MD 20892 USA. [Thiels, Edda] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1145.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651002067 ER PT J AU Uusitalo, U Lee, HS Aroonsson, CA Vehik, K Yang, JM Hummel, S Butterworth, M Lernmark, A Rewers, M Hagopian, W She, JX Simell, O Ziegler, A Akolkar, B Krischer, J Virtanen, SM Norris, JM AF Uusitalo, Ulla Lee, Hye-Seung Aroonsson, Carin Andren Vehik, Kendra Yang, Jimin Hummel, Sandra Butterworth, Martha Lernmark, Ake Rewers, Marian Hagopian, William She, Jin-Xiong Simell, Olli Ziegler, Anette Akolkar, Beena Krischer, Jeffrey Virtanen, Suvi M. Norris, Jill M. TI Early infant feeding and islet autoimmunity in The Environmental Determinants of Diabetes in the Young (TEDDY) Study SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Rewers, Marian] Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. [Norris, Jill M.] Colorado Sch Publ Hlth, Aurora, CO USA. [Hummel, Sandra; Ziegler, Anette] Diabet Res Inst, Munich, Germany. [Aroonsson, Carin Andren; Lernmark, Ake] Lund Univ, Malmo, Sweden. [She, Jin-Xiong] Med Coll Georgia, Augusta, GA 30912 USA. [Virtanen, Suvi M.] Natl Inst Hlth & Welf, Helsinki, Finland. [Akolkar, Beena] NIH, Bethesda, MD 20892 USA. [Hagopian, William] Pacific Northwest Diabet Res Inst, Seattle, WA USA. [Uusitalo, Ulla; Lee, Hye-Seung; Vehik, Kendra; Yang, Jimin; Butterworth, Martha; Krischer, Jeffrey] Univ S Florida, Tampa, FL USA. [Simell, Olli] Univ Turku, Turku, Finland. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1038.5 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000255 ER PT J AU Vandeput, F Szabo-Fresnais, N Ahmad, F Kho, C Lee, A Krall, J Hajjar, R Manganiello, V Movsesian, M AF Vandeput, Fabrice Szabo-Fresnais, Nicolas Ahmad, Faiyaz Kho, Changwon Lee, Ahyoung Krall, Judith Hajjar, Roger Manganiello, Vincent Movsesian, Matthew TI Phosphorylation regulates association of PDE3A isoforms with distinct interactomes SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kho, Changwon; Lee, Ahyoung; Hajjar, Roger] Mt Sinai Sch Med, New York, NY USA. [Ahmad, Faiyaz; Manganiello, Vincent] NIH, Bethesda, MD 20892 USA. [Vandeput, Fabrice; Szabo-Fresnais, Nicolas; Krall, Judith; Movsesian, Matthew] Univ Utah, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1013.23 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000082 ER PT J AU Wang, H Troy, L Fox, C Meigs, J McKeown, N Jacques, P AF Wang, Huifen Troy, Lisa Fox, Caroline Meigs, James McKeown, Nicola Jacques, Paul TI Longitudinal association of dairy consumption with changes in blood pressure and incident hypertension SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wang, Huifen; McKeown, Nicola; Jacques, Paul] Tufts Univ, USDA, Human Nutr Res Ctr Aging, JM, Boston, MA 02111 USA. [Meigs, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fox, Caroline] NHLBI Framingham Heart Study, Framingham, MA USA. [Troy, Lisa] Univ Massachusetts, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1018.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000113 ER PT J AU Wang, XY Kali, C Justin, K Kissling, G Li, R Eling, T AF Wang, Xingya Kali, Chrysovergis Justin, Kosak Kissling, Grace Li, Ruifang Eling, Thomas TI hNAG-1 increases survival by regulating metabolism and insulin/IGF-1/mTOR signaling SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kissling, Grace] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Wang, Xingya; Kali, Chrysovergis; Justin, Kosak; Li, Ruifang; Eling, Thomas] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Wang, Xingya] Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou, Zhejiang, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA LB432 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651004400 ER PT J AU Zhu, YY Hernandez, L Dong, YQ Himes, J Hirschfeld, S Forman, M AF Zhu, Yeyi Hernandez, Ladia Dong, Yongquan Himes, John Hirschfeld, Steven Forman, Michele TI Longer breastfeeding reduces the positive relationships among gestational weight gain, birthweight, and childhood growth SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hirschfeld, Steven] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Himes, John] Univ Minnesota, Minneapolis, MN USA. [Zhu, Yeyi; Hernandez, Ladia; Dong, Yongquan; Forman, Michele] Univ Texas Austin, Austin, TX 78712 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1017.11 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000106 ER PT J AU Yaniv, Y Maltsev, VA AF Yaniv, Yael Maltsev, Victor A. TI Numerical modeling calcium and CaMKII effects in the SA node SO FRONTIERS IN PHARMACOLOGY LA English DT Review DE cardiac pacemaker; sinoatrial node; numerical modeling; calcium; CaMKII; ion channels ID CARDIAC-PACEMAKER CELLS; PROTEIN-KINASE-II; RHYTHMIC CA2+ CLOCK; PIG SINOATRIAL NODE; FUNNY CURRENT; SARCOPLASMIC-RETICULUM; HEART-FAILURE; SINUS NODE; CALMODULIN; RELEASE AB Sinoatrial node (SAN) is the primary heart pacemaker which initiates each heartbeat under normal conditions. Numerous experimental data have demonstrated that Ca2+- and CaMKII-dependent processes are crucially important for regulation of SAN cells. However, specific mechanisms of this regulation and their relative contribution to pacemaker function remain mainly unknown. Our review summarizes available data and existing numerical modeling approaches to understand Ca2+ and CaMKII effects on the SAN. Data interpretation and future directions to address the problem are given within the coupled-clock theory, i.e., a modern view on the cardiac pacemaker cell function generated by a system of sarcolemmal and intracellular proteins. C1 [Yaniv, Yael; Maltsev, Victor A.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Yaniv, Yael] Technion Israel Inst Technol, Dept Biomed Engn, IL-32000 Haifa, Israel. RP Maltsev, VA (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM maltsevvi@grc.nia.nih.gov RI Yaniv, Yael/B-3311-2015 OI Yaniv, Yael/0000-0002-5183-6284 FU Intramural Research Program of the NIH, National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 47 TC 7 Z9 7 U1 1 U2 8 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-9812 J9 FRONT PHARMACOL JI Front. Pharmacol. PD APR 1 PY 2014 VL 5 AR 58 DI 10.3389/fphar.2014.00058 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AX6XZ UT WOS:000347062700002 PM 24744732 ER PT J AU Kirkpatrick, SI Reedy, J Kahle, LL Harris, JL Ohri-Vachaspati, P Krebs-Smith, SM AF Kirkpatrick, Sharon I. Reedy, Jill Kahle, Lisa L. Harris, Jennifer L. Ohri-Vachaspati, Punam Krebs-Smith, Susan M. TI Fast-food menu offerings vary in dietary quality, but are consistently poor SO PUBLIC HEALTH NUTRITION LA English DT Article DE Fast food; Dietary quality; Healthy Eating Index-2005; Dietary guidance; Food environment ID ENERGY-INTAKE; YOUNG-ADULTS; US ADULTS; CONSUMPTION; CHILDREN; RECOMMENDATIONS; ASSOCIATIONS; RESTAURANTS; ADOLESCENTS; GUIDANCE AB Objective: To evaluate five popular fast-food chains' menus in relation to dietary guidance. Design: Menus posted on chains' websites were coded using the Food and Nutrient Database for Dietary Studies and MyPyramid Equivalents Database to enable Healthy Eating Index-2005 (HEI-2005) scores to be assigned. Dollar or value and kids' menus and sets of items promoted as healthy or nutritious were also assessed. Setting: Five popular fast-food chains in the USA. Subjects: Not applicable. Results: Full menus scored lower than 50 out of 100 possible points on the HEI-2005. Scores for Total Fruit, Whole Grains and Sodium were particularly dismal. Compared with full menus, scores on dollar or value menus were 3 points higher on average, whereas kids' menus scored 10 points higher on average. Three chains marketed subsets of items as healthy or nutritious; these scored 17 points higher on average compared with the full menus. No menu or subset of menu items received a score higher than 72 out of 100 points. Conclusions: The poor quality of fast-food menus is a concern in light of increasing away-from-home eating, aggressive marketing to children and minorities, and the tendency for fast-food restaurants to be located in low-income and minority areas. The addition of fruits, vegetables and legumes; replacement of refined with whole grains; and reformulation of offerings high in sodium, solid fats and added sugars are potential strategies to improve fast-food offerings. The HEI may be a useful metric for ongoing monitoring of fast-food menus. C1 [Kirkpatrick, Sharon I.; Reedy, Jill; Krebs-Smith, Susan M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kahle, Lisa L.] Informat Management Serv Inc, Rockville, MD USA. [Harris, Jennifer L.] Yale Univ, Rudd Ctr Food Policy & Obes, New Haven, CT USA. [Ohri-Vachaspati, Punam] Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ USA. RP Kirkpatrick, SI (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4005, Bethesda, MD 20892 USA. EM kirkpatricksi@mail.nih.gov OI Kirkpatrick, Sharon/0000-0001-9896-5975 FU Robert Wood Johnson Foundation; Rudd Foundation FX This research was funded in part by the Robert Wood Johnson Foundation and the Rudd Foundation. NR 28 TC 12 Z9 12 U1 2 U2 10 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 EI 1475-2727 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD APR PY 2014 VL 17 IS 4 BP 924 EP 931 DI 10.1017/S1368980012005563 PG 8 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA AW6TX UT WOS:000346402200026 PM 23317511 ER PT J AU Vinson, CA AF Vinson, Cynthia A. TI Using Concept Mapping to Develop a Conceptual Framework for Creating Virtual Communities of Practice to Translate Cancer Research into Practice SO PREVENTING CHRONIC DISEASE LA English DT Article AB Introduction Translating government-funded cancer research into clinical practice can be accomplished via virtual communities of practice that include key players in the process: researchers, health care practitioners, and intermediaries. This study, conducted from November 2012 through January 2013, examined issues that key stakeholders believed should be addressed to create and sustain government-sponsored virtual communities of practice to integrate cancer control research, practice, and policy and demonstrates how concept mapping can be used to present relevant issues. Methods Key stakeholders brainstormed statements describing what is needed to create and sustain virtual communities of practice for moving cancer control research into practice. Participants rated them on importance and feasibility, selected most relevant statements, and sorted them into clusters. I used concept mapping to examine the issues identified and multidimensional scaling analyses to create a 2-dimensional conceptual map of the statement clusters. Results Participants selected 70 statements and sorted them into g major clusters related to creating and sustaining virtual communities of practice: 1) standardization of best practices, 2) external validity, 3) funding and resources, 4) social learning and collaboration, 5) cooperation, 6) partnerships, 7) inclusiveness, 8) social determinants and cultural competency, and 9) preparing the environment. Researchers, health care practitioners, and intermediaries were in relative agreement regarding issues of importance for creating these communities. Conclusion Virtual communities of practice can be created to address the needs of researchers, health care practitioners, and intermediaries by using input from these key stakeholders. Increasing linkages between these subgroups can improve the translation of research into practice. Similarities and differences between groups can provide valuable information to assist the government in developing virtual communities of practice. C1 NCI, Bethesda, MD 20892 USA. RP Vinson, CA (reprint author), NCI, 9609 Med Ctr Dr,Room 4E446, Bethesda, MD 20892 USA. EM cvinson@mail.nih.gov NR 16 TC 0 Z9 0 U1 0 U2 4 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 APR PY 2014 VL 11 AR 130280 DI 10.5888/pcd11.130280 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AR3XG UT WOS:000343521900014 ER PT J AU Wasserman, D AF Wasserman, David TI Assisted Death: A Study in Ethics and Law SO MIND LA English DT Book Review RP Wasserman, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Rm 1C144 9000 Rockville Pike, Bethesda, MD 20892 USA. EM david.wasserman@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0026-4423 EI 1460-2113 J9 MIND JI Mind PD APR PY 2014 VL 123 IS 490 BP 650 EP 653 DI 10.1093/mind/fzu067 PG 4 WC Philosophy SC Philosophy GA AQ3VA UT WOS:000342720400031 ER PT J AU Edeling, MA Austin, SK Shrestha, B Dowd, KA Mukherjee, S Nelson, CA Johnson, S Mabila, MN Christian, EA Rucker, J Pierson, TC Diamond, MS Fremont, DH AF Edeling, Melissa A. Austin, S. Kyle Shrestha, Bimmi Dowd, Kimberly A. Mukherjee, Swati Nelson, Christopher A. Johnson, Syd Mabila, Manu N. Christian, Elizabeth A. Rucker, Joseph Pierson, Theodore C. Diamond, Michael S. Fremont, Daved H. TI Potent Dengue Virus Neutralization by a Therapeutic Antibody with Low Monovalent Affinity Requires Bivalent Engagement SO PLOS PATHOGENS LA English DT Article ID WEST-NILE-VIRUS; MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN; STRUCTURAL BASIS; DOMAIN-III; MEDIATED NEUTRALIZATION; ENCEPHALITIS-VIRUS; MOLECULAR-GRAPHICS; ANTIGEN COMPLEXES; FAB FRAGMENTS AB We recently described our most potently neutralizing monoclonal antibody, E106, which protected against lethal Dengue virus type 1 (DENV-1) infection in mice. To further understand its functional properties, we determined the crystal structure of E106 Fab in complex with domain III (DIII) of DENV-1 envelope (E) protein to 2.45 angstrom resolution. Analysis of the complex revealed a small antibody-antigen interface with the epitope on DIII composed of nine residues along the lateral ridge and A-strand regions. Despite strong virus neutralizing activity of E106 IgG at picomolar concentrations, E106 Fab exhibited a similar to 20,000-fold decrease in virus neutralization and bound isolated DIII, E, or viral particles with only a micromolar monovalent affinity. In comparison, E106 IgG bound DENV-1 virions with nanomolar avidity. The E106 epitope appears readily accessible on virions, as neutralization was largely temperature-independent. Collectively, our data suggest that E106 neutralizes DENV-1 infection through bivalent engagement of adjacent DIII subunits on a single virion. The isolation of anti-flavivirus antibodies that require bivalent binding to inhibit infection efficiently may be a rare event due to the unique icosahedral arrangement of envelope proteins on the virion surface. C1 [Edeling, Melissa A.; Austin, S. Kyle; Shrestha, Bimmi; Nelson, Christopher A.; Diamond, Michael S.; Fremont, Daved H.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. [Dowd, Kimberly A.; Mukherjee, Swati; Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Johnson, Syd] MacroGenics, Rockville, MD USA. [Mabila, Manu N.; Christian, Elizabeth A.; Rucker, Joseph] Integral Mol, Philadelphia, PA USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Diamond, Michael S.; Fremont, Daved H.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Fremont, Daved H.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Fremont, DH (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. EM fremont@wustl.edu FU Pediatric Dengue Vaccine Initiative; NIAID; NIH [R01-AI077955, U01-AI061373, U54 AI057160]; NIAID [HHSN272200700058C, HHSN272201200026C, HHSN272200900055C] FX This work was supported by the Pediatric Dengue Vaccine Initiative, the intramural program of NIAID, and NIH grants R01-AI077955, U01-AI061373, U54 AI057160 (Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research), and NIAID contracts HHSN272200700058C and HHSN272201200026C (Center for Structural Genomics of Infectious Disease) and HHSN272200900055C (B Cell Epitope Discovery and Mechanisms of Antibody Protection). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 10 Z9 10 U1 0 U2 6 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 APR PY 2014 VL 10 IS 4 AR e1004072 DI 10.1371/journal.ppat.1004072 PG 10 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AP4FW UT WOS:000342033600033 PM 24743696 ER PT J AU Pollitt, LC Huijben, S Sim, DG Salathe, RM Jones, MJ Read, AF AF Pollitt, Laura C. Huijben, Silvie Sim, Derek G. Salathe, Rahel M. Jones, Matthew J. Read, Andrew F. TI Rapid Response to Selection, Competitive Release and Increased Transmission Potential of Artesunate-Selected Plasmodium chabaudi Malaria Parasites SO PLOS PATHOGENS LA English DT Article ID ANTIMALARIAL-DRUG RESISTANCE; ARTEMISININ RESISTANCE; FALCIPARUM-MALARIA; TREATMENT FAILURE; WESTERN CAMBODIA; RODENT MALARIA; STABLE RESISTANCE; CLEARANCE RATE; INFECTIONS; CHEMOTHERAPY AB The evolution of drug resistance, a key challenge for our ability to treat and control infections, depends on two processes: de-novo resistance mutations, and the selection for and spread of resistant mutants within a population. Understanding the factors influencing the rates of these two processes is essential for maximizing the useful lifespan of drugs and, therefore, effective disease control. For malaria parasites, artemisinin-based drugs are the frontline weapons in the fight against disease, but reports from the field of slower parasite clearance rates during drug treatment are generating concern that the useful lifespan of these drugs may be limited. Whether slower clearance rates represent true resistance, and how this provides a selective advantage for parasites is uncertain. Here, we show that Plasmodium chabaudi malaria parasites selected for resistance to artesunate (an artemisinin derivative) through a step-wise increase in drug dose evolved slower clearance rates extremely rapidly. In single infections, these slower clearance rates, similar to those seen in the field, provided fitness advantages to the parasite through increased overall density, recrudescence after treatment and increased transmission potential. In mixed infections, removal of susceptible parasites by drug treatment led to substantial increases in the densities and transmission potential of resistant parasites (competitive release). Our results demonstrate the double-edged sword for resistance management: in our initial selection experiments, no parasites survived aggressive chemotherapy, but after selection, the fitness advantage for resistant parasites was greatest at high drug doses. Aggressive treatment of mixed infections resulted in resistant parasites dominating the pool of gametocytes, without providing additional health benefits to hosts. Slower clearance rates can evolve rapidly and can provide a strong fitness advantage during drug treatment in both single and mixed strain infections. C1 [Pollitt, Laura C.; Huijben, Silvie; Sim, Derek G.; Salathe, Rahel M.; Jones, Matthew J.; Read, Andrew F.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Pollitt, Laura C.] Univ Edinburgh, Ctr Immunol Infect & Evolut, Edinburgh, Midlothian, Scotland. [Read, Andrew F.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. [Read, Andrew F.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Pollitt, LC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. EM laura.pollitt@googlemail.com FU Institute of General Medical Science of the National Institutes of Health [R01 GM089932] FX This study was funded by the Institute of General Medical Science (R01 GM089932 to AFR) of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish or the preparation of the manuscript. NR 79 TC 8 Z9 8 U1 1 U2 15 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 APR PY 2014 VL 10 IS 4 AR e1004019 DI 10.1371/journal.ppat.1004019 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AP4FW UT WOS:000342033600013 PM 24763470 ER PT J AU Portugal, S Moebius, J Skinner, J Doumbo, S Doumtabe, D Kone, Y Dia, S Kanakabandi, K Sturdevant, DE Virtaneva, K Porcella, SF Li, SP Doumbo, OK Kayentao, K Ongoiba, A Traore, B Crompton, PD AF Portugal, Silvia Moebius, Jacqueline Skinner, Jeff Doumbo, Safiatou Doumtabe, Didier Kone, Younoussou Dia, Seydou Kanakabandi, Kishore Sturdevant, Daniel E. Virtaneva, Kimmo Porcella, Stephen F. Li, Shanping Doumbo, Ogobara K. Kayentao, Kassoum Ongoiba, Aissata Traore, Boubacar Crompton, Peter D. TI Exposure-Dependent Control of Malaria-Induced Inflammation in Children SO PLOS PATHOGENS LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; TROPHOZOITE-INDUCED INFECTIONS; BRAIN ENDOTHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; GENE-SPECIFIC CONTROL; REGULATORY T-CELLS; CLINICAL IMMUNITY; RETROSPECTIVE EXAMINATION; ENDOTOXIN TOLERANCE; PHAGOCYTIC-ACTIVITY AB In malaria-naive individuals, Plasmodium falciparum infection results in high levels of parasite-infected red blood cells (iRBCs) that trigger systemic inflammation and fever. Conversely, individuals in endemic areas who are repeatedly infected are often asymptomatic and have low levels of iRBCs, even young children. We hypothesized that febrile malaria alters the immune system such that P. falciparum re-exposure results in reduced production of pro-inflammatory cytokines/chemokines and enhanced anti-parasite effector responses compared to responses induced before malaria. To test this hypothesis we used a systems biology approach to analyze PBMCs sampled from healthy children before the six-month malaria season and the same children seven days after treatment of their first febrile malaria episode of the ensuing season. PBMCs were stimulated with iRBC in vitro and various immune parameters were measured. Before the malaria season, children's immune cells responded to iRBCs by producing pro-inflammatory mediators such as IL-1 beta, IL-6 and IL-8. Following malaria there was a marked shift in the response to iRBCs with the same children's immune cells producing lower levels of pro-inflammatory cytokines and higher levels of anti-inflammatory cytokines (IL-10, TGF-beta). In addition, molecules involved in phagocytosis and activation of adaptive immunity were upregulated after malaria as compared to before. This shift was accompanied by an increase in P. falciparum-specific CD4(+) Foxp3(-) T cells that co-produce IL-10, IFN-gamma and TNF; however, after the subsequent six-month dry season, a period of markedly reduced malaria transmission, P. falciparum-inducible IL-10 production remained partially upregulated only in children with persistent asymptomatic infections. These findings suggest that in the face of P. falciparum re-exposure, children acquire exposure-dependent P. falciparum-specific immunoregulatory responses that dampen pathogenic inflammation while enhancing anti-parasite effector mechanisms. These data provide mechanistic insight into the observation that P. falciparum-infected children in endemic areas are often afebrile and tend to control parasite replication. C1 [Portugal, Silvia; Moebius, Jacqueline; Skinner, Jeff; Li, Shanping; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Doumbo, Safiatou; Doumtabe, Didier; Kone, Younoussou; Dia, Seydou; Doumbo, Ogobara K.; Kayentao, Kassoum; Ongoiba, Aissata; Traore, Boubacar] Univ Sci Tech & Technol Bamako, Mali Int Ctr Excellence Res, Bamako, Mali. [Kanakabandi, Kishore; Sturdevant, Daniel E.; Virtaneva, Kimmo; Porcella, Stephen F.] NIAID, Rocky Mt Lab, Res Technol Sect, Genom Unit,NIH, Hamilton, MT 59840 USA. RP Crompton, PD (reprint author), NIAID, 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, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 86 TC 31 Z9 31 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2014 VL 10 IS 4 AR e1004079 DI 10.1371/journal.ppat.1004079 PG 16 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AP4FW UT WOS:000342033600036 PM 24743880 ER PT J AU Qi, HF Olson, CA Wu, NC Ke, RA Loverdo, C Chu, V Truong, S Remenyi, R Chen, ZG Du, YS Su, SY Al-Mawsawi, LQ Wu, TT Chen, SH Lin, CY Zhong, WD Lloyd-Smith, JO Sun, R AF Qi, Hangfei Olson, C. Anders Wu, Nicholas C. Ke, Ruian Loverdo, Claude Chu, Virginia Truong, Shawna Remenyi, Roland Chen, Zugen Du, Yushen Su, Sheng-Yao Al-Mawsawi, Laith Q. Wu, Ting-Ting Chen, Shu-Hua Lin, Chung-Yen Zhong, Weidong Lloyd-Smith, James O. Sun, Ren TI A Quantitative High-Resolution Genetic Profile Rapidly Identifies Sequence Determinants of Hepatitis C Viral Fitness and Drug Sensitivity SO PLOS PATHOGENS LA English DT Article ID VIRUS NONSTRUCTURAL PROTEIN; REPLICATION COMPLEX INHIBITOR; 4-KINASE III ALPHA; NS5A INHIBITOR; RNA-BINDING; GENOTYPE 1; IN-VITRO; RESISTANCE MUTATIONS; CELL-CULTURE; BMS-790052 AB Widely used chemical genetic screens have greatly facilitated the identification of many antiviral agents. However, the regions of interaction and inhibitory mechanisms of many therapeutic candidates have yet to be elucidated. Previous chemical screens identified Daclatasvir (BMS-790052) as a potent nonstructural protein 5A (NS5A) inhibitor for Hepatitis C virus (HCV) infection with an unclear inhibitory mechanism. Here we have developed a quantitative high-resolution genetic (qHRG) approach to systematically map the drug-protein interactions between Daclatasvir and NS5A and profile genetic barriers to Daclatasvir resistance. We implemented saturation mutagenesis in combination with next-generation sequencing technology to systematically quantify the effect of every possible amino acid substitution in the drug-targeted region (domain IA of NS5A) on replication fitness and sensitivity to Daclatasvir. This enabled determination of the residues governing drug-protein interactions. The relative fitness and drug sensitivity profiles also provide a comprehensive reference of the genetic barriers for all possible single amino acid changes during viral evolution, which we utilized to predict clinical outcomes using mathematical models. We envision that this high-resolution profiling methodology will be useful for next-generation drug development to select drugs with higher fitness costs to resistance, and also for informing the rational use of drugs based on viral variant spectra from patients. C1 [Qi, Hangfei; Olson, C. Anders; Remenyi, Roland; Du, Yushen; Al-Mawsawi, Laith Q.; Wu, Ting-Ting; Sun, Ren] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Wu, Nicholas C.; Sun, Ren] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. [Ke, Ruian; Loverdo, Claude; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA. [Chu, Virginia; Truong, Shawna] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA USA. [Chen, Zugen] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. [Su, Sheng-Yao; Chen, Shu-Hua; Lin, Chung-Yen] Acad Sinica, Inst Informat Sci, Taipei, Taiwan. [Su, Sheng-Yao] Natl Yang Ming Univ, Inst Biomed Informat, Taipei 112, Taiwan. [Zhong, Weidong] Novartis Inst BioMed Res, Dept Infect Dis, Emeryville, CA USA. [Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Sun, Ren] Zhejiang Univ, Sch Med, Hangzhou 310003, Zhejiang, Peoples R China. RP Sun, R (reprint author), Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. EM rsun@mednet.ucla.edu RI Lloyd-Smith, James/K-4080-2012; Wu, Nicholas/H-3822-2015; OI Lloyd-Smith, James/0000-0001-7941-502X; Wu, Nicholas/0000-0002-9078-6697; Loverdo, Claude/0000-0002-0888-1717 FU National Natural Science Foundation of China (NSFC) [81172314]; National Science Foundation [EF-0928690]; National Institute of Health [AI078133]; Margaret E. Early Medical Research Trust [P30CA016042, P30AI028697]; De Logi Chair in Biological Sciences; RAPIDD program of the Science & Technology Directorate of the US Department of Homeland Security; Fogarty International Center, National Institutes of Health; NCI Cancer Education Grant [R25 CA 098010] FX This work was supported by the following grants: National Natural Science Foundation of China (NSFC) 81172314, National Science Foundation EF-0928690 (JOLS) and National Institute of Health AI078133 (RS), Margaret E. Early Medical Research Trust, P30CA016042 (Jonson Comprehensive Cancer Center) and P30AI028697 (UCLA AIDS Institute/CFAR). JOLS is grateful for the support of the De Logi Chair in Biological Sciences and the RAPIDD program of the Science & Technology Directorate of the US Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. CAO was supported by the NCI Cancer Education Grant, R25 CA 098010. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 22 Z9 22 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2014 VL 10 IS 4 AR e1004064 DI 10.1371/journal.ppat.1004064 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AP4FW UT WOS:000342033600030 PM 24722365 ER PT J AU O'Sullivan, C Edgerly, M Velarde, M Wilkerson, J Venkatesan, AM Pittaluga, S Yang, SX Nguyen, D Balasubramaniam, S Fojo, T AF O'Sullivan, Ciara Edgerly, Maureen Velarde, Margarita Wilkerson, Julia Venkatesan, Aradhana M. Pittaluga, Stefania Yang, Sherry X. Nguyen, Dat Balasubramaniam, Sanjeeve Fojo, Tito TI The VEGF Inhibitor Axitinib Has Limited Effectiveness as a Therapy for Adrenocortical Cancer SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ADRENAL-CORTICAL CARCINOMA; BREAST-CANCER; SOLID TUMORS; PHASE-II; GROWTH; SUNITINIB; MITOTANE; SERIES; TRIAL; BEVACIZUMAB AB Context: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis in need of more effective treatment options. Published evidence indicates many ACCs express the vascular endothelial growth factor receptor (VEGFR), suggesting inhibiting vascular endothelial growth factor signaling could potentially impact tumor growth. Objective: The objective of the study was to determine the antitumor efficacy of axitinib (AG-013736), a potent, selective inhibitor of VEGFR1, -2, and -3. Design: This was a phase II, open-label trial using a two-stage design. Patients: Thirteen patients with metastatic ACC previously treated with at least one chemotherapy regimen with or without mitotane participated in the study. Intervention: Starting axitinib dose was 5 mg orally twice daily. Dose escalations were permitted if the administered dose was tolerable. Results: Thirteen patients were enrolled. Dose escalation was possible in seven patients, but the majority could not tolerate a dose higher than the starting 5 mg, twice-daily dose for prolonged periods of time. All patients experienced known grade 1/2 toxicities, and 10 of 13 patients had at least one grade 3/4 adverse event. No patient tumor could be scored as a Response Evaluation Criteria in Solid Tumors response, although the growth rate on therapy compared with that prior to starting axitinib was reduced in 4 of the 13 patients. The median progression-free survival was 5.48 months, and the median overall survival was longer than 13.7 months. Conclusion: Axitinib has limited effectiveness in ACC. Together with 48 patients previously reported who received either sorafenib or sunitinib, a total of 61 ACC patients have now been treated with a VEGFR tyrosine kinase inhibitor without an objective Response Evaluation Criteria in Solid Tumors response. Future trials in ACC should look to other targets for possible active agents. C1 [O'Sullivan, Ciara; Edgerly, Maureen; Velarde, Margarita; Wilkerson, Julia; Balasubramaniam, Sanjeeve; Fojo, Tito] NCI, Med Oncol Branch, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Ctr Canc Res, Pathol Lab, Ctr Clin,NIH, Bethesda, MD 20892 USA. [Yang, Sherry X.; Nguyen, Dat] NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, Ctr Clin,NIH, Bethesda, MD 20892 USA. [Venkatesan, Aradhana M.] NCI, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP O'Sullivan, C (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ciara.o'sullivan@nih.gov; fojot@mail.nih.gov OI Wilkerson, Julia/0000-0002-6965-0867; Balasubramaniam, Sanjeeve/0000-0002-0643-2117 NR 33 TC 15 Z9 15 U1 0 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 APR PY 2014 VL 99 IS 4 BP 1291 EP 1297 DI 10.1210/jc.2013-2298 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP7UU UT WOS:000342283500051 PM 24423320 ER PT J AU Harper, S King, NB Meersman, SC Reichman, ME Breen, N Lynch, J AF Harper, Sam King, Nicholas B. Meersman, Stephen C. Reichman, Marsha E. Breen, Nancy Lynch, John TI Implicit value judgments in the measurement of health inequalities SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC HEALTH LA Spanish DT Article DE Health inequalities; measurement; ethics; health policy ID SOCIOECONOMIC INEQUALITIES; CANCER-MORTALITY; UNITED-STATES; TRENDS; DISPARITIES; POLICY; COUNTRIES; EQUALITY; GRADIENT; QUALITY AB Context. Quantitative estimates of the magnitude, direction, and rate of change of health inequalities play a crucial role in creating and assessing policies aimed at eliminating the disproportionate burden of disease in disadvantaged populations. It is generally assumed that the measurement of health inequalities is a value-neutral process, providing objective data that are then interpreted using normative judgments about whether a particular distribution of health is just, fair, or socially acceptable. Methods. We discuss five examples in which normative judgments play a role in the measurement process itself, through either the selection of one measurement strategy to the exclusion of others or the selection of the type, significance, or weight assigned to the variables being measured. Findings. Overall, we find that many commonly used measures of inequality are value laden and that the normative judgments implicit in these measures have important consequences for interpreting and responding to health inequalities. Conclusions. Because values implicit in the generation of health inequality measures may lead to radically different interpretations of the same underlying data, we urge researchers to explicitly consider and transparently discuss the normative judgments underlying their measures. We also urge policymakers and other consumers of health inequalities data to pay close attention to the measures on which they base their assessments of current and future health policies. C1 [Harper, Sam; King, Nicholas B.; Meersman, Stephen C.; Reichman, Marsha E.; Breen, Nancy; Lynch, John] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Harper, Sam; King, Nicholas B.; Meersman, Stephen C.; Reichman, Marsha E.; Breen, Nancy; Lynch, John] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Harper, Sam; King, Nicholas B.; Meersman, Stephen C.; Reichman, Marsha E.; Breen, Nancy; Lynch, John] NCI, Bethesda, MD 20892 USA. [Harper, Sam; King, Nicholas B.; Meersman, Stephen C.; Reichman, Marsha E.; Breen, Nancy; Lynch, John] Univ S Australia, Adelaide, SA 5001, Australia. [Harper, Sam; King, Nicholas B.; Meersman, Stephen C.; Reichman, Marsha E.; Breen, Nancy; Lynch, John] Univ Bristol, Bristol BS8 1TH, Avon, England. RP Harper, S (reprint author), McGill Univ, Montreal, PQ H3A 2T5, Canada. EM sam.harper@mcgill.ca RI Lynch, John/A-4797-2008; OI Lynch, John/0000-0003-2781-7902; Harper, Sam/0000-0002-2767-1053 FU PHS HHS [263-MQ-611198] NR 60 TC 2 Z9 3 U1 3 U2 10 PU PAN AMER HEALTH ORGANIZATION PI WASHINGTON PA 525 23RD ST NW, WASHINGTON, DC 20037 USA SN 1020-4989 J9 REV PANAM SALUD PUBL JI Rev. Panam. Salud Publica PD APR PY 2014 VL 35 IS 4 BP 293 EP 304 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AP6EU UT WOS:000342171200010 PM 24870010 ER PT J AU Koonin, EV Yutin, N AF Koonin, Eugene V. Yutin, Natalya TI The Dispersed Archaeal Eukaryome and the Complex Archaeal Ancestor of Eukaryotes SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID UBIQUITIN-LIKE PROTEINS; HORIZONTAL GENE-TRANSFER; CELL-DIVISION; BACTERIAL CYTOSKELETON; ORTHOLOGOUS GENES; PROVIDES EVIDENCE; RNA-POLYMERASES; ORIGIN; EVOLUTION; GENOME AB The ancestral set of eukaryotic genes is a chimera composed of genes of archaeal and bacterial origins thanks to the endosymbiosis event that gave rise to the mitochondria and apparently antedated the last common ancestor of the extant eukaryotes. The proto-mitochondrial endosymbiont is confidently identified as an alpha-proteobacterium. In contrast, the archaeal ancestor of eukaryotes remains elusive, although evidence is accumulating that it could have belonged to a deep lineage within the TACK (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) superphylum of the Archaea. Recent surveys of archaeal genomes show that the apparent ancestors of several key functional systems of eukaryotes, the components of the archaeal "eukaryome," such as ubiquitin signaling, RNA interference, and actin-based and tubulin-based cytoskeleton structures, are identifiable in different archaeal groups. We suggest that the archaeal ancestor of eukaryotes was a complex form, rooted deeply within the TACK superphylum, that already possessed some quintessential eukaryotic features, in particular, a cytoskeleton, and perhaps was capable of a primitive form of phagocytosis that would facilitate the engulfment of potential symbionts. This putative group of Archaea could have existed for a relatively short time before going extinct or undergoing genome streamlining, resulting in the dispersion of the eukaryome. This scenario might explain the difficulty with the identification of the archaeal ancestor of eukaryotes despite the straightforward detection of apparent ancestors to many signature eukaryotic functional systems. C1 [Koonin, Eugene V.; Yutin, Natalya] 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 U.S. Department of Health and Human Services FX We thank Thijs Ettema, Kira Makarova, and Bill Martin for useful discussions. Our research is supported by intramural funds of the U.S. Department of Health and Human Services (to the National Library of Medicine, NIH). NR 116 TC 36 Z9 36 U1 2 U2 21 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 APR PY 2014 VL 6 IS 4 AR a016188 DI 10.1101/cshperspect.a016188 PG 16 WC Cell Biology SC Cell Biology GA AO8AR UT WOS:000341575100002 PM 24691961 ER PT J AU Weigert, R AF Weigert, Roberto TI Imaging the Dynamics of Endocytosis in Live Mammalian Tissues SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID INTRAVITAL 2-PHOTON MICROSCOPY; RECEPTOR-MEDIATED ENDOCYTOSIS; POLARIZED EPITHELIAL-CELLS; KIDNEY PROXIMAL TUBULE; BLOOD-BRAIN-BARRIER; IN-VIVO; PLASMA-MEMBRANE; REGULATED EXOCYTOSIS; CATIONIZED FERRITIN; CHOROID-PLEXUS AB In mammalian cells, endocytosis plays a pivotal role in regulating several basic cellular functions. Up to now, the dynamics and the organization of the endocytic pathways have been primarily investigated in reductionist model systems such as cell and organ cultures. Although these experimental models have been fully successful in unraveling the endocytic machinery at a molecular level, our understanding of the regulation and the role of endocytosis in vivo has been limited. Recently, advancements in intravital microscopy have made it possible to extend imaging in live animals to subcellular structures, thus revealing new aspects of the molecular machineries regulating membrane trafficking that were not previously appreciated in vitro. Here, we focus on the use of intravital microscopy to study endocytosis in vivo, and discuss how this approach will allow addressing two fundamental questions: (1) how endocytic processes are organized in mammalian tissues, and (2) how they contribute to organ physiopathology. C1 Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Weigert, R (reprint author), Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM weigertr@mail.nih.gov FU NIH, National Institute of Dental and Craniofacial Research FX This research is supported by the Intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research. I thank Dr. Julie Donaldson and Dr. Natalie Porat-Shliom for critical reading of the manuscript. NR 101 TC 3 Z9 3 U1 0 U2 5 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 APR PY 2014 VL 6 IS 4 AR a017012 DI 10.1101/cshperspect.a017012 PG 12 WC Cell Biology SC Cell Biology GA AO8AR UT WOS:000341575100007 PM 24691962 ER PT J AU Blum, MR Bauer, D da Costa, BR Wirth, CD Cappola, AR Peeters, RP Asvold, BO Fink, HA den Elzen, WP Luben, RN Imaizumi, M Langhammer, A Bremner, AP Gogakos, A Eastell, R Strotmeyer, ES Wallace, E Hoff, M Khaw, KT Ceresini, G Rivadeneira, F Ferrucci, L Uitterlinden, A Williams, GR Westendorp, RG Walsh, JP Gussekloo, J Aujesky, D Rodondi, N AF Blum, Manuel R. Bauer, Douglas da Costa, Bruno R. Wirth, Christina D. Cappola, Anne R. Peeters, Robin P. Asvold, Bjorn O. Fink, Howard A. den Elzen, Wendy P. Luben, Robert N. Imaizumi, Misa Langhammer, Arnulf Bremner, Alexandra P. Gogakos, Apostolos Eastell, Richard Strotmeyer, Elsa S. Wallace, Erin Hoff, Mari Khaw, Kay-Tee Ceresini, Graziano Rivadeneira, Fernando Ferrucci, Luigi Uitterlinden, Andre Williams, Graham R. Westendorp, Rudi G. Walsh, John P. Gussekloo, Jacobijn Aujesky, Drahomir Rodondi, Nicolas TI SUBCLINICAL THYROID DYSFUNCTION AND FRACTURE RISK: AN INDIVIDUAL PARTICIPANT DATA ANALYSIS OF PROSPECTIVE COHORTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Blum, Manuel R.; Wirth, Christina D.; Aujesky, Drahomir; Rodondi, Nicolas] Univ Hosp Bern, Inselspital, CH-3010 Bern, Switzerland. [Bauer, Douglas] Univ Calif San Francisco, San Francisco, CA 94143 USA. [da Costa, Bruno R.] Univ Bern, Bern, Switzerland. [Cappola, Anne R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Peeters, Robin P.; Rivadeneira, Fernando; Uitterlinden, Andre] Univ Rotterdam, Rotterdam, Netherlands. [Asvold, Bjorn O.; Langhammer, Arnulf] Norwegian Univ Sci & Technol, N-7034 Trondheim, Norway. [Fink, Howard A.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Fink, Howard A.] VA Med Ctr, Minneapolis, MN USA. [den Elzen, Wendy P.; Westendorp, Rudi G.; Gussekloo, Jacobijn] Leiden Univ, Med Ctr, Leiden, Netherlands. [Luben, Robert N.; Khaw, Kay-Tee] Univ Cambridge, Cambridge, England. [Imaizumi, Misa] Radiat Effects Res Fdn, Nagasaki, Japan. [Bremner, Alexandra P.; Walsh, John P.] Univ Western Australia, Crawley, WA, Australia. [Gogakos, Apostolos; Williams, Graham R.] Univ London Imperial Coll Sci Technol & Med, London, England. [Eastell, Richard] Univ Sheffield, Sheffield, S Yorkshire, England. [Strotmeyer, Elsa S.] Univ Pittsburgh, Pittsburgh, PA USA. [Wallace, Erin] Univ Washington, Seattle, WA 98195 USA. [Hoff, Mari] Nord Trondelag Hosp Trust, Levanger, Norway. [Ceresini, Graziano] Univ Hosp Parma, Parma, Italy. [Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA. [Walsh, John P.] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S212 EP S213 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201134 ER PT J AU Burke, HB Hoang, A Becher, D Fontelo, P Gimbel, RW AF Burke, Harry B. Hoang, Albert Becher, Dorothy Fontelo, Paul Gimbel, Ronald W. TI ELECTRONIC HEALTH RECORDS IMPROVE CLINICAL NOTE QUALITY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Burke, Harry B.; Hoang, Albert; Becher, Dorothy; Gimbel, Ronald W.] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. [Fontelo, Paul] Natl Lib Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S84 EP S84 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200202 ER PT J AU Mundkur, M Abhyankar, S Callaghan, FM McDonald, CJ AF Mundkur, Mallika Abhyankar, Swapna Callaghan, Fiona M. McDonald, Clement J. TI AN ACHILLES HEEL OF DISPARITIES RESEARCH: MISSING RACIAL DATA IN A STUDY OF MORTALITY AFTER CRITICAL ILLNESS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Mundkur, Mallika; Abhyankar, Swapna; Callaghan, Fiona M.; McDonald, Clement J.] NIH, Bethesda, MD 20892 USA. [Mundkur, Mallika] George Washington Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S19 EP S19 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200048 ER PT J AU Phillips, KA Epstein, DH Jobes, ML Preston, KL AF Phillips, Karran A. Epstein, David H. Jobes, Michelle L. Preston, Kenzie L. TI SMARTPHONE-REPORTED STRESS AND DRUG EVENTS AND DAY-END PERCEIVED STRESS, HASSLES, AND MOOD IN METHADONE-MAINTAINED INDIVIDUALS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Phillips, Karran A.; Epstein, David H.; Jobes, Michelle L.; Preston, Kenzie L.] NIDA, NIH, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S209 EP S210 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201126 ER PT J AU Thomas, HN Evans, GW Berlowitz, D Bonds, DE Chertow, GM Conroy, MB Foy, C Glasser, S Lewis, CE Riley, WT Russell, L Williams, O Hess, R AF Thomas, Holly N. Evans, Gregory W. Berlowitz, Dan Bonds, Denise E. Chertow, Glenn M. Conroy, Molly B. Foy, Capri Glasser, Stephen Lewis, Cora E. Riley, William T. Russell, Laurie Williams, Olubunmi Hess, Rachel TI THE RELATION BETWEEN ANTIHYPERTENSIVE MEDICATION AND SEXUAL FUNCTION IN WOMEN: BASELINE DATA FROM THE SPRINT STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Thomas, Holly N.; Conroy, Molly B.; Hess, Rachel] Univ Pittsburgh, Pittsburgh, PA USA. [Thomas, Holly N.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Evans, Gregory W.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Berlowitz, Dan] Bedford VA Hosp, Bedford, MA USA. [Berlowitz, Dan] Boston Univ, Sch Med, Boston, MA 02118 USA. [Bonds, Denise E.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Foy, Capri; Russell, Laurie] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Glasser, Stephen; Lewis, Cora E.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Riley, William T.] NIMH, Bethesda, MD 20892 USA. [Williams, Olubunmi] Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S231 EP S231 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201177 ER PT J AU Groveman, BR Dolan, MA Taubner, LM Kraus, A Wickner, RB Caughey, B AF Groveman, Bradley R. Dolan, Michael A. Taubner, Lara M. Kraus, Allison Wickner, Reed B. Caughey, Byron TI In defense of parallel-in-register beta sheet structures in PrPSc amyloids SO PRION LA English DT Meeting Abstract C1 [Groveman, Bradley R.; Taubner, Lara M.; Kraus, Allison; Caughey, Byron] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Dolan, Michael A.] NIAID, Theoret & Computat Biophys Grp, NIH, Bethesda, MD 20892 USA. [Wickner, Reed B.] NIDDK, LBG, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA 22 BP 10 EP 10 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900025 ER PT J AU Elder, A Henderson, DM Nalls, AV Wilham, JM Caughey, B Hoover, EA Kincaid, AE Bartz, JC Mathiason, CK AF Elder, Alan Henderson, Davin M. Nalls, Amy V. Wilham, Jason M. Caughey, Byron Hoover, Edward A. Kincaid, Anthony E. Bartz, Jason C. Mathiason, Candace K. TI In vitro temporal assessment of CWD and TME blood-borne prions SO PRION LA English DT Meeting Abstract C1 [Elder, Alan; Henderson, Davin M.; Nalls, Amy V.; Hoover, Edward A.; Mathiason, Candace K.] Colorado State Univ, Ft Collins, CO 80523 USA. [Wilham, Jason M.; Caughey, Byron] NIH Rocky Mt Lab, Hamilton, MT USA. [Kincaid, Anthony E.; Bartz, Jason C.] Creighton Univ, Omaha, NE 68178 USA. RI Mathiason, Candace/E-7843-2017 OI Mathiason, Candace/0000-0002-5920-4556 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA O.10 BP 16 EP 16 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900038 ER PT J AU Orru, CD Bongianni, M Tonoli, G Hughson, AG Ferrari, S Groveman, BR Sacchetto, L Fiorini, M Pocchiari, M Monaco, S Caughey, B Zanusso, G AF Orru, Christina D. Bongianni, Matilde Tonoli, Giovanni Hughson, Andrew G. Ferrari, Sergio Groveman, Bradley R. Sacchetto, Luca Fiorini, Michele Pocchiari, Maurizio Monaco, Salvatore Caughey, Byron Zanusso, Gianluigi TI How to perform olfactory mucosa brushing in patients with Creutzfeldt-Jakob disease SO PRION LA English DT Meeting Abstract C1 [Orru, Christina D.; Bongianni, Matilde; Hughson, Andrew G.; Groveman, Bradley R.; Caughey, Byron] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Orru, Christina D.] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. [Bongianni, Matilde; Ferrari, Sergio; Fiorini, Michele; Monaco, Salvatore; Zanusso, Gianluigi] Univ Verona, Dept Neurol & Movement Sci, I-37100 Verona, Italy. [Tonoli, Giovanni; Sacchetto, Luca] Azienda Osped Univ Integrata, Clin Otorinolaringoiatr, Verona, Italy. [Pocchiari, Maurizio] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA O.23 BP 22 EP 23 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900051 ER PT J AU Vieira, TCRG Cordeiro, Y Caughey, B Silva, JL AF Vieira, Tuane C. R. G. Cordeiro, Yraima Caughey, Byron Silva, Jerson L. TI Heparin binding confers prion stability and impairs its aggregation SO PRION LA English DT Meeting Abstract DE inhibition of amyloid aggregation; prion conversion; glycosaminoglycan; neurodegeneration C1 [Vieira, Tuane C. R. G.; Silva, Jerson L.] Inst Nacl Ciencia & Tecnol Biol Estrutural & Bioi, Ctr Nacl Ressonancia Magnet Nucl Jiri Jonas, Inst Bioquim Med Leopoldo De Meis, Rio De Janeiro, Brazil. [Cordeiro, Yraima] Univ Fed Rio de Janeiro, Fac Farm, Rio De Janeiro, Brazil. [Caughey, Byron] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.15 BP 31 EP 31 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900070 ER PT J AU Manca, M Haley, NJ Perra, D Orru, CD Monello, R Powers, J Wild, M Caughey, B AF Manca, Matteo Haley, Nicholas J. Perra, Daniela Orru, Christina D. Monello, Ryan Powers, Jenny Wild, Margaret Caughey, Byron TI Development of an antemortem test for chronic wasting disease based on RT-QuIC of rectal biopsy and nasal brushings SO PRION LA English DT Meeting Abstract C1 [Manca, Matteo; Perra, Daniela; Orru, Christina D.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT USA. [Manca, Matteo; Perra, Daniela; Orru, Christina D.] Univ Cagliari, Dept Biomed Sci, Monserrato, Italy. [Haley, Nicholas J.] Kansas State Univ, Coll Vet Med, Dept Diagnost Med & Pathobiol, Manhattan, KS 66506 USA. [Monello, Ryan; Powers, Jenny; Wild, Margaret] Natl Pk Serv, Ft Collins, CO USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.120 BP 81 EP 81 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900175 ER PT J AU Hoover, EA Henderson, DM Denkers, ND Mathiason, CK Manca, M Caughey, B AF Hoover, Edward A. Henderson, Davin M. Denkers, Nathaniel D. Mathiason, Candace K. Manca, Matteo Caughey, Byron TI Abundant prion shedding in CWD-infected deer revealed by Realtime conversion SO PRION LA English DT Meeting Abstract C1 [Hoover, Edward A.; Henderson, Davin M.; Denkers, Nathaniel D.; Mathiason, Candace K.] Colorado State Univ, Prion Res Ctr, Ft Collins, CO 80523 USA. [Manca, Matteo; Caughey, Byron] NIAID, Lab Persistent Viral Dis, Hamilton, MT USA. [Manca, Matteo] Univ Cagliari, Dept Biomed Sci, Monserrato, Italy. RI Mathiason, Candace/E-7843-2017 OI Mathiason, Candace/0000-0002-5920-4556 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.141 BP 90 EP 90 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900196 ER PT J AU Blanco, RA de Wolf, C Tan, BC Smith, AJA Orru, C Caughey, B Manson, JC McCutcheon, S AF Blanco, Richard Alejo de Wolf, Chris Tan, Boon Chin Smith, Allister J. A. Orru, Christina Caughey, Byron Manson, Jean C. McCutcheon, Sandra TI QuIC amplification of BSE infected sheep blood identifies prion aggregates in peripheral blood cells and plasma SO PRION LA English DT Meeting Abstract C1 [Blanco, Richard Alejo; de Wolf, Chris; Tan, Boon Chin; Smith, Allister J. A.; Manson, Jean C.; McCutcheon, Sandra] Univ Edinburgh, Roslin Inst, Neurobiol Div, Edinburgh, Midlothian, Scotland. [Blanco, Richard Alejo; de Wolf, Chris; Tan, Boon Chin; Smith, Allister J. A.; Manson, Jean C.; McCutcheon, Sandra] Univ Edinburgh, R D SVS, Edinburgh, Midlothian, Scotland. [Orru, Christina; Caughey, Byron] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, Hamilton, MT USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.152 BP 96 EP 96 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900207 ER PT J AU Bongianni, M Orru, CD Tonoli, G Hughson, AG Ferrari, S Groveman, BR Sacchetto, L Fiorini, M Pocchiari, M Monaco, S Caughey, B Zanusso, G AF Bongianni, Matilde Orru, Christina D. Tonoli, Giovanni Hughson, Andrew G. Ferrari, Sergio Groveman, Bradley R. Sacchetto, Luca Fiorini, Michele Pocchiari, Maurizio Monaco, Salvatore Caughey, Byron Zanusso, Gianluigi TI Comparison of brushes and swabs for olfactory mucosa sampling and RT-QuIC analysis of patients with Creutzfeldt-Jakob disease SO PRION LA English DT Meeting Abstract C1 [Bongianni, Matilde; Orru, Christina D.; Hughson, Andrew G.; Groveman, Bradley R.; Caughey, Byron] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Bongianni, Matilde; Ferrari, Sergio; Fiorini, Michele; Monaco, Salvatore; Zanusso, Gianluigi] Univ Verona, Dept Neurol & Movement Sci, I-37100 Verona, Italy. [Orru, Christina D.] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. [Tonoli, Giovanni; Sacchetto, Luca] Azienda Osped Univ Integrata, Clin Otorinolaringoiatr, Verona, Italy. [Pocchiari, Maurizio] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.196 BP 118 EP 118 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900251 ER PT J AU Vascellari, S Hughson, AG Cardone, F Pocchiari, M Caughey, B Orru, CD Pani, A AF Vascellari, Sarah Hughson, Andrew G. Cardone, Franco Pocchiari, Maurizio Caughey, Byron Orru, Christina D. Pani, Alessandra TI RT-QuIC detection of PrPsCJD spiked into human urine SO PRION LA English DT Meeting Abstract ID QUAKING-INDUCED CONVERSION; CEREBROSPINAL-FLUID; DISEASE; PRIONS C1 [Vascellari, Sarah; Orru, Christina D.; Pani, Alessandra] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. [Hughson, Andrew G.; Caughey, Byron; Orru, Christina D.] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Cardone, Franco; Pocchiari, Maurizio] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. RI Cardone, Franco/D-1724-2009 OI Cardone, Franco/0000-0002-2376-0470 NR 12 TC 0 Z9 0 U1 1 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.207 BP 123 EP 124 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900262 ER PT J AU Hammal, Z Cohn, JF George, DT AF Hammal, Zakia Cohn, Jeffrey F. George, David T. TI Interpersonal Coordination of Head Motion in Distressed Couples SO IEEE TRANSACTIONS ON AFFECTIVE COMPUTING LA English DT Article DE Interpersonal coordination; head motion; windowed cross-correlation; actor-partner analysis ID FACIAL EXPRESSION; DYADIC CONVERSATION; PERCEPTION; MOVEMENTS; CONFLICT; EMOTION; MODELS; RECOGNITION; ASSOCIATION; AGREEMENT AB In automatic emotional expression analysis, head motion has been considered mostly a nuisance variable, something to control when extracting features for action unit or expression detection. As an initial step toward understanding the contribution of head motion to emotion communication, we investigated the interpersonal coordination of rigid head motion in intimate couples with a history of interpersonal violence. Episodes of conflict and non-conflict were elicited in dyadic interaction tasks and validated using linguistic criteria. Head motion parameters were analyzed using Student's paired t-tests; actor-partner analyses to model mutual influence within couples; and windowed cross-correlation to reveal dynamics of change in direction of influence over time. Partners' RMS angular displacement for yaw and RMS angular velocity for pitch and yaw each demonstrated strong mutual influence between partners. Partners' RMS angular displacement for pitch was higher during conflict. In both conflict and non-conflict, head angular displacement and angular velocity for pitch and yaw were strongly correlated, with frequent shifts in lead-lag relationships. The overall amount of coordination between partners' head movement was more highly correlated during non-conflict compared with conflict interaction. While conflict increased head motion, it served to attenuate interpersonal coordination. C1 [Hammal, Zakia; Cohn, Jeffrey F.] Carnegie Mellon Univ, Inst Robot, Pittsburgh, PA 15260 USA. [Cohn, Jeffrey F.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [George, David T.] NIAAA, Div Intramural Clin & Biol Res, NIA, Bethesda, MD 20892 USA. RP Hammal, Z (reprint author), Carnegie Mellon Univ, Inst Robot, Pittsburgh, PA 15260 USA. EM zakia_hammal@yahoo.fr; jeffcohn@cs.cmu.edu; tedg@lcs.niaaa.nih.gov FU National Institute of Mental Health of the National Institutes of Health [MH096951] FX Research reported in this publication was supported in part by the National Institute of Mental Health of the National Institutes of Health under Award Number MH096951. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 66 TC 3 Z9 3 U1 2 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1949-3045 J9 IEEE T AFFECT COMPUT JI IEEE Trans. Affect. Comput. PD APR-JUN PY 2014 VL 5 IS 2 BP 155 EP 167 DI 10.1109/TAFFC.2014.2326408 PG 13 WC Computer Science, Artificial Intelligence; Computer Science, Cybernetics SC Computer Science GA AN2PQ UT WOS:000340428200005 PM 26167256 ER PT J AU Ombrello, MJ Sikora, KA Kastner, DL AF Ombrello, Michael J. Sikora, Keith A. Kastner, Daniel L. TI Genetics, genomics, and their relevance to pathology and therapy SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY LA English DT Article DE Pediatric rheumatology; Somatic mosaicism; Genome-wide association study; Targeted deep resequencing; miRNA; lncRNA ID JUVENILE IDIOPATHIC ARTHRITIS; WIDE ASSOCIATION ANALYSIS; LARGE NONCODING RNAS; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI; RARE VARIANTS; LOW-FREQUENCY; AUTOINFLAMMATORY DISEASE; GENOTYPE IMPUTATION; NLRP3 INFLAMMASOME AB Genetic and genomic investigations are a starting point for the study of human disease, seeking to discover causative variants relevant to disease pathophysiology. Over the past 5 years, massively parallel, high-throughput, next-generation sequencing techniques have revolutionized genetics and genomics, identifying the causes of many Mendelian diseases. The application of whole-genome sequencing and whole-exome sequencing to large populations has produced several publicly available sequence datasets that have revealed the scope of human genetic variation and have contributed to important methodological advances in the study of both common and rare genetic variants in genetically complex diseases. The importance of noncoding genetic variation has been highlighted by the Encyclopedia of DNA Elements (ENCODE) project and National Institutes of Health (NIH) Roadmap Epigenomics Program and integrated analyses of these datasets, together with disease-specific datasets, will provide an important and powerful tool for determining the mechanisms through which disease-associated, noncoding variation influences disease risk. Published by Elsevier Ltd. C1 [Ombrello, Michael J.; Sikora, Keith A.] NIAMSD, NIH, DHHS, Bethesda, MD 20892 USA. [Kastner, Daniel L.] NHGRI, NIH, DHHS, Bethesda, MD 20892 USA. RP Ombrello, MJ (reprint author), NIAMSD, NIH, DHHS, 9000 Rockville Pike,Bldg 10,Room 10C101A,MSC 1560, Bethesda, MD 20892 USA. EM michael.ombrello@nih.gov; keith.sikora@nih.gov; daniel.kastner@nih.gov FU Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. NR 98 TC 10 Z9 11 U1 3 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6942 EI 1521-1770 J9 BEST PRACT RES CL RH JI Best Pract. Res. Clin. Rheumatol. PD APR PY 2014 VL 28 IS 2 BP 175 EP 189 DI 10.1016/j.berh.2014.05.001 PG 15 WC Rheumatology SC Rheumatology GA AM2SN UT WOS:000339701200002 PM 24974057 ER PT J AU Charbonneau, B Moysich, KB Kalli, KR Oberg, AL Vierkant, RA Fogarty, ZC Block, MS Maurer, MJ Goergen, KM Fridley, BL Cunningham, JM Rider, DN Preston, C Hartmann, LC Lawrenson, K Wang, C Tyrer, J Song, HL Defazio, A Johnatty, SE Doherty, JA Phelan, CM Sellers, TA Ramirez, SM Vitonis, AF Terry, KL Van den Berg, D Pike, MC Wu, AH Berchuck, A Gentry-Maharaj, A Ramus, SJ Diergaarde, B Shen, H Jensen, A Menkiszak, J Cybulski, C Lubinski, J Ziogas, A Rothstein, JH McGuire, V Sieh, W Lester, J Walsh, C Vergote, I Lambrechts, S Despierre, E Garcia-Closas, M Yang, H Brinton, LA Spiewankiewicz, B Rzepecka, IK Dansonka-Mieszkowska, A Seibold, P Rudolph, A Paddock, LE Orlow, I Lundvall, L Olson, SH Hogdall, CK Schwaab, I Du Bois, A Harter, P Flanagan, JM Brown, R Paul, J Ekici, AB Beckmann, M Hein, A Eccles, D Lurie, G Hays, LE Bean, YT Pejovic, T Goodman, MT Campbell, I Fasching, PA Konecny, G Kaye, SB Heitz, F Hogdall, E Bandera, EV Chang-Claude, J Kupryjanczyk, J Wentzensen, N Lambrechts, D Karlan, BY Whittemore, AS Culver, HA Gronwald, J Levine, DA Kjaer, SK Menon, U Schildkraut, JM Pearce, CL Cramer, DW Rossing, MA Chenevix-Trench, G Pharoah, PDP Gayther, SA Ness, RB Odunsi, K Sucheston, LE Knutson, KL Goode, EL AF Charbonneau, Bridget Moysich, Kirsten B. Kalli, Kimberly R. Oberg, Ann L. Vierkant, Robert A. Fogarty, Zachary C. Block, Matthew S. Maurer, Matthew J. Goergen, Krista M. Fridley, Brooke L. Cunningham, Julie M. Rider, David N. Preston, Claudia Hartmann, Lynn C. Lawrenson, Kate Wang, Chen Tyrer, Jonathan Song, Honglin defazio, Anna Johnatty, Sharon E. Doherty, Jennifer A. Phelan, Catherine M. Sellers, Thomas A. Ramirez, Starr M. Vitonis, Allison F. Terry, Kathryn L. Van den Berg, David Pike, Malcolm C. Wu, Anna H. Berchuck, Andrew Gentry-Maharaj, Aleksandra Ramus, Susan J. Diergaarde, Brenda Shen, Howard Jensen, Allan Menkiszak, Janusz Cybulski, Cezary Lubinski, Jan Ziogas, Argyrios Rothstein, Joseph H. McGuire, Valerie Sieh, Weiva Lester, Jenny Walsh, Christine Vergote, Ignace Lambrechts, Sandrina Despierre, Evelyn Garcia-Closas, Montserrat Yang, Hannah Brinton, Louise A. Spiewankiewicz, Beata Rzepecka, Iwona K. Dansonka-Mieszkowska, Agnieszka Seibold, Petra Rudolph, Anja Paddock, Lisa E. Orlow, Irene Lundvall, Lene Olson, Sara H. Hogdall, Claus K. Schwaab, Ira Du Bois, Andreas Harter, Philipp Flanagan, James M. Brown, Robert Paul, James Ekici, Arif B. Beckmann, MatthiasW. Hein, Alexander Eccles, Diana Lurie, Galina Hays, Laura E. Bean, Yukie T. Pejovic, Tanja Goodman, Marc T. Campbell, Ian Fasching, Peter A. Konecny, Gottfried Kaye, Stanley B. Heitz, Florian Hogdall, Estrid Bandera, Elisa V. Chang-Claude, Jenny Kupryjanczyk, Jolanta Wentzensen, Nicolas Lambrechts, Diether Karlan, Beth Y. Whittemore, Alice S. Culver, Hoda Anton Gronwald, Jacek Levine, Douglas A. Kjaer, Susanne K. Menon, Usha Schildkraut, Joellen M. Pearce, Celeste Leigh Cramer, Daniel W. Rossing, Mary Anne Chenevix-Trench, Georgia Pharoah, Paul D. P. Gayther, Simon A. Ness, Roberta B. Odunsi, Kunle Sucheston, Lara E. Knutson, Keith L. Goode, Ellen L. CA AOCS Grp ACS TI Large-Scale Evaluation of Common Variation in Regulatory T Cell-Related Genes and Ovarian Cancer Outcome SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID METAANALYSIS; ASSOCIATION; IDENTIFICATION; POLYMORPHISMS; VARIANTS; LOCUS AB The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22-1.64; P = 5.7 x 10(-6)], rs791587 (HR, 1.36; 95% CI, 1.17-1.57; P = 6.2 x 10(-5)), rs2476491 (HR, 1.40; 95% CI, 1.19-1.64; P = 5.6 x 10(-5)), and rs10795763 (HR, 1.35; 95% CI, 1.17-1.57; P = 7.9 x 10(-5)), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54-0.82; P = 9.3 x 10(-5)) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer. (C) 2014 AACR. C1 [Charbonneau, Bridget; Ramirez, Starr M.; Goode, Ellen L.] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Kalli, Kimberly R.; Block, Matthew S.] Mayo Clin, Dept Med Oncol, Rochester, MN USA. [Oberg, Ann L.; Vierkant, Robert A.; Fogarty, Zachary C.; Maurer, Matthew J.; Goergen, Krista M.; Rider, David N.; Wang, Chen] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA. [Cunningham, Julie M.] Mayo Clin, Div Expt Pathol, Dept Lab Med & Pathol, Rochester, MN USA. [Preston, Claudia; Knutson, Keith L.] Mayo Clin, Dept Immunol, Rochester, MN USA. [Hartmann, Lynn C.] Mayo Clin, Dept Obstet & Gynecol, Rochester, MN USA. [Moysich, Kirsten B.; Odunsi, Kunle; Sucheston, Lara E.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Pike, Malcolm C.; Orlow, Irene; Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA. [Fridley, Brooke L.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA. [Lawrenson, Kate; Van den Berg, David; Pike, Malcolm C.; Wu, Anna H.; Ramus, Susan J.; Shen, Howard; Pearce, Celeste Leigh; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA. [Goodman, Marc T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA USA. [Fasching, Peter A.; Konecny, Gottfried] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA USA. [Ziogas, Argyrios; Culver, Hoda Anton] Univ Calif Irvine, Sch Med, Ctr Canc Genet Res & Prevent, Dept Epidemiol, Irvine, CA USA. [Rothstein, Joseph H.; McGuire, Valerie; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Palo Alto, CA USA. [Tyrer, Jonathan; Song, Honglin; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge, England. [Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Inst Womens Hlth, Gynaecol Canc Res Ctr, London, England. [Garcia-Closas, Montserrat] Breakthrough Breast Canc Res Ctr, London, England. [Flanagan, James M.; Brown, Robert] Imperial Coll London, Dept Surg & Canc, London, England. [Garcia-Closas, Montserrat] Royal Marsden Hosp, Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England. [Kaye, Stanley B.] Royal Marsden Hosp, Inst Canc Res, Div Clin Studies, Sutton, Surrey, England. [Paul, James] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland. [Eccles, Diana] Univ Southampton, Southampton Univ Hosp, Fac Med, Southampton, Hants, England. [defazio, Anna] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Dept Gynaecol, Westmead, NSW, Australia. [Johnatty, Sharon E.; Chenevix-Trench, Georgia] Queensland Inst Med Res, Div Canc, Herston, Qld, Australia. [Campbell, Ian; AOCS Grp] Peter MacCallum Canc Inst, Div Res, Melbourne, Vic 3000, Australia. [Campbell, Ian] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Sect Biostat & Epidemiol, Lebanon, NH USA. [Phelan, Catherine M.; Sellers, Thomas A.] H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Dept Canc Epidemiol, Tampa, FL USA. [Knutson, Keith L.] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA. [Vitonis, Allison F.; Terry, Kathryn L.; Cramer, Daniel W.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Vitonis, Allison F.; Terry, Kathryn L.; Cramer, Daniel W.] Harvard Univ, Sch Med, Boston, MA USA. [Terry, Kathryn L.; Cramer, Daniel W.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27706 USA. [Schildkraut, Joellen M.] Duke Canc Inst, Detect & Control Res Program, Durham, NC USA. [Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC USA. [Diergaarde, Brenda] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Lundvall, Lene; Hogdall, Claus K.; Kjaer, Susanne K.] Rigshosp, Copenhagen Univ Hosp, Dept Gynaecol, Copenhagen, Denmark. [Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark. [Menkiszak, Janusz] Pomeranian Med Univ, Dept Surg Gynecol & Gynecol Oncol Adults, Szczecin, Poland. [Cybulski, Cezary; Lubinski, Jan; Gronwald, Jacek] Pomeranian Med Univ, Int Hereditary Canc Ctr, Szczecin, Poland. [Spiewankiewicz, Beata] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Rzepecka, Iwona K.; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Gynecol Oncol, Warsaw, Poland. [Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn] Maria Sklodowska Curie Mem Canc Ctr, Dept Pathol, Warsaw, Poland. [Lambrechts, Diether] Inst Oncol, Warsaw, Poland. [Lambrechts, Diether] Univ Hosp Leuven, Dept Obstet & Gynecol, Div Gynecol Oncol, Leuven, Belgium. [Yang, Hannah; Brinton, Louise A.; Wentzensen, Nicolas] Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium. [Seibold, Petra; Rudolph, Anja; Chang-Claude, Jenny] Univ Leuven, VIB, Vesalius Res Ctr, Leuven, Belgium. [Schwaab, Ira] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium. [Du Bois, Andreas; Harter, Philipp; Heitz, Florian] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Du Bois, Andreas; Harter, Philipp; Heitz, Florian] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Ekici, Arif B.] Inst Humanagenet, Wiesbaden, Germany. [Beckmann, MatthiasW.; Hein, Alexander; Fasching, Peter A.] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany. [Paddock, Lisa E.] Kliniken Essen Mitte Evang Huyssens Stiftung Knap, Dept Gynecol & Gynecol Oncol, Essen, Germany. [Bandera, Elisa V.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Lurie, Galina] Univ Erlangen Nurnberg, Dept Gynecol & Obstet, Univ Hosp Erlangen, Erlangen, Germany. [Hays, Laura E.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Jersey Dept Hlth, New Brunswick, NJ USA. [Bean, Yukie T.; Pejovic, Tanja; ACS] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Bean, Yukie T.; Pejovic, Tanja] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI USA. [Rossing, Mary Anne] Knight Canc Inst, Dept Hematol & Oncol, Portland, OR USA. [Rossing, Mary Anne] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Ness, Roberta B.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Ness, Roberta B.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA USA. [Ness, Roberta B.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. RP Goode, EL (reprint author), Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN 55905 USA. EM egoode@mayo.edu RI Menkiszak, Janusz/I-4036-2014; Johnatty, Sharon/R-8890-2016; Gronwald, Jacek/A-4576-2017; Whittemore, Alice/F-9925-2014; Hein, Alexander/F-6999-2010; Bandera, Elisa/M-4169-2014; Fridley, Brooke/D-8315-2015; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; deFazio, Anna/D-3939-2013; Bowtell, David/H-1007-2016; Wang, Chen/B-3244-2011; OI Johnatty, Sharon/0000-0002-7888-1966; Gronwald, Jacek/0000-0002-3643-2871; Hein, Alexander/0000-0003-2601-3398; Bandera, Elisa/0000-0002-8789-2755; Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; deFazio, Anna/0000-0003-0057-4744; Bowtell, David/0000-0001-9089-7525; Wang, Chen/0000-0003-2638-3081; Kjaer, Susanne/0000-0002-8347-1398; Diergaarde, Brenda/0000-0002-3578-6547; Ramus, Susan/0000-0003-0005-7798; Orlow, Irene/0000-0001-6234-6961 FU Ovarian Cancer Research Fund [PPD/RPCI.07]; Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative [U19-CA148112]; National Health and Medical Research Council; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; American Cancer Society [SIOP-06-090-06, CRTG-00-196-01-CCE]; California Cancer Research Program [00-01389V-20170, N01-CN25403, 2II0200]; Canadian Institutes for Health Research; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; Cancer Institute of New Jersey; Cancer Research UK [C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689, C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692]; Celma Mastry Ovarian Cancer Foundation; Danish Cancer Society [94-222-52]; ELAN Program of the University of Erlangen-Nuremberg; Eve Appeal (Oak Foundation); Helsinki University Central Hospital Research Fund; Helse Vest; Imperial Experimental Cancer Research Centre [C1312/A15589]; 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; U.S. National Cancer Institute [K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P20-GM103418, P30-CA072720, P30-CA15083, P30-CA168524, P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA61107, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA136924, R01-CA149429, R03-CA113148, R03-CA115195, R21-GM86689, R37-CA070867, R37-CA70867, U01-CA069417, U01-CA071966]; U.S. Army Medical Research and Material Command [DAMD17-98-1-8659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1- 0669, W81XWH-10-1-0280]; National Health and Medical Research Council of Australia [199600, 400413, 400281]; German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research [01 GB 9401]; state of Baden-Wurttemberg through Medical Faculty of the University of Ulm [P.685]; Minnesota Ovarian Cancer Alliance; Mayo Foundation; Fred C. and Katherine B. Andersen Foundation; Lon V. Smith Foundation [LVS-39420]; Polish Committee for Scientific Research [4P05C 028 14, 2P05A 068 27]; Oak Foundation; OHSU Foundation; Mermaid I project; Rudolf-Bartling Foundation; U.K. 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; WorkSafeBC; European Community [223175, HEALTH-F2-2009-223175]; NIH - Post-Cancer GWAS initiative (GAME-ON initiative) [R01-CA128978, 1 U19-CA148537]; Department of Defense [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) [MOP-86727]; Komen Foundation for the Cure; Breast Cancer Research Foundation; [R25 CA92049] FX The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative (U19-CA148112). G. Chenevix-Trench and P.M. Webb are supported by the National Health and Medical Research Council. B.Y. Karlan holds an American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). B. Charbonneau was supported by R25 CA92049. Andrew Berchuck holds the Barbara Thomason Ovarian Cancer Research Professorship from the American Cancer Society (SIOP-06-090-06).; Funding of the constituent OCAC studies was provided by the American Cancer Society (CRTG-00-196-01-CCE); the California Cancer Research Program (00-01389V-20170, N01-CN25403, and 2II0200); the Canadian Institutes for Health Research; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124, C536/A13086, and C536/A6689); the Celma Mastry Ovarian Cancer Foundation; the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; The Eve Appeal (Oak Foundation); the Helsinki University Central Hospital Research Fund; Helse Vest; Imperial Experimental Cancer Research Centre (C1312/A15589); 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; the U.S. National Cancer Institute (K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P20-GM103418, P30-CA072720, P30-CA15083, P30-CA168524, P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA61107, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA136924, R01-CA149429, R03-CA113148, R03-CA115195, R21-GM86689, R37-CA070867, R37-CA70867, U01-CA069417, U01-CA071966, and Intramural research funds); the U.S. Army Medical Research and Material Command (DAMD17-98-1-8659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1- 0669, and W81XWH-10-1-0280); the National Health and Medical Research Council of Australia (199600, 400413, and 400281); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401); the state of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P.685); the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Polish Committee for Scientific Research (4P05C 028 14 and 2P05A 068 27); the Oak Foundation; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the U.K. 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.; Funding for the iCOGS infrastructure came from the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692), the NIH (R01-CA128978) and its Post-Cancer GWAS initiative (No. 1 U19-CA148537 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, and the Breast Cancer Research Foundation, and CIHR MOP-86727. NR 30 TC 9 Z9 9 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD APR PY 2014 VL 2 IS 4 BP 332 EP 340 DI 10.1158/2326-6066.CIR-13-0136 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA AM7GO UT WOS:000340033600008 PM 24764580 ER PT J AU Bedognetti, D Wang, E Marincola, FM AF Bedognetti, Davide Wang, Ena Marincola, Francesco M. TI Meta-analysis and metagenes CXCL-13-driven signature as a robust marker of intratumoral immune response and predictor of breast cancer chemotherapeutic outcome SO ONCOIMMUNOLOGY LA English DT Editorial Material DE immunotherapy; gene-expression; breast cancer; CXCL-13; melanoma; biomarkers; immunotherapy; neoadjuvant chemotherapy; gene signature ID METASTATIC MELANOMA; THERAPY; IMMUNOTHERAPY; IMMUNOSURVEILLANCE; REJECTION; PATHWAYS C1 [Bedognetti, Davide; Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Bedognetti, Davide; Wang, Ena; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol, Bethesda, MD USA. [Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar. RP Bedognetti, D (reprint author), NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM davide.bedognetti@nih.gov OI Bedognetti, Davide/0000-0002-5857-773X NR 22 TC 7 Z9 7 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD APR PY 2014 VL 3 IS 4 AR e28727 DI 10.4161/onci.28727 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA AM6EL UT WOS:000339955700034 ER PT J AU Chen, X Wakefield, LM Oppenheim, JJ AF Chen, Xin Wakefield, Lalage M. Oppenheim, Joost J. TI Synergistic antitumor effects of a TGF beta inhibitor and cyclophosphamide SO ONCOIMMUNOLOGY LA English DT Editorial Material DE anti-TGF beta antibody; chemoimmunotherapy; cyclophosphamide ID REGULATORY T-CELLS; CANCER-IMMUNOTHERAPY; TH17 CELLS AB In a mouse model of breast carcinoma, the combination of cyclophosphamide and transforming growth factor beta 1,2,3 ( TGF beta 1,2,3)-targeting antibody achieved superior antineoplastic effects. This novel paradigm of synergistic chemoimmunotherapy promises to improve the clinical outcome of cancer patients with micrometastases, and thus deserves further investigation. C1 [Chen, Xin] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA. [Chen, Xin; Oppenheim, Joost J.] NCI, Ctr Canc Res, Lab Mol Immunoregulat, Canc Inflammat Program, Frederick, MD 21701 USA. [Wakefield, Lalage M.] NCI, Ctr Canc Res, Lab Canc Biol & Genet, Frederick, MD 21701 USA. RP Chen, X (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA. EM chenxin@mail.nih.gov; oppenhej@mail.nih.gov OI Chen, Xin/0000-0002-2628-4027 NR 10 TC 5 Z9 5 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD APR PY 2014 VL 3 IS 4 AR e28247 DI 10.4161/onci.28247 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA AM6EL UT WOS:000339955700005 ER PT J AU Gameiro, SR Ardiani, A Kwilas, A Hodge, JW AF Gameiro, Sofia R. Ardiani, Andressa Kwilas, Anna Hodge, James W. TI Radiation-induced survival responses promote immunogenic modulation to enhance immunotherapy in combinatorial regimens SO ONCOIMMUNOLOGY LA English DT Editorial Material DE radiation therapy; immunogenic modulation; antigen-processing machinery; calreticulin; ER-stress; CTL-mediated lysis; therapeutic cancer vaccine; immunotherapy ID CELL-DEATH; THERAPY; CANCER; IMMUNITY AB Tumor cells that survive radiation are more sensitive to T-cell-mediated lysis due to a spectrum of biological adaptations to cellular stress (defined as immunogenic modulation), including enhanced antigen processing and cell-surface presence of calreticulin. This mechanism can be exploited to maximize clinical benefit in patients receiving radiotherapy plus immunotherapy. C1 [Gameiro, Sofia R.; Ardiani, Andressa; Kwilas, Anna; Hodge, James W.] NCI, Recombinant Vaccine Grp, Lab Tumor Immunol & Biol, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Hodge, JW (reprint author), NCI, Recombinant Vaccine Grp, Lab Tumor Immunol & Biol, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM jh241d@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 10 TC 13 Z9 14 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD APR PY 2014 VL 3 IS 4 AR e28643 DI 10.4161/onci.28643 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA AM6EL UT WOS:000339955700031 ER PT J AU Madan, RA Heery, CR Gulley, JL AF Madan, Ravi A. Heery, Christopher R. Gulley, James L. TI Poxviral-based vaccine elicits immunologic responses in prostate cancer patients SO ONCOIMMUNOLOGY LA English DT Editorial Material DE prostate cancer; cancer vaccine; immune response; T-cell responses; antigen spreading ID SURVIVAL; PSA AB Prostvac is a poxviral-based vaccine designed to target prostate-specific antigen (PSA) in prostate cancer patients. Recently, the potential toxicity and immunological impact of this immunotherapy were reviewed in the context of new clinical data. Our findings suggest that Prostvac is safe and elicits anticancer immune responses, both alone and in combinatorial approaches. C1 [Madan, Ravi A.; Heery, Christopher R.; Gulley, James L.] NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. [Madan, Ravi A.; Gulley, James L.] NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 10 TC 5 Z9 5 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD APR PY 2014 VL 3 IS 4 AR e28611 DI 10.4161/onci.28611 PG 2 WC Oncology; Immunology SC Oncology; Immunology GA AM6EL UT WOS:000339955700030 PM 25097802 ER PT J AU Robb, JA Gulley, ML Fitzgibbons, PL Kennedy, MF Cosentino, LM Washington, K Dash, RC Branton, PA Jewell, SD Lapham, RL AF Robb, James A. Gulley, Margaret L. Fitzgibbons, Patrick L. Kennedy, Mary F. Cosentino, L. Mark Washington, Kay Dash, Rajesh C. Branton, Philip A. Jewell, Scott D. Lapham, Rosanna L. TI A Call to Standardize Preanalytic Data Elements for Biospecimens SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PATHOLOGISTS GUIDELINE RECOMMENDATIONS; CLINICAL-ONCOLOGY-COLLEGE; AMERICAN-SOCIETY; BREAST-CANCER AB Context.-Biospecimens must have appropriate clinical annotation (data) to ensure optimal quality for both patient care and research. Clinical preanalytic variables are the focus of this study. Objectives.-To define the essential preanalytic variables (data fields) that should be attached to every collected biospecimen and to provide a complete list of such variables, along with their relative importance, which can vary, depending on downstream use, institutional needs, and information technology capabilities. Design.-The College of American Pathologists Diagnostic Intelligence and Health Information Technology Committee sponsored a Biorepository Working Group to develop a ranked list of the preanalytic variables for annotating biospecimens. Members of the working group were experts in anatomic, clinical, and molecular pathology; biobanking; medical informatics; and accreditation. Several members had experience with federal government programs, such as the National Cancer Institute's Biospecimens and Biorepository Branch and the National Cancer Institute's Community Cancer Center Program. Potential preanalytic variables were identified and ranked along with available supporting evidence, definitions, and potential negative effects if the variable was not attached to the biospecimen. Additional national and international stakeholders reviewed the draft manuscript. Results.-The ranked listing of 170 preanalytic variables produced can be used as a guide for site-specific implementation into patient care and/or research biorepository processes. Conclusions.-In our collective experience, it is often difficult to choose which of the many preanalytic variables to attach to any specific set of biospecimens used for patient care and/or research. The provided ranked list should aid in the selection of preanalytic variables for a given biospecimen collection. C1 [Gulley, Margaret L.] Univ N Carolina, Dept Pathol, Chapel Hill, NC USA. [Fitzgibbons, Patrick L.] St Jude Med Ctr, Dept Pathol, Fullerton, CA USA. [Kennedy, Mary F.] Coll Amer Pathologists, Northfield, MN USA. [Cosentino, L. Mark] Biogen Idec Inc, Dept Translat Med, Cambridge, MA USA. [Washington, Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Dash, Rajesh C.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC USA. [Branton, Philip A.] NCI, Biorepositories & Biospecimens Res Branch, NIH, Rockville, MD USA. [Jewell, Scott D.] Van Andel Inst, Dept Biospecimen Sci, Grand Rapids, MI USA. [Lapham, Rosanna L.] Spartanburg Reg Med Ctr, Dept Pathol, Spartanburg, SC USA. RP Robb, JA (reprint author), 11613 Kensington Court, Boca Raton, FL 33428 USA. EM jarobb33@yahoo.com OI Fitzgibbons, Patrick/0000-0002-2998-6913 NR 19 TC 17 Z9 17 U1 0 U2 3 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2014 VL 138 IS 4 BP 526 EP 537 DI 10.5858/arpa.2013-0250-CP PG 12 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA AM0QY UT WOS:000339552200009 PM 23937609 ER PT J AU Guzman-Hernandez, ML Potter, G Egervari, K Kiss, JZ Balla, T AF Guzman-Hernandez, Maria Luisa Potter, Gael Egervari, Kristof Kiss, Jozsef Z. Balla, Tamas TI Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; MESSENGER-RNA STABILITY; HEPARIN-BINDING DOMAIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; EXTRACELLULAR-MATRIX; BIOLOGICAL-ACTIVITY; FACTOR RECEPTORS; CYCLOPHILIN-B; LIVING CELLS AB Vascular endothelial growth factor (VEGF) is a critical regulator of endothelial cell differentiation and vasculogenesis during both development and tumor vascularization. VEGF-165 is a major form that is secreted from the cells via a poorly characterized pathway. Here we use green fluorescent protein- and epitope-tagged VEGF-165 and find that its early trafficking between the endoplasmic reticulum and the Golgi requires the small GTP-binding proteins Sar1 and Arf1 and that its glycosylation in the Golgi compartment is necessary for efficient post-Golgi transport and secretion from the cells. The relative temperature insensitivity of VEGF secretion and its Sar1 and Arf1 inhibitory profiles distinguish it from other cargoes using the "constitutive" secretory pathway. Prominent features of VEGF secretion are the retention of the protein on the outer surface of the plasma membrane and the stimulation of its secretion by Ca2+ and protein kinase C. Of importance, shedding of VEGF-165 from the cell surface together with other membrane components appears to be a unique feature by which some VEGF is delivered to the surroundings to exert its known biological actions. Understanding VEGF trafficking can reveal additional means by which tumor vascularization can be inhibited by pharmacological interventions. C1 [Guzman-Hernandez, Maria Luisa; Balla, Tamas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Potter, Gael; Egervari, Kristof; Kiss, Jozsef Z.] Univ Geneva, Dept Neurosci, CH-1211 Geneva 4, Switzerland. RP Balla, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. EM ballat@mail.nih.gov OI Balla, Tamas/0000-0002-9077-3335 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health; Swiss National Foundation [31003A_140940/1] FX We are grateful to Ben Zion Levi, Julie Donaldson, and Paul Randazzo for DNA constructs. Confocal imaging was performed at the Microscopy and Imaging Core of the National Institute of Child Health and Human Development, National Institutes of Health, with the kind assistance of Vincent Schram and James T. Russell. Part of this research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. This work was also supported by the Swiss National Foundation (grant number 31003A_140940/1) to J.Z.K. NR 57 TC 9 Z9 9 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR 1 PY 2014 VL 25 IS 7 BP 1061 EP 1072 DI 10.1091/mbc.E13-07-0418 PG 12 WC Cell Biology SC Cell Biology GA AM1SZ UT WOS:000339629900008 PM 24501421 ER PT J AU Phillips, SJ Arnesen, SJ Love, CB AF Phillips, Steven J. Arnesen, Stacey J. Love, Cynthia B. TI The Language of Disease Outbreaks, Disasters, and Public Health Emergencies: The Role of the US National Library of Medicine SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Editorial Material C1 [Phillips, Steven J.; Arnesen, Stacey J.; Love, Cynthia B.] NIH, Disaster Informat Management Res Ctr, Specialized Informat Serv Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Phillips, SJ (reprint author), Natl Lib Med, Specialized Informat Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM steven_phillips@nlm.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1935-7893 EI 1938-744X J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD APR PY 2014 VL 8 IS 2 BP 112 EP 113 DI 10.1017/dmp.2014.32 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AL3XL UT WOS:000339064900001 ER PT J AU Terrault, NA Stravitz, RT Lok, ASF Everson, GT Brown, RS Kulik, LM Olthoff, KM Saab, S Adeyi, O Argo, CK Everhart, JE Rodrigo, DR AF Terrault, Norah A. Stravitz, R. Todd Lok, Anna S. F. Everson, Greg T. Brown, Robert S., Jr. Kulik, Laura M. Olthoff, Kim M. Saab, Sammy Adeyi, Ovedele Argo, Curtis K. Everhart, Jay E. Rodrigo, Del R. CA A2ALL Study Grp TI Hepatitis C Disease Severity in Living Versus Deceased Donor Liver Transplant Recipients: An Extended Observation Study SO HEPATOLOGY LA English DT Article ID FIBROSIS PROGRESSION; GRAFT-SURVIVAL; UNITED-STATES; RECURRENCE; VIRUS; DIFFERENCE; INFECTION; CIRRHOSIS; OUTCOMES; PATIENT AB Donor factors influence hepatitis C virus (HCV) disease severity in liver transplant (LT) recipients. Living donors, because they are typically young and have short cold ischemic times, may be advantageous for HCV-infected patients. Among HCV-infected patients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) surviving >90 days and followed for a median 4.7 years, advanced fibrosis (Ishak stage >= 3) and graft loss were determined. The 5-year cumulative risk of advanced fibrosis was 44% and 37% in living donor LT (LDLT) and deceased donor LT (DDLT) patients (P = 0.16), respectively. Aspartate aminotransferase (AST) activity at LT (hazard ratio [HR] = 1.38 for doubling of AST, P = 0.005) and biliary strictures (HR = 2.68, P = 0.0001) were associated with advanced fibrosis, but LDLT was not (HR = 1.11, 95% confidence interval [CI] 0.73-1.69, P = 0.63). The 5-year unadjusted patient and graft survival probabilities were 79% and 78% in LDLT, and 77% and 75% in DDLT (P = 0.43 and 0.32), with 27% and 20% of LDLT and DDLT graft losses due to HCV (P = 0.45). Biliary strictures (HR = 2.25, P = 0.0006), creatinine at LT (HR = 1.74 for doubling of creatinine, P = 0.0004), and AST at LT (HR = 1.36 for doubling of AST, P = 0.004) were associated with graft loss, but LDLT was not (HR = 0.76, 95% CI: 0.49-1.18, P = 0.23). Conclusion: Donor type does not affect the probability of advanced fibrosis or patient and graft survival in HCV-infected recipients. Thus, while LDLT offers the advantage of shorter wait times, there is no apparent benefit for HCV disease progression. Biliary strictures have a negative effect on HCV fibrosis severity and graft survival, and a high AST at LT may be an important predictor of fibrosis risk post-LT. (Hepatology 2014;59:1311-1319) C1 [Terrault, Norah A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Stravitz, R. Todd] Virginia Commonwealth Univ, Richmond, VA USA. [Lok, Anna S. F.; Rodrigo, Del R.] Univ Michigan, Ann Arbor, MI 48109 USA. [Everson, Greg T.] Univ Colorado, Boulder, CO 80309 USA. [Brown, Robert S., Jr.] Columbia Univ, New York, NY USA. [Kulik, Laura M.] Northwestern Univ, Evanston, IL USA. [Olthoff, Kim M.] Univ Penn, Philadelphia, PA 19104 USA. [Saab, Sammy] Univ Calif Los Angeles, Los Angeles, CA USA. [Adeyi, Ovedele] Univ Toronto, Toronto, ON, Canada. [Argo, Curtis K.] Univ Virginia, Charlottesville, VA USA. [Everhart, Jay E.] NIH, Bethesda, MD 20892 USA. RP Terrault, NA (reprint author), Univ Calif San Francisco, Div Gastroenterol & Hepatol, 513 Parnassus Ave,Room S357, San Francisco, CA 94143 USA. EM norah.terrault@ucsf.edu FU National Institute of Diabetes & Digestive & Kidney Diseases [U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531, U01-DK62536]; Health Resources and Services Administration (HRSA); American Society of Transplant Surgeons (ASTS) FX Supported by the National Institute of Diabetes & Digestive & Kidney Diseases through cooperative agreements (grants U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531, and U01-DK62536). Additional support was provided by the Health Resources and Services Administration (HRSA) and the American Society of Transplant Surgeons (ASTS). NR 25 TC 6 Z9 6 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 APR PY 2014 VL 59 IS 4 BP 1311 EP 1319 DI 10.1002/hep.26920 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD4VQ UT WOS:000333249800016 PM 24677192 ER PT J AU Berzofsky, JA AF Berzofsky, Jay A. TI Strategies and mechanisms for vaccine induction of mucosal T cell immunity SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract CT 15th Annual International Meeting of the Institute-of-Human-Virology CY SEP 08-12, 2013 CL Moscow, RUSSIA SP Inst Human Virol, Univ Maryland Sch Med, Inst Human Virol C1 [Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR PY 2014 VL 65 SU 2 MA 116 BP 46 EP 46 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3LD UT WOS:000339028300016 ER PT J AU Margolis, L AF Margolis, Leonid TI Male-to-Female HIV-1 Transmission: Lessons from Ex Vivo SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract CT 15th Annual International Meeting of the Institute-of-Human-Virology CY SEP 08-12, 2013 CL Moscow, RUSSIA SP Inst Human Virol, Univ Maryland Sch Med, Inst Human Virol C1 [Margolis, Leonid] NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR PY 2014 VL 65 SU 2 MA 124 BP 51 EP 51 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3LD UT WOS:000339028300022 ER PT J AU Kottilil, S AF Kottilil, Shyam TI Hepatitis C Treatment Update: Current Status and Future Direcctions SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract CT 15th Annual International Meeting of the Institute-of-Human-Virology CY SEP 08-12, 2013 CL Moscow, RUSSIA SP Inst Human Virol, Univ Maryland Sch Med, Inst Human Virol C1 [Kottilil, Shyam] NIAID, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR PY 2014 VL 65 SU 2 MA 158 BP 68 EP 68 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3LD UT WOS:000339028300053 ER PT J AU Iantorno, M Campia, U Di Daniele, N Nistico, S Forleo, GB Cardillo, C Tesauro, M AF Iantorno, M. Campia, U. Di Daniele, N. Nistico, S. Forleo, G. B. Cardillo, C. Tesauro, M. TI OBESITY, INFLAMMATION AND ENDOTHELIAL DYSFUNCTION SO JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS LA English DT Editorial Material DE obesity; inflammation; atherosclerosis; endothelial dysfunction ID NECROSIS-FACTOR-ALPHA; ANGIOTENSIN-ALDOSTERONE SYSTEM; BODY-FAT DISTRIBUTION; METABOLIC SYNDROME; NITRIC-OXIDE; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; ADIPOSE-TISSUE; MYOCARDIAL-INFARCTION; ENOS ACTIVITY AB Cardiovascular disease is the leading cause of morbidity and mortality in obese individuals. Obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to originate from disruption in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, impair vascular homeostasis and lead to endothelial dysfunction. An altered endothelial cell phenotype and endothelial dysfunction are common among all obesity-related complications. A crucial aspect of endothelial dysfunction is reduced nitric oxide (NO) bioavailability. A systemic pro-inflammatory state in combination with hyperglycemia, insulin resistance, oxidative stress and activation of the renin angiotensin system are systemic disturbances in obese individuals that contribute independently and synergistically to decreasing NO bioavailability. On the other hand, pro-inflammatory cytokines are locally produced by perivascular fat and act through a paracrine mechanism to independently contribute to endothelial dysfunction and smooth muscle cell dysfunction and to the pathogenesis of vascular disease in obese individuals. The promising discovery that obesity-induced vascular dysfunction is, at least in part, reversible, with weight loss strategies and drugs that promote vascular health, has not been sufficiently proved to prevent the cardiovascular complication of obesity on a large scale. In this review we discuss the pathophysiological mechanisms underlying inflammation and vascular damage in obese patients. C1 [Iantorno, M.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Campia, U.] MedStar Cardiovasc Res Network Washington, Washington, DC USA. [Di Daniele, N.; Forleo, G. B.; Tesauro, M.] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy. [Nistico, S.] UniV Catanzaro, Dept Hlth Sci, I-88100 Catanzaro, Italy. [Cardillo, C.] Catholic Univ, Rome, Italy. RP Nistico, S (reprint author), UniV Catanzaro, Dept Hlth Sci, Viale Europa, I-88100 Catanzaro, Italy. EM steven.nistico@gmail.com NR 57 TC 29 Z9 33 U1 2 U2 6 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0393-974X EI 1724-6083 J9 J BIOL REG HOMEOS AG JI J. Biol. Regul. Homeost. Agents PD APR-JUN PY 2014 VL 28 IS 2 BP 169 EP 176 PG 8 WC Endocrinology & Metabolism; Immunology; Medicine, Research & Experimental; Physiology SC Endocrinology & Metabolism; Immunology; Research & Experimental Medicine; Physiology GA AL7JE UT WOS:000339309300001 PM 25001649 ER PT J AU Vandenberg, LN Gerona, RR Kannan, K Taylor, JA van Breemen, RB Dickenson, CA Liao, CY Yuan, Y Newbold, RR Padmanabhan, V vom Saal, FS Woodruff, TJ AF Vandenberg, Laura N. Gerona, Roy R. Kannan, Kurunthachalam Taylor, Julia A. van Breemen, Richard B. Dickenson, Carrie A. Liao, Chunyang Yuan, Yang Newbold, Retha R. Padmanabhan, Vasantha vom Saal, Frederick S. Woodruff, Tracey J. TI A round robin approach to the analysis of bisphenol a (BPA) in human blood samples SO ENVIRONMENTAL HEALTH LA English DT Article DE Biomonitoring; Contamination; Endocrine disruptor; Linearity; Metabolite; Toxicokinetics ID ESTROGEN-RECEPTOR-ALPHA; TANDEM MASS-SPECTROMETRY; IN-VITRO FERTILIZATION; HUMAN EXPOSURE; ENVIRONMENTAL CHEMICALS; LIQUID-CHROMATOGRAPHY; ENDOCRINE DISRUPTORS; WIDESPREAD EXPOSURE; BIOLOGICAL SAMPLES; CIRCULATING LEVELS AB Background: Human exposure to bisphenol A (BPA) is ubiquitous, yet there are concerns about whether BPA can be measured in human blood. This Round Robin was designed to address this concern through three goals: 1) to identify collection materials, reagents and detection apparatuses that do not contribute BPA to serum; 2) to identify sensitive and precise methods to accurately measure unconjugated BPA (uBPA) and BPA-glucuronide (BPA-G), a metabolite, in serum; and 3) to evaluate whether inadvertent hydrolysis of BPA-G occurs during sample handling and processing. Methods: Four laboratories participated in this Round Robin. Laboratories screened materials to identify BPA contamination in collection and analysis materials. Serum was spiked with concentrations of uBPA and/or BPA-G ranging from 0.09-19.5 (uBPA) and 0.5-32 (BPA-G) ng/mL. Additional samples were preserved unspiked as 'environmental' samples. Blinded samples were provided to laboratories that used LC/MSMS to simultaneously quantify uBPA and BPA-G. To determine whether inadvertent hydrolysis of BPA metabolites occurred, samples spiked with only BPA-G were analyzed for the presence of uBPA. Finally, three laboratories compared direct and indirect methods of quantifying BPA-G. Results: We identified collection materials and reagents that did not introduce BPA contamination. In the blinded spiked sample analysis, all laboratories were able to distinguish low from high values of uBPA and BPA-G, for the whole spiked sample range and for those samples spiked with the three lowest concentrations (0.5-3.1 ng/ml). By completion of the Round Robin, three laboratories had verified methods for the analysis of uBPA and two verified for the analysis of BPA-G (verification determined by: 4 of 5 samples within 20% of spiked concentrations). In the analysis of BPA-G only spiked samples, all laboratories reported BPA-G was the majority of BPA detected (92.2 - 100%). Finally, laboratories were more likely to be verified using direct methods than indirect ones using enzymatic hydrolysis. Conclusions: Sensitive and accurate methods for the direct quantification of uBPA and BPA-G were developed in multiple laboratories and can be used for the analysis of human serum samples. BPA contamination can be controlled during sample collection and inadvertent hydrolysis of BPA conjugates can be avoided during sample handling. C1 [Vandenberg, Laura N.] Univ Massachusetts, Sch Publ Hlth, Div Environm Hlth Sci, Amherst, MA 01003 USA. [Gerona, Roy R.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Kannan, Kurunthachalam] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Kannan, Kurunthachalam] SUNY Albany, Albany, NY USA. [Taylor, Julia A.; vom Saal, Frederick S.] Univ Missouri, Div Biol Sci, Columbia, MO USA. [van Breemen, Richard B.; Yuan, Yang] Univ Illinois, Coll Pharm, Chicago, IL USA. [Dickenson, Carrie A.; Woodruff, Tracey J.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Program Reprod Hlth & Environm, San Francisco, CA 94117 USA. [Liao, Chunyang] NY State Dept Publ Hlth, Wadsworth Ctr, Albany, NY USA. [Newbold, Retha R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Padmanabhan, Vasantha] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Padmanabhan, Vasantha] Univ Michigan, Reprod Sci Program, Ann Arbor, MI 48109 USA. RP Woodruff, TJ (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Program Reprod Hlth & Environm, San Francisco, CA 94117 USA. EM woodrufft@obgyn.ucsf.edu RI Padmanabhan, Vasantha/C-8558-2017 OI Padmanabhan, Vasantha/0000-0002-8443-7212 FU NIEHS [R21ES017763, R01 HD31544, 1P01 ES02284401, P20 ES018135, R01 ES017005]; NON ARRA SUPP [A112807]; NICHD [R01 HD021341]; USEPA [P20 STAR RD83467801, RD 83543601] FX The authors gratefully acknowledge helpful discussions and contributions from Dr. Jerrold Heindel and Dr. John Bucher throughout the process and conduct of the round robin and for the support they offered from NIEHS and NTP. We also thank Mr. Matthew Friesen, Mr. Ke Huang and Ms. Guannan Li for technical assistance. We acknowledge contributions from numerous scientists that participated in the earliest discussions of how to design a round robin analysis including Drs. Shanna Swan, Richard Stahlhut, Wade Welshons, Antonia Calafat, and Daniel Doerge. Finally, we acknowledge grant funding: NIEHS R21ES017763, R21ES017763 NON ARRA SUPP A112807, NIEHS R01 HD31544, NIEHS 1P01 ES02284401, NIEHS P20 ES018135, NIEHS R01 ES017005, NICHD R01 HD021341 and USEPA P20 STAR RD83467801 and RD 83543601. NR 93 TC 37 Z9 37 U1 2 U2 28 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 APR 1 PY 2014 VL 13 AR 25 DI 10.1186/1476-069X-13-25 PG 20 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA AL1OE UT WOS:000338894000001 PM 24690217 ER PT J AU Niciu, MJ Mathews, DC Nugent, AC Ionescu, DF Furey, ML Richards, EM Machado-Vieira, R Zarate, CA AF Niciu, Mark J. Mathews, Daniel C. Nugent, Allison C. Ionescu, Dawn F. Furey, Maura L. Richards, Erica M. Machado-Vieira, Rodrigo Zarate, Carlos A., Jr. TI DEVELOPING BIOMARKERS IN MOOD DISORDERS RESEARCH THROUGH THE USE OF RAPID-ACTING ANTIDEPRESSANTS SO DEPRESSION AND ANXIETY LA English DT Article DE biomarker; predictor; mediator; moderator; depression; major depressive disorder; bipolar disorder; bipolar depression; drug development; neuroimaging ID D-ASPARTATE ANTAGONIST; INFLAMMATORY-BOWEL-DISEASE; MAJOR DEPRESSIVE DISORDER; TREATMENT RESPONSE; DRUG DEVELOPMENT; BIPOLAR DEPRESSION; ALCOHOL DEPENDENCE; MAMMALIAN TARGET; MENTAL-DISORDERS; SYSTEMS BIOLOGY AB An impediment to progress in mood disorders research is the lack of analytically valid and qualified diagnostic and treatment biomarkers. Consistent with the National Institute of Mental Health (NIMH)'s Research Domain Criteria (RDoC) initiative, the lack of diagnostic biomarkers has precluded us from moving away from a purely subjective (symptom-based) toward a more objective diagnostic system. In addition, treatment response biomarkers in mood disorders would facilitate drug development and move beyond trial-and-error toward more personalized treatments. As such, biomarkers identified early in the pathophysiological process are proximal biomarkers (target engagement), while those occurring later in the disease process are distal (disease pathway components). One strategy to achieve this goal in biomarker development is to increase efforts at the initial phases of biomarker development (i.e. exploration and validation) at single sites with the capability of integrating multimodal approaches across a biological systems level. Subsequently, resultant putative biomarkers could then undergo characterization and surrogacy as these latter phases require multisite collaborative efforts. We have used multimodal approaches - genetics, proteomics/metabolomics, peripheral measures, multimodal neuroimaging, neuropsychopharmacological challenge paradigms and clinical predictors - to explore potential predictor and mediator/moderator biomarkers of the rapid-acting antidepressants ketamine and scopolamine. These exploratory biomarkers may then be used for a priori stratification in larger multisite controlled studies during the validation and characterization phases with the ultimate goal of surrogacy. In sum, the combination of target engagement and well-qualified disease-related measures are crucial to improve our pathophysiological understanding, personalize treatment selection, and expand our armamentarium of novel therapeutics. C1 [Niciu, Mark J.; Nugent, Allison C.; Ionescu, Dawn F.; Furey, Maura L.; Richards, Erica M.; Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Niciu, Mark J.; Nugent, Allison C.; Ionescu, Dawn F.; Furey, Maura L.; Richards, Erica M.; Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Mathews, Daniel C.] Lundbeck LLC, Deerfield, IL USA. RP Zarate, CA (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, 10 Ctr Dr,MSC 1282,Bldg 10CRC,Room 7-5342, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Niciu, Mark/J-1766-2014; Ionescu, Dawn/K-5675-2015; OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Niciu, Mark/0000-0002-5612-3021; Nugent, Allison/0000-0003-2569-2480 FU NARSAD; Brain & Behavior Research Foundation Mood Disorders Research Award FX Employer: IRP-NIMH-NIH-DHHS; Contract grant sponsor: NARSAD Independent Investigator and the Brain & Behavior Research Foundation Mood Disorders Research Award (to C.A.Z.). NR 58 TC 15 Z9 15 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD APR PY 2014 VL 31 IS 4 BP 297 EP 307 DI 10.1002/da.22224 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AE7JW UT WOS:000334174900004 PM 24353110 ER PT J AU Zhao, JJ Zhang, Z Luan, Y Zou, ZS Sun, YL Li, YG Jin, L Zhou, CB Fu, JL Gao, B Fu, YX Wang, FS AF Zhao, Juanjuan Zhang, Zheng Luan, Yan Zou, Zhengsheng Sun, Yanling Li, Yonggang Jin, Lei Zhou, Chunbao Fu, Junliang Gao, Bin Fu, Yangxin Wang, Fu-Sheng TI Pathological Functions of Interleukin-22 in Chronic Liver Inflammation and Fibrosis With Hepatitis B Virus Infection by Promoting T Helper 17 Cell Recruitment SO HEPATOLOGY LA English DT Article ID STELLATE CELLS; CARBON-TETRACHLORIDE; PEDIATRIC-PATIENTS; VIRAL-HEPATITIS; TH17 CELLS; INJURY; IL-22; DISEASE; ACTIVATION; CIRRHOSIS AB It is well established that interleukin (IL)-22 has hepatoprotective and antifibrotic functions in acute liver injury models; however, its function in patients with liver fibrosis and liver cirrhosis (LC) remains obscure. In the current study, we demonstrated that expression of numerous IL-22 pathway-associated genes was significantly up-regulated in hepatitis B virus (HBV)-infected liver tissues, compared to normal controls, through microarray analysis. In agreement with these findings, liver-infiltrating IL-22(+) cells were largely increased in HBV-infected patients with LC, compared to those without LC or healthy subjects, and were positively associated with liver fibrosis staging scores. Immunohistochemistry and flow cytometric analyses revealed that IL-22 was produced by multiple intrahepatic immune cells and, preferentially, by T-helper (Th) 17 cells in LC patients. In an HBV transgenic (Tg) mouse model of T-cell-mediated chronic liver inflammation and fibrosis, blockade of IL-22 attenuated hepatic expression of chemokine (C-X-C motif) ligand 10 and chemokine (C-C motif) ligand 20 (CCL20) and subsequently reduced Th17 recruitment and liver inflammation and fibrosis progression. In vitro treatment with IL-22 stimulated hepatic stellate cells (HSCs) to secrete several chemokines and subsequently promoted Th17 cell chemotaxis. Blocking C-X-C chemokine receptor type 3 or CCL20 reduced Th17 cell chemotaxis by IL-22-treated HSCs. Conclusions: IL-22 plays a pathological role in exacerbating chronic liver inflammation and fibrosis by recruiting hepatic Th17 cells in HBV-infected patients and HBV Tg mice. (Hepatology 2014;59:1331-1342) C1 [Zhao, Juanjuan; Zhang, Zheng; Jin, Lei; Zhou, Chunbao; Fu, Junliang; Wang, Fu-Sheng] Beijing 302 Hosp, Res Ctr Biol Therapy, Beijing 100039, Peoples R China. [Luan, Yan; Fu, Yangxin] Chinese Acad Sci, Inst Biophys, Key Lab Infect & Immun, Beijing 100080, Peoples R China. [Zou, Zhengsheng] Beijing 302 Hosp, Ctr Noninfect Liver Dis, Beijing 100039, Peoples R China. [Sun, Yanling] Beijing 302 Hosp, Res Ctr Liver Transplantat, Beijing 100039, Peoples R China. [Li, Yonggang] Beijing 302 Hosp, Integrat Med Ctr, Beijing 100039, Peoples R China. [Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. RP Wang, FS (reprint author), Beijing 302 Hosp, Res Ctr Biol Therapy, 100 Western 4th Ring Middle Rd, Beijing 100039, Peoples R China. EM fswang302@163.com OI fu, yang-xin/0000-0001-8441-6617 FU National Natural Science Foundation of China [31170865]; National Key Basic Research Program of China [2012CB519005, 2009CB522507]; National Grand Program on Key Infectious Disease [2013ZX10002001-001-003, 2012ZX10002-007-002]; National Science Fund for Outstanding Young Scholars [81222024] FX This work was supported by the The National Natural Science Foundation of China (31170865), the National Key Basic Research Program of China (2012CB519005 and 2009CB522507), the National Grand Program on Key Infectious Disease (2013ZX10002001-001-003 and 2012ZX10002-007-002), and the National Science Fund for Outstanding Young Scholars (81222024). NR 46 TC 46 Z9 55 U1 3 U2 16 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 APR PY 2014 VL 59 IS 4 BP 1331 EP 1342 DI 10.1002/hep.26916 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD4VQ UT WOS:000333249800018 PM 24677193 ER PT J AU Li, QZ Hu, JY Ding, J Zheng, G AF Li, Qizhai Hu, Jiyuan Ding, Juan Zheng, Gang TI Fisher's method of combining dependent statistics using generalizations of the gamma distribution with applications to genetic pleiotropic associations SO BIOSTATISTICS LA English DT Article DE Dependent tests; Fisher's combination; Gamma distributions; Genetic pleiotropic associations; Genome-wide association studies; Type I error ID SAMPLE-SIZE; TESTS; TRAITS; POWER AB A classical approach to combine independent test statistics is Fisher's combination of p-values, which follows the chi(2) distribution. When the test statistics are dependent, the gamma distribution (GD) is commonly used for the Fisher's combination test (FCT). We propose to use two generalizations of the GD: the generalized and the exponentiated GDs. We study some properties of mis-using the GD for the FCT to combine dependent statistics when one of the two proposed distributions are true. Our results show that both generalizations have better control of type I error rates than the GD, which tends to have inflated type I error rates at more extreme tails. In practice, common model selection criteria (e. g. Akaike information criterion/Bayesian information criterion) can be used to help select a better distribution to use for the FCT. A simple strategy of the two generalizations of the GD in genome-wide association studies is discussed. Applications of the results to genetic pleiotrophic associations are described, where multiple traits are tested for association with a single marker. C1 [Li, Qizhai; Ding, Juan] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China. [Hu, Jiyuan] Fudan Univ, Inst Biostat, Sch Life Sci, Shanghai 200433, Peoples R China. [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Li, QZ (reprint author), Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China. EM liqz@amss.ac.cn FU National Institutes of Health [NO1-AR-2-2263, RO1-AR-44422]; National Arthritis Foundation; National Nature Science Foundation of China [61134013, 11371353] FX The GAW16 data were gathered with the support of grants from the National Institutes of Health (NO1-AR-2-2263 and RO1-AR-44422, Peter K. Gregersen, PI), and the National Arthritis Foundation. The use of the data was approved by GAW16. Research of Qizhai Li is partially supported by National Nature Science Foundation of China, Nos 61134013, 11371353. NR 23 TC 5 Z9 5 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 EI 1468-4357 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2014 VL 15 IS 2 BP 284 EP 295 DI 10.1093/biostatistics/kxt045 PG 12 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA AK0NM UT WOS:000338110100006 PM 24174580 ER PT J AU Cooper, IDG AF Cooper, Ina Diane G. TI Renal Medicine. SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Book Review C1 [Cooper, Ina Diane G.] NIH, NIH Lib, Bethesda, MD 20892 USA. RP Cooper, IDG (reprint author), NIH, NIH Lib, Bldg 10, Bethesda, MD 20892 USA. EM diane.cooper@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 3 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 APR PY 2014 VL 102 IS 2 BP 135 EP 135 DI 10.3163/1536-5050.102.2.021 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA AK4WB UT WOS:000338423800021 ER PT J AU Volle, C Dalal, Y AF Volle, Catherine Dalal, Yamini TI Histone variants: the tricksters of the chromatin world SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID IN-VIVO; PEDIATRIC GLIOBLASTOMA; CRYSTAL-STRUCTURE; NUCLEOSOME; GENOME; ORGANIZATION; MECHANISM; YEAST; IDENTIFICATION; CHROMOSOMES AB The eukaryotic genome exists in vivo at an equimolar ratio with histones, thus forming a polymer composed of DNA and histone proteins. Each nucleosomal unit in this polymer provides versatile capabilities and dynamic range. Substitutions of the individual components of the histone core with structurally distinct histone variants and covalent modifications alter the local fabric of the chromatin fiber, resulting in epigenetic changes that can be regulated by the cell. In this review, we highlight recent advances in the study of histone variant structure, assembly, and inheritance, their influence on nucleosome positioning, and their cumulative effect upon gene expression, DNA repair and the progression of disease. We also highlight fundamental questions that remain unanswered regarding the behavior of histone variants and their influence on cellular function in the normal and diseased states. C1 [Volle, Catherine; Dalal, Yamini] NCI, Chromatin Struct & Epigenet Mech Team, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Dalal, Y (reprint author), NCI, Chromatin Struct & Epigenet Mech Team, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. EM dalaly@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999, ZIA BC011206-06, ZIA BC011209-06] NR 45 TC 14 Z9 15 U1 1 U2 17 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X EI 1879-0380 J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2014 VL 25 BP 8 EP 14 DI 10.1016/j.gde.2013.11.006 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA AJ8ZX UT WOS:000337997700003 PM 24463272 ER PT J AU Nazer, E Lei, EP AF Nazer, Ezequiel Lei, Elissa P. TI Modulation of chromatin modifying complexes by noncoding RNAs in trans SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID INSULATOR; BINDING; CTCF; MECHANISMS; TARGETS; SITES; CELLS; JPX AB Increasing evidence supports a central role for ncRNA in numerous aspects of chromatin function. For instance, ncRNAs can act as a scaffold for the recruitment of certain chromatin modifying complexes to specific sites within the genome. It is easily imaginable how this can occur in cis, but examples also exist whereby targeting of complexes by ncRNA occurs in trans to the site of transcription. Moreover, association of an ncRNA with a particular locus can trigger localization of the gene to a subnuclear structure harboring a specialized transcriptional environment. In this review, we discuss new insights into the mechanisms by which ncRNAs function in trans with respect to Polycomb Group, chromatin insulator, and dosage compensation complexes in mammals and/or Drosophila. C1 [Nazer, Ezequiel; Lei, Elissa P.] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Lei, EP (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. EM leielissa@niddk.nih.gov FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases FX We would like to thank R. Dale, V. Sartorelli, and members of the Lei laboratory for comments on the manuscript. This work was funded by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 30 TC 5 Z9 5 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X EI 1879-0380 J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2014 VL 25 BP 68 EP 73 DI 10.1016/j.gde.2013.11.019 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA AJ8ZX UT WOS:000337997700011 PM 24534715 ER PT J AU Konc, J Janezic, D AF Konc, Janez Janezic, Dusanka TI Binding site comparison for function prediction and pharmaceutical discovery SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID LOCAL-STRUCTURE ALIGNMENT; PROTEIN DATA-BANK; WEB SERVER; IDENTIFICATION; ALGORITHM; SIMILARITY; MOTIFS; DRUG; PDB; CLASSIFICATION AB While structural genomics resulted in thousands of new protein crystal structures, we still do not know the functions of most of these proteins. One reason for this shortcoming is their unique sequences or folds, which leaves them assigned as proteins of 'unknown function'. Recent advances in and applications of cutting edge binding site comparison algorithms for binding site detection and function prediction have begun to shed light on this problem. Here, we review these algorithms and their use in function prediction and pharmaceutical discovery. Finding common binding sites in weakly related proteins may lead to the discovery of new protein functions and to novel ways of drug discovery. C1 [Konc, Janez] Natl Inst Chem, Ljubljana, Slovenia. [Janezic, Dusanka] Univ Primorska, Fac Math Nat Sci & Informat Technol, Koper, Slovenia. [Konc, Janez] NIH, Bethesda, MD 20892 USA. RP Janezic, D (reprint author), Univ Primorska, Fac Math Nat Sci & Informat Technol, Koper, Slovenia. EM dusanka.janezic@upr.si FU Slovenian Research Agency [P1-0002]; Fulbright Grant FX The authors acknowledge financial support through Grant P1-0002 of the Slovenian Research Agency. JK also acknowledges financial support through Fulbright Grant. NR 52 TC 12 Z9 12 U1 4 U2 13 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X EI 1879-033X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD APR PY 2014 VL 25 BP 34 EP 39 DI 10.1016/j.sbi.2013.11.012 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AJ7LD UT WOS:000337877300007 PM 24878342 ER PT J AU Semba, RD Cotch, MF Gudnason, V Eiriksdottir, G Harris, TB Sun, K Klein, R Jonasson, F Ferrucci, L Schaumberg, DA AF Semba, Richard D. Cotch, Mary Frances Gudnason, Vilmundur Eiriksdottir, Gudny Harris, Tamara B. Sun, Kai Klein, Ronald Jonasson, Fridbert Ferrucci, Luigi Schaumberg, Debra A. TI Serum Carboxymethyllysine, an Advanced Glycation End Product, and Age-Related Macular Degeneration The Age, Gene/Environment Susceptibility-Reykjavik Study SO JAMA OPHTHALMOLOGY LA English DT Article ID COMPLEMENT FACTOR-H; RISK-FACTORS; POOLED FINDINGS; 3 CONTINENTS; LYSINE; MACULOPATHY; ACCUMULATION; ASSOCIATION; ENDPRODUCTS; PENTOSIDINE AB IMPORTANCE Advanced glycation end products have been implicated in the pathogenesis of age-related macular degeneration (AMD). OBJECTIVE To investigate the relationship between serum carboxymethyllysine (CML), a major circulating advanced glycation end product, and AMD in older adults. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of a population-based sample of 4907 older adults (aged-66 years) in the Age, Gene/Environment Susceptibility-Reykjavik Study in Iceland. EXPOSURES Serum CML and risk factors for AMD. MAIN OUTCOMES AND MEASURES Early or late AMD, assessed through fundus images taken through dilated pupils using a 45 digital camera and grading for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. RESULTS Of the 4907 participants, 1025 (20.9%) had early AMD and 276 (5.6%) had late AMD. Mean (SD) serum CML concentrations among adults with no AMD, early AMD, and late AMD (exudative AMD and pure geographic atrophy) were 618.8 (195.5), 634.2 (206.4), and 638.4 (192.0) ng/mL, respectively (to convert to micromoles per liter, multiply by 0.00489; P =.07). Log serum CML (per 1-SD increase) was not associated with any AMD (early and late AMD) (odds ratio = 0.97; 95% CI, 0.90-1.04; P=.44) or with late AMD (odds ratio =0.94; 95% CI, 0.82-1.08; P =.36) in respective multivariable logistic regression models adjusting for age, sex, body mass index, smoking, and renal function. CONCLUSIONS AND RELEVANCE Higher serum CML concentration had no significant cross-sectional association with prevalent AMD in this large population-based cohort of older adults in Iceland. C1 [Semba, Richard D.; Sun, Kai] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. [Gudnason, Vilmundur; Eiriksdottir, Gudny] Iceland Heart Assoc, Reykjavik, Iceland. [Gudnason, Vilmundur; Jonasson, Fridbert] Univ Iceland, Dept Med, Reykjavik, Iceland. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Klein, Ronald] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. [Jonasson, Fridbert] Landspitali Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA. [Schaumberg, Debra A.] Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Moran Ctr Translat Med, Salt Lake City, UT USA. RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 400 N Broadway,Smith Bldg,M015, Baltimore, MD 21287 USA. EM rdsemba@jhmi.edu RI Gudnason, Vilmundur/K-6885-2015; OI Gudnason, Vilmundur/0000-0001-5696-0084; Cotch, Mary Frances/0000-0002-2046-4350 FU National Institutes of Health [R01 AG027012, R01 EY017362]; Intramural Research Program of the National Eye Institute [ZIAEYO0401]; Intramural Research Program of the National Institute on Aging [NO1-AG-1-2100]; Icelandic Heart Association; Icelandic Parliament; University of Iceland Research Fund; Research to Prevent Blindness FX This work was supported by grants R01 AG027012 and R01 EY017362 from the National Institutes of Health, grant ZIAEYO0401 from the Intramural Research Program of the National Eye Institute, grant NO1-AG-1-2100 from the Intramural Research Program of the National Institute on Aging, the Icelandic Heart Association, the Icelandic Parliament, the University of Iceland Research Fund, and a Lew Wasserman Merit Award to Dr Semba from Research to Prevent Blindness. NR 42 TC 4 Z9 4 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD APR PY 2014 VL 132 IS 4 BP 464 EP 470 DI 10.1001/jamaophthalmol.2013.7664 PG 7 WC Ophthalmology SC Ophthalmology GA AJ7QF UT WOS:000337890500013 PM 24481410 ER PT J AU Wong, JR Tucker, MA Kleinerman, RA Devesa, SS AF Wong, Jeannette R. Tucker, Margaret A. Kleinerman, Ruth A. Devesa, Susan S. TI Retinoblastoma Incidence Patterns in the US Surveillance, Epidemiology, and End Results Program SO JAMA OPHTHALMOLOGY LA English DT Article ID UNITED-STATES; CANCER INCIDENCE; CHILDREN; TRENDS; AGE AB IMPORTANCE Several studies have found no temporal or demographic differences in the incidence of retinoblastoma except for age at diagnosis, whereas other studies have reported variations in incidence by sex and race/ethnicity. OBJECTIVE To examine updated US retinoblastoma incidence patterns by sex, age at diagnosis, laterality, race/ethnicity, and year of diagnosis. DESIGN. SETTING, AND PARTICIPANTS The Surveillance, Epidemiology, and End Results (SEER) databases were examined for retinoblastoma incidence patterns by demographic and tumor characteristics. We studied 721 children in SEER 18 registries, 659 in SEER 13 registries, and 675 in SEER 9 registries. MAIN OUTCOMES AND MEASURES Incidence rates, incidence rate ratios (IRRs), and annual percent changes in rates. RESULTS During 2000-2009 in SEER 18, there was a significant excess of total retinoblastoma among boys compared with girls (IRR, 1.18; 95% CI, 1.02 to 1.36), in contrast to earlier reports of a female predominance. Bilateral retinoblastoma among white Hispanic boys was significantly elevated relative to white non-Hispanic boys (IRR, 1.81; 95% CI, 1.22 to 2.79) and white Hispanic girls (IRR, 1.75; 95% CI, 1.11 to 2.91) because of less rapid decreases in bilateral rates since the 1990s among white Hispanic boys than among the other groups. Retinoblastoma rates among white non-Hispanics decreased significantly since 1992 among those younger than 1 year and since 1998 among those with bilateral disease. CONCLUSIONS AND RELEVANCE Although changes in the availability of prenatal screening practices for retinoblastoma may have contributed to these incidence patterns, further research is necessary to determine their actual effect on the changing incidence of retinoblastoma in the US population. In addition, consistent with other cancers, an excess of retinoblastoma diagnosed in boys suggests a potential effect of sex on cancer origin. C1 [Wong, Jeannette R.; Kleinerman, Ruth A.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Rockville, MD 20850 USA. [Tucker, Margaret A.] NCI, Human Genet Program, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Rockville, MD 20850 USA. [Devesa, Susan S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Rockville, MD 20850 USA. RP Wong, JR (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, 9609 Med Ctr Dr,Room 7E514, Rockville, MD 20850 USA. EM jeannette.wong@nih.gov RI Tucker, Margaret/B-4297-2015; OI Kleinerman, Ruth/0000-0001-7415-2478 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute FX The design and conduct of this study was supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. NR 27 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD APR PY 2014 VL 132 IS 4 BP 478 EP 483 DI 10.1001/jamaophthalmol.2013.8001 PG 6 WC Ophthalmology SC Ophthalmology GA AJ7QF UT WOS:000337890500015 PM 24577366 ER PT J AU Kaivorinne, AL Moilanen, V Kervinen, M Renton, AE Traynor, BJ Majamaa, K Remes, AM AF Kaivorinne, Anna-Lotta Moilanen, Virpi Kervinen, Marko Renton, Alan E. Traynor, Bryan J. Majamaa, Kari Remes, Anne M. TI Novel TARDBP Sequence Variant and C9ORF72 Repeat Expansion in a Family With Frontotemporal Dementia SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE frontotemporal lobar degeneration; frontotemporal dementia; mutation; TARDBP; TDP-43; C9ORF72 ID AMYOTROPHIC-LATERAL-SCLEROSIS; LOBAR DEGENERATION; MUTATIONS; DISEASE AB Frontotemporal lobar degeneration (FTLD) is a genetically heterogenous syndrome and has been associated most recently with a hexanucleotide repeat expansion within the C9ORF72 gene. Pathogenic TDP-43 gene (TARDBP) mutations have been identified in amyotrophic lateral sclerosis, but the role of TARDBP mutations in FTLD is more contradictory. To investigate the role of TARDBP mutations in a clinical series of Finnish FTLD patients, we sequenced TARDBP exons 1 to 6 in 77 FTLD patients. No evident pathogenic mutations were found. We identified a novel heterozygous c. 876_878delCAG sequence variant in 2 related patients with behavioral variant frontotemporal dementia without amyotrophic lateral sclerosis. The variant is predicted to cause an amino acid deletion of serine at position 292 (p.Ser292del). However, p.Ser292del was also found in 1 healthy middle-aged control. Interestingly, both patients carried the C9ORF72 expansion. Therefore, the TARDBP variant p.Ser292del might be considered a rare polymorphism and the C9ORF72 repeat expansion the actual disease-causing mutation in the family. Our results suggest that TARDBP mutations are a rare cause of FTLD. However, the interaction of several genetic factors needs to be taken into account when investigating neurodegenerative diseases. C1 [Kaivorinne, Anna-Lotta; Moilanen, Virpi; Majamaa, Kari] Univ Oulu, Inst Clin Med, Dept Neurol, Oulu, Finland. [Kervinen, Marko] Univ Oulu, Dept Ophthalmol, Inst Clin Med, SF-90220 Oulu, Finland. [Kaivorinne, Anna-Lotta; Kervinen, Marko; Majamaa, Kari] Oulu Univ Hosp, Clin Res Ctr, Oulu, Finland. [Renton, Alan E.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Remes, Anne M.] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland. RP Remes, AM (reprint author), Univ Eastern Finland, Dept Neurol, Inst Clin Med, POB 1627, FIN-70211 Kuopio, Finland. EM anne.remes@uef.fi FU Finnish Medical Foundation; Health Care Foundation of Northern Finland; Oulu University Hospital; NIH, National Institute on Aging [Z01-AG000949-02] FX Supported in part by the Finnish Medical Foundation, the Health Care Foundation of Northern Finland, the clinical EVO grants from Oulu University Hospital, and the Intramural Research Programs of the NIH, National Institute on Aging (Z01-AG000949-02). NR 10 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 EI 1546-4156 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD APR-JUN PY 2014 VL 28 IS 2 BP 190 EP 193 PG 4 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA AJ5BF UT WOS:000337694900015 PM 22892647 ER PT J AU Potter, WZ Brady, LS AF Potter, William Z. Brady, Linda S. TI Current drug development for antidepressants and ideas addressing downstream glutamate: the ketamine example SO CNS SPECTRUMS LA English DT Editorial Material ID SCHIZOPHRENIA; DEPRESSION C1 [Potter, William Z.; Brady, Linda S.] NIMH, Bethesda, MD 20892 USA. RP Potter, WZ (reprint author), NIH, 6001 Execut Blvd,Rm 7204, Rockville, MD 20892 USA. EM bill.potter@nih.gov NR 9 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD APR PY 2014 VL 19 IS 2 BP 112 EP 114 DI 10.1017/S1092852914000029 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AJ5SM UT WOS:000337748000003 PM 24565466 ER PT J AU Egan, JM Chia, CW AF Egan, Josephine M. Chia, Chee W. TI Incretin Therapy and Pancreatic Pathologies: Background Pathology Versus Drug-Induced Pathology in Rats SO DIABETES LA English DT Editorial Material ID RECEPTOR ACTIVATION; EXOCRINE PANCREAS; NO EVIDENCE; EXENATIDE; SITAGLIPTIN; ENDOCRINE; RISK; LIRAGLUTIDE; POPULATION; DYSPLASIA C1 [Egan, Josephine M.; Chia, Chee W.] NIA, NIH, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIA, NIH, Baltimore, MD 21224 USA. EM eganj@mail.nih.gov FU Intramural NIH HHS NR 31 TC 3 Z9 3 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD APR PY 2014 VL 63 IS 4 BP 1174 EP 1178 DI 10.2337/db13-1909 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AJ4FO UT WOS:000337628000007 PM 24651798 ER PT J AU Staten, MA Kelley, DE AF Staten, Myrlene A. Kelley, David E. TI Using Oral Challenge Testing to Assess Insulin Action and Secretion With Mathematical Modeling SO DIABETES LA English DT Editorial Material ID GLUCOSE-TOLERANCE TEST; BETA-CELL FUNCTION; SENSITIVITY; MEAL; LIMITATIONS; RESISTANCE; INDEXES C1 [Staten, Myrlene A.] NIDDK, NIH, Bethesda, MD 20892 USA. [Kelley, David E.] Merck Res Labs, Kenilworth, NJ USA. RP Staten, MA (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM statenm@niddk.nih.gov NR 19 TC 3 Z9 3 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD APR PY 2014 VL 63 IS 4 BP 1188 EP 1190 DI 10.2337/db13-1839 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AJ4FO UT WOS:000337628000011 PM 24651802 ER PT J AU Muniyappa, R Sowers, JR AF Muniyappa, Ranganath Sowers, James R. TI Glycogen Synthase Kinase-3 beta and Cathepsin B in Diabetic Endothelial Progenitor Cell Dysfunction: An Old Player Finds a New Partner SO DIABETES LA English DT Editorial Material ID INHIBITION; PROMISE; ANGIOGENESIS; CHALLENGES; THERAPY; DISEASE C1 [Muniyappa, Ranganath] NIDDK, Clin Endocrine Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Sowers, James R.] Univ Missouri, Sch Med, Dept Med Pharmacol & Physiol, Dept Internal Med, Columbia, MO 65211 USA. [Sowers, James R.] Univ Missouri, Sch Med, Diabet & Cardiovasc Ctr, Columbia, MO USA. [Sowers, James R.] Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA. RP Sowers, JR (reprint author), Univ Missouri, Sch Med, Dept Med Pharmacol & Physiol, Dept Internal Med, Columbia, MO 65211 USA. EM sowersj@health.missouri.edu FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL073101, R01 HL107910] NR 22 TC 4 Z9 5 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD APR PY 2014 VL 63 IS 4 BP 1194 EP 1197 DI 10.2337/db14-0004 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AJ4FO UT WOS:000337628000013 PM 24651804 ER PT J AU Jackson, DW Rohani, P AF Jackson, D. W. Rohani, Pejman TI Perplexities of pertussis: recent global epidemiological trends and their potential causes SO EPIDEMIOLOGY AND INFECTION LA English DT Review DE Bordetella pertussis ID SCHOOL IMMUNIZATION REQUIREMENTS; BORDETELLA-PERTUSSIS; WHOOPING-COUGH; UNITED-STATES; NONMEDICAL EXEMPTIONS; ANTIGENIC DIVERGENCE; FUTURE CONTROL; VACCINATION; IMPACT; RESURGENCE AB Recent much-publicized increases in pertussis case reports in some countries with high vaccine coverage have raised concerns about its current and future control. The ubiquity of this trend, however, remains unexamined. In an attempt to paint a global picture, we used case counts to determine which countries experienced statistically significant trends in incidence over the past two decades and to map changes in incidence during this period. These data reveal that pertussis resurgence is not a universal phenomenon. The heterogeneity in incidence trends, even in countries with superficially similar demography, socioeconomic conditions and vaccination programmes, is striking and requires explanation. In this opinion piece, we review and assess the multifaceted proposed explanations incorporating evolution, population dynamics, and the details of immunization programmes. While we do not solve the riddle that is pertussis epidemiology, we highlight critical aspects that are likely to hold the key to understanding its worldwide epidemiology. C1 [Jackson, D. W.; Rohani, Pejman] Univ Michigan, Ann Arbor, MI 48109 USA. [Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. [Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Jackson, DW (reprint author), 323 West Hall,1085 S Univ, Ann Arbor, MI USA. EM dougjack@dougjackson.net FU RAPIDD program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Vaccine Modeling Initiative of the Bill and Melinda Gates Foundation; National Institutes of Health [1R01AI101155] FX P. R. was supported by the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health, the Vaccine Modeling Initiative of the Bill and Melinda Gates Foundation and by a grant from the National Institutes of Health (1R01AI101155). NR 80 TC 32 Z9 32 U1 1 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 EI 1469-4409 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD APR PY 2014 VL 142 IS 4 BP 672 EP 684 DI 10.1017/S0950268812003093 PG 13 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AJ5FY UT WOS:000337709300001 PM 23324361 ER PT J AU Chen, S Young, MF Chakravarti, S Birk, DE AF Chen, Shoujun Young, Marian F. Chakravarti, Shukti Birk, David E. TI Interclass small leucine-rich repeat proteoglycan interactions regulate collagen fibrillogenesis and corneal stromal assembly SO MATRIX BIOLOGY LA English DT Article DE Corneal stroma; Biglycan; Lumican; Collagen; Fibrillogenesis; Stromal organization ID KERATAN SULFATE PROTEOGLYCAN; DEFICIENT MICE; LUMICAN-DEFICIENT; FIBRIL SEGMENTS; HIGH MYOPIA; NULL MICE; DECORIN; BIGLYCAN; FIBROMODULIN; FIBROBLASTS AB The corneal stroma is enriched in small leucine-rich proteoglycans (SLRPs), including both class I (decorin and biglycan) and class II (lumican, keratocan and fibromodulin). Transparency is dependent on the assembly and maintenance of a hierarchical stromal organization and SLRPs are critical regulatory molecules. We hypothesize that cooperative interclass SLAP interactions are involved in the regulation of stromal matrix assembly. We test this hypothesis using a compound Bgn(-/0)/Lum(-/-) mouse model and single Lum(-/-)or Bgn(-/0) mouse models and wild type controls. SLRP expression was investigated using immuno-localization and immuno-blots. Structural relationships were defined using ultrastructural and morphometric approaches while transparency was analyzed using in vivo confocal microscopy. The compound Bgn(-/0)/Lum(-/-) corneas demonstrated gross opacity that was not seen in the Bgn(-/0) or wild type corneas and greater than that in the Lum(-/-) mice. The Bgn(-/0)/Lum(-/-) corneas exhibited significantly increased opacity throughout the stroma compared to posterior opacity in the Lum(-/-) and no opacity in Bgn(-/0) or wild type corneas. In the Bgn(-/0)/Lum(-/-) corneas there were abnormal lamellar and fibril structures consistent with the functional deficit in transparency. Lamellar structure was disrupted across the stroma with disorganized fibrils, and altered fibril packing. In addition, fibrils had larger and more heterogeneous diameters with an abnormal structure consistent with abnormal fibril growth. This was not observed in the Bgn(-/0) or wild type corneas and was restricted to the posterior stroma in Lum(-/-) mice. The data demonstrate synergistic interclass regulatory interactions between lumican and biglycan. These interactions are involved in regulating both lamellar structure as well as collagen fibrillogenesis and therefore, corneal transparency. (C) 2014 Elsevier B.V. All rights reserved. C1 [Chen, Shoujun; Birk, David E.] Univ S Florida, Morsani Coll Med, Dept Mol Pharmacol & Physiol, Tampa, FL 33612 USA. [Young, Marian F.] NIDCR, NIH, Bethesda, MD USA. [Chakravarti, Shukti] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Birk, DE (reprint author), Univ S Florida, Coll Med, Dept Mol Pharmacol & Physiol, 12901 Bruce B Downs Blvd,MDC08, Tampa, FL 33612 USA. EM dbirk@health.usf.edu RI Birk, David/I-4072-2012 OI Birk, David/0000-0002-4865-9088 FU NIH [EY005129]; Intramural program of the NIDCR, NIH FX This study was supported by NIH/NEI grant EY005129 and by the Intramural program of the NIDCR, NIH. NR 39 TC 22 Z9 23 U1 1 U2 14 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 APR PY 2014 VL 35 SI SI BP 103 EP 111 DI 10.1016/j.matbio.2014.01.004 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AJ3HG UT WOS:000337556500015 PM 24447998 ER PT J AU Berendsen, AD Pinnow, EL Maeda, A Brown, AC McCartney-Francis, N Kram, V Owens, RT Robey, PG Holmbeck, K de Castro, LF Kilts, TM Young, MF AF Berendsen, Agnes D. Pinnow, Emily L. Maeda, Azusa Brown, Aaron C. McCartney-Francis, Nancy Kram, Vardit Owens, Rick T. Robey, Pamela G. Holmbeck, Kenn de Castro, Luis F. Kilts, Tina M. Young, Marian F. TI Biglycan modulates angiogenesis and bone formation during fracture healing SO MATRIX BIOLOGY LA English DT Article DE Biglycan; Fracture healing; Angiogenesis; Callus; Mineralization ID MATRIX COMPONENT BIGLYCAN; OSTEOGENESIS IMPERFECTA; ENDOTHELIAL-CELLS; DEFICIENT MICE; MOUSE MODEL; PROTEOGLYCANS; OSTEOPOROSIS; EXPRESSION; DECORIN; LOCALIZATION AB Matrix proteoglycans such as biglycan (Bgn) dominate skeletal tissue and yet its exact role in regulating bone function is still unclear. In this paper we describe the potential role of (Bgn) in the fracture healing process. We hypothesized that Bgn could regulate fracture healing because of previous work showing that it can affect normal bone formation. To test this hypothesis, we created fractures in femurs of 6-week-old male wild type (WT or Bgn+/0) and Bgn-deficient (Bgn-KO or Bgn-/0) mice using a custom-made standardized fracture device, and analyzed the process of healing overtime. The formation of a callus around the fracture site was observed at both 7 and 14 days post-fracture in WT and Bgn-deficient mice and immunohistochemistry revealed that Bgn was highly expressed in the fracture callus of WT mice, localizing within woven bone and cartilage. Micro-computed tomography (mu CT) analysis of the region surrounding the fracture line showed that the Bgn-deficient mice had a smaller callus than WT mice. Histology of the same region also showed the presence of less cartilage and woven bone in the Bgn-deficient mice compared to WT mice. Picrosirius red staining of the callus visualized under polarized light showed that there was less fibrillar collagen in the Bgn-deficient mice, a finding confirmed by immunohistochemistry using antibodies to type I collagen. Interestingly, real time RT-PCR of the callus at 7 days post-fracture showed a significant decrease in relative vascular endothelial growth factor A (VEGF) gene expression by Bgn-deficient mice as compared to WT. Moreover, VEGF was shown to bind directly to Bgn through a solid-phase binding assay. The inability of Bgn to directly enhance VEGF-induced signaling suggests that Bgn has a unique role in regulating vessel formation, potentially related to VEGF storage or stabilization in the matrix. Taken together, these results suggest that Bgn has a regulatory role in the process of bone formation during fracture healing, and further, that reduced angiogenesis could be the molecular basis. Published by Elsevier B.V. C1 [Berendsen, Agnes D.; Pinnow, Emily L.; Maeda, Azusa; Brown, Aaron C.; McCartney-Francis, Nancy; Kram, Vardit; Robey, Pamela G.; Holmbeck, Kenn; de Castro, Luis F.; Kilts, Tina M.; Young, Marian F.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Owens, Rick T.] LifeCell Corp, Branchburg, NJ 08876 USA. RP Young, MF (reprint author), NIDCR, NIH, Bldg 30,Room 225, Bethesda, MD 20892 USA. EM myoung@dir.nidcr.nih.gov FU Intramural Research Program of the NIH, NIDCR FX We would like to thank Dr. Louis Gerstenfeld and Dr. David Kohn for advice on experimental methodologies and analyses. This research was supported by the Intramural Research Program of the NIH, NIDCR. NR 34 TC 22 Z9 22 U1 3 U2 16 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 APR PY 2014 VL 35 SI SI BP 223 EP 231 DI 10.1016/j.matbio.2013.12.004 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AJ3HG UT WOS:000337556500027 PM 24373744 ER PT J AU Shapiro, SZ AF Shapiro, Stuart Z. TI Clinical Development of Candidate HIV Vaccines: Different Problems for Different Vaccines SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID INFECTION; REPLICATION; STRATEGIES; CHALLENGE; THERAPY; SIV AB Realization of individual and public health benefit from an HIV vaccine requires clinical testing to demonstrate efficacy. To facilitate clinical testing, preclinical HIV vaccine developers should consider the realities of clinical practice and the conduct of clinical trials in product design. There are several essentially different approaches to prophylactic HIV vaccine design: (1) induce immunity that allows infection but reduces initial peak viremia and viral load set point; (2) induce immunity that allows infection but controls viremia to below the level of detection; (3) induce immunity that allows infection but promotes viral clearance before disease (classic vaccine approach); (4) induce "sterilizing immunity'' that prevents acquisition of infection. Each approach presents different challenges for clinical product development. Current clinical trial practices and evolving treatment standards may make it infeasible to perform an efficacy trial of a preventive vaccine that only modestly reduces viremia. A vaccine that promotes control of viremia to below the level of detection is testable but will require extended follow-up to determine how long virus control persists; once control is lost boosting with the same vaccine may not be useful. A vaccine that permits infection but promotes subsequent complete clearance of the virus from the body will require the development and validation of an effective assay for virus clearance. A vaccine that prevents acquisition of infection is the most straightforward to test in the clinic, but escalating costs require more attention by vaccine developers to understanding how the vaccine works and the breadth of protection. All types of vaccine require attention to effect size to ensure adequate powering of efficacy trials. C1 NIAID, Vaccine Res Program, Div Aids, Bethesda, MD 20892 USA. RP Shapiro, SZ (reprint author), NIAID, Vaccine Res Program, Div Aids, 6700-B Rockledge Dr,Room 5146, Bethesda, MD 20892 USA. EM sshapiro@niaid.nih.gov NR 18 TC 6 Z9 6 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2014 VL 30 IS 4 BP 325 EP + DI 10.1089/aid.2013.0114 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AJ2LH UT WOS:000337486800001 PM 24168166 ER PT J AU Longosz, AF Serwadda, D Nalugoda, F Kigozi, G Franco, V Gray, RH Quinn, TC Eshleman, SH Laeyendecker, O AF Longosz, Andrew F. Serwadda, David Nalugoda, Fred Kigozi, Godfrey Franco, Veronica Gray, Ronald H. Quinn, Thomas C. Eshleman, Susan H. Laeyendecker, Oliver TI Impact of HIV Subtype on Performance of the Limiting Antigen-Avidity Enzyme Immunoassay, the Bio-Rad Avidity Assay, and the BED Capture Immunoassay in Rakai, Uganda SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID UNITED-STATES; E INFECTION; AFRICA; SEROCONVERSION; DIVERSITY; THAILAND AB Previous studies demonstrated that individuals with subtype D HIV infection who had been infected for 2 or more years were frequently misclassified as assay positive using cross-sectional incidence assays. Samples from 510 subjects (212 subtype A, 298 subtype D) who were infected for 2.2 to 14.5 years (median 5.4 years) and were not virally suppressed were tested using an LAg-Avidity enzyme immunoassay (LAg-Avidity EIA), Bio-Rad Avidity assay, and BED capture enzyme immunoassay (BED-CEIA). The performance of these three assays was evaluated using various assay cutoff values [LAg-Avidity EIA: < 1.0 OD-n and < 2.0 OD-n; Bio-Rad Avidity assay: < 40% avidity index (AI) and < 80% AI; BED-CEIA: < 0.8 OD-n]. The mean LAg-Avidity EIA result was higher for subtype A than D (4.54 +/- 0.95 vs. 3.86 +/- 1.26, p < 0.001); the mean Bio-Rad Avidity assay result was higher for subtype A than D (88.9%+/- 12.5% vs. 75.1 +/- 30.5, p < 0.001); and the mean BED-CEIA result was similar for the two subtypes (2.2 +/- 1.2 OD-n for subtype A, 2.2 +/- 1.3 OD-n for subtype D, p < 0.9). The frequency of misclassification was higher for individuals with subtype D infection compared to those with subtype A infection, using either the LAg-Avidity EIA with a cutoff of < 2.0 OD-n or the Bio-Rad Avidity assay with cutoffs of < 40% or < 80% AI. No subtype-specific differences in assay performance were observed using the BED-CEIA. Sex and age were not significantly associated with misclassification by any assay. The LAg-Avidity EIA with a cutoff < 1.0 OD-n had the lowest frequency of misclassification in this Ugandan population. C1 [Longosz, Andrew F.; Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD 21205 USA. [Serwadda, David; Nalugoda, Fred; Kigozi, Godfrey; Gray, Ronald H.] Rakai Hlth Sci Program, Rakai, Uganda. [Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Franco, Veronica; Gray, Ronald H.; Quinn, Thomas C.; Eshleman, Susan H.; Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Laeyendecker, O (reprint author), NIAID, LIR, NIH, 855 North Wolfe St,Room 538A, Baltimore, MD 21205 USA. EM olaeyen1@jhmi.edu OI Laeyendecker, Oliver/0000-0002-6429-4760 FU HIV Prevention Trials Network (HPTN) - National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Child Health and Human Development (NICH/HD); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH), Office of AIDS Research, National Institutes of Health (NIH), Department of Health and Human Services [UM1-AI068613-Eshleman]; NIH, NIAID [R01-A134826, K22-AI092150-01, R01-A134265]; NICHD [R01-HD 050180]; Bill and Melinda Gates Foundation [22006]; Division of Intramural Research, NIAID, NIH; [R01-AI095068] FX Sources of funding: (1) The HIV Prevention Trials Network (HPTN), funded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Child Health and Human Development (NICH/HD), National Institute of Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH), Office of AIDS Research, National Institutes of Health (NIH), Department of Health and Human Services (UM1-AI068613-Eshleman), and (2) R01-AI095068 (Eshleman/Brookmeyer). The studies that collected samples used for analysis were funded by the NIH, NIAID (R01-A134826, K22-AI092150-01, and R01-A134265), NICHD (R01-HD 050180), and the Bill and Melinda Gates Foundation (Grant 22006). Additional support was provided by the Division of Intramural Research, NIAID, NIH. NR 28 TC 14 Z9 15 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2014 VL 30 IS 4 BP 339 EP 344 DI 10.1089/aid.2013.0169 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AJ2LH UT WOS:000337486800007 PM 24083837 ER PT J AU Vaccari, M Fenizia, C Ma, ZM Hryniewicz, A Boasso, A Doster, MN Miller, CJ Lindegardh, N Tarning, J Landay, AL Shearer, GM Franchini, G AF Vaccari, Monica Fenizia, Claudio Ma, Zhong-Min Hryniewicz, Anna Boasso, Adriano Doster, Melvin N. Miller, Christopher J. Lindegardh, Niklas Tarning, Joel Landay, Alan L. Shearer, Gene M. Franchini, Genoveffa TI Transient Increase of Interferon-Stimulated Genes and No Clinical Benefit by Chloroquine Treatment During Acute Simian Immunodeficiency Virus Infection of Macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID NONPATHOGENIC SIV INFECTION; IMMUNOSTIMULATORY CPG-OLIGODEOXYNUCLEOTIDES; PLASMACYTOID DENDRITIC CELLS; CHRONIC HIV-INFECTION; IMMUNE ACTIVATION; ANTIRETROVIRAL THERAPY; T-CELLS; HIV-1-INFECTED PATIENTS; RHEUMATOID-ARTHRITIS; SOOTY MANGABEYS AB Simian immunodeficiency virus (SIV) infection leads to AIDS in experimentally infected Rhesus macaques similarly to HIV-infected humans. In contrast, SIV infection of natural hosts is characterized by a down-regulation of innate acute responses to the virus within a few weeks of infection and results in limited pathology. Chloroquine (CQ) has been used in the treatment or prevention of malaria and has recently been shown to cause a decrease of immune activation and CD4 cell loss in HIV-infected individuals treated with antiretroviral therapy. Here, we treated Rhesus macaques with CQ during the acute phase of SIVmac251 infection with the intent to decrease viral-induced immune activation and possibly limit disease progression. Contrary to what was expected, CQ treatment resulted in a temporary increased expression of interferon (IFN)-stimulating genes and it worsened the recovery of CD4(+) T cells in the blood. Our findings confirm recent results observed in asymptomatic HIV-infected patients and suggest that CQ does not provide an obvious benefit in the absence of antiretroviral therapy. C1 [Vaccari, Monica; Fenizia, Claudio; Hryniewicz, Anna; Doster, Melvin N.; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. [Ma, Zhong-Min; Miller, Christopher J.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Boasso, Adriano; Shearer, Gene M.] NCI, Expt Immunol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Lindegardh, Niklas; Tarning, Joel] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand. [Lindegardh, Niklas; Tarning, Joel] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England. [Landay, Alan L.] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA. RP Franchini, G (reprint author), Anim Models & Retroviral Vaccine Sect, 9000 Rockville Pike,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov OI Boasso, Adriano/0000-0001-9673-6319 FU National Cancer Institute, National Institutes of Health; Welcome Trust of Great Britain FX We would like to thank J. Treece, D. Weiss, and P. Markham for animal husbandry and care and Teresa Habina for manuscript editing. This work was supported by federal funds from the National Cancer Institute, National Institutes of Health. The Mahidol-Oxford Tropical Medicine Research Unit is supported by the Welcome Trust of Great Britain. NR 52 TC 7 Z9 7 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2014 VL 30 IS 4 BP 355 EP U42 DI 10.1089/aid.2013.0218 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AJ2LH UT WOS:000337486800009 PM 24251542 ER PT J AU Fert, I Cagnard, N Glatigny, S Letourneur, F Jacques, S Smith, JA Colbert, RA Taurog, JD Chiocchia, G Araujo, LM Breban, M AF Fert, Ingrid Cagnard, Nicolas Glatigny, Simon Letourneur, Franck Jacques, Sebastien Smith, Judith A. Colbert, Robert A. Taurog, Joel D. Chiocchia, Gilles Araujo, Luiza M. Breban, Maxime TI Reverse Interferon Signature Is Characteristic of Antigen-Presenting Cells in Human and Rat Spondyloarthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID HLA-B27 TRANSGENIC RATS; PRONE HLA-B27-TRANSGENIC RATS; SPLEEN DENDRITIC CELLS; REGULATORY T-CELLS; ANKYLOSING-SPONDYLITIS; INFLAMMATORY DISEASE; TH17 CELLS; SPONDYLARTHRITIS; EXPRESSION; MODEL AB Objective. In HLA-B27-transgenic rats, the development of a disorder that mimics spondyloarthritis (SpA) is highly correlated with dendritic cell (DC) dysfunction. The present study was undertaken to analyze the underlying mechanisms of this via transcriptome analysis. Methods. Transcriptome analysis of ex vivo-purified splenic CD103 + CD4 + DCs from B27-transgenic rats and control rats was performed. Transcriptional changes in selected genes were confirmed by quantitative reverse transcriptase-polymerase chain reaction. A meta-analysis of our rat data and published data on gene expression in macrophages from ankylosing spondylitis (AS) patients was further performed. Results. Interferon (IFN) signaling was the most significantly affected pathway in DCs from B27-transgenic rats; the majority of genes connected to IFN were underexpressed in B27-transgenic rats as compared to controls. This pattern was already present at disease onset, persisted over time, and was conserved in 2 disease-prone B27-transgenic rat lines. In DCs from B27-transgenic rats, we further found an up-regulation of suppressor of cytokine signaling 3 (which may account for reverse IFN signaling) and a down-regulation of interleukin-27 (a cytokine that opposes Th17 differentiation and promotes Treg cells). The meta-analysis of data on conventional DCs from rats and data on monocyte-derived macrophages from humans revealed 7 IFN-regulated genes that were negatively regulated in both human and rat SpA (i. e., IRF1, STAT1, CXCL9, CXCL10, IFIT3, DDX60, and EPSTI1). Conclusion. Our results suggest that expression of HLA-B27 leads to a defect in IFN gamma signaling in antigen-presenting cells in both B27-transgenic rats and SpA patients, which may result in Th17 expansion and Treg cell alteration (as shown in B27-transgenic rats) and contribute to disease pathogenesis. C1 [Fert, Ingrid; Glatigny, Simon; Chiocchia, Gilles; Araujo, Luiza M.; Breban, Maxime] Univ Paris 05, Sorbonne Paris Cite, Lab Excellence Inflamex, Inst Cochin, Paris, France. [Fert, Ingrid; Glatigny, Simon; Letourneur, Franck; Jacques, Sebastien; Chiocchia, Gilles; Araujo, Luiza M.; Breban, Maxime] CNRS, UMR 8104, INSERM, U1016, Paris, France. [Cagnard, Nicolas] Univ Paris 05, Paris, France. [Cagnard, Nicolas] Hop Necker Enfants Malad, Paris, France. [Letourneur, Franck; Jacques, Sebastien] Univ Paris 05, Inst Cochin, Paris, France. [Smith, Judith A.] Univ Wisconsin, Madison Sch Med & Publ Hlth, Madison, WI 53706 USA. [Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Taurog, Joel D.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Breban, Maxime] Hop Ambroise Pare, F-92100 Boulogne, France. [Breban, Maxime] Versailles St Quentin En Yvelines Univ, Boulogne, France. RP Breban, M (reprint author), Hop Ambroise Pare, Serv Rhumatol, 9 Ave Charles de Gaulle, F-92100 Boulogne, France. EM maxime.breban@apr.aphp.fr RI Cagnard, Nicolas/K-2754-2014; chiocchia, gilles/F-6287-2013 OI Cagnard, Nicolas/0000-0002-9051-1896; chiocchia, gilles/0000-0001-9973-0940 FU French National Agency for Research (ANR-Physiopath); Investissements d'Avenir Programme grant [ANR-11-IDEX-0005-02]; INSERM FX Supported by a DCSPA (Molecular Role of HLA-B27 in Spondylarthritis, From Animal Model to Human Disease) grant from the French National Agency for Research (ANR-Physiopath 2007-2011), an Investissements d'Avenir Programme grant (ANR-11-IDEX-0005-02), and by INSERM. NR 44 TC 14 Z9 14 U1 0 U2 9 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 APR PY 2014 VL 66 IS 4 BP 841 EP 851 DI 10.1002/art.38318 PG 11 WC Rheumatology SC Rheumatology GA AJ0QR UT WOS:000337361000010 PM 24757137 ER PT J AU Inamoto, Y Pidala, J Chai, XY Kurland, BF Weisdorf, D Flowers, MED Palmer, J Arai, S Jacobsohn, D Cutler, C Jagasia, M Goldberg, JD Martin, PJ Pavletic, SZ Vogelsang, GB Lee, SJ Carpenter, P AF Inamoto, Yoshihiro Pidala, Joseph Chai, Xiaoyu Kurland, Brenda F. Weisdorf, Daniel Flowers, Mary E. D. Palmer, Jeanne Arai, Sally Jacobsohn, David Cutler, Corey Jagasia, Madan Goldberg, Jenna D. Martin, Paul J. Pavletic, Steven Z. Vogelsang, Georgia B. Lee, Stephanie J. Carpenter, Paul A. TI Assessment of Joint and Fascia Manifestations in Chronic Graft-Versus-Host Disease SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; CHRONIC GVHD; CLINICAL-TRIALS; RISK-FACTORS; VALIDATION; CRITERIA; VALIDITY; OUTCOMES AB Objective. To investigate the usefulness of various scales for evaluating joint and fascia manifestations in patients with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation, and to compare the scales in terms of simplicity of use and ability to yield reliable and clinically meaningful results. Methods. In a prospective, multicenter, longitudinal, observational cohort of patients with chronic GVHD (n = 567), we evaluated 3 scales proposed for assessing joint status: the National Institutes of Health (NIH) joint/fascia scale, the Hopkins fascia scale, and the Photographic Range of Motion (P-ROM) scale. Ten other scales were also tested for assessment of symptoms, quality of life, and physical functions. Results. Joint and fascia manifestations were present at study enrollment in 164 (29%) of the patients. Limited range of motion was most frequent at the wrists or fingers. Among the 3 joint assessment scales, changes in the NIH scale correlated with both clinician-and patient-perceived improvement of joint and fascia manifestations, with higher sensitivity than the Hopkins fascia scale. Changes in all 3 scales correlated with clinician-and patient-perceived worsening, but the P-ROM scale was the most sensitive in this regard. Onset of joint and fascia manifestations was not associated with subsequent mortality. Conclusion. Joint and fascia manifestations are common in patients with chronic GVHD and should be assessed carefully in these patients. Our results support the use of the NIH joint/fascia scale and P-ROM scale to assess joint and fascia manifestations. The NIH scale better captures improvement, while the P-ROM scale better captures worsening. The utility of these scales could also be tested in the rheumatic diseases. C1 [Inamoto, Yoshihiro; Chai, Xiaoyu; Kurland, Brenda F.; Flowers, Mary E. D.; Martin, Paul J.; Pavletic, Steven Z.; Carpenter, Paul A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Kurland, Brenda F.] Univ Pittsburgh, Pittsburgh, PA USA. [Weisdorf, Daniel] Univ Minnesota, Minneapolis, MN USA. [Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Arai, Sally] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Jacobsohn, David] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Goldberg, Jenna D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Pavletic, Steven Z.] NCI, NIH, Bethesda, MD 20892 USA. [Vogelsang, Georgia B.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Carpenter, P (reprint author), Fred Hutchinson Canc Res Ctr, D5-290,POB 19024, Seattle, WA 98109 USA. EM pcarpent@fhcrc.org OI Kurland, Brenda/0000-0002-5669-0595 FU NIH [CA-118953, CA-163438, CA-047904]; NIH Office of Rare Diseases Research at the National Center for Advancing Translational Science; National Cancer Institute [U54-CA-163438]; Fred Hutchinson Cancer Research Center FX Supported by the NIH (grants CA-118953, CA-163438, and CA-047904). The Chronic GVHD Consortium is a part of the NIH Rare Diseases Clinical Research Network, which is supported through collaboration between the NIH Office of Rare Diseases Research at the National Center for Advancing Translational Science, the National Cancer Institute (grant U54-CA-163438), and the Fred Hutchinson Cancer Research Center. NR 26 TC 13 Z9 13 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 APR PY 2014 VL 66 IS 4 BP 1044 EP 1052 DI 10.1002/art.38293 PG 9 WC Rheumatology SC Rheumatology GA AJ0QR UT WOS:000337361000031 PM 24757155 ER PT J AU Nagineni, CN Raju, R Nagineni, KK Kommineni, VK Cherukuri, A Kutty, RK Hooks, JJ Detrick, B AF Nagineni, Chandrasekharam N. Raju, Raghavan Nagineni, Krishnasai K. Kommineni, Vijay K. Cherukuri, Aswini Kutty, R. Krishnan Hooks, John J. Detrick, Barbara TI Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial Cells: Potential Nutraceutical for Age-related Macular Degeneration SO AGING AND DISEASE LA English DT Article DE Resveratrol; VEGF; SIRT1; Cytokines; Retina; Retinal pigment epithelium; Age-related macular degeneration ID ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL NEOVASCULAR MEMBRANES; OCULAR NEOVASCULARIZATION; TRANS-RESVERATROL; VISUAL FUNCTION; EYE DISEASE; IN-VIVO; THERAPY; DRUSEN; BETA AB Age-related macular degeneration (AMD) is a sight threating retinal eye disease that affects millions of aging individuals world-wide. Choroid-retinal pigment epithelium (RPE)-neuroretina axis in the posterior compartment of the eye is the primary site of AMD pathology. There are compelling evidence to indicate association of vascular endothelial growth factors (VEGF) to AMD. Here, we report the inhibitory actions of resveratrol (RSV) on inflammatory cytokine, TGF-beta and hypoxia induced VEGF secretion by human retinal pigment epithelial cells (HRPE). HRPE cultures prepared from aged human donor eyes were used for the studies in this report. HRPE secreted both VEGF-A and VEGF-C in small quantities constitutively. Stimulation with a mixture of inflammatory cytokines (IFN-gamma, TNF-alpha, IL-1 beta), significantly increased the secretion of both VEGF-A and VEGF-C. RSV, in a dose dependent (10-50 uM) manner, suppressed VEGF-A and VEGF-C secretion induced by inflammatory cytokines significantly. RT-PCR analysis indicated that effects of RSV on VEGF secretion were possibly due to decreased mRNA levels. TGF-beta. and cobalt chloride (hypoxia mimic) also upregulated HRPE cell production of VEGF-A, and this was inhibited by RSV. In contrast, RSV had no effect on anti-angiogenic molecules, endostatin and pigment epithelial derived factor secretion. Studies using an in vitro scratch assay revealed that wound closure was also inhibited by RSV. These results demonstrate that RSV can suppress VEGF secretion induced by inflammatory cytokines, TGF-beta and hypoxia. Under pathological conditions, over expression of VEGF is known to worsen AMD. Therefore, RSV may be useful as nutraceutical in controlling pathological choroidal neovascularization processes in AMD. C1 [Nagineni, Chandrasekharam N.; Kommineni, Vijay K.; Hooks, John J.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Raju, Raghavan] Georgia Regents Univ, Dept Lab Med, Augusta, GA USA. [Raju, Raghavan] Georgia Regents Univ, Dept Imaging & Radiol Sci, Augusta, GA USA. [Raju, Raghavan] Georgia Regents Univ, Dept Biochem & Mol Biol, Augusta, GA USA. [Nagineni, Krishnasai K.] Univ Maryland, Sch Publ Policy, College Pk, MD 20742 USA. [Cherukuri, Aswini; Kutty, R. Krishnan] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. [Detrick, Barbara] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Detrick, B (reprint author), Johns Hopkins Med Inst, Baltimore, MD 21205 USA. EM naginenic@gmail.com; bdetrick@jhmi.edu FU National Eye Institute, National Institutes of Health; NIH [GM101927] FX This research was supported by intramural research program of the National Eye Institute, National Institutes of Health, and extramural grants NIH GM101927 (RR). NR 66 TC 22 Z9 22 U1 2 U2 9 PU INT SOC AGING & DISEASE PI FORT WORTH PA EDITORIAL OFF, 3400 CAMP BOWIE BLVD, FORT WORTH, TX 76106 USA SN 2152-5250 J9 AGING DIS JI Aging Dis. PD APR PY 2014 VL 5 IS 2 BP 88 EP 100 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AI5KM UT WOS:000336905200002 PM 24729934 ER PT J AU de Almeida, ALC Teixido-Tura, G Choi, EY Opdahl, A Fernandes, VRS Wu, CO Bluemke, DA Lima, JAC AF Cerqueira de Almeida, Andre Luiz Teixido-Tura, Gisela Choi, Eui-Young Opdahl, Anders Fernandes, Veronica R. S. Wu, Colin O. Bluemke, David A. Lima, Joao A. C. TI Metabolic Syndrome, Strain, and Reduced Myocardial Function: Multi-Ethnic Study of Atherosclerosis SO ARQUIVOS BRASILEIROS DE CARDIOLOGIA LA English DT Article DE Atherosclerosis; Metabolic X Syndrome; Diabetes Mellitus / mortality; Ventricular Dysfunction / physiopathology; Ethnic Group ID 2-DIMENSIONAL SPECKLE TRACKING; LEFT-VENTRICULAR DYSFUNCTION; SUBCLINICAL ATHEROSCLEROSIS; ASYMPTOMATIC INDIVIDUALS; CARDIOVASCULAR RISK; EJECTION FRACTION; CARDIAC STRUCTURE; ECHOCARDIOGRAPHY; DISEASE; IMPACT AB Background: Subclinical cardiovascular disease is prevalent in patients with Metabolic Syndrome (MetSyn). Left ventricular (LV) circumferential strain (epsilon(CC)) and longitudinal strain (epsilon(LL)), assessed by Speckle Tracking Echocardiography (STE), are indices of systolic function: shortening is indicated by negative strain, and thus, the more negative the strain, the better the LV systolic function. They have been used to demonstrate subclinical ventricular dysfunction in several clinical disorders. Objective: We hypothesized that MetSyn is associated with impaired myocardial function, as assessed by STE. Methods: We analyzed Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent STE and were evaluated for all MetSyn components. Results: Among the 133 participants included [women: 63%; age: 65 +/- 9 years (mean +/- SD)], the prevalence of MetSyn was 31% (41/133). Individuals with MetSyn had lower epsilon(CC) and lower epsilon(LL) than those without MetSyn (-16.3% +/- 3.5% vs. -18.4% +/- 3.7%, p < 0.01; and -12.1% +/- 2.5% vs. -13.9% +/- 2.3%, p < 0.01, respectively). The LV ejection fraction (LVEF) was similar in both groups (p = 0.09). In multivariate analysis, MetSyn was associated with less circumferential myocardial shortening as indicated by less negative epsilon(CC) (B = 2.1%, 95% CI: 0.6-3.5, p < 0.01) even after adjusting for age, ethnicity, LV mass, and LVEF). Likewise, presence of MetSyn (B = 1.3%, 95% CI: 0.3-2.2, p < 0.01) and LV mass (B = 0.02%, 95% CI: 0.01-0.03, p = 0.02) were significantly associated with less longitudinal myocardial shortening as indicated by less negative epsilon(LL) after adjustment for ethnicity, LVEF, and creatinine. Conclusion: Left ventricular epsilon(CC) and epsilon(LL), markers of subclinical cardiovascular disease, are impaired in asymptomatic individuals with MetSyn and no history of myocardial infarction, heart failure, and/or LVEF < 50%. C1 [Cerqueira de Almeida, Andre Luiz; Teixido-Tura, Gisela; Choi, Eui-Young; Opdahl, Anders; Fernandes, Veronica R. S.; Lima, Joao A. C.] Johns Hopkins Univ, Baltimore, MD USA. [Cerqueira de Almeida, Andre Luiz] Univ Feira de Santana, Feira De Santana, BA, Brazil. [Wu, Colin O.] NHLBI, Bethesda, MD 20892 USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA. RP de Almeida, ALC (reprint author), Rua Alto Paraguai 280, BR-44085232 Feira De Santana, BA, Brazil. EM andrealmeida@cardiol.br RI Opdahl, Anders/I-7580-2015 OI Opdahl, Anders/0000-0002-0599-592X FU National Heart, Lung and Blood Institute (Bethesda, Maryland, USA) FX This study was funded by National Heart, Lung and Blood Institute (Bethesda, Maryland, USA). NR 37 TC 6 Z9 8 U1 0 U2 4 PU ARQUIVOS BRASILEIROS CARDIOLOGIA PI RIO DE JANEIRO PA AVENIDA MARECHAL CAMARA 160-330 CENTRO, RIO DE JANEIRO, RJ 20 020-907, BRAZIL SN 0066-782X J9 ARQ BRAS CARDIOL JI Arq. Bras. Cardiol. PD APR PY 2014 VL 102 IS 4 BP 327 EP 335 DI 10.5935/abc.20140040 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3SZ UT WOS:000336784200006 PM 24844874 ER PT J AU Zainabadi, K Jain, AV Donovan, FX Elashoff, D Rao, NP Murty, VV Chandrasekharappa, SC Srivatsan, ES AF Zainabadi, Kayvan Jain, Anuja V. Donovan, Frank X. Elashoff, David Rao, Nagesh P. Murty, Vundavalli V. Chandrasekharappa, Settara C. Srivatsan, Eri S. TI One in four individuals of African-American ancestry harbors a 5.5 kb deletion at chromosome 11q13.1 SO GENOMICS LA English DT Article DE Cervical cancer; Chromosome 11q13.1; 5.5 kb deletion; African American ancestry; Single nucleotide polymorphisms; Linkage disequilibrium; Common fragile site ID RARE FRAGILE SITES; TUMOR-SUPPRESSOR GENE; CERVICAL-CANCER; MOLECULAR-BASIS; HOMOZYGOUS DELETIONS; GENOME INSTABILITY; COMMON; COPY; REGION; CELLS AB Cloning and sequencing of 5.5 kb deletion at chromosome 11q13.1 from the HeLa cells, tumorigenic hybrids and two fibroblast cell lines have revealed homologous recombination between AluSx and AluY resulting in the deletion of intervening sequences. Long-range PCR of the 5.5 kb sequence in 494 normal lymphocyte samples showed heterozygous deletion in 28.3% of African-American ancestry samples but only in 4.8% of Caucasian samples (p < 0.0001). This observation is strengthened by the copy number variation (CNV) data of the HapMap samples which showed that this deletion occurs in 27% of YRI (Yoruba - West African) population but none in non-African populations. The HapMap analysis further identified strong linkage disequilibrium between 5 single nucleotide polymorphisms and the 5.5 kb deletion in people of African ancestry. Computational analysis of 175 kb sequence surrounding the deletion site revealed enhanced flexibility, low thermodynamic stability, high repetitiveness, and stable stem-loop/hairpin secondary structures that are hallmarks of common fragile sites. Published by Elsevier Inc. C1 [Zainabadi, Kayvan; Jain, Anuja V.; Srivatsan, Eri S.] Univ Calif Los Angeles, David Geffen Sch Med, VAGLAHS West Los Angeles, Dept Surg,Div Gen Surg, Los Angeles, CA 90073 USA. [Donovan, Frank X.; Chandrasekharappa, Settara C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Elashoff, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. [Rao, Nagesh P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. [Murty, Vundavalli V.] Columbia Univ Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA. RP Srivatsan, ES (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VAGLAHS, Dept Surg, Los Angeles, CA 90073 USA. EM esrivats@ucla.edu FU UCLA Student Research Program; American Association for Cancer Research (AACR); Frederick R. Waingrow Research Fellowship; Howard Hughes Research Fellowship; VAGLAHS; West Los Angeles Surgical Education Research Center; Veterans Administration, Washington, DC FX We are deeply indebted to Neta Ben-Porat from Dr. Batsheva Kerem's group at The Hebrew University for her generous technical assistance with the FLEXSTAB/TWISTFLEX analysis, and to Dr. Michael Zuker of Washington University for his assistance with the MFold program. We would also like to thank Dr. Marilene Wang for the proof reading of the manuscript FXD and SCC gratefully acknowledge the Intramural Program of the National Human Genome Research Institute, Bethesda, MD. This work was supported by: UCLA Student Research Program; the American Association for Cancer Research (AACR); the Frederick R. Waingrow Research Fellowship and the Howard Hughes Research Fellowship to KZ and by funds from the VAGLAHS, the West Los Angeles Surgical Education Research Center; and Merit grant from the Veterans Administration, Washington, DC to ESS. NR 44 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD APR PY 2014 VL 103 IS 4 BP 276 EP 287 DI 10.1016/j.ygeno.2014.01.001 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AI5DF UT WOS:000336884900004 PM 24412158 ER PT J AU Friedman, DJ Wang, N Meigs, JB Hoffmann, U Massaro, JM Fox, CS Magnani, JW AF Friedman, Daniel J. Wang, Na Meigs, James B. Hoffmann, Udo Massaro, Joseph M. Fox, Caroline S. Magnani, Jared W. TI Pericardial Fat is Associated With Atrial Conduction: The Framingham Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE atrium; conduction; electrocardiography; epidemiology; obesity ID EPICARDIAL ADIPOSE-TISSUE; BODY-MASS INDEX; ATHEROSCLEROSIS RISK; INTRATHORACIC FAT; OBESE SUBJECTS; FIBRILLATION; HEALTH; COMMUNITIES; PREVALENCE; MORPHOLOGY AB Background-Obesity is associated with altered atrial electrophysiology and a prominent risk factor for atrial fibrillation. Body mass index, the most widely used adiposity measure, has been related to atrial electrical remodeling. We tested the hypothesis that pericardial fat is independently associated with electrocardiographic measures of atrial conduction. Methods and Results-We performed a cross-sectional analysis of 1946 Framingham Heart Study participants (45% women) to determine the relation between pericardial fat and atrial conduction as measured by P wave indices (PWI): PR interval, P wave duration (P-duration), P wave amplitude (P-amplitude), P wave area (P-area), and P wave terminal force (P-terminal). We performed sex-stratified linear regression analyses adjusted for relevant clinical variables and ectopic fat depots. Each 1-SD increase in pericardial fat was significantly associated with PR interval (beta=1.7 ms, P=0.049), P-duration (beta=2.3 ms, P<0.001), and P-terminal (beta=297 mu V.ms, P<0.001) among women; and P-duration (beta=1.2 ms, P=0.002), P-amplitude (beta=-2.5 mu V, P<0. 001), and P-terminal (beta=160 mu V.ms, P=0.002) among men. Among both sexes, pericardial fat was significantly associated with P-duration in analyses additionally adjusting for visceral fat or intrathoracic fat; a similar but non-significant trend existed with P-terminal. Among women, pericardial fat was significantly associated with P wave area after adjustment for visceral and intrathoracic fat. Conclusions-Pericardial fat is associated with atrial conduction as quantified by PWI, even with adjustment for extracardiac fat depots. Further studies are warranted to identify the mechanisms through which pericardial fat may modify atrial electrophysiology and promote subsequent risk for arrhythmogenesis. C1 [Friedman, Daniel J.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Wang, Na] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Massaro, Joseph M.; Fox, Caroline S.; Magnani, Jared W.] NHLBI, Framingham, MA USA. [Massaro, Joseph M.; Fox, Caroline S.; Magnani, Jared W.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Magnani, Jared W.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. RP Magnani, JW (reprint author), Boston Univ, Sect Cardiovasc Med, Sch Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Friedman, Daniel /0000-0001-5791-1954 FU American Heart Association [09FTF219028]; Boston University School of Medicine Department of Medicine Career Investment Award; NIH [2K24 DK080140]; National Heart, Lung, and Blood Institute [R21HL1060926]; Framingham Heart Study contract [N01-HC25195] FX Dr Magnani is supported by American Heart Association award 09FTF219028 and a Boston University School of Medicine Department of Medicine Career Investment Award, and Dr Meigs by NIH grant 2K24 DK080140. This work was supported by National Heart, Lung, and Blood Institute grant R21HL1060926 and Framingham Heart Study contract N01-HC25195. NR 30 TC 11 Z9 11 U1 0 U2 5 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 APR PY 2014 VL 3 IS 2 AR e000477 DI 10.1161/JAHA.113.000477 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3XC UT WOS:000336798000012 PM 24595189 ER PT J AU Magnani, JW Yin, XY McManus, DD Chuang, ML Cheng, SS Lubitz, SA Arora, G Manning, WJ Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Yin, Xiaoyan McManus, David D. Chuang, Michael L. Cheng, Susan Lubitz, Steven A. Arora, Garima Manning, Warren J. Ellinor, Patrick T. Benjamin, Emelia J. TI Genetic Loci Associated With Atrial Fibrillation: Relation to Left Atrial Structure in the Framingham Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE atrial fibrillation; cohort studies; genetics; left atrium; single nucleotide polymorphism ID GENOME-WIDE ASSOCIATION; LONGITUDINAL TRACKING; CHROMOSOME 4Q25; COMMON VARIANTS; RISK SCORE; M-MODE; SUSCEPTIBILITY; COHORT; METAANALYSIS; COMMUNITY AB Background-Atrial fibrillation (AF) results in significant morbidity and mortality. Genome-wide association studies (GWAS) have identified genetic variants associated with AF. Whether genetic variants associated with AF are also associated with atrial structure, an intermediate phenotype for AF, has had limited investigation. We sought to investigate associations between single nucleotide polymorphisms (SNPs) and atrial structure obtained by cardiovascular imaging in the Framingham Heart Study. Methods and Results-We selected 11 SNPs that have been associated with AF in GWAS. We examined the SNPs' relations to cross-sectional left atrial (LA) dimensions (determined by transthoracic echocardiography) and LA volume (determined by cardiovascular magnetic resonance [CMR]) employing linear regression. The total sample included 1555 participants with CMR LA volume (age 60 +/- 9 years, 53% women) and 6861 participants with echocardiographic LA diameter (age 48 +/- 13 years, 52% women) measured. We employed a significance threshold of P<0.0023 to account for multiple testing of the 11 SNPs and 2 LA measures. In a primary analysis, no SNPs were significantly related to the LA measures. Likewise, in secondary analyses excluding individuals with prevalent AF (n=77, CMR sample; n=105, echocardiography sample) no SNPs were related to LA volume or diameter. Conclusion-In a community-based cohort, we did not identify a statistically significant association between selected SNPs associated with AF and measures of LA anatomy. Further investigations with larger longitudinally assessed samples and a broader array of SNPs may be necessary to determine the relation between genetic loci associated with AF and atrial structure. C1 [Magnani, Jared W.; Yin, Xiaoyan; McManus, David D.; Chuang, Michael L.; Cheng, Susan; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Magnani, Jared W.; Yin, Xiaoyan; McManus, David D.; Chuang, Michael L.; Cheng, Susan; Benjamin, Emelia J.] Boston Univ Framingham Heart Study, Framingham, MA USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Yin, Xiaoyan] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [McManus, David D.] Univ Massachusetts, Dept Med, Cardiol Sect, Worcester, MA 01605 USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Cardiovasc Med, Boston, MA 02115 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Arora, Garima; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Arora, Garima; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Arora, Garima; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF219028, 13EIA14220013]; NIH [5R21HL106092, 2RO1HL092577, RC1-HL101056, 1R01HL102214, RO1 HL70279, 1RO1HL104156, 1K24HL105780, 6R01-NS17950, N01-HC25195]; Boston University School of Medicine Department of Medicine Career Investment Award FX This work was supported by grants from the American Heart Association (Award 09FTF219028) to Dr Magnani and (13EIA14220013) to Dr Ellinor, and from the NIH to Dr Magnani (5R21HL106092), Drs Benjamin and Ellinor (2RO1HL092577), Dr. Benjamin (RC1-HL101056, 1R01HL102214), Dr Manning (RO1 HL70279), and Dr Ellinor (1RO1HL104156, 1K24HL105780) and 6R01-NS17950, N01-HC25195. This work was further supported by a Boston University School of Medicine Department of Medicine Career Investment Award to Dr Magnani. NR 32 TC 1 Z9 1 U1 0 U2 3 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 APR PY 2014 VL 3 IS 2 AR e000616 DI 10.1161/JAHA.113.000616 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3XC UT WOS:000336798000033 PM 24695651 ER PT J AU Sui, YP Park, SH Helsley, RN Sunkara, M Gonzalez, FJ Morris, AJ Zhou, CC AF Sui, Yipeng Park, Se-Hyung Helsley, Robert N. Sunkara, Manjula Gonzalez, Frank J. Morris, Andrew J. Zhou, Changcheng TI Bisphenol A Increases Atherosclerosis in Pregnane X Receptor-Humanized ApoE Deficient Mice SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE atherosclerosis; cells; receptors; risk factors ID NUCLEAR RECEPTOR; HUMAN URINE; LACTATIONAL EXPOSURE; ETHINYL ESTRADIOL; RISK-ASSESSMENT; DISEASE; METABOLISM; ACTIVATION; MECHANISMS; ALPHA AB Background-Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA has recently been associated with increased risk of cardiovascular disease (CVD) in multiple large-scale human population studies, but the underlying mechanisms remain elusive. We previously reported that BPA activates the pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism and has pro-atherogenic effects in animal models upon activation. Interestingly, BPA is a potent agonist of human PXR but does not activate mouse or rat PXR signaling, which confounds the use of rodent models to evaluate mechanisms of BPA-mediated CVD risk. This study aimed to investigate the atherogenic mechanism of BPA using a PXR-humanized mouse model. Methods and Results-A PXR-humanized ApoE deficient (huPXR center dot ApoE(-/-)) mouse line was generated that respond to human PXR ligands and feeding studies were performed to determine the effects of BPA exposure on atherosclerosis development. Exposure to BPA significantly increased atherosclerotic lesion area in the aortic root and brachiocephalic artery of huPXR center dot ApoE(-/-) mice by 104% (P<0.001) and 120% (P<0.05), respectively. By contrast, BPA did not affect atherosclerosis development in the control littermates without human PXR. BPA exposure did not affect plasma lipid levels but increased CD36 expression and lipid accumulation in macrophages of huPXR center dot ApoE(-/-) mice. Conclusion-These findings identify a molecular mechanism that could link BPA exposure to increased risk of CVD in exposed individuals. PXR is therefore a relevant target for future risk assessment of BPA and related environmental chemicals in humans. C1 [Sui, Yipeng; Park, Se-Hyung; Helsley, Robert N.; Zhou, Changcheng] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY 40536 USA. [Morris, Andrew J.; Zhou, Changcheng] Univ Kentucky, Saha Cardiovasc Res Ctr, Lexington, KY 40536 USA. [Sunkara, Manjula; Morris, Andrew J.] Univ Kentucky, Div Cardiovasc Med, Lexington, KY 40536 USA. [Gonzalez, Frank J.] NCI, Ctr Canc Res, Lab Metab, Bethesda, MD 20892 USA. RP Zhou, CC (reprint author), Univ Kentucky, Grad Ctr Nutr Sci, Saha Cardiovasc Res Ctr, 900 S Limestone St,517 Wethington Bldg, Lexington, KY 40536 USA. EM c.zhou@uky.edu FU NIH [P30HL101300, P20GM103527, R01ES023470, T32HL072743]; American Heart Association [09SDG2150176, 14POST18740064]; University of Kentucky Superfund Research Center [P42ES007380] FX This work was supported in part by NIH grants (P30HL101300, P20GM103527, R01ES023470), and American Heart Association grant 09SDG2150176. Morris and Sunkara were supported by the University of Kentucky Superfund Research Center grant P42ES007380; Helsley was supported by NIH training grant T32HL072743; and Sui was supported by American Heart Association Postdoctoral Fellowship 14POST18740064. NR 59 TC 11 Z9 12 U1 0 U2 7 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 APR PY 2014 VL 3 IS 2 AR e000492 DI 10.1161/JAHA.113.000492 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3XC UT WOS:000336798000049 PM 24755147 ER PT J AU Shtivelman, E Davies, MA Hwu, P Yang, J Lotem, M Oren, M Flaherty, KT Fisher, DE AF Shtivelman, Emma Davies, Michael A. Hwu, Patrick Yang, James Lotem, Michal Oren, Moshe Flaherty, Keith T. Fisher, David E. TI Pathways and therapeutic targets in melanoma SO ONCOTARGET LA English DT Review DE melanoma; targeted therapy; immune therapy ID CIRCULATING TUMOR-CELLS; PHASE-II TRIAL; CUTANEOUS MALIGNANT-MELANOMA; SELECTIVE BRAF INHIBITION; METASTATIC UVEAL MELANOMA; PULSED DENDRITIC CELLS; DOSE IMATINIB MESYLATE; STAGE IV MELANOMA; T-CELLS; B-RAF AB This review aims to summarize the current knowledge of molecular pathways and their clinical relevance in melanoma. Metastatic melanoma was a grim diagnosis, but in recent years tremendous advances have been made in treatments. Chemotherapy provided little benefit in these patients, but development of targeted and new immune approaches made radical changes in prognosis. This would not have happened without remarkable advances in understanding the biology of disease and tremendous progress in the genomic (and other "omics") scale analyses of tumors. The big problems facing the field are no longer focused exclusively on the development of new treatment modalities, though this is a very busy area of clinical research. The focus shifted now to understanding and overcoming resistance to targeted therapies, and understanding the underlying causes of the heterogeneous responses to immune therapy. C1 [Shtivelman, Emma] Canc Commons, Palo Alto, CA 94301 USA. [Davies, Michael A.; Hwu, Patrick] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Yang, James] NCI, NIH, Washington, DC USA. [Lotem, Michal] Hadassah Hebrew Univ Hosp, Jerusalem, Israel. [Oren, Moshe] Weizmann Inst Sci, IL-76100 Rehovot, Israel. [Flaherty, Keith T.; Fisher, David E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Shtivelman, E (reprint author), Canc Commons, Palo Alto, CA 94301 USA. EM emma@cancercommons.org FU NCI NIH HHS [P01 CA163222]; NIAMS NIH HHS [R01 AR043369] NR 348 TC 50 Z9 51 U1 0 U2 21 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR PY 2014 VL 5 IS 7 BP 1701 EP 1752 PG 52 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AI6EZ UT WOS:000336965400002 PM 24743024 ER PT J AU Fallon, J Tighe, R Kradjian, G Guzman, W Bernhardt, A Neuteboom, B Lan, Y Sabzevari, H Schlom, J Greiner, JW AF Fallon, Jonathan Tighe, Robert Kradjian, Giorgio Guzman, Wilson Bernhardt, Anna Neuteboom, Berend Lan, Yan Sabzevari, Helen Schlom, Jeffrey Greiner, John W. TI The immunocytokine NHS-IL12 as a potential cancer therapeutic SO ONCOTARGET LA English DT Article DE immunocytokine; interleukin-12; tumor necrosis therapy; T cells; immunotherapy ID CELL STIMULATORY FACTOR; RECOMBINANT HUMAN INTERLEUKIN-12; MONOCLONAL-ANTIBODY; T-CELLS; ANTITUMOR-ACTIVITY; TUMOR-REGRESSION; GAMMA PRODUCTION; FUSION PROTEINS; MESSENGER-RNAS; SOLID TUMORS AB Targeted delivery of IL-12 might turn this cytokine into a safer, more effective cancer therapeutic. Here we describe a novel immunocytokine, NHS-IL12, consisting of two molecules of IL-12 fused to a tumor necrosis-targeting human IgG1 (NHS76). The addition of the human IgG1 moiety resulted in a longer plasma half-life of NHS-IL12 than recombinant IL-12, and a selective targeting to murine tumors in vivo. Data from both in vitro assays using human PBMCs and in vivo primate studies showed that IFN-gamma production by immune cells is attenuated following treatment with the immunocytokine, suggesting an improved toxicity profile than seen with recombinant IL-12 alone. NHS-IL12 was superior to recombinant IL-12 when evaluated as an anti-tumor agent in three murine tumor models. Mechanistic studies utilizing immune cell subset-depleting antibodies, flow cytometric methods, and in vitro cytotoxicity and ELISA assays all indicated that the anti-tumor effects of NHS-IL12 were primarily CD8+ T cell-dependent and likely IL-12-mediated. Combining NHS-IL12 treatment with a cancer vaccine, radiation, or chemotherapy resulted in greater anti-tumor effects than each individual therapy alone. These preclinical findings provide a rationale for the clinical testing of this immunocytokine, both as a single agent and in combination with vaccines, radiation and chemotherapy. C1 [Fallon, Jonathan; Schlom, Jeffrey; Greiner, John W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, Bethesda, MD 20892 USA. [Tighe, Robert; Kradjian, Giorgio; Guzman, Wilson; Bernhardt, Anna; Neuteboom, Berend; Lan, Yan; Sabzevari, Helen] EMD Serono Res & Dev Inst, Billerica, MA USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, Bethesda, MD 20892 USA. EM js141c@nih.gov FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH; EMD Serono; National Cancer Institute FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH as well as through a Cooperative Research and Development Agreement (CRADA) between EMD Serono and the National Cancer Institute. NR 48 TC 12 Z9 12 U1 3 U2 9 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR PY 2014 VL 5 IS 7 BP 1869 EP 1884 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AI6EZ UT WOS:000336965400014 PM 24681847 ER PT J AU Xu, P Dauter, Z Kovac, P AF Xu, Peng Dauter, Zbigniew Kovac, Pavol TI Synthesis, Characterization, and Crystal Structure of Sodium (Methyl alpha-D-Mannopyranosid)uronate Monohydrate SO SYNTHESIS-STUTTGART LA English DT Article DE mannuronic acid; oxidation; chemoselective methylation; TEMPO; HPLC ID X-RAY-DIFFRACTION; D-MANNURONIC ACID; GLUCURONIC-ACID; HYPOCHLORITE; DERIVATIVES; OXIDATION; ALCOHOLS; ETHERS; TEMPO AB TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl)-mediated oxidation of methyl alpha-D-mannopyranoside with sodium hypochlorite gave sodium (methyl alpha-D-mannopyranosid)uronate, which was obtained as a crystalline monohydrate in similar to 70% yield without chromatography. Its purity was proved by NMR spectroscopy, a newly developed HPLC method, combustion analysis, and X-ray crystallography. The crystal structure, solved from synchrotron diffraction data in space group P2(1)2(1)2(1), revealed that the packing of the uronate molecules is connected by an extensive network of hydrogen bonds, and that the Na+ ion is coordinated by six oxygen ligands from one water and three surrounding sugar molecules. C1 [Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA. [Dauter, Zbigniew] NCI, Macromol Crystallog Lab, Argonne Natl Lab, Argonne, IL 60439 USA. RP Kovac, P (reprint author), NIDDK, LBC, NIH, Bethesda, MD 20892 USA. EM kpn@helix.nih.gov FU NIH, NCI; NIH, NIDDK FX This research was supported by the Intramural Research Program of the NIH, NCI, and NIDDK. NR 24 TC 1 Z9 1 U1 1 U2 6 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0039-7881 EI 1437-210X J9 SYNTHESIS-STUTTGART JI Synthesis PD APR PY 2014 VL 46 IS 8 BP 1073 EP 1078 DI 10.1055/s-0033-1340843 PG 6 WC Chemistry, Organic SC Chemistry GA AI4MG UT WOS:000336838900007 ER PT J AU Stolka, K Ndom, P Hemingway-Foday, J Iriondo-Perez, J Miley, W Labo, N Stella, J Abassora, M Woelk, G Ryder, R Whitby, D Smith, JS AF Stolka, Kristen Ndom, Paul Hemingway-Foday, Jennifer Iriondo-Perez, Jeniffer Miley, Wendell Labo, Nazzarena Stella, Jennifer Abassora, Mahamat Woelk, Godfrey Ryder, Robin Whitby, Denise Smith, Jennifer S. TI Risk factors for Kaposi's sarcoma among HIV-positive individuals in a case control study in Cameroon SO CANCER EPIDEMIOLOGY LA English DT Article DE Kaposi's sarcoma (KS); Kaposi's sarcoma herpesvirus (KSHV); Human herpesvirus 8 (HHV-8); Human Immunodeficiency Virus (HIV); Risk factors; Cameroon ID SUB-SAHARAN AFRICA; HUMAN-HERPESVIRUS-8 INFECTION; HERPESVIRUS; TRANSMISSION; PREVALENCE; UGANDA; AIDS; ANTIBODIES; CHILDREN; ETIOLOGY AB Background: Individuals co-infected with Kaposi's sarcoma herpesvirus (KSHV) and Human Immunodeficiency Virus (HIV) are at greatly increased risk of developing Kaposi's sarcoma (KS). The objective of the current analysis is to identify risk cofactors for KS among HIV-positive individuals. Methods: We conducted a case-control study of KS in Cameroon on 161 HIV-positive and 14 HIV-negative cases and 680 HIV-positive and 322 HIV-negative controls. Participants answered a physician-administered questionnaire and provided blood and saliva specimens. Antibodies against KSHV lytic, K8.1, and latent, ORF73, antigens were measured by ELISA to determine KSHV serostatus. Conditional logistic regression was performed to determine multivariate odds ratios (OR) and 95% confidence intervals (CI) for risk factors associated with KS among HIV-positive cases and controls. Results: Overall, 98% (158) of HIV-positive cases, 100% (14) of HIV-negative cases, 81% (550) of HIV-positive controls, and 80% (257) of HIV-negative controls were KSHV seropositive. Risk factors for KS among HIV-positive individuals included KSHV seropositivity (OR = 9.6; 95% CI 2.9, 31.5), non-use of a mosquito bed net (OR 1.9; 95% CI 1.2, 2.9), minority ethnicity (OR = 3.1; 95% CI 1.1, 9.3), treatment from a traditional healer (OR = 2.3; 95% CI 1.5, 3.7), history of transfusion (OR = 2.4; 95% CI 1.5, 3.9), and family history of cancer (OR = 1.9; 95% CI 1.1, 3.1). Conclusion: KSHV seroprevalence of >= 80% indicates a high prevalence in the general population in Cameroon. Among HIV-positive individuals, the strong association of KS with non-use of mosquito nets and treatment from traditional healers are compelling findings, consistent with recently reported data from East Africa. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Stolka, Kristen; Hemingway-Foday, Jennifer; Iriondo-Perez, Jeniffer] RTI Int, Res Triangle Pk, NC 27709 USA. [Ndom, Paul] SOCHIMIO, Yaounde, Cameroon. [Miley, Wendell; Labo, Nazzarena; Whitby, Denise] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Viral Oncol Sect, Frederick, MD 21702 USA. [Labo, Nazzarena] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Stella, Jennifer] Univ Calif San Francisco, San Francisco, CA 94102 USA. [Abassora, Mahamat; Woelk, Godfrey] Expanded Program Immunizat, Garoua, Cameroon. [Woelk, Godfrey] Elizabeth Glaser Pediat AIDS Fdn, Washington, DC 20036 USA. [Ryder, Robin] Univ Calif San Diego, San Diego, CA 92103 USA. [Smith, Jennifer S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. RP Stolka, K (reprint author), RTI Int, 3040 East Cornwallis Rd, Res Triangle Pk, NC 27709 USA. EM kstolka@rti.org RI Labo, Nazzarena/H-8655-2012 OI Labo, Nazzarena/0000-0001-5953-4064 FU NCI, NIH [N01-CO-12400, HHSN261200800001E]; NIAID, NIH [1U01AI069927] FX We would like to acknowledge the study staff at SOCHIMIO for their work in recruiting and enrolling participants; the IeDEA Central Africa staff and clinical officers in Cameroon for collaborating with study staff; and the staff at the Global Viral Forecasting Institute (GVFI) in Yaounde for providing controlled climate storage space for the biological specimens. Acknowledgment is also given to Joseph Meyer, who designed and produced Fig. 1 map of Cameroon ethnicities. This project has been funded in part with federal funds from the NCI, NIH under contract N01-CO-12400 and HHSN261200800001E and NIAID, NIH, under contract 1U01AI069927. NR 42 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 EI 1877-783X J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD APR PY 2014 VL 38 IS 2 BP 137 EP 143 DI 10.1016/j.canep.2014.02.006 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AI0GZ UT WOS:000336525600006 PM 24631417 ER PT J AU Meulepas, JM Ronckers, CM Smets, AMJB Nievelstein, RAJ Jahnen, A Lee, C Kieft, M Lameris, JS van Herk, M Greuter, MJW Jeukens, CRLPN van Straten, M Visser, O van Leeuwen, FE Hauptmann, M AF Meulepas, Johanna M. Ronckers, Cecile M. Smets, Anne M. J. B. Nievelstein, Rutger A. J. Jahnen, Andreas Lee, Choonsik Kieft, Mariette Lameris, Johan S. van Herk, Marcel Greuter, Marcel J. W. Jeukens, Cecile R. L. P. N. van Straten, Marcel Visser, Otto van Leeuwen, Flora E. Hauptmann, Michael TI Leukemia and brain tumors among children after radiation exposure from CT scans: design and methodological opportunities of the Dutch Pediatric CT Study SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Computed tomography; Cohort study; Leukemia; Children; Methodology; Low dose radiation ID COMPUTED-TOMOGRAPHY; SOCIOECONOMIC-STATUS; CHILDHOOD LEUKEMIA; CANCER-MORTALITY; NORTHERN ENGLAND; DOWN-SYNDROME; RISK; COHORT; NETHERLANDS; PREVALENCE AB Computed tomography (CT) scans are indispensable in modern medicine; however, the spectacular rise in global use coupled with relatively high doses of ionizing radiation per examination have raised radiation protection concerns. Children are of particular concern because they are more sensitive to radiation-induced cancer compared with adults and have a long lifespan to express harmful effects which may offset clinical benefits of performing a scan. This paper describes the design and methodology of a nationwide study, the Dutch Pediatric CT Study, regarding risk of leukemia and brain tumors in children after radiation exposure from CT scans. It is a retrospective record-linkage cohort study with an expected number of 100,000 children who received at least one electronically archived CT scan covering the calendar period since the introduction of digital archiving until 2012. Information on all archived CT scans of these children will be obtained, including date of examination, scanned body part and radiologist's report, as well as the machine settings required for organ dose estimation. We will obtain cancer incidence by record linkage with external databases. In this article, we describe several approaches to the collection of data on archived CT scans, the estimation of radiation doses and the assessment of confounding. The proposed approaches provide useful strategies for data collection and confounder assessment for general retrospective record-linkage studies, particular those using hospital databases on radiological procedures for the assessment of exposure to ionizing or non-ionizing radiation. C1 [Meulepas, Johanna M.; Kieft, Mariette; van Leeuwen, Flora E.; Hauptmann, Michael] Netherlands Canc Inst, Dept Epidemiol & Biostat, NL-1066 CX Amsterdam, Netherlands. [Ronckers, Cecile M.] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, Dept Pediat Oncol, NL-1105 AZ Amsterdam, Netherlands. [Smets, Anne M. J. B.; Lameris, Johan S.] Univ Amsterdam, Acad Med Ctr, Dept Radiol, NL-1105 AZ Amsterdam, Netherlands. [Nievelstein, Rutger A. J.] Univ Med Ctr, Dept Radiol, Utrecht, Netherlands. [Jahnen, Andreas] Publ Res Ctr Henri Tudor, Luxembourg, Luxembourg. [Lee, Choonsik] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [van Herk, Marcel] Netherlands Canc Inst, Dept Radiat Oncol, NL-1066 CX Amsterdam, Netherlands. [Greuter, Marcel J. W.] Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Groningen, Netherlands. [Jeukens, Cecile R. L. P. N.] Maastricht Univ, Med Ctr, Dept Radiol, Maastricht, Netherlands. [van Straten, Marcel] Erasmus MC Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Visser, Otto] Comprehens Canc Ctr Netherlands, Dept Registrat & Res, Utrecht, Netherlands. RP Hauptmann, M (reprint author), Netherlands Canc Inst, Dept Epidemiol & Biostat, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. EM m.hauptmann@nki.nl RI Lee, Choonsik/C-9023-2015; van Herk, Marcel/P-6307-2015 OI Lee, Choonsik/0000-0003-4289-9870; van Herk, Marcel/0000-0001-6448-898X FU European Community [269912-EPI-CT]; Association for International Cancer Research (AICR) [12-1155]; Dutch Cancer Society FX We sincerely thank all hospitals who provided and will provide data for our study. Without the dedicated support by numerous professionals in the participating radiology departments, this study would not be possible. This study was funded by the European Community Seventh Framework Programme (FP7/2007-2013) under Grant Agreement Number 269912-EPI-CT: 'Epidemiological study to quantify risks for paediatric computerized topography and to optimise doses' and by the Association for International Cancer Research (AICR) with Grant 12-1155. Dr. Ronckers is supported by the Dutch Cancer Society. Funders had no involvement in the study design, data collection, analysis and interpretation, the writing of the report, or the decision to submit the paper for publication. NR 34 TC 16 Z9 17 U1 1 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 EI 1573-7284 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD APR PY 2014 VL 29 IS 4 BP 293 EP 301 DI 10.1007/s10654-014-9900-9 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AI3YK UT WOS:000336801600008 PM 24748424 ER PT J AU Watson, JL Ryan, L Silverberg, N Cahan, V Bernard, MA AF Watson, Jennifer L. Ryan, Laurie Silverberg, Nina Cahan, Vicky Bernard, Marie A. TI Obstacles And Opportunities In Alzheimer's Clinical Trial Recruitment SO HEALTH AFFAIRS LA English DT Article ID COGNITIVE IMPAIRMENT; OLDER-ADULTS; DISEASE; RETENTION; PARTICIPATION; CAREGIVERS; REGISTRY; AD AB The 2012 National Plan to Address Alzheimer's Disease set an ambitious goal: to both prevent and effectively treat Alzheimer's disease by 2025. To reach this goal, tens of thousands of volunteers will be needed to participate in clinical trials to test promising new interventions and therapies. To mobilize these volunteers and their health care providers to participate in future clinical trials, it will be necessary to achieve a better understanding of the barriers keeping people from participating in Alzheimer's research; form innovative partnerships among researchers, health care and social service providers, and the public; and develop more-effective outreach strategies. In this article we explore recruitment issues, including those unique to Alzheimer's studies, and we suggest concrete steps such as establishing a structured consortium linking all of the registries of Alzheimer's trials and establishing new partnerships with community and local organizations that can build trust and understanding among patients, caregivers, and providers. C1 [Watson, Jennifer L.] NIA, NIH, Bethesda, MD 20892 USA. [Ryan, Laurie] NIA, Dementias Aging Branch, Bethesda, MD 20892 USA. [Silverberg, Nina] NIA, Alzheimers Dis Ctr Program, Bethesda, MD 20892 USA. [Cahan, Vicky] NIA, Off Commun & Publ Liaison, Bethesda, MD 20892 USA. [Bernard, Marie A.] NIA, Bethesda, MD 20892 USA. RP Watson, JL (reprint author), NIA, NIH, Bethesda, MD 20892 USA. EM watsonjl@nia.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 35 TC 1 Z9 1 U1 4 U2 10 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD APR PY 2014 VL 33 IS 4 BP 574 EP 579 DI 10.1377/hlthaff.2013.1314 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AI2CN UT WOS:000336664600009 PM 24711317 ER PT J AU Glass, RI AF Glass, Roger I. TI A career in public health The chance to save lives by the millions SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Editorial Material C1 [Glass, Roger I.] US Natl Inst Hlth NIH, Fogarty Int Ctr, Bethesda, MD USA. [Glass, Roger I.] US Natl Inst Hlth NIH, Bethesda, MD USA. RP Glass, RI (reprint author), US Natl Inst Hlth NIH, Fogarty Int Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD APR PY 2014 VL 10 IS 4 BP 819 EP 821 DI 10.4161/hv.29045 PG 3 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA AI1ZO UT WOS:000336655000010 PM 24784846 ER PT J AU Winhusen, TM Brigham, GS Kropp, F Lindblad, R Gardin, JG Penn, P Hodgkins, C Kelly, TM Douaihy, A McCann, M Love, LD DeGravelles, E Bachrach, K Sonne, SC Hiott, B Haynes, L Sharma, G Lewis, DF VanVeldhuisen, P Theobald, J Ghitza, U AF Winhusen, Theresa M. Brigham, Gregory S. Kropp, Frankie Lindblad, Robert Gardin, John G., II Penn, Pat Hodgkins, Candace Kelly, Thomas M. Douaihy, Antoine McCann, Michael Love, Lee D. DeGravelles, Eliot Bachrach, Ken Sonne, Susan C. Hiott, Bob Haynes, Louise Sharma, Gaurav Lewis, Daniel F. VanVeldhuisen, Paul Theobald, Jeff Ghitza, Udi TI A Randomized Trial of Concurrent Smoking-Cessation and Substance Use Disorder Treatment in Stimulant-Dependent Smokers SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SUSTAINED-RELEASE BUPROPION; RECEPTOR PARTIAL AGONIST; CIGARETTE-SMOKING; NICOTINE PATCH; TOBACCO DEPENDENCE; ABUSE TREATMENT; DRUG-USE; COCAINE; PLACEBO; VARENICLINE AB Objective: To evaluate the impact of concurrent treatments for substance use disorder and nicotine-dependence for stimulant-dependent patients. Method: A randomized, 10-week trial with follow-up at 3 and 6 months after smoking quit date conducted at 12 substance use disorder treatment programs between February 2010 and July 2012. Adults meeting DSM-IV-TR criteria for cocaine and/or methamphetamine dependence and interested in quitting smoking were randomized to treatment as usual (n = 271) or treatment as usual with smoking-cessation treatment (n = 267). All participants received treatment as usual for substance use disorder treatment. Participants assigned to treatment as usual with concurrent smoking-cessation treatment received weekly individual smoking cessation counseling and extended-release bupropion (300 mg/d) during weeks 1-10. During post-quit treatment (weeks 4-10), participants assigned to treatment as usual with smoking-cessation treatment received a nicotine inhaler and contingency management for smoking abstinence. Weekly proportion of stimulant-abstinent participants during the treatment phase, as assessed by urine drug screens and self-report, was the primary outcome. Secondary measures included other substance/nicotine use outcomes and treatment attendance. Results: There were no significant treatment effects on stimulant-use outcomes, as measured by the primary outcome and stimulant-free days, on drug-abstinence, or on attendance. Participants assigned to treatment as usual with smoking-cessation treatment, relative to those assigned to treatment as usual, had significantly better outcomes for drug-free days at 6-month follow-up (chi(2)(1) = 4.09, P < .05), with a decrease in drug-free days from baseline of -1.3% in treatment as usual with smoking-cessation treatment and of -7.6% in treatment as usual. Participants receiving treatment as usual with smoking-cessation treatment, relative to those receiving treatment as usual, had significantly better outcomes on smoking point-prevalence abstinence (25.5% vs 2.2%; chi(2)(1) = 44.69, P < .001; OR = 18.2). Conclusions: These results suggest that providing smoking-cessation treatment to illicit stimulant-dependent patients in outpatient substance use disorder treatment will not worsen, and may enhance, abstinence from nonnicotine substance use. C1 [Winhusen, Theresa M.; Brigham, Gregory S.; Kropp, Frankie; Lewis, Daniel F.; Theobald, Jeff] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45220 USA. [Brigham, Gregory S.] Maryhaven, Columbus, OH USA. [Lindblad, Robert; Sharma, Gaurav; VanVeldhuisen, Paul] EMMES Corp, Rockville, MD USA. [Ghitza, Udi] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA. [Gardin, John G., II] ADAPT Inc, Roseburg, OR USA. [Penn, Pat] La Frontera Ctr Inc, Tucson, AZ USA. [Hodgkins, Candace] Gateway Community Serv, Jacksonville, FL USA. [Kelly, Thomas M.; Douaihy, Antoine] Addict Med Serv, Pittsburgh, PA USA. [McCann, Michael] Matrix Inst Addict, Rancho Cucamonga, CA USA. [Bachrach, Ken] Tarzana Treatment Ctr, Tarzana, CA USA. [Love, Lee D.] Gibson Recovery, Cape Girardeau, MO USA. [DeGravelles, Eliot] Nexus Recovery Inc, Dallas, TX USA. [Sonne, Susan C.] Dorchester Alcohol & Drug Commiss, Summerville, SC USA. [Hiott, Bob] Behav Hlth Serv Pickens Cty, Pickens, SC USA. [Haynes, Louise] Lexington Richland Alcohol & Drug Abuse Council, Columbia, SC USA. RP Winhusen, TM (reprint author), Univ Cincinnati, 3210 Jefferson Ave, Cincinnati, OH 45220 USA. EM winhusen@carc.uc.edu OI Winhusen, Theresa/0000-0002-3364-0739; Brigham, Gregory/0000-0003-1150-4493 FU National Institute on Drug Abuse (NIDA) Center for the Clinical Trials Network (CCTN) [U10-DA013732, U10-DA020036, U10-DA013720, U10-DA013045, U10-DA013727, U10-DA020024, U10-DA015815] FX This study was supported by the following grants from the National Institute on Drug Abuse (NIDA) Center for the Clinical Trials Network (CCTN): U10-DA013732 to University of Cincinnati (Dr Winhusen); U10-DA020036 to University of Pittsburgh (D. Daley, PhD), U10-DA013720 to University of Miami School of Medicine (J. Szapocznik, PhD, and L. Metsch, PhD); U10-DA013045 to University of California Los Angeles (W. Ling, MD); U10-DA013727 to Medical University of South Carolina (K. Brady, MD, PhD); U10-DA020024 to University of Texas Southwestern Medical Center (M. Trivedi, MD); U10-DA015815 to University NR 36 TC 18 Z9 18 U1 0 U2 10 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 APR PY 2014 VL 75 IS 4 BP 336 EP 343 DI 10.4088/JCP.13m08449 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AI0HA UT WOS:000336525700007 PM 24345356 ER PT J AU Shaikh, AR Butte, AJ Schully, SD Dalton, WS Khoury, MJ Hesse, BW AF Shaikh, Abdul R. Butte, Atul J. Schully, Sheri D. Dalton, William S. Khoury, Muin J. Hesse, Bradford W. TI Collaborative Biomedicine in the Age of Big Data: The Case of Cancer SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE biomedical research; crowdsourcing; health information technology; innovation; precision medicine ID MEDICINE AB Biomedicine is undergoing a revolution driven by high throughput and connective computing that is transforming medical research and practice. Using oncology as an example, the speed and capacity of genomic sequencing technologies is advancing the utility of individual genetic profiles for anticipating risk and targeting therapeutics. The goal is to enable an era of "P4" medicine that will become increasingly more predictive, personalized, preemptive, and participative over time. This vision hinges on leveraging potentially innovative and disruptive technologies in medicine to accelerate discovery and to reorient clinical practice for patient-centered care. Based on a panel discussion at the Medicine 2.0 conference in Boston with representatives from the National Cancer Institute, Moffitt Cancer Center, and Stanford University School of Medicine, this paper explores how emerging sociotechnical frameworks, informatics platforms, and health-related policy can be used to encourage data liquidity and innovation. This builds on the Institute of Medicine's vision for a "rapid learning health care system" to enable an open source, population-based approach to cancer prevention and control. C1 [Shaikh, Abdul R.] PricewaterhouseCoopers LLP, Mclean, VA 22102 USA. [Butte, Atul J.] Stanford Univ, Dept Pediat, Sch Med, Div Syst Med, Stanford, CA 94305 USA. [Schully, Sheri D.; Khoury, Muin J.; Hesse, Bradford W.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Dalton, William S.] Univ S Florida, H Lee Moffitt Canc Ctr, DeBartolo Family Personalized Med Inst, Tampa, FL 33682 USA. RP Shaikh, AR (reprint author), PricewaterhouseCoopers LLP, 1800 Tysons Blvd, Mclean, VA 22102 USA. EM shaikh@us.pwc.com OI Hesse, Bradford/0000-0003-1142-1161 NR 26 TC 10 Z9 12 U1 11 U2 70 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 APR PY 2014 VL 16 IS 4 BP 143 EP 147 AR e101 DI 10.2196/jmir.2496 PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AH9YJ UT WOS:000336501600011 PM 24711045 ER PT J AU Maeurer, M Schito, M Zumla, A AF Maeurer, Markus Schito, Marco Zumla, Alimuddin TI Totally-drug-resistant tuberculosis: hype versus hope SO LANCET RESPIRATORY MEDICINE LA English DT Editorial Material ID MYCOBACTERIUM-TUBERCULOSIS; STRAINS C1 [Maeurer, Markus] Karolinska Inst, Therapeut Immunol Div, Dept Lab Med, SE-14186 Stockholm, Sweden. [Maeurer, Markus] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. [Schito, Marco] NIAID, Henry M Jackson Fdn, Div Aids, TB Clin Res Branch,NIH, Bethesda, MD 20892 USA. [Zumla, Alimuddin] UCL, Div Infect & Immun, London, England. [Zumla, Alimuddin] Univ Coll London Hosp NHS Trust, Dept Med Microbiol, London, England. RP Maeurer, M (reprint author), Karolinska Inst, Therapeut Immunol Div, Dept Lab Med, Halsovagen F79, SE-14186 Stockholm, Sweden. EM markus.maeurer@ki.se OI Zumla, Alimuddin/0000-0002-5111-5735 NR 16 TC 2 Z9 2 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD APR PY 2014 VL 2 IS 4 BP 256 EP 257 DI 10.1016/S2213-2600(14)70020-7 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AI2VG UT WOS:000336715600013 PM 24717619 ER PT J AU Kaufmann, SHE Lange, C Rao, M Balaji, KN Lotze, M Schito, M Zumla, AI Maeurer, M AF Kaufmann, Stefan H. E. Lange, Christoph Rao, Martin Balaji, Kithiganahalli N. Lotze, Michael Schito, Marco Zumla, Alimuddin I. Maeurer, Markus TI Progress in tuberculosis vaccine development and host-directed therapies-a state of the art review SO LANCET RESPIRATORY MEDICINE LA English DT Review ID MULTIDRUG-RESISTANT TUBERCULOSIS; HISTONE DEACETYLASE INHIBITORS; INFLAMMATORY-BOWEL-DISEASE; ACTIVATED PROTEIN-KINASE; PPD-POSITIVE ADULTS; T-CELL RESPONSES; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; INTERFERON-GAMMA; IMMUNE-RESPONSES AB Tuberculosis continues to kill 1.4 million people annually. During the past 5 years, an alarming increase in the number of patients with multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis has been noted, particularly in eastern Europe, Asia, and southern Africa. Treatment outcomes with available treatment regimens for drug-resistant tuberculosis are poor. Although substantial progress in drug development for tuberculosis has been made, scientific progress towards development of interventions for prevention and improvement of drug treatment outcomes have lagged behind. Innovative interventions are therefore needed to combat the growing pandemic of multidrug-resistant and extensively drug-resistant tuberculosis. Novel adjunct treatments are needed to accomplish improved cure rates for multidrug-resistant and extensively drug-resistant tuberculosis. A novel, safe, widely applicable, and more effective vaccine against tuberculosis is also desperately sought to achieve disease control. The quest to develop a universally protective vaccine for tuberculosis continues. So far, research and development of tuberculosis vaccines has resulted in almost 20 candidates at different stages of the clinical trial pipeline. Host-directed therapies are now being developed to refocus the anti-Mycobacterium tuberculosis-directed immune responses towards the host; a strategy that could be especially beneficial for patients with multidrug-resistant tuberculosis or extensively drug-resistant tuberculosis. As we are running short of canonical tuberculosis drugs, more attention should be given to host-directed preventive and therapeutic intervention measures. C1 [Kaufmann, Stefan H. E.] Max Planck Inst Infect Biol, Dept Immunol, Berlin, Germany. [Lange, Christoph] German Ctr Infect Res DZIF, Div Clin Infect Dis, Med Clin, Res Ctr Borstel, Borstel, Germany. [Balaji, Kithiganahalli N.] Indian Inst Sci, Dept Microbiol & Cell Biol, Bangalore 560012, Karnataka, India. [Lotze, Michael] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Lotze, Michael] Univ Pittsburgh, Sch Hlth Sci, Hillman Canc Ctr, Pittsburgh, PA USA. [Schito, Marco] NIAID, Henry M Jackson Fdn, Div Aids, TB Clin Res Branch,NIH, Bethesda, MD 20892 USA. [Zumla, Alimuddin I.] UCL, Ctr Clin Microbiol, Div Infect & Immun, London, England. [Zumla, Alimuddin I.] UCL Hosp NHS Fdn Trust, London, England. [Rao, Martin; Maeurer, Markus] Karolinska Inst, Ctr Allogene Stem Cell Transplantat CAST, Therapeut Immunol TIM, Dept Lab Med, SE-14186 Stockholm, Sweden. RP Maeurer, M (reprint author), Karolinska Inst, LabMed, Karolinska Univ Hosp Huddinge, Halsovagen F79, SE-14186 Stockholm, Sweden. EM Markus.Maeurer@ki.se RI Kaufmann, Stefan HE/I-5454-2014; OI Rao, Martin/0000-0002-0579-1097; Kaufmann, Stefan HE/0000-0001-9866-8268; Zumla, Alimuddin/0000-0002-5111-5735 FU Bill & Melinda Gates Foundation Grand Challenges in Global Health Program [BMGF GC6-74, 37772]; European Union's Seventh Framework Programme (EU FP7) project NEWTBVAC [HEALTH-F3-2009-241745]; European Union's Seventh Framework Programme (EU FP7) project ADITEC [HEALTH-F4-2011-280873]; Innovative Medicines Initiative (IMI) Joint Undertaking (JU) "Biomarkers for Enhanced Vaccine Safety" project BioVacSafe (IMI JU) [115308]; German Center for Infection Research (DZIF) for ClinTB [DZIF-ClinTB: 80002063 TTU 02.704]; European Union's Seventh Framework Programme TB PANNET Project [EU FP7 TB PANNET: 223681]; German Ministry of Education and Research (BMBF) TB [01KI1007B TP E]; UK Medical Research Council; European Union FW7 Rid-RTI; European Developing Countries Clinical trials Partnership (EDCTP); UBS Optimus Foundation, Switzerland; NIHR Biomedical Research centre, University College Hospitals, London, UK; Swedish Heart and Lung foundation (HLF); Vinnova (Sweden); Vetenskapsradet (Swedish Research Council); Sweden and European Developing Countries Clinical trials Partnership (EDCTP); National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200800014C]; Vinnova, Sweden, Department of Biotechnology (DBT), India, Council of Scientific & Industrial Research (CSIR), India; National Institutes of Health [P01 CA 101944-04] FX SHEK receives grants from the Bill & Melinda Gates Foundation Grand Challenges in Global Health Program (BMGF GC6-74, #37772), the European Union's Seventh Framework Programme (EU FP7) projects NEWTBVAC (HEALTH-F3-2009-241745), ADITEC (HEALTH-F4-2011-280873; and the Innovative Medicines Initiative (IMI) Joint Undertaking (JU) "Biomarkers for Enhanced Vaccine Safety" project BioVacSafe (IMI JU Grant No. 115308)". SHEK thanks Mary Louise Grossman for help in the preparation of this manuscript and Diane Schad for help in preparing figure 3. CL receives grants to support this work from the German Center for Infection Research (DZIF) for ClinTB (DZIF-ClinTB: 80002063 TTU 02.704); European Union's Seventh Framework Programme TB PANNET Project (EU FP7 TB PANNET: 223681); German Ministry of Education and Research (BMBF) TB or not TB project (01KI1007B TP E). AIZ receives grants from the UK Medical Research Council, European Union FW7 Rid-RTI, European Developing Countries Clinical trials Partnership (EDCTP), UBS Optimus Foundation, Switzerland, and the NIHR Biomedical Research centre, University College Hospitals, London, UK. MM receives grants from the Swedish Heart and Lung foundation (HLF), Vinnova (Sweden), Vetenskapsradet (Swedish Research Council), Sweden and European Developing Countries Clinical trials Partnership (EDCTP). MS receives grants from the National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200800014C. KNB receives grants from Vinnova, Sweden, Department of Biotechnology (DBT), India, Council of Scientific & Industrial Research (CSIR), India. ML receives grants from the National Institutes of Health (Grant reference no: P01 CA 101944-04). NR 212 TC 85 Z9 88 U1 4 U2 31 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD APR PY 2014 VL 2 IS 4 BP 301 EP 320 DI 10.1016/S2213-2600(14)70033-5 PG 20 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AI2VG UT WOS:000336715600026 PM 24717627 ER PT J AU Grobman, WA Bailit, JL Rice, MM Wapner, RJ Reddy, UM Varner, MW Thorp, JM Leveno, KJ Caritis, SN Iams, JD Tita, AT Saade, G Sorokin, Y Rouse, DJ Blackwell, SC Tolosa, JE Van Dorsten, JP AF Grobman, William A. Bailit, Jennifer L. Rice, Madeline Murguia Wapner, Ronald J. Reddy, Uma M. Varner, Michael W. Thorp, John M., Jr. Leveno, Kenneth J. Caritis, Steve N. Iams, Jay D. Tita, Alan T. Saade, George Sorokin, Yoram Rouse, Dwight J. Blackwell, Sean C. Tolosa, Jorge E. Van Dorsten, J. Peter CA Eunice Kennedy Shriver Natl Inst TI Frequency of and Factors Associated With Severe Maternal Morbidity SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SCORING SYSTEM; VALIDATION; PREGNANCY; DELIVERY AB OBJECTIVE: To estimate the frequency of severe maternal morbidity, assess its underlying etiologies, and develop a scoring system to predict its occurrence. METHODS: This was a secondary analysis of a Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network cohort of 115,502 women and their neonates born in 25 hospitals across the United States over a 3-year period. Women were classified as having severe maternal morbidity according to a scoring system that takes into account the occurrence of red blood cell transfusion (more than three units), intubation, unanticipated surgical intervention, organ failure, and intensive care unit admission. The frequency of severe maternal morbidity was calculated and the underlying etiologies determined. Multivariable analysis identified patient factors present on admission that were independently associated with severe maternal morbidity; these were used to develop a prediction model for severe maternal morbidity. RESULTS: Among 115,502 women who delivered during the study period, 332 (2.9/1,000 births, 95% confidence interval 2.6-3.2) experienced severe maternal morbidity. Postpartum hemorrhage was responsible for approximately half of severe maternal morbidity. Multiple patient factors were found to be independently associated with severe maternal morbidity and were used to develop a predictive model with an area under the receiver operating characteristic curve of 0.80. CONCLUSION: Severe maternal morbidity occurs in approximately 2.9 per 1,000 births, is most commonly the result of postpartum hemorrhage, and occurs more commonly in association with several identifiable patient characteristics. C1 Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. Columbia Univ, New York, NY USA. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Pittsburgh, Pittsburgh, PA USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Texas Med Branch, Galveston, TX 77555 USA. Wayne State Univ, Detroit, MI USA. Brown Univ, Providence, RI 02912 USA. Univ Texas Hlth Sci Ctr Houston, Childrens Mem Hermann Hosp, Houston, TX 77030 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Med Univ S Carolina, Charleston, SC 29425 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Grobman, WA (reprint author), Northwestern Univ, Dept Obstet & Gynecol, Feinberg Sch Med, 250 East Super St,Suite 05-2175, Chicago, IL 60611 USA. EM w-grobman@northwestern.edu RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD21410, HD27869, HD27915, HD27917, HD34116, HD34208, HD36801, HD40500, HD40512, HD40544, HD40545, HD40560, HD40485, HD53097, HD53118]; National Center for Research Resources [UL1 RR024989, 5UL1 RR025764] FX The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HD21410, HD27869, HD27915, HD27917, HD34116, HD34208, HD36801, HD40500, HD40512, HD40544, HD40545, HD40560, HD40485, HD53097, HD53118) and the National Center for Research Resources (UL1 RR024989; 5UL1 RR025764) and its contents do not necessarily represent the official views of the NICHD, National Center for Research Resources, or the National Institutes of Health. NR 13 TC 28 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2014 VL 123 IS 4 BP 804 EP 810 DI 10.1097/AOG.0000000000000173 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI4BC UT WOS:000336809300012 PM 24785608 ER PT J AU Rasmussen, DA Volz, EM Koelle, K AF Rasmussen, David A. Volz, Erik M. Koelle, Katia TI Phylodynamic Inference for Structured Epidemiological Models SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID MAXIMUM-LIKELIHOOD-ESTIMATION; MONTE-CARLO; POPULATION-DYNAMICS; SEXUAL TRANSMISSION; COALESCENT APPROACH; HIV-INFECTION; SEQUENCES; HISTORY; RATES; PARAMETERS AB Coalescent theory is routinely used to estimate past population dynamics and demographic parameters from genealogies. While early work in coalescent theory only considered simple demographic models, advances in theory have allowed for increasingly complex demographic scenarios to be considered. The success of this approach has lead to coalescent-based inference methods being applied to populations with rapidly changing population dynamics, including pathogens like RNA viruses. However, fitting epidemiological models to genealogies via coalescent models remains a challenging task, because pathogen populations often exhibit complex, nonlinear dynamics and are structured by multiple factors. Moreover, it often becomes necessary to consider stochastic variation in population dynamics when fitting such complex models to real data. Using recently developed structured coalescent models that accommodate complex population dynamics and population structure, we develop a statistical framework for fitting stochastic epidemiological models to genealogies. By combining particle filtering methods with Bayesian Markov chain Monte Carlo methods, we are able to fit a wide class of stochastic, nonlinear epidemiological models with different forms of population structure to genealogies. We demonstrate our framework using two structured epidemiological models: a model with disease progression between multiple stages of infection and a two-population model reflecting spatial structure. We apply the multi-stage model to HIV genealogies and show that the proposed method can be used to estimate the stage-specific transmission rates and prevalence of HIV. Finally, using the two-population model we explore how much information about population structure is contained in genealogies and what sample sizes are necessary to reliably infer parameters like migration rates. C1 [Rasmussen, David A.; Koelle, Katia] Duke Univ, Dept Biol, Durham, NC 27710 USA. [Volz, Erik M.] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London, England. [Koelle, Katia] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Rasmussen, DA (reprint author), Duke Univ, Dept Biol, Durham, NC 27710 USA. EM david.rasmussen@duke.edu FU U.S. National Science Foundation; NIAID K01 Career Development Award [AI91440]; NSF [NSF-EF-08-27416]; James S. McDonnell Foundation FX DAR was funded by U.S. National Science Foundation Graduate Research Fellowship. EMV was supported by an NIAID K01 Career Development Award (AI91440). KK was supported by a NSF grant (NSF-EF-08-27416) and by a Complex Systems grant from the James S. McDonnell Foundation to KK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 20 Z9 20 U1 1 U2 17 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 APR PY 2014 VL 10 IS 4 AR e1003570 DI 10.1371/journal.pcbi.1003570 PG 16 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA AI0AF UT WOS:000336507500026 PM 24743590 ER PT J AU Vrancken, B Rambaut, A Suchard, MA Drummond, A Baele, G Derdelinckx, I Van Wijngaerden, E Vandamme, AM Van Laethem, K Lemey, P AF Vrancken, Bram Rambaut, Andrew Suchard, Marc A. Drummond, Alexei Baele, Guy Derdelinckx, Inge Van Wijngaerden, Eric Vandamme, Anne-Mieke Van Laethem, Kristel Lemey, Philippe TI The Genealogical Population Dynamics of HIV-1 in a Large Transmission Chain: Bridging within and among Host Evolutionary Rates SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PHYLOGENETIC ANALYSIS; RNA VIRUSES; MOLECULAR EPIDEMIOLOGY; GENOTYPIC RESISTANCE; SEQUENCE ALIGNMENT; DRUG-RESISTANCE; MODEL SELECTION; BAYES FACTORS; WITHIN-HOST AB Transmission lies at the interface of human immunodeficiency virus type 1 (HIV-1) evolution within and among hosts and separates distinct selective pressures that impose differences in both the mode of diversification and the tempo of evolution. In the absence of comprehensive direct comparative analyses of the evolutionary processes at different biological scales, our understanding of how fast within-host HIV-1 evolutionary rates translate to lower rates at the between host level remains incomplete. Here, we address this by analyzing pol and env data from a large HIV-1 subtype C transmission chain for which both the timing and the direction is known for most transmission events. To this purpose, we develop a new transmission model in a Bayesian genealogical inference framework and demonstrate how to constrain the viral evolutionary history to be compatible with the transmission history while simultaneously inferring the within-host evolutionary and population dynamics. We show that accommodating a transmission bottleneck affords the best fit our data, but the sparse within-host HIV-1 sampling prevents accurate quantification of the concomitant loss in genetic diversity. We draw inference under the transmission model to estimate HIV-1 evolutionary rates among epidemiologically-related patients and demonstrate that they lie in between fast intra-host rates and lower rates among epidemiologically unrelated individuals infected with HIV subtype C. Using a new molecular clock approach, we quantify and find support for a lower evolutionary rate along branches that accommodate a transmission event or branches that represent the entire backbone of transmitted lineages in our transmission history. Finally, we recover the rate differences at the different biological scales for both synonymous and non-synonymous substitution rates, which is only compatible with the store and retrieve' hypothesis positing that viruses stored early in latently infected cells preferentially transmit or establish new infections upon reactivation. Author Summary Since its discovery three decades ago, the HIV epidemic has unfolded into one of the most devastating pandemics in human history. When HIV replication cannot be completely inhibited, the fast-evolving retrovirus continuously evades intra-host immune and drug selective pressure, but diversifies according to more neutral epidemiological dynamics at the interhost level. Limited evidence suggests that the virus may evolve faster in a single host than in a population of hosts, and various hypotheses have been put forward to explain this phenomenon. Here, we develop a new computational approach aimed at integrating host transmission information with pathogen genealogical reconstructions. We apply this approach to comprehensive sequence data sets sampled from a large HIV-1 subtype C transmission chain, and in addition to providing several insights into the reconstruction of HIV-1 transmissions histories and its associated population dynamics, we find that transmission decreases the HIV-1 evolutionary rate. The fact that we also identify this decline for substitutions that do not alter amino acid substitutions provides evidence against hypotheses that invoke selection forces. Instead, our findings support earlier reports that new infections start preferentially with less evolved variants, which may be stored in latently infected cells, and this may vary among different HIV-1 subtypes. C1 [Vrancken, Bram; Baele, Guy; Vandamme, Anne-Mieke; Van Laethem, Kristel; Lemey, Philippe] Katholieke Univ Leuven, Rega Inst, Dept Microbiol & Immunol, Leuven, Belgium. [Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland. [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, Dept Biostat, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Drummond, Alexei] Univ Auckland, Allan Wilson Ctr Mol Ecol & Evolut, Auckland 1, New Zealand. [Derdelinckx, Inge; Van Wijngaerden, Eric] Univ Hosp Leuven, Leuven, Belgium. [Vandamme, Anne-Mieke] Univ Nova Lisboa, Ctr Malaria & Outras Doencas Tropicais, Inst Higiene & Med Trop, P-1200 Lisbon, Portugal. [Vandamme, Anne-Mieke] Univ Nova Lisboa, Unidade Microbiol, P-1200 Lisbon, Portugal. RP Vrancken, B (reprint author), Katholieke Univ Leuven, Rega Inst, Dept Microbiol & Immunol, Leuven, Belgium. EM bram.vrancken@rega.kuleuven.be RI Vandamme, Anne Mieke/I-4127-2012; Drummond, Alexei/A-3209-2010; Van Laethem, Kristel/R-6282-2016; OI Vandamme, Anne Mieke/0000-0002-6594-2766; Drummond, Alexei/0000-0003-4454-2576; Van Laethem, Kristel/0000-0001-6036-2271; Rambaut, Andrew/0000-0003-4337-3707 FU Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT Vlaanderen); National Science Foundation [DMS-1264153]; Rutherford Discovery Fellowship from the Royal Society of New Zealand; Onderzoeksfonds KU Leuven/Research Fund KU Leuven; European Union [278433-PREDEMICS]; ERC [260864]; Fonds voor Wetenschappelijk Onderzoek Vlaanderen [G.0611.09N, 1.5.236.11N]; Interuniversity Attraction Poles Programme, Belgian State, Belgian Science Policy [IUAP-VI P6/41]; European Community [223131]; KU Leuven [PF/10/018]; Belgian Ministry of Social Affairs within the Health Insurance System FX BV was supported by a PhD grant from the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT Vlaanderen). MAS is partially supported by National Science Foundation grant DMS-1264153. AD is supported by a Rutherford Discovery Fellowship from the Royal Society of New Zealand. This work was made possible by funding of the Onderzoeksfonds KU Leuven/Research Fund KU Leuven. The research leading to these results has received funding from the European Union Seventh Framework Programme [FP7/2007-2013] under Grant Agreement nr 278433-PREDEMICS and ERC Grant Agreement nr 260864. This work was supported in part by grants from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (G.0611.09N and 1.5.236.11N), by a grant from the Interuniversity Attraction Poles Programme, Belgian State, Belgian Science Policy (IUAP-VI P6/41), by the European Community's Seventh Framework Programme (FP7/2007-2013) under the project "Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN, grant 223131), by KU Leuven (Program Financing no. PF/10/018) and by the AIDS Reference Laboratory of Leuven that receives support from the Belgian Ministry of Social Affairs through a fund within the Health Insurance System. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 71 TC 21 Z9 21 U1 4 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 APR PY 2014 VL 10 IS 4 AR e1003505 DI 10.1371/journal.pcbi.1003505 PG 16 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA AI0AF UT WOS:000336507500025 PM 24699231 ER PT J AU Perez-Edgar, K Hardee, JE Guyer, AE Benson, BE Nelson, EE Gorodetsky, E Goldman, D Fox, NA Pine, DS Ernst, M AF Perez-Edgar, Koraly Hardee, Jillian E. Guyer, Amanda E. Benson, Brenda E. Nelson, Eric E. Gorodetsky, Elena Goldman, David Fox, Nathan A. Pine, Daniel S. Ernst, Monique TI DRD4 and striatal modulation of the link between childhood behavioral inhibition and adolescent anxiety SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE fMRI; caudate; reward; genetics; temperament ID DOPAMINE-RECEPTOR OVERPRODUCTION; NUCLEUS-ACCUMBENS; COGNITIVE CONTROL; SOCIAL ANXIETY; BASAL GANGLIA; TEMPERAMENT; DISORDERS; CHILDREN; BRAIN; ASSOCIATION AB Behavioral inhibition (BI), a temperament characterized by vigilance to novelty, sensitivity to approach-withdrawal cues and social reticence in childhood, is associated with risk for anxiety in adolescence. Independent studies link reward hyper-responsivity to BI, adolescent anxiety and dopamine gene variants. This exploratory study extends these observations by examining the impact of DRD4 genotype and reward hyper-responsivity on the BI-anxiety link. Adolescents (N = 78) completed a monetary incentive delay task in the fMRI environment. Participants were characterized based on a continuous score of BI and the 7-repeat allele (7R+) of the DRD4 functional polymorphism. Parent-report and self-report measures of anxiety were also collected. Across the entire sample, striatal activation increased systematically with increases in the magnitude of anticipated monetary gains and losses. DRD4 status moderated the relation between BI and activation in the caudate nucleus. Childhood BI was associated with parent report of adolescent anxiety among 7R+ participants with elevated levels of striatal response to incentive cues. DRD4 genotype influenced the relations among neural response to incentives, early childhood BI and anxiety. The findings help refine our understanding of the role reward-related brain systems play in the emergence of anxiety in temperamentally at-risk individuals, building a foundation for future larger scale studies. C1 [Perez-Edgar, Koraly] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Perez-Edgar, Koraly] Penn State Univ, Ctr Child Study, University Pk, PA 16802 USA. [Hardee, Jillian E.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Guyer, Amanda E.] Univ Calif Davis, Dept Human Ecol, Davis, CA 95616 USA. [Guyer, Amanda E.] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95616 USA. [Benson, Brenda E.; Nelson, Eric E.; Pine, Daniel S.; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci Branch SDAN, NIH, Bethesda, MD 20892 USA. [Gorodetsky, Elena; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. [Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA. RP Perez-Edgar, K (reprint author), Penn State Univ, Dept Psychol, Ctr Child Study, USB 1, University Pk, PA 16802 USA. EM kxp24@psu.edu RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Nelson, Eric/0000-0002-3376-2453; Perez-Edgar, Koraly/0000-0003-4051-9563; Hardee, Jillian/0000-0001-8230-3045 FU NICHD NIH HHS [R37 HD017899, R37HD17899]; NIMH NIH HHS [U01 MH074454, K01 MH073569, MH073569, MH074454, MH080076, MH094633, R01 MH094633] NR 67 TC 9 Z9 9 U1 3 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD APR PY 2014 VL 9 IS 4 BP 445 EP 453 DI 10.1093/scan/nst001 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AH9UI UT WOS:000336488700007 PM 23314010 ER PT J AU Kan-no, H Saito, Y Omoto, S Minato, S Wakamatsu, H Natori, Y Imamichi, T Takahata, H Yoshimura, Y AF Kan-no, Hiroya Saito, Yukako Omoto, Shun Minato, Sakie Wakamatsu, Hideaki Natori, Yoshihiro Imamichi, Tomozumi Takahata, Hiroki Yoshimura, Yuichi TI Synthesis of a Dihydropyranonucleoside Using an Oxidative Glycosylation Reaction Mediated by Hypervalent Iodine SO SYNTHESIS-STUTTGART LA English DT Article DE glycosylation; nucleoside; oxidation; iodine; antiviral ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO; REPLICATION; NUCLEOSIDES; DERIVATIVES; INFECTIVITY; PROTECTION; INHIBITORS; BCH-189; DESIGN AB As a part of our ongoing studies of structure-activity relationships regarding cyclohexenyl nucleosides, we were prompted to synthesize a dihydropyranonucleoside as a potential anti-HIV agent. The synthesis of a glycal moiety started from but-2-enediol, which was converted into a di-PMB derivative in several steps. The introduction of an allyl group followed by ring-closing metathesis gave a dihydropyran derivative. After isomerization of the double bond catalyzed by Wilkinson's catalyst, the resulting glycal, 2,3-bis[(4-methoxybenzyloxy)methyl]-3,4-dihydro-2H-pyran, was subjected to an oxidative glycosylation reaction mediated by hypervalent iodine. Treatment of 2,3-bis[(4-methoxybenzyloxy)methyl]-3,4-dihydro-2H-pyran with (PhSe)(2)/PhI(OAc)(2)/TMSOTf (cat.) gave the desired pyranyluracils as a mixture of anomers that were converted into the final target, dihydropyranocytidine, after several manipulations and separation of the anomers. C1 [Kan-no, Hiroya; Saito, Yukako; Omoto, Shun; Minato, Sakie; Wakamatsu, Hideaki; Natori, Yoshihiro; Takahata, Hiroki; Yoshimura, Yuichi] Tohoku Pharmaceut Univ, Fac Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9818558, Japan. [Imamichi, Tomozumi] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Takahata, H (reprint author), Tohoku Pharmaceut Univ, Fac Pharmaceut Sci, Aoba Ku, 4-4-1 Komatsushima, Sendai, Miyagi 9818558, Japan. EM yoshimura@tohoku-pharm.ac.jp OI Wakamatsu, Hideaki/0000-0003-4802-6288 FU JSPS [24590143]; Ministry of Education, Culture, Sport, Science, and Technology, Japan (MEXT) FX This work was supported in part by a Grant-in-Aid for Scientific Research (No. 24590143, Y.Y.) from JSPS and by a grant of Strategic Research Foundation Grant-aided Project for Private Universities from Ministry of Education, Culture, Sport, Science, and Technology, Japan (MEXT), 2010-2014. NR 29 TC 3 Z9 3 U1 1 U2 5 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0039-7881 EI 1437-210X J9 SYNTHESIS-STUTTGART JI Synthesis PD APR PY 2014 VL 46 IS 7 BP 879 EP 886 DI 10.1055/s-0033-1340663 PG 8 WC Chemistry, Organic SC Chemistry GA AI4MF UT WOS:000336838800005 ER PT J AU Sangare, M Hendrickson, B Sango, HA Chen, KL Nofziger, J Amara, A Dutra, A Schindler, AB Guindo, A Traore, M Harmison, G Pak, E Yaro, FN Bricceno, K Grunseich, C Chen, GB Boehm, M Zukosky, K Bocoum, N Meilleur, KG Daou, F Bagayogo, K Coulibaly, YI Diakite, M Fay, MP Lee, HS Saad, A Gribaa, M Singleton, AB Maiga, Y Auh, S Landoure, G Fairhurst, RM Burnett, BG Scholl, T Fischbeck, KH AF Sangare, Modibo Hendrickson, Brant Sango, Hammadoun Ali Chen, Kelian Nofziger, Jonathan Amara, Abdelbasset Dutra, Amalia Schindler, Alice B. Guindo, Aldiouma Traore, Mahamadou Harmison, George Pak, Evgenia Yaro, Fatoumata N'Go Bricceno, Katherine Grunseich, Christopher Chen, Guibin Boehm, Manfred Zukosky, Kristen Bocoum, Nouhoum Meilleur, Katherine G. Daou, Fatoumata Bagayogo, Koumba Coulibaly, Yaya Ibrahim Diakite, Mahamadou Fay, Michael P. Lee, Hee-Suk Saad, Ali Gribaa, Moez Singleton, Andrew B. Maiga, Youssoufa Auh, Sungyoung Landoure, Guida Fairhurst, Rick M. Burnett, Barrington G. Scholl, Thomas Fischbeck, Kenneth H. TI Genetics of Low Spinal Muscular Atrophy Carrier Frequency in Sub-Saharan Africa SO ANNALS OF NEUROLOGY LA English DT Article ID MOTOR-NEURON GENE; MOLECULAR ANALYSIS; COPY NUMBER; NAIP GENES; SMN1 GENE; SMA; POPULATION; CONVERSION; PHENOTYPE; DELETION AB ObjectiveSpinal muscular atrophy (SMA) is one of the most common severe hereditary diseases of infancy and early childhood in North America, Europe, and Asia. SMA is usually caused by deletions of the survival motor neuron 1 (SMN1) gene. A closely related gene, SMN2, modifies the disease severity. SMA carriers have only 1 copy of SMN1 and are relatively common (1 in 30-50) in populations of European and Asian descent. SMN copy numbers and SMA carrier frequencies have not been reliably estimated in Malians and other sub-Saharan Africans. MethodsWe used a quantitative polymerase chain reaction assay to determine SMN1 and SMN2 copy numbers in 628 Malians, 120 Nigerians, and 120 Kenyans. We also explored possible mechanisms for SMN1 and SMN2 copy number differences in Malians, and investigated their effects on SMN mRNA and protein levels. ResultsThe SMA carrier frequency in Malians is 1 in 209, lower than in Eurasians. Malians and other sub-Saharan Africans are more likely to have 3 copies of SMN1 than Eurasians, and more likely to lack SMN2 than Europeans. There was no evidence of gene conversion, gene locus duplication, or natural selection from malaria resistance to account for the higher SMN1 copy numbers in Malians. High SMN1 copy numbers were not associated with increased SMN mRNA or protein levels in human cell lines. InterpretationSMA carrier frequencies are much lower in sub-Saharan Africans than in Eurasians. This finding is important to consider in SMA genetic counseling in individuals with black African ancestry. Ann Neurol 2014;75:525-532 C1 [Sangare, Modibo; Chen, Kelian; Nofziger, Jonathan; Schindler, Alice B.; Harmison, George; Bricceno, Katherine; Grunseich, Christopher; Zukosky, Kristen; Meilleur, Katherine G.; Burnett, Barrington G.; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Sangare, Modibo] George Washington Univ, Inst Biomed Sci, Washington, DC USA. [Hendrickson, Brant; Scholl, Thomas] Lab Corp Amer, Westborough, MA USA. [Sango, Hammadoun Ali; Guindo, Aldiouma; Traore, Mahamadou; Bocoum, Nouhoum; Daou, Fatoumata; Bagayogo, Koumba; Coulibaly, Yaya Ibrahim; Landoure, Guida] Univ Bamako, Fac Med & Odontostomatol, Bamako, Mali. [Amara, Abdelbasset; Saad, Ali; Gribaa, Moez] Farhat Hached Univ Hosp, Lab Human Cytogenet Mol Genet & Reprod Biol, Sousse, Tunisia. [Dutra, Amalia; Pak, Evgenia] NHGRI, Lab Cytogenet & Microscopy Core, NIH, Bethesda, MD 20892 USA. [Yaro, Fatoumata N'Go; Landoure, Guida] Univ Hosp Ctr Point G, Neurol Serv, Bamako, Mali. [Chen, Guibin; Boehm, Manfred] NHLBI, NIH, Bethesda, MD 20892 USA. [Meilleur, Katherine G.] NINR, NIH, Bethesda, MD 20892 USA. [Diakite, Mahamadou] Univ Bamako, Fac Pharm, Bamako, Mali. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Lee, Hee-Suk; Auh, Sungyoung] NINDS, Clin Neurosci Program, NIH, Bethesda, MD 20892 USA. [Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Maiga, Youssoufa] Univ Hosp Ctr Gabriel Toure, Bamako, Mali. [Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Fischbeck, KH (reprint author), NINDS, Neurogenet Branch, NIH, 35-2A1000,35 Convent Dr, Bethesda, MD 20892 USA. EM kf@ninds.nih.gov RI Singleton, Andrew/C-3010-2009; OI Amara, Abdelbasset/0000-0002-4504-7772; Fay, Michael P./0000-0002-8643-9625 FU NIH National Institute of Neurologic Disorders and Stroke (NINDS); National Institute of Allergy and Infectious Diseases FX This work was supported by intramural research funding from the NIH National Institute of Neurologic Disorders and Stroke (NINDS) and National Institute of Allergy and Infectious Diseases. NR 40 TC 3 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2014 VL 75 IS 4 BP 525 EP 532 DI 10.1002/ana.24114 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AG2GL UT WOS:000335234200007 PM 24515897 ER PT J AU Roshandel, G Khoshnia, M Sotoudeh, M Merat, S Etemadi, A Nickmanesh, A Norouzi, A Pourshams, A Poustchi, H Semnani, S Ghasemi-Kebria, F Noorbakhsh, R Abnet, C Dawsey, SM Malekzadeh, R AF Roshandel, Gholamreza Khoshnia, Masoud Sotoudeh, Masoud Merat, Shahin Etemadi, Arash Nickmanesh, Arash Norouzi, Alireza Pourshams, Akram Poustchi, Hossein Semnani, Shahryar Ghasemi-Kebria, Fatemeh Noorbakhsh, Roya Abnet, Christian Dawsey, Sanford M. Malekzadeh, Reza TI Endoscopic Screening for Precancerous Lesions of the Esophagus in a High Risk Area in Northern Iran SO ARCHIVES OF IRANIAN MEDICINE LA English DT Article DE Esophageal squamous cell carcinoma; endoscopic screening; northern Iran ID SQUAMOUS-CELL CARCINOMA; ASYMPTOMATIC ADULTS; CYTOLOGIC DETECTION; EARLY-DIAGNOSIS; CANCER; CHINA; POPULATION; LINXIAN; DYSPLASIA; SAMPLERS AB Background: Esophageal squamous cell carcinoma (ESCC) is a major health problem in many developing countries, including Iran. ESCC has a very poor prognosis, largely due to late diagnosis. As a first step in developing an early detection and treatment program, we conducted a population-based endoscopic screening for ESCC and its precursor lesion, esophageal squamous dysplasia (ESD), in asymptomatic adults from Golestan Province, northern Iran (a high-risk area for ESCC) to evaluate the feasibility of such a program and to document the prevalence and risk factor correlates of ESD. Methods: This cross-sectional study was conducted among participants of the Golestan Cohort Study (GCS), a population-based cohort of 50,000 adults in eastern Golestan Province. Randomly selected GCS participants were invited by telephone. Those who accepted were referred to a central endoscopy clinic. Eligible subjects who consented were asked to complete a brief questionnaire. Detailed information about selected risk factors was obtained from the GCS main database. Endoscopic examination with was performed with Lugol's iodine staining; biopsies were taken from unstained lesions as well as the normally stained mucosa of the esophagus, and the biopsies were diagnosed by expert pathologists according to previously described criteria. Results: In total, 1906 GCS subjects were invited, of whom only 302 (15.8%) were successfully enrolled. Esophagitis (29.5%) and ESD (6.0%) were the most common pathological diagnoses. Turkmen ethnicity (adjusted OR = 8.61; 95%CI: 2.48-29.83), being older than the median age (OR = 7.7; 95% CI: 1.99-29.87), and using deep frying cooking methods (OR = 4.65; 95%CI: 1.19-18.22) were the strongest predictors for ESD. There were significant relationships between esophagitis and smoking (p-value<0.001), drinking hot tea (P value = 0.02) and lack of education (P value = 0.004). Conclusion: We observed a low rate of participation in endoscopic screening. The overall prevalence of ESD was 6.0%. Developing non-endoscopic primary screening methods and screening individuals with one or more risk factors may improve these rates. C1 [Roshandel, Gholamreza; Sotoudeh, Masoud; Merat, Shahin; Etemadi, Arash; Nickmanesh, Arash; Pourshams, Akram; Poustchi, Hossein; Noorbakhsh, Roya; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Oncol Res Ctr, Digest Dis Res Inst, Shariati Hosp, Tehran, Iran. [Roshandel, Gholamreza; Khoshnia, Masoud; Norouzi, Alireza; Semnani, Shahryar; Ghasemi-Kebria, Fatemeh] Golestan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan, Iran. [Etemadi, Arash; Abnet, Christian; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Khoshnia, M (reprint author), Golestan Res Ctr Gastroenterol & Hepatol, 10th Azar Alley,4th Azar St, Gorgan, Golestan Provin, Iran. EM khoshniamd@gmail.com RI Abnet, Christian/C-4111-2015; Etemadi, Arash/C-1386-2016; Norouzi, Alireza/L-6872-2016; Roshandel, gholamreza/N-2260-2016; Semnani, Shahryar/N-2270-2016; Khoshnia, Masoud/P-5665-2016; OI Abnet, Christian/0000-0002-3008-7843; Etemadi, Arash/0000-0002-3458-1072; Norouzi, Alireza/0000-0003-4227-7350; Roshandel, gholamreza/0000-0002-5494-0722; Semnani, Shahryar/0000-0002-8768-6142; Khoshnia, Masoud/0000-0001-7352-8058; Malekzadeh, Reza/0000-0003-1043-3814 FU Digestive Disease Research Institute (DDRI); Tehran University of Medical Sciences (TUMS); Golestan Research Center of Gastroenterology and Hepatology (GRCGH); Golestan University of Medical Sciences (GOUMS); National Cancer Institute, NIH FX The authors would like to thank Dr. Sharifi, Ms. Kor, Dr. Khalilipour Dr. Abaie, Mr. Yolmeh, Ataie, Mrs. Nasi and Mrs. Mohammadi for their valuable work in data collection and sample processing. This study was supported by the Digestive Disease Research Institute (DDRI) affiliated with Tehran University of Medical Sciences (TUMS); the Golestan Research Center of Gastroenterology and Hepatology (GRCGH) affiliated with Golestan University of Medical Sciences (GOUMS); and in part by the Intramural Research Program of the National Cancer Institute, NIH. NR 38 TC 6 Z9 6 U1 0 U2 3 PU ACAD MEDICAL SCIENCES I R IRAN PI TEHRAN PA PO BOX 19395-5655, TEHRAN, 00000, IRAN SN 1029-2977 J9 ARCH IRAN MED JI Arch. Iran. Med. PD APR PY 2014 VL 17 IS 4 SI SI BP 246 EP 252 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AH8WX UT WOS:000336420000004 PM 24724600 ER PT J AU Caccuri, F Rueckert, C Giagulli, C Schulze, K Basta, D Zicari, S Marsico, S Cervi, E Fiorentini, S Slevin, M Guzman, CA Caruso, A AF Caccuri, Francesca Rueckert, Christine Giagulli, Cinzia Schulze, Kai Basta, Daniele Zicari, Sonia Marsico, Stefania Cervi, Edoardo Fiorentini, Simona Slevin, Mark Guzman, Carlos A. Caruso, Arnaldo TI HIV-1 Matrix Protein p17 Promotes Lymphangiogenesis and Activates the Endothelin-1/Endothelin B Receptor Axis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE angiogenesis factor; endothelin-1; HIV-1; lymphatic endothelial cells; MAP kinase signaling pathways; p17 matrix protein ID LYMPHATIC ENDOTHELIAL-CELLS; AIDS-RELATED LYMPHOMAS; WEIBEL-PALADE BODIES; PROINFLAMMATORY CYTOKINES; ANTIRETROVIRAL-THERAPY; EMERGING ROLE; CANCER; ANGIOGENESIS; MACROPHAGES; METASTASIS AB Objective AIDS-related lymphomas are high grade and aggressively metastatic with poor prognosis. Lymphangiogenesis is essential in supporting proliferation and survival of lymphoma, as well as tumor dissemination. Data suggest that aberrant lymphangiogenesis relies on action of HIV-1 proteins rather than on a direct effect of the virus itself. HIV-1 matrix protein p17 was found to accumulate and persist in lymph nodes of patients even under highly active antiretroviral therapy. Because p17 was recently found to exert a potent proangiogenic activity by interacting with chemokine (C-X-C motif) receptors 1 and 2, we tested the prolymphangiogenic activity of the viral protein. Approach and Results Human primary lymph node-derived lymphatic endothelial cells were used to perform capillary-like structure formation, wound healing, spheroids, and Western blot assays after stimulation with or without p17. Here, we show that p17 promotes lymphangiogenesis by binding to chemokine (C-X-C motif) receptor-1 and chemokine (C-X-C motif) receptor-2 expressed on lymph node-derived lymphatic endothelial cells and activating the Akt/extracellular signal-regulated kinase signaling pathway. In particular, it was found to induce capillary-like structure formation, sprout formation from spheroids, and increase lymph node-derived lymphatic endothelial cells motility. The p17 lymphangiogenic activity was, in part, sustained by activation of the endothelin-1/endothelin receptor B axis. A Matrigel plug assay showed that p17 was able to promote the outgrowth of lymphatic vessels in vivo, demonstrating that p17 directly regulates lymphatic vessel formation. Conclusions Our results suggest that p17 may generate a prolymphangiogenic microenvironment and plays a role in predisposing the lymph node to lymphoma growth and metastasis. This finding offers new opportunities to identify treatment strategies in combating AIDS-related lymphomas. C1 [Caccuri, Francesca; Giagulli, Cinzia; Basta, Daniele; Zicari, Sonia; Fiorentini, Simona; Caruso, Arnaldo] Univ Brescia, Dept Mol & Translat Med, Microbiol Sect, Brescia, Italy. [Cervi, Edoardo] Univ Brescia, Dept Med & Surg Sci, Vasc Surg Sect, Brescia, Italy. [Caccuri, Francesca] NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA. [Rueckert, Christine; Schulze, Kai; Guzman, Carlos A.] Helmholtz Ctr Infect Res, Dept Vaccinol & Appl Microbiol, Braunschweig, Germany. [Marsico, Stefania] Univ Calabria, Dept Pharmacobiol, I-87036 Cosenza, Italy. [Slevin, Mark] Manchester Metropolitan Univ, Sch Healthcare Sci, Manchester M15 6BH, Lancs, England. RP Caruso, A (reprint author), Univ Brescia, Dept Mol & Translat Med, Microbiol Sect, Brescia, Italy. EM caruso@med.unibs.it OI Cervi, Edoardo/0000-0002-3127-2864; MARSICO, Stefania/0000-0003-1598-0526 FU Istituto Superiore di Sanita (AIDS grant) [40G.16]; Bonino-Pulejo Foundation (Messina, Italy) FX This work was supported by the Istituto Superiore di Sanita (AIDS grant 40G.16) and, in part, by the Bonino-Pulejo Foundation (Messina, Italy). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. NR 47 TC 9 Z9 9 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2014 VL 34 IS 4 BP 846 EP 856 DI 10.1161/ATVBAHA.113.302478 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AG7OM UT WOS:000335607500023 PM 24482377 ER PT J AU Yin, XY Subramanian, S Hwang, SJ O'Donnell, CJ Fox, CS Courchesne, P Muntendam, P Gordon, N Adourian, A Juhasz, P Larson, MG Levy, D AF Yin, Xiaoyan Subramanian, Subha Hwang, Shih-Jen O'Donnell, Christopher J. Fox, Caroline S. Courchesne, Paul Muntendam, Pieter Gordon, Neal Adourian, Aram Juhasz, Peter Larson, Martin G. Levy, Daniel TI Protein Biomarkers of New-Onset Cardiovascular Disease Prospective Study From the Systems Approach to Biomarker Research in Cardiovascular Disease Initiative SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE biological markers; cardiovascular diseases; epidemiology; myocardial infarction; proteomics ID CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; FUNCTIONAL-ACTIVITY; HEART-DISEASE; RISK-FACTORS; CYCLOPHILIN; TETRANECTIN; EVENTS; GENE; ATHEROSCLEROSIS AB Objective Incorporation of novel plasma protein biomarkers may improve current models for prediction of atherosclerotic cardiovascular disease (ASCVD) risk. Approach and Results We used discovery mass spectrometry (MS) to determine plasma concentrations of 861 proteins in 135 myocardial infarction (MI) cases and 135 matched controls. Then, we measured 59 markers by targeted MS in 336 ASCVD case-control pairs. Associations with MI or ASCVD were tested in single-marker and multiple-marker analyses adjusted for established ASCVD risk factors. Twelve single markers from discovery MS were associated with MI incidence (at P<0.01), adjusting for clinical risk factors. Seven proteins in aggregate (cyclophilin A, cluster of differentiation 5 molecule [CD5] antigen-like, cell-surface glycoprotein mucin cell surface associated protein 18 [MUC-18], collagen- 1 [XVIII] chain, salivary -amylase 1, C-reactive protein, and multimerin-2) were highly associated with MI (P<0.0001) and significantly improved its prediction compared with a model with clinical risk factors alone (C-statistic of 0.71 versus 0.84). Through targeted MS, 12 single proteins were predictors of ASCVD (at P<0.05) after adjusting for established risk factors. In multiple-marker analyses, 4 proteins in combination (-1-acid glycoprotein 1, paraoxonase 1, tetranectin, and CD5 antigen-like) predicted incident ASCVD (P<0.0001) and moderately improved the C-statistic from the model with clinical covariates alone (C-statistic of 0.69 versus 0.73). Conclusions Proteomics profiling identified single- and multiple-marker protein panels that are associated with new-onset ASCVD and may lead to a better understanding of underlying disease mechanisms. Our findings include many novel protein biomarkers that, if externally validated, may improve risk assessment for MI and ASCVD. C1 [Yin, Xiaoyan; Subramanian, Subha; Hwang, Shih-Jen; O'Donnell, Christopher J.; Fox, Caroline S.; Courchesne, Paul; Larson, Martin G.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Yin, Xiaoyan; Larson, Martin G.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Subramanian, Subha; Hwang, Shih-Jen; O'Donnell, Christopher J.; Fox, Caroline S.; Levy, Daniel] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Subramanian, Subha; Hwang, Shih-Jen; O'Donnell, Christopher J.; Fox, Caroline S.; Levy, Daniel] NHLBI, Populat Sci Branch, Bethesda, MD 20892 USA. [Muntendam, Pieter; Gordon, Neal; Adourian, Aram; Juhasz, Peter] BG Med Inc, Waltham, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Levy, Daniel] Boston Med Ctr, Dept Med, Boston, MA USA. [Levy, Daniel] Boston Med Ctr, Div Cardiol, Boston, MA USA. RP Levy, D (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM levyd@nih.gov FU National Institutes of Health [N01-HC-25195]; Division of Intramural Research of the National Heart, Lung, and Blood Institute FX The Framingham Heart Study is funded by the National Institutes of Health contract N01-HC-25195; this research was also supported by the Division of Intramural Research of the National Heart, Lung, and Blood Institute. NR 27 TC 19 Z9 19 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2014 VL 34 IS 4 BP 939 EP 945 DI 10.1161/ATVBAHA.113.302918 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AG7OM UT WOS:000335607500034 PM 24526693 ER PT J AU Napolitano, R Dhami, J Ohuma, EO Ioannou, C Conde-Agudelo, A Kennedy, SH Villar, J Papageorghiou, AT AF Napolitano, R. Dhami, J. Ohuma, E. O. Ioannou, C. Conde-Agudelo, A. Kennedy, S. H. Villar, J. Papageorghiou, A. T. TI Pregnancy dating by fetal crown-rump length: a systematic review of charts SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Review DE Crown-rump length; dating chart; gestational age; pregnancy dating; ultrasound ID LAST MENSTRUAL PERIOD; INTRAUTERINE GROWTH RESTRICTION; HUMAN CHORIONIC-GONADOTROPIN; ASSESSING GESTATIONAL-AGE; 1ST TRIMESTER; TRANSVAGINAL SONOGRAPHY; ULTRASONIC MEASUREMENT; BIPARIETAL DIAMETER; EMBRYONIC LENGTH; ULTRASONOGRAPHIC MEASUREMENTS AB BackgroundFetal crown-rump length (CRL) measurement by ultrasound in the first trimester is the standard method for pregnancy dating; however, a multitude of CRL equations to estimate gestational age (GA) are reported in the literature. ObjectiveTo evaluate the methodological quality used in studies reporting CRL equations to estimate GA using a set of predefined criteria. Search strategySearches of MEDLINE, EMBASE, and CINAHL databases, from 1948 to 31 January 2011, and secondary reference sources, were performed. Selection criteriaObservational ultrasound studies, where the primary aim was to create equations for GA estimation using a CRL measurement. Data collection and analysisIncluded studies were scored against predefined independently agreed methodological criteria: an overall quality score was calculated for each study. Main resultsThe searches yielded 1142 citations. Two reviewers screened the papers and independently assessed the full-text versions of 29 eligible studies. The highest potential for bias was noted in inclusion and exclusion criteria, and in maternal demographic characteristics. No studies had systematic ultrasound quality-control measures. The four studies with the highest scores (lowest risk of bias) satisfied 18 or more of the 29 criteria; these showed lower variation in GA estimation than the remaining, lower-scoring studies. This was particularly evident at the extremes of GA. Author's conclusionsConsiderable methodological heterogeneity and limitations exist in studies reporting CRL equations for estimating GA, and these result in a wide range of estimated GAs for any given CRL; however, when studies with the highest methodological quality are used, this range is reduced. C1 [Napolitano, R.; Dhami, J.; Ohuma, E. O.; Ioannou, C.; Kennedy, S. H.; Villar, J.; Papageorghiou, A. T.] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England. [Conde-Agudelo, A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA. [Conde-Agudelo, A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA. [Kennedy, S. H.; Villar, J.; Papageorghiou, A. T.] Univ Oxford, Oxford Maternal & Perinatal Hlth Inst, Green Templeton Coll, Oxford, England. RP Papageorghiou, AT (reprint author), John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Oxford OX3 9DU, England. EM aris.papageorghiou@obs-gyn.ox.ac.uk FU Bill & Melinda Gates Foundation; Oxford Partnership Comprehensive Biomedical Research Centre; Department of Health's National Institute for Health Research (NIHR) Biomedical Research Centres FX All authors are part of the INTERGROWTH-21st Project, an international study of fetal growth (www.intergrowth21.org.uk) funded by the Bill & Melinda Gates Foundation to the University of Oxford, for which we are very grateful. C. Ioannou and A. T. Papageorghiou are supported by the Oxford Partnership Comprehensive Biomedical Research Centre, with funding from the Department of Health's National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme. NR 86 TC 15 Z9 15 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD APR PY 2014 VL 121 IS 5 BP 556 EP 565 DI 10.1111/1471-0528.12478 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AE9MF UT WOS:000334331200006 PM 24387345 ER PT J AU Flegel, WA Johnson, ST Keller, MA Klapper, EB Khuu, HM Moulds, JM Seltsam, AW Stack, G St-Louis, M Tormey, CA Wagner, FF Weinstock, C Yazer, MH Denomme, GA AF Flegel, Willy A. Johnson, Susan T. Keller, Margaret A. Klapper, Ellen B. Khuu, Hanh M. Moulds, Joann M. Seltsam, Axel W. Stack, Gary St-Louis, Maryse Tormey, Christopher A. Wagner, Franz F. Weinstock, Christof Yazer, Mark H. Denomme, Gregory A. TI Molecular immunohaematology round table discussions at the AABB Annual Meeting, Boston 2012 SO BLOOD TRANSFUSION LA English DT Article ID CELL TRANSPLANTATION; STEM-CELL; ABO; TRANSFUSION; PATIENT; SAMPLES C1 [Flegel, Willy A.; Khuu, Hanh M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Johnson, Susan T.; Denomme, Gregory A.] BloodCtr Wisconsin, Milwaukee, WI USA. [Keller, Margaret A.] Amer Red Cross, Philadelphia, PA USA. [Klapper, Ellen B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Moulds, Joann M.] Lifeshare Blood Ctr, Shreveport, LA USA. [Seltsam, Axel W.; Wagner, Franz F.] German Red Cross Blood Serv NSTOB, Springe, Germany. [Stack, Gary; Tormey, Christopher A.] Yale Univ, Sch Med, New Haven, CT USA. [St-Louis, Maryse] Hema Quebec, Quebec City, PQ, Canada. [Weinstock, Christof] German Red Cross Blood Serv Baden Wurttemberg Hes, Inst Clin Transfus Med & Immunogenet Ulm, Ulm, Germany. [Yazer, Mark H.] Inst Transfus Med, Pittsburgh, PA USA. RP Flegel, WA (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM bill.flegel@nih.gov RI Stack, Gary/E-9646-2014; OI Stack, Gary/0000-0002-6501-7255; Denomme, Gregory/0000-0001-8727-1679 FU Intramural Research Program of the NIH Clinical Center FX This work was supported by the Intramural Research Program of the NIH Clinical Center. NR 17 TC 3 Z9 3 U1 0 U2 0 PU SIMITI SERVIZI SRL PI MILAN PA VIA DESIDERIO 21, MILAN, 20131, ITALY SN 1723-2007 J9 BLOOD TRANSFUS-ITALY JI Blood Transf. PD APR PY 2014 VL 12 IS 2 BP 280 EP 286 DI 10.2450/2013.0022-13 PG 7 WC Hematology SC Hematology GA AH7VY UT WOS:000336344700021 PM 24333058 ER PT J AU Issaq, SH Teicher, BA Monks, A AF Issaq, Sameer H. Teicher, Beverly A. Monks, Anne TI Bioenergetic properties of human sarcoma cells help define sensitivity to metabolic inhibitors SO CELL CYCLE LA English DT Article DE sarcoma; rhabdomyosarcoma; osteosarcoma; bioenergetics; 2-DG; metformin ID OXIDATIVE STRESS; IN-VIVO; CANCER; 2-DEOXYGLUCOSE; OSTEOSARCOMA; RHABDOMYOSARCOMA; APOPTOSIS; METFORMIN; TARGETS AB Sarcomas represent a diverse group of malignancies with distinct molecular and pathological features. A better understanding of the alterations associated with specific sarcoma subtypes is critically important to improve sarcoma treatment. Renewed interest in the metabolic properties of cancer cells has led to an exploration of targeting metabolic dependencies as a therapeutic strategy. In this study, we have characterized key bioenergetic properties of human sarcoma cells in order to identify metabolic vulnerabilities between sarcoma subtypes. We have also investigated the effects of compounds that inhibit glycolysis or mitochondrial respiration, either alone or in combination, and examined relationships between bioenergetic parameters and sensitivity to metabolic inhibitors. Using 2-deoxy-D-glucose (2-DG), a competitive inhibitor of glycolysis, oligomycin, an inhibitor of mitochondrial ATP synthase, and metformin, a widely used anti-diabetes drug and inhibitor of complex I of the mitochondrial respiratory chain, we evaluated the effects of metabolic inhibition on sarcoma cell growth and bioenergetic function. Inhibition of glycolysis by 2-DG effectively reduced the viability of alveolar rhabdomyosarcoma cells vs. embryonal rhabdomyosarcoma, osteosarcoma, and normal cells. Interestingly, inhibitors of mitochondrial respiration did not significantly affect viability, but were able to increase sensitivity of sarcomas to inhibition of glycolysis. Additionally, inhibition of glycolysis significantly reduced intracellular ATP levels, and sensitivity to 2-DG-induced growth inhibition was related to respiratory rates and glycolytic dependency. Our findings demonstrate novel relationships between sarcoma bioenergetics and sensitivity to metabolic inhibitors, and suggest that inhibition of metabolic pathways in sarcomas should be further investigated as a potential therapeutic strategy. C1 [Issaq, Sameer H.; Monks, Anne] Leidos Biomed Res Inc, Mol Pharmacol Branch, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Teicher, Beverly A.] NCI, Div Canc Treatment & Diag, Rockville, MD USA. RP Monks, A (reprint author), Leidos Biomed Res Inc, Mol Pharmacol Branch, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM monksa@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported, in part, by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. NR 23 TC 4 Z9 5 U1 1 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2014 VL 13 IS 7 BP 1152 EP 1161 DI 10.4161/cc.28010 PG 10 WC Cell Biology SC Cell Biology GA AG5JR UT WOS:000335455800016 PM 24553119 ER PT J AU Magnani, JW Benjamin, EJ AF Magnani, Jared W. Benjamin, Emelia J. TI Where Do We Come From? Where Are We Going? Adverse Outcomes in Catheter Ablation for Atrial Fibrillation SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Editorial Material DE Editorials; atrial fibrillation; catheter ablation; outcome assessment (health care); pericardium; women ID PROCEDURAL VOLUME; WORLDWIDE SURVEY; COMPLICATIONS; SAFETY; EFFICACY; THERAPY; TRIAL C1 [Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Boston, MA USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01HL102214, 2R01HL092577-05, R01 HL092577, R01 HL102214]; NIA NIH HHS [1R03AG045075, R03 AG045075] NR 23 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD APR PY 2014 VL 7 IS 2 BP 195 EP 197 DI 10.1161/CIRCEP.114.001577 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG1XO UT WOS:000335209700004 PM 24736422 ER PT J AU Magnani, JW Moser, CB Murabito, JM Sullivan, LM Wang, N Ellinor, PT Vasan, RS Benjamin, EJ Coviello, AD AF Magnani, Jared W. Moser, Carlee B. Murabito, Joanne M. Sullivan, Lisa M. Wang, Na Ellinor, Patrick T. Vasan, Ramachandran S. Benjamin, Emelia J. Coviello, Andrea D. TI Association of Sex Hormones, Aging, and Atrial Fibrillation in Men The Framingham Heart Study SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE aging; atrial fibrillation; epidemiology; men ID POPULATION-BASED COHORT; LOW TESTOSTERONE LEVELS; LOW SERUM TESTOSTERONE; ELDERLY-MEN; ATHEROSCLEROSIS RISK; METABOLIC SYNDROME; CARDIOVASCULAR-DISEASE; MORTALITY; ESTRADIOL; FAILURE AB Background Endogenous sex hormones have been related to cardiovascular outcomes and mortality. We hypothesized that sex hormones are related to atrial fibrillation (AF) in a community-based cohort of middle-aged to older men. Methods and Results We examined testosterone, estradiol, and dehydroepiandrosterone sulfate in relation to incident AF in men participating in the Framingham Heart Study. We assessed the 10-year risk of AF in multivariable-adjusted hazard models. The cohort consisted of 1251 men (age, 68.08.2 years), of whom 275 developed incident AF. We identified a significant interaction between age and testosterone and, therefore, stratified men into age 55 to 69 years (n=786), 70 to 79 years (n=351), and 80 years (n=114). In men aged 55 to 69 years, each 1 SD decrease in testosterone was associated with hazard ratio (HR) 1.30 (95% confidence interval [CI], 1.07-1.59) for incident AF. The association between testosterone and 10-year incident AF in men 70 to 79 years did not reach statistical significance. In men 80 years, a 1 SD decrease in testosterone was associated with HR 3.53 (95% CI, 1.96-6.37) for AF risk. Estradiol was associated with incident AF (HR, 1.12; 95% CI, 1.01-1.26). Dehydroepiandrosterone sulfate had a borderline association with risk of AF that was not statistically significant (HR, 1.12; 95% CI, 0.99-1.28). Conclusions Testosterone and estradiol are associated with incident AF in a cohort of older men. Testosterone deficiency in men 80 years is strongly associated with AF risk. The clinical and electrophysiological mechanisms underlying the associations between sex hormones and AF in older men merit continued investigation. C1 [Magnani, Jared W.; Murabito, Joanne M.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Coviello, Andrea D.] NHLBI, Boston, MA USA. [Magnani, Jared W.; Murabito, Joanne M.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Coviello, Andrea D.] Boston Univ, Framingham Heart Study, Boston, MA 02118 USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Murabito, Joanne M.] Boston Univ, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Coviello, Andrea D.] Boston Univ, Dept Med, Div Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Moser, Carlee B.; Sullivan, Lisa M.; Wang, Na] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.; Coviello, Andrea D.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF219028, 13EIA14220013]; National Institutes of Health [1R03AG045075, HL092577, RO1AG028321, RC1-HL01056, 1R01HL102214, R01 AG29451, 1RO1HL104156, 1K24HL105780, RO1HL094755, 6R01-NS17950, N01-HC25195]; Boston University School of Medicine Department of Medicine Career Investment Award FX This work was supported by an American Heart Association award to J.W.M. (09FTF219028) and P.T.E (13EIA14220013). This work was supported by grants from the National Institutes of Health 1R03AG045075 (to J.W.M.), HL092577 (to E.J.B. and P.T.E.), RO1AG028321, RC1-HL01056, 1R01HL102214 (to E.J.B.), R01 AG29451 (to J.M.M.), 1RO1HL104156, 1K24HL105780 (to P.T.E.), RO1HL094755 (to A.D.C.), 6R01-NS17950, and N01-HC25195, J.W.M. is further supported by a Boston University School of Medicine Department of Medicine Career Investment Award. The authors are solely responsible for the design and conduct of this study, the study analyses, and the drafting and editing of the article, and its final contents. NR 43 TC 12 Z9 12 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD APR PY 2014 VL 7 IS 2 BP 307 EP 312 DI 10.1161/CIRCEP.113.001322 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG1XO UT WOS:000335209700021 PM 24610804 ER PT J AU Lee, HM Giguere, PM Roth, BL AF Lee, Hyeong-Min Giguere, Patrick M. Roth, Bryan L. TI DREADDs: novel tools for drug discovery and development SO DRUG DISCOVERY TODAY LA English DT Review ID PROTEIN-COUPLED RECEPTORS; DESIGNED G(I)-COUPLED RECEPTOR; FUNCTIONAL SELECTIVITY; CONDITIONAL EXPRESSION; SEROTONIN RECEPTORS; SIGNAL-TRANSDUCTION; TRANSGENIC MICE; PATHWAYS; LIGANDS; TARGETS AB Since the invention of the first designer receptors exclusively activated by designer drugs (DREADDs), these engineered G protein-coupled receptors (GPCRs) have been widely applied in investigations of biological processes and behaviors. DREADD technology has emerged as a powerful tool with great potential for drug discovery and development. DREADDs can facilitate the identification of druggable targets and enable researchers to explore the activities of novel drugs against both known and orphan GPCRs. Here, we discuss how DREADDs can be used as novel tools for drug discovery and development. C1 [Roth, Bryan L.] Univ N Carolina, Div Chem Biol & Med Chem, Chapel Hill Med Sch, Dept Pharmacol, Chapel Hill, NC 27514 USA. Univ N Carolina, Chapel Hill Med Sch, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27514 USA. RP Roth, BL (reprint author), Univ N Carolina, Div Chem Biol & Med Chem, Chapel Hill Med Sch, Dept Pharmacol, 4072 Genetic Med Bldg, Chapel Hill, NC 27514 USA. EM bryan_roth@med.unc.edu RI Lee, HM/D-2777-2011; Roth, Bryan/F-3928-2010 FU NIDA NIH HHS [R01 DA017204]; NIMH NIH HHS [R01 MH061887, U19 MH082441] NR 44 TC 28 Z9 29 U1 3 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 EI 1878-5832 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD APR PY 2014 VL 19 IS 4 BP 469 EP 473 DI 10.1016/j.drudis.2013.10.018 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH5UL UT WOS:000336196500015 PM 24184433 ER PT J AU Noureddin, M Wright, EC Ghany, MG AF Noureddin, Mazen Wright, Elizabeth C. Ghany, Marc G. TI Disease Progression During Advanced Fibrosis: IL28B Genotype or HCV RNA Levels? Reply SO HEPATOLOGY LA English DT Letter C1 [Noureddin, Mazen; Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Wright, Elizabeth C.] NIDDK, Off Director, NIH, Bethesda, MD 20892 USA. RP Noureddin, M (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 2 TC 0 Z9 0 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 APR PY 2014 VL 59 IS 4 BP 1651 EP 1651 DI 10.1002/hep.26690 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD4VQ UT WOS:000333249800053 PM 23959972 ER PT J AU Wang, J You, XZ Wu, WS Guillen, MR Cabrerizo, M Sullivan, J Donner, E Bjornson, B Gaillard, WD Adjouadi, M AF Wang, Jin You, Xiaozhen Wu, Wensong Guillen, Magno R. Cabrerizo, Mercedes Sullivan, Joseph Donner, Elizabeth Bjornson, Bruce Gaillard, William D. Adjouadi, Malek TI Classification of FMRI Patterns-A Study of the Language Network Segregation in Pediatric Localization Related Epilepsy SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; language networks; PCA; eigensystem; eigenvectors; lateralization index; visual rating system; nearest neighbor classifier; distance-based fuzzy classifier ID FUNCTIONAL MRI; BRAIN ACTIVATION; HEMISPHERIC LATERALIZATION; WADA TEST; DOMINANCE; CHILDREN; TASK; REORGANIZATION; OPTIMIZATION; REGISTRATION AB This article describes a pattern classification algorithm for pediatric epilepsy using fMRI language-related activation maps. 122 fMRI datasets from a control group (64) and localization related epilepsy patients (58) provided by five children's hospitals were used. Each subject performed an auditory description decision task. Using the artificial data as training data, incremental Principal Component Analysis was used in order to generate the feature space while overcoming memory requirements of large datasets. The nearest-neighbor classifier (NNC) and the distance-based fuzzy classifier (DFC) were used to perform group separation into left dominant, right dominant, bilateral, and others. The results show no effect of age, age at seizure onset, seizure duration, or seizure etiology on group separation. Two sets of parameters were significant for group separation, the patient vs. control populations and handedness. Of the 122 real datasets, 90 subjects gave the same classification results across all the methods (three raters, LI, bootstrap LI, NNC, and DFC). For the remaining datasets, 18 cases for the IPCA-NNC and 21 cases for the IPCA-DFC agreed with the majority of the five classification results (three visual ratings and two LI results). Kappa values vary from 0.59 to 0.73 for NNC and 0.61 to 0.75 for DFC, which indicate good agreement between NNC or DFC with traditional methods. The proposed method as designed can serve as an alternative method to corroborate existing LI and visual rating classification methods and to resolve some of the cases near the boundaries in between categories. Hum Brain Mapp 35:1446-1460, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Wang, Jin; You, Xiaozhen; Guillen, Magno R.; Cabrerizo, Mercedes; Adjouadi, Malek] Florida Int Univ, Dept Elect & Comp Engn, Miami, FL 33174 USA. [You, Xiaozhen] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. [Wu, Wensong] Florida Int Univ, Dept Math & Stat, Miami, FL 33174 USA. [Guillen, Magno R.] Miami Childrens Hosp, Miami, FL USA. [Sullivan, Joseph] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Donner, Elizabeth] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Bjornson, Bruce] BC Childrens Hosp, Vancouver, BC, Canada. [Gaillard, William D.] George Washington Univ, Childrens Natl Med Ctr, Dept Neurosci, Washington, DC USA. [Gaillard, William D.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. RP Adjouadi, M (reprint author), Florida Int Univ, Coll Engn & Comp, 10555 W Flagler St,EAS 2672, Miami, FL 33174 USA. EM adjouadi@fiu.edu RI Bjornson, Bruce/A-8616-2010; OI Bjornson, Bruce/0000-0002-1465-6196; Guilen, Magno/0000-0001-9649-8429 FU National Science Foundation [CNS-0959985HRD-0833093CNS-1042341]; NINDS [R01 NS44280]; Children's Research Institute Avery Award, Intellectual and Developmental Disabilities Research Center at Children's National Medical Center [NIH IDDRC P30HD40677]; General Clinic Research Center [NIH GCRC M01-RR13297]; American Epilepsy Society FX Contract grant sponsor: National Science Foundation; Contract grant number: CNS-0959985HRD-0833093CNS-1042341; Contract grant sponsor: NINDS; Contract grant number: R01 NS44280 (Partnership for Pediatric Research Epilepsy Foundation); Contract grant sponsor: Children's Research Institute Avery Award, Intellectual and Developmental Disabilities Research Center at Children's National Medical Center; Contract grant number: NIH IDDRC P30HD40677; Contract; Contract grant sponsor: General Clinic Research Center; Contract grant number: NIH GCRC M01-RR13297; Contract grant sponsor: American Epilepsy Society. NR 71 TC 7 Z9 7 U1 0 U2 4 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 APR PY 2014 VL 35 IS 4 BP 1446 EP 1460 DI 10.1002/hbm.22265 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AE9MP UT WOS:000334332200029 PM 23450847 ER PT J AU Oh, YS Galis, ZS AF Oh, Young S. Galis, Zorina S. TI Anatomy of Success The Top 100 Cited Scientific Reports Focused On Hypertension Research SO HYPERTENSION LA English DT Review ID HIGH BLOOD-PRESSURE; JOINT NATIONAL COMMITTEE; INDEPENDENT PREDICTOR; IMPACT FACTOR; 7TH REPORT; PREVENTION; ARTICLES; PREVALENCE; PROGNOSIS; DISEASE C1 [Oh, Young S.; Galis, Zorina S.] NHLBI, Vasc Biol & Hypertens Branch, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. RP Oh, YS (reprint author), NHLBI, Vasc Biol & Hypertens Branch, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8106, Bethesda, MD 20892 USA. EM yoh@mail.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 36 TC 10 Z9 10 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD APR PY 2014 VL 63 IS 4 BP 641 EP 647 DI 10.1161/HYPERTENSIONAHA.113.02677 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC7CT UT WOS:000332685500015 PM 24379185 ER PT J AU Longosz, AF Morrison, CS Chen, PL Arts, E Nankya, I Salata, RA Franco, V Quinn, TC Eshleman, SH Laeyendecker, O AF Longosz, Andrew F. Morrison, Charles S. Chen, Pai-Lien Arts, Eric Nankya, Immaculate Salata, Robert A. Franco, Veronica Quinn, Thomas C. Eshleman, Susan H. Laeyendecker, Oliver TI Immune Responses in Ugandan Women Infected With Subtypes A andDHIV Using the BED Capture Immunoassay and an Antibody Avidity Assay SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE subtype; incidence; BED-CEIA; avidity; immune response; Uganda ID HIV INCIDENCE ESTIMATION; VIRUS INCIDENCE RATES; ENZYME-IMMUNOASSAY; ANTIRETROVIRAL TREATMENT; SPECIFICITY; SEROCONVERSION; CHALLENGES; AFRICA; RAKAI AB Introduction:Analysis of samples from Uganda using serologic HIV incidence assays reveal that individuals with subtype D infection often have weak humoral immune responses to HIV infection. It is unclear whether this reflects a poor initial response to infection or a waning antibody response later in infection.Materials and Methods:Samples (N = 2614) were obtained from 114 women aged 18-45 years in the Ugandan Genital Shedding and Disease Progression Study cohort (2001-2009; 82 subtype A, 32 subtype D; median 23 samples/women, range 3-41 samples, median follow-up of 6.6 years). Samples were analyzed using the BED capture immunoassay (cutoff, 0.8 OD-n) and the avidity assay (cutoff, 90% Avidity Index). Antibody maturation was assessed by having the BED capture enzyme immunoassay (BED-CEIA) or avidity value exceed the assay cutoff 1 or 2 years after infection. The waning antibody response was measured by having the BED-CEIA or avidity value fall >20% below the maximum value.Results:For the BED-CEIA, 8 women with subtype A infection and 3 women with subtype D infection never progressed previously the cutoff value (median, 5.9 years follow-up after infection). Six women with subtype D infection never achieved an avidity index >90%. Subtype did not impact the proportion of women whose assay values regressed by >20% of the maximal value (for BED-CEIA: 33% for A, 41% for D, P = 0.51; for avidity: 1% for A, 6% for D, P = 0.19).Discussion:The higher frequency of misclassification of individuals with long-term subtype D infection as recently infected using serologic incidence assays reflects a weak initial antibody response to HIV infection that is sustained over time. C1 [Longosz, Andrew F.; Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD USA. [Morrison, Charles S.; Chen, Pai-Lien] Family Hlth Int 360, Clin Sci, Durham, NC USA. [Arts, Eric; Nankya, Immaculate; Salata, Robert A.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Franco, Veronica; Quinn, Thomas C.; Eshleman, Susan H.; Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Laeyendecker, O (reprint author), NIAID, Div Intramural Res, NIH, 855 North Wolfe St,Room 538A, Baltimore, MD USA. EM olaeyen1@jhmi.edu OI Laeyendecker, Oliver/0000-0002-6429-4760 FU Centers for Disease Control and Prevention (CDC) [200-2010-35109-00001]; HIV Prevention Trials Network (HPTN); National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Office of AIDS Research, of the National Institutes of Health (NIH); Department of Health and Human Services (DHHS) [UM1-AI068613]; NIAID [R01-AI095068]; Division of Intramural Research, NIAID, and NIH FX Supported by the Centers for Disease Control and Prevention (CDC) under contract no. 200-2010-35109-00001. The research was also supported by the HIV Prevention Trials Network (HPTN) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the Office of AIDS Research, of the National Institutes of Health (NIH), Department of Health and Human Services (DHHS) (UM1-AI068613) and (NIAID) R01-AI095068. An additional funding was provided in part by the Division of Intramural Research, NIAID, and NIH. NR 32 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 1 PY 2014 VL 65 IS 4 BP 390 EP 396 DI 10.1097/QAI.0000000000000006 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AD3PU UT WOS:000333159000010 PM 24583613 ER PT J AU Chen, M Jen, I Chen, YH Lin, MW Bhatia, K Sharp, GB Law, MG Chen, YMA AF Chen, Marcelo Jen, Ian Chen, Yi-Hsien Lin, Ming-Wei Bhatia, Kishor Sharp, Gerald B. Law, Matthew G. Chen, Yi-Ming Arthur TI Cancer Incidence in a Nationwide HIV/AIDS Patient Cohort in Taiwan in 1998-2009 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; AIDS; standardized incidence rates; cancer ID ACTIVE ANTIRETROVIRAL THERAPY; HIV OBSERVATIONAL DATABASE; COLORECTAL-CANCER; VIRUS; RISK; AIDS; INFECTION; PEOPLE; ERA; ASIA AB Background:The aims of this study were to investigate the cancer incidence and risk in HIV/AIDS patients relative to the general population in Taiwan.Methods:Using Taiwan's National Health Insurance Research Database, 15,269 HIV/AIDS patients were identified between 1998 and 2009. Gender-specific incidence densities (IDs) of both AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC) after HIV infection were calculated. Age-, sex-, and period-adjusted standardized incidence rates (SIRs) were obtained using 1.8 million people from the general population as controls.Results:A total of 1117 male and 165 female HIV/AIDS patients were diagnosed with cancer. Non-Hodgkin lymphoma (n = 196; ID = 328.79/100,000 person-years) and cervical cancer (n = 50; ID = 712.08/100,000 person-years) were the most common ADCs, whereas liver cancer (n = 125; ID = 184.52/100,000 person-years) and colon cancer (n = 11; ID = 156.66/100,000 person-years) were the most common NADCs in males and females, respectively. Period-adjusted gender-specific ADC and NADC rates decreased from more than 1500 cases/100,000 person-years to less than 500 cases/100,000 person-years (P < 0.001 for trend). SIRs of ADCs and NADCs also decreased. However, relative to the general population, increased SIRs were still seen for most cancers, many of which had an infectious etiology. The highest SIRs in ADCs and NADCs were seen in Kaposi sarcoma [SIR = 298.0, 95% confidence interval (CI): 258.16 to 343.85] and anal cancer (SIR = 19.10, 95% CI: 12.80 to 27.50).Conclusion:This study showed that although the cancer incidence rates have significantly decreased in the highly active antiretroviral therapy era, HIV/AIDS patients were still at increased risk of ADCs and most NADCs. Cancer screening, especially for infection-related NADCs, should therefore be promoted. C1 [Chen, Marcelo] Mackay Mem Hosp, Dept Urol, Taipei, Taiwan. [Chen, Marcelo] Mackay Jr Coll Med Nursing & Management, Dept Cosmet Applicat & Management, Taipei, Taiwan. [Chen, Marcelo] Mackay Med Coll, Sch Med, New Taipei City, Taiwan. [Jen, Ian; Lin, Ming-Wei] Natl Yang Ming Univ, Dept & Inst Publ Hlth, Taipei 112, Taiwan. [Chen, Yi-Hsien; Chen, Yi-Ming Arthur] Kaohsiung Med Univ, Ctr Infect Dis & Canc Res, Kaohsiung 807, Taiwan. [Bhatia, Kishor] NCI, AIDS Malignancy Program, NIH, Bethesda, MD 20892 USA. [Sharp, Gerald B.] NIAID, Epidemiol Branch, Basic Sci Program, Div AIDS,NIH, Bethesda, MD 20892 USA. [Law, Matthew G.] Univ New S Wales, Kirby Inst, Sydney, NSW, Australia. [Chen, Yi-Ming Arthur] Kaohsiung Med Univ, Coll Med, Dept Microbiol, Kaohsiung 807, Taiwan. [Chen, Yi-Ming Arthur] Kaohsiung Med Univ, Coll Med, Inst Med Res, Kaohsiung 807, Taiwan. RP Chen, YMA (reprint author), Kaohsiung Med Univ, Ctr Infect Dis & Canc Res, Kaohsiung 807, Taiwan. EM arthur@kmu.edu.tw FU Asia Pacific HIV Research Collaboration, an initiative of TREAT Asia, a program of amfAR; Foundation for AIDS Research; US National Institute of Health's National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute, as part of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) [U01AI069907]; Dutch Ministry of Foreign Affairs through Stichting Aids Fonds; Australian Government Department of Health and Ageing; Faculty of Medicine, the University of New South Wales FX Supported in part by the Asia Pacific HIV Research Collaboration, an initiative of TREAT Asia, a program of amfAR, the Foundation for AIDS Research, with support from the US National Institute of Health's National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Cancer Institute, as part of the International Epidemiologic Databases to Evaluate AIDS (IeDEA; U01AI069907), and from the Dutch Ministry of Foreign Affairs through a partnership with Stichting Aids Fonds. The Kirby Institute is funded by the Australian Government Department of Health and Ageing and is affiliated with the Faculty of Medicine, the University of New South Wales. NR 33 TC 6 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 1 PY 2014 VL 65 IS 4 BP 463 EP 472 DI 10.1097/QAI.0000000000000065 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AD3PU UT WOS:000333159000019 PM 24583616 ER PT J AU Coyne, GO Madan, RA Gulley, JL AF Coyne, Geraldine O'Sullivan Madan, Ravi A. Gulley, James L. TI Nivolumab: Promising Survival Signal Coupled With Limited Toxicity Raises Expectations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RECOMBINANT INTERLEUKIN-2 THERAPY; RESISTANT PROSTATE-CANCER; DOSE-ESCALATION TRIAL; METASTATIC MELANOMA; PHASE-III; IPILIMUMAB; DACARBAZINE; VACCINE; SAFETY C1 [Coyne, Geraldine O'Sullivan; Madan, Ravi A.; Gulley, James L.] NCI, Bethesda, MD 20892 USA. RP Coyne, GO (reprint author), NCI, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; OI Gulley, James/0000-0002-6569-2912; O'Sullivan Coyne, Geraldine/0000-0002-2918-6326 NR 13 TC 15 Z9 15 U1 1 U2 5 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 APR 1 PY 2014 VL 32 IS 10 BP 986 EP 988 DI 10.1200/JCO.2013.54.5996 PG 3 WC Oncology SC Oncology GA AG0XF UT WOS:000335138400005 ER PT J AU Brennan-Laun, SE Ezelle, HJ Li, XL Hassel, BA AF Brennan-Laun, Sarah E. Ezelle, Heather J. Li, Xiao-Ling Hassel, Bret A. TI RNase-L Control of Cellular mRNAs: Roles in Biologic Functions and Mechanisms of Substrate Targeting SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Review ID PROTEIN-KINASE PKR; INTERFERON-TREATED CELLS; AU-RICH-ELEMENT; ANTIVIRAL INNATE IMMUNITY; BINDING-PROTEIN; 2-5A-DEPENDENT RNASE; PROSTATE-CANCER; ENCEPHALOMYOCARDITIS VIRUS; RIBONUCLEASE-L; GROWTH-FACTOR AB RNase-L is a mediator of type 1 interferon-induced antiviral activity that has diverse and critical cellular roles, including the regulation of cell proliferation, differentiation, senescence and apoptosis, tumorigenesis, and the control of the innate immune response. Although RNase-L was originally shown to mediate the endonucleolytic cleavage of both viral and ribosomal RNAs in response to infection, more recent evidence indicates that RNase-L also functions in the regulation of cellular mRNAs as an important mechanism by which it exerts its diverse biological functions. Despite this growing body of work, many questions remain regarding the roles of mRNAs as RNase-L substrates. This review will survey known and putative mRNA substrates of RNase-L, propose mechanisms by which it may selectively cleave these transcripts, and postulate future clinical applications. C1 [Brennan-Laun, Sarah E.; Ezelle, Heather J.; Hassel, Bret A.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Brennan-Laun, Sarah E.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Ezelle, Heather J.; Hassel, Bret A.] Baltimore Vet Affairs Med Ctr, Res Serv, Baltimore, MD USA. [Li, Xiao-Ling] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Hassel, BA (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, 660 West Baltimore St,Howard Hall Room 324, Baltimore, MD 21201 USA. EM bhassel@som.umaryland.edu FU NIH [AI077556]; VA Merit Award; NIH T32 Cancer Biology Training Grant; National Cancer Institute [T32CA154274] FX Research described in this review was funded in part by NIH Grant AI077556 (B. A. H.), a VA Merit Award (B. A. H.), and the NIH T32 Cancer Biology Training Grant (S. E. B.-L.). The project described was supported by Award No. T32CA154274 from the National Cancer Institute. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 126 TC 14 Z9 14 U1 1 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 EI 1557-7465 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD APR 1 PY 2014 VL 34 IS 4 BP 275 EP 288 DI 10.1089/jir.2013.0147 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA AE1WR UT WOS:000333763800007 PM 24697205 ER PT J AU Blackshear, PJ Perera, L AF Blackshear, Perry J. Perera, Lalith TI Phylogenetic Distribution and Evolution of the Linked RNA-Binding and NOT1-Binding Domains in the Tristetraprolin Family of Tandem CCCH Zinc Finger Proteins SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Review ID AU-RICH ELEMENT; MESSENGER-RNA; SCHIZOSACCHAROMYCES-POMBE; IRON-DEFICIENCY; TNF-ALPHA; DEADENYLATION; DEGRADATION; RECRUITMENT; ZFP36L3; COMPLEX AB In humans, the tristetraprolin or TTP family of CCCH tandem zinc finger (TZF) proteins comprises 3 members, encoded by the genes ZFP36, ZFP36L1, and ZFP36L2. These proteins have direct orthologues in essentially all vertebrates studied, with the exception of birds, which appear to lack a version of ZFP36. Additional family members are found in rodents, amphibians, and fish. In general, the encoded proteins contain 2 critical macromolecular interaction domains: the CCCH TZF domain, which is necessary for high-affinity binding to AU-rich elements in mRNA; and an extreme C-terminal domain that, in the case of TTP, interacts with NOT1, the scaffold of a large multi-protein complex that contains deadenylases. TTP and its related proteins act by first binding to AU-rich elements in mRNA, and then recruiting deadenylases to the mRNA, where they can processively remove the adenosine residues from the poly(A) tail. Highly conserved TZF domains have been found in unicellular eukaryotes such as yeasts, and these domains can bind AU-rich elements that resemble those bound by the mammalian proteins. However, certain fungi appear to lack proteins with intact TZF domains, and the TTP family proteins that are expressed in other fungi often lack the characteristic C-terminal NOT1 binding domain found in the mammalian proteins. For these reasons, we investigated the phylogenetic distribution of the relevant sequences in available databases. Both domains are present in family member proteins from most lineages of eukaryotes, suggesting their mutual presence in a common ancestor. However, the vertebrate type of NOT1-binding domain is missing in most fungi, and the TZF domain itself has disappeared or degenerated in recently evolved fungi. Nonetheless, both domains are present together in the proteins from several unicellular eukaryotes, including at least 1 fungus, and they seem to have remained together during the evolution of metazoans. C1 [Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. [Perera, Lalith] NIEHS, Lab Struct Biol, Res Triangle Pk, NC 27709 USA. RP Blackshear, PJ (reprint author), NIEHS, Lab Signal Transduct, F1-13,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM black009@niehs.nih.gov FU NIEHS, NIH FX The authors are grateful to the members of their laboratories for helpful discussions, and to Guang Hu and Dori Germolec for useful comments on this article. They thank Marc Fabian for the coordinates of the original TTP-NOT1 crystal structure, Sebastian Shimeld for helpful discussions, and Melissa Wells for insights on Pneumocystis. This study was supported by the Intramural Research Program of the NIEHS, NIH. NR 27 TC 12 Z9 12 U1 3 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 EI 1557-7465 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD APR 1 PY 2014 VL 34 IS 4 BP 297 EP 306 DI 10.1089/jir.2013.0150 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA AE1WR UT WOS:000333763800009 PM 24697206 ER PT J AU Anton, LC Yewdell, JW AF Anton, Luis C. Yewdell, Jonathan W. TI Translating DRiPs: MHC class I immunosurveillance of pathogens and tumors SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE antigen processing; cotranslational degradation; translation; ribosome; compartmentalization; nuclear translation ID MAJOR HISTOCOMPATIBILITY COMPLEX; DEFECTIVE RIBOSOMAL PRODUCTS; MESSENGER-RNA DECAY; PROTEIN-QUALITY CONTROL; NEWLY SYNTHESIZED POLYPEPTIDES; CYTOTOXIC LYMPHOCYTES-T; ELONGATION-FACTOR 1A; OPEN READING FRAME; NUCLEAR TRANSLATION; ENDOPLASMIC-RETICULUM AB Review on the generation of antigenic peptides. MHC class I molecules display oligopeptides on the cell surface to enable T cell immunosurveillance of intracellular pathogens and tumors. Speed is of the essence in detecting viruses, which can complete a full replication cycle in just hours, whereas tumor detection is typically a finding-the-needle-in-the-haystack exercise. We review current evidence supporting a nonrandom, compartmentalized selection of peptidogenic substrates that focuses on rapidly degraded translation products as a main source of peptide precursors to optimize immunosurveillance of pathogens and tumors. C1 [Anton, Luis C.] Univ Autonoma Madrid, Consejo Super Invest Cient, Ctr Biol Mol Severo Ochoa, Madrid, Spain. [Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 33, Bethesda, MD 20892 USA. EM jyewdell@niaid.nih.gov RI Anton, Luis/C-4740-2013 OI Anton, Luis/0000-0001-9665-011X FU Spanish Ministerio de Economia y Competitividad; Fundacion Ramon Areces; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health FX L.C.A. is supported by a grant from the Spanish Ministerio de Economia y Competitividad. The Centro de Biologia Molecular Severo Ochoa is supported by an institutional grant from the Fundacion Ramon Areces (L. C. A.). J.W.Y. is generously supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health. NR 175 TC 23 Z9 23 U1 0 U2 11 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD APR PY 2014 VL 95 IS 4 BP 551 EP 562 DI 10.1189/jlb.1113599 PG 12 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA AG3UW UT WOS:000335346300001 PM 24532645 ER PT J AU Kohr, MJ Evangelista, AM Ferlito, M Steenbergen, C Murphy, E AF Kohr, Mark J. Evangelista, Alicia M. Ferlito, Marcella Steenbergen, Charles Murphy, Elizabeth TI S-nitrosylation of TRIM72 at cysteine 144 is critical for protection against oxidation-induced protein degradation and cell death SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Tripartite motif-containing protein 72; Mitsugumin 53; S-nitrosylation; Oxidation; Cardioprotection; Cell death ID MEMBRANE REPAIR; MYOCARDIAL INJURY; NITROSOTHIOLS AB Oxidative stress and membrane damage following myocardial ischemia/reperfusion injury are important contributors to cardiomyocyte death and the loss of myocardial function. Our previous study identified cysteine 144 (C144) of tripartite motif-containing protein 72 (TRIM72) as a potential site for S-nitrosylation (SNO). TRIM72 is a cardioprotective membrane repair protein that can be both activated and targeted for degradation by different oxidative modifications. Consistent with the potential regulation of TRIM72 by various oxidative modifications, we found that SNO levels increased at C144 of TRIM72 with ischemic preconditioning. Therefore, to investigate the role of 044 in the regulation of TRIM72 function, we mutated 044 of TRIM72 to a serine residue (TRIM72(C144S)), and expressed either TRIM72(WT) or TRIM72(C144S) in HEK-293 cells, which lack endogenous TRIM72, in order to examine the effect of this mutation on the functional stability of TRIM72 and on cell survival. We hypothesized that SNO of TRIM72 stabilizes the protein, thus allowing for membrane repair and enhanced cell survival. Upon treatment with hydrogen peroxide (H2O2), we found that TRIM72(WT) levels were decreased, but not TRIM72(C144S) and this correlated with increased H2O2-induced cell death in TRIM72(WT) cells. Additionally, we found that treatment with the cardioprotective S-nitrosylating agent S-nitrosoglutathione (GSNO), was able to preserve TRIM72(WT) protein levels and enhance TRIM72(WT)-mediated cell survival, but had no effect on TRIM72(C144S) levels. Consistent with our hypothesis, GSNO was also found to increase SNO levels and inhibit H2O2-induced irreversible oxidation for TRIM72(WT) without affecting TRIM72(C144S). In further support of our hypothesis, GSNO blocked the ischemia/reperfusion-induced decrease in TRIM72 levels and reduced infarct size in a Langendorff-perfused heart model. The results of these studies have important implications for cardioprotection and suggest that SNO of TRIM72 at C144 prevents the oxidation-induced degradation of TRIM72 following oxidative insult, therefore enhancing cardiomyocyte survival. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Kohr, Mark J.; Evangelista, Alicia M.; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Kohr, Mark J.; Steenbergen, Charles] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Cardiovasc Pathol, Baltimore, MD 21205 USA. [Ferlito, Marcella] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. RP Kohr, MJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Div Cardiovasc Pathol, 632 Ross Res Bldg 720 Rutland Ave, Baltimore, MD 21205 USA. EM mkohr1@jhmi.edu OI Kohr, Mark/0000-0002-6034-5962 FU NHLBI/NIH Intramural Program [ZO1HL006059, ZO1HL002066]; NIH [1K99HL114721, 5R01HL039752]; American Heart Association [12BGIA11780030] FX This work was supported by the NHLBI/NIH Intramural Program (ZO1HL006059 and ZO1HL002066, AE and EM), NIH grants 1K99HL114721 (MK) and 5R01HL039752 (CS), and the American Heart Association (12BGIA11780030, MK). We would also like to acknowledge the technical assistance of the NHLBI/NIH Light Microscopy Core Facility and the NHLBI/NIH Proteomics Core Facility. NR 24 TC 14 Z9 18 U1 0 U2 11 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD APR PY 2014 VL 69 BP 67 EP 74 DI 10.1016/j.yjmcc.2014.01.010 PG 8 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA AH7UF UT WOS:000336340100008 PM 24487118 ER PT J AU Almeida-Suhett, CP Li, Z Marini, AM Braga, MFM Eiden, LE AF Almeida-Suhett, Camila P. Li, Zheng Marini, Ann M. Braga, Maria F. M. Eiden, Lee E. TI Temporal Course of Changes in Gene Expression Suggests a Cytokine-Related Mechanism for Long-Term Hippocampal Alteration after Controlled Cortical Impact SO JOURNAL OF NEUROTRAUMA LA English DT Article DE Ccl2; Lcn2; mild traumatic brain injury (mTBI); controlled cortical injury (CCI); Ccl7 ID TRAUMATIC BRAIN-INJURY; HEAD-INJURY; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE; MOUSE MODEL; RAT; CHEMOKINES; MODULATION; IMPAIRMENT; ASTROCYTES AB Mild traumatic brain injury (mTBI) often has long-term effects on cognitive function and social behavior. Altered gene expression may be predictive of long-term psychological effects of mTBI, even when acute clinical effects are minimal or transient. Controlled cortical impact (CCI), which causes concussive, but nonpenetrant, trauma to underlying (non-cortical) brain, resulting in persistent changes in hippocampal synaptic function, was used as a model of mTBI. The hippocampal transcriptomes of sham-operated or injured male rats at 1, 7, and 30 days postinjury were examined using microarrays comprising a comprehensive set of expressed genes, subsequently confirmed by quantitative reverse-transcriptase polymerase chain reaction. Transcripts encoding the chemokines, chemokine (C-C motif) ligand (Ccl)2 and Ccl7, inflammatory mediators lipocalin-2 (Lcn2) and tissue inhibitor of metalloproteinase 1 (Timp1), immunocyte activators C-C chemokine receptor type 5 (Ccr5) and Fc fragment of IgG, low affinity IIb, receptor (CD32) (Fcgr2b), the major histocompatibility complex II immune response-related genes, Cd74 and RT1 class II, locus Da (RT1-Da), the complement component, C3, and the transcription factor, Kruppel-like factor 4 (Klf4), were identified as early (Ccl2, Ccl7, Lcn2, and Timp1), intermediate (Ccr5, Fcgr2b, Cd74, RT1-Da, and C3), and late (Klf4) markers for bilateral hippocampal response to CCI. Ccl2 and Ccl7 transcripts were up-regulated within 24 h after CCI, and their elevation subsided within 1 week of injury. Other transcriptional changes occurred later and were more stable, some persisting for at least 1 month, suggesting that short-term inflammatory responses trigger longer-term alteration in the expression of genes previously associated with injury, aging, and neuronal function in the brain. These transcriptional responses to mTBI may underlie long-term changes in excitatory and inhibitory neuronal imbalance in hippocampus, leading to long-term behavioral consequences of mTBI. C1 [Almeida-Suhett, Camila P.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Program Neurosci, Bethesda, MD 20814 USA. [Li, Zheng] Natl Inst Mental Hlth, Unit Synapse Dev & Plast, Bethesda, MD 20892 USA. [Marini, Ann M.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Neurol, Bethesda, MD 20814 USA. [Braga, Maria F. M.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Anat, Bethesda, MD 20814 USA. [Braga, Maria F. M.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Physiol, Bethesda, MD 20814 USA. [Braga, Maria F. M.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Genet, Bethesda, MD 20814 USA. [Braga, Maria F. M.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Psychiat, Bethesda, MD 20814 USA. [Eiden, Lee E.] Natl Inst Mental Hlth, Sect Mol Neurosci, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Eiden, LE (reprint author), Natl Inst Mental Hlth, Sect Mol Neurosci, Lab Cellular & Mol Regulat, 9000 Rockville Pike Bldg 49,Room 5A-38, Bethesda, MD 20892 USA. EM eidenl@mail.nih.gov RI Li, Zheng/I-8016-2014; OI Li, Zheng/0000-0002-2978-2531; Eiden, Lee/0000-0001-7524-944X FU NIMH Intramural Research Program; Department of Defense FX The authors thank Charisse Winston (NIMH-IRP Technical IRTA) and Dr. Babru Samal (NIMH Bioinformatics Core Specialist), for contributions to early phases of this work, and Dr. Abdel Eklahloun (Core Manager, NIHGRI-NIMH-NINCDS Microarray Core Facility) for invaluable assistance and consultation throughout the duration of these experiments. Work reported here was funded, in part, by the NIMH Intramural Research Program and by a grant from the Department of Defense administered through the Center for Neuroscience and Regenerative Medicine. The contributions of Djida Ait-Ali, who participated in the project as a Henry M. Jackson Foundation Research Fellow, are acknowledged here in lieu of co-authorship for which her written permission could not be obtained. NR 47 TC 11 Z9 11 U1 0 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD APR 1 PY 2014 VL 31 IS 7 BP 683 EP 690 DI 10.1089/neu.2013.3029 PG 8 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA AD7PB UT WOS:000333455000010 PM 24344922 ER PT J AU Yucesoy, B Johnson, VJ Lummus, ZL Kashon, ML Rao, M Bannerman-Thompson, H Frye, B Wang, W Gautrin, D Cartier, A Boulet, LP Sastre, J Quirce, S Tarlo, SM Germolec, DR Luster, MI Bernstein, DI AF Yucesoy, Berran Johnson, Victor J. Lummus, Zana L. Kashon, Michael L. Rao, Marepalli Bannerman-Thompson, Hansen Frye, Bonnie Wang, Wei Gautrin, Denyse Cartier, Andre Boulet, Louis-Philippe Sastre, Joaquin Quirce, Santiago Tarlo, Susan M. Germolec, Dori R. Luster, Michael I. Bernstein, David I. TI Genetic Variants in the Major Histocompatibility Complex Class I and Class II Genes Are Associated With Diisocyanate-Induced Asthma SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID HLA CLASS-II; ISOCYANATE-INDUCED ASTHMA; INDUCED OCCUPATIONAL ASTHMA; EXPOSED WORKERS; POPULATION; ANTIBODIES; SENSITIZATION; ANNOTATION; CONJUGATE; HAPLOTYPE AB Objective: To investigate the association between single nucleotide polymorphisms (SNPs) located across the major histocompatibility complex and susceptibility to diisocyanate-induced asthma (DA). Methods: The study population consisted of 140 diisocyanate-exposed workers. Genotyping was performed using the Illumina GoldenGate major histocompatibility complex panels. Results: The HLA-E rs1573294 and HLA-DPB1 rs928976 SNPs were associated with an increased risk of DA under dominant (odds ratio [OR], 6.27; 95% confidence interval [CI], 2.37 to 16.6; OR, 2.79, 95% CI, 0.99 to 7.81, respectively) and recessive genetic models (OR, 6.27, 95% CI, 1.63 to 24.13; OR, 10.10, 95% CI, 3.16 to 32.33, respectively). The HLA-B rs1811197, HLA-DOA rs3128935, and HLA-DQA2 rs7773955 SNPs conferred an increased risk of DA in a dominant model (OR, 7.64, 95% CI, 2.25 to 26.00; OR, 19.69, 95% CI, 2.89 to 135.25; OR, 8.43, 95% CI, 3.03 to 23.48, respectively). Conclusion: These results suggest that genetic variations within HLA genes play a role in DA risk. C1 [Yucesoy, Berran; Kashon, Michael L.; Frye, Bonnie; Wang, Wei] NIOSH, Hlth Effects Lab Div, CDC, Morgantown, WV USA. [Johnson, Victor J.] BRT, Morrisville, NC USA. [Yucesoy, Berran; Lummus, Zana L.; Bernstein, David I.] Univ Cincinnati, Div Immunol Allergy & Rheumatol, Dept Med, Cincinnati, OH 45267 USA. [Rao, Marepalli; Bannerman-Thompson, Hansen] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH 45267 USA. [Gautrin, Denyse; Cartier, Andre] Univ Montreal, Hop Sacre Coeur Montreal, Ste Foy, PQ, Canada. [Boulet, Louis-Philippe] Univ Laval, Hop Laval, Ste Foy, PQ G1K 7P4, Canada. [Sastre, Joaquin] Fdn Jimenez Diaz, Dept Allergy, E-28040 Madrid, Spain. CIBER Enfermedades Resp CIBERES, Madrid, Spain. [Quirce, Santiago] Hosp La Paz IdiPAZ, Dept Allergy, Madrid, Spain. [Tarlo, Susan M.] Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada. [Germolec, Dori R.] NIEHS, Toxicol Branch, DNTP, Res Triangle Pk, NC 27709 USA. [Luster, Michael I.] W Virginia Univ, Sch Publ Hlth, Morgantown, WV 26506 USA. RP Yucesoy, B (reprint author), Univ Cincinnati, Coll Med, Div Immunol Allergy & Rheumatol, Cincinnati, OH 45267 USA. EM yucesobn@ucmail.uc.edu FU National Institute of Environmental Health Sciences [Y1-ES0001]; National Institute for Occupational Safety and Health [Y1-ES0001]; NIOSH/CDC [R01 OH 008795]; CDC Seed Funding for Public Health Genomics Research Program FX This work was supported in part by an interagency agreement between National Institute of Environmental Health Sciences and National Institute for Occupational Safety and Health (Agreement No. Y1-ES0001), NIOSH/CDC R01 OH 008795 and CDC Seed Funding for Public Health Genomics Research Program. The authors declare no conflict of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health. This article may be the work product of an employee or a group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH); however, the statements, opinions, or conclusions contained therein do not necessarily represent the statements, opinions, or conclusions of NIEHS, NIH, or the US government. NR 42 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD APR PY 2014 VL 56 IS 4 BP 382 EP 387 DI 10.1097/JOM.0000000000000138 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AG6ZJ UT WOS:000335567400013 PM 24709764 ER PT J AU Arteta, M Campbell, A Nouraie, M Rana, S Onyekwere, OC Ensing, G Sable, C Dham, N Darbari, D Luchtman-Jones, L Kato, GJ Gladwin, MT Castro, OL Minniti, CP Gordeuk, VR AF Arteta, Manuel Campbell, Andrew Nouraie, Mehdi Rana, Sohail Onyekwere, Onyinye C. Ensing, Gregory Sable, Craig Dham, Niti Darbari, Deepika Luchtman-Jones, Lori Kato, Gregory J. Gladwin, Mark T. Castro, Oswaldo L. Minniti, Caterina P. Gordeuk, Victor R. TI Abnormal Pulmonary Function and Associated Risk Factors in Children and Adolescents With Sickle Cell Anemia SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE sickle cell anemia; pulmonary function tests; obstructive pulmonary function; lactate dehydrogenase; reticulocyte count ID ACUTE CHEST SYNDROME; REGURGITANT JET VELOCITY; LOWER AIRWAY-OBSTRUCTION; LUNG-FUNCTION; METHACHOLINE CHALLENGE; SOMATIC GROWTH; DISEASE; ASTHMA; ADULTS; STANDARDIZATION AB Obstructive and restrictive pulmonary changes develop in children with sickle cell disease, but reports conflict as to the type of change that predominates. We prospectively performed spirometry, plethysmography, and lung diffusing capacity in 146 children aged 7 to 20 years with hemoglobin SS or S-0-thalassemia. Nineteen percent of the patients had obstructive physiology as defined according to guidelines of the American Thoracic Society. In addition, 9% had restrictive physiology and 11% had abnormal but not categorized physiology. Increasing age, patient-reported or family-reported history of asthma or wheezing, and higher lactate dehydrogenase concentration were independent predictors of obstruction as reflected in lower forced expiratory volume in the first second/forced vital capacity. In conclusion, abnormal pulmonary function, most often obstructive, is common in children with hemoglobin SS and S-0-thalassemia. Full pulmonary function testing should be performed in children with hemoglobin SS or S-0-thalassemia, especially with history of asthma or wheezing and accentuated elevations in hemolytic markers. C1 [Arteta, Manuel; Campbell, Andrew; Ensing, Gregory] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Nouraie, Mehdi; Rana, Sohail; Onyekwere, Onyinye C.; Castro, Oswaldo L.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Sable, Craig; Dham, Niti; Darbari, Deepika; Luchtman-Jones, Lori] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. [Kato, Gregory J.; Minniti, Caterina P.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Gladwin, Mark T.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Gordeuk, Victor R.] Univ Illinois, Sickle Cell Ctr, Chicago, IL 60612 USA. RP Gordeuk, VR (reprint author), Univ Illinois, Sickle Cell Ctr, M-C 712,Suite 172,Clin Sci Bldg,820 South Wood St, Chicago, IL 60612 USA. EM vgordeuk@uic.edu RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU NHLBI [1 (R01 HL079912-02), 2 (R25 HL003679-08)]; Howard University GCRC from NCRR, NIH, Bethesda, MD [2 (MOI RR10284-10)]; Division of Intramural Research of the National Institutes of Health [1 ZIA HL006016-03] FX Supported in part by Grant Nos. 1 (R01 HL079912-02) and 2 (R25 HL003679-08) from NHLBI, by Howard University GCRC Grant No. 2 (MOI RR10284-10) from NCRR, NIH, Bethesda, MD, and by the Division of Intramural Research of the National Institutes of Health (No. 1 ZIA HL006016-03). NR 32 TC 6 Z9 6 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1077-4114 EI 1536-3678 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD APR PY 2014 VL 36 IS 3 BP 185 EP 189 DI 10.1097/MPH.0000000000000011 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AG3XE UT WOS:000335352400016 PM 24309610 ER PT J AU Thomas, A Lee, JH Abdullaev, Z Park, KS Pineda, M Saidkhodjaeva, L Miettinen, M Wang, YS Pack, SD Giaccone, G AF Thomas, Anish Lee, Jih-Hsiang Abdullaev, Zied Park, Kang-Seo Pineda, Marbin Saidkhodjaeva, Lola Miettinen, Markku Wang, Yisong Pack, Svetlana D. Giaccone, Giuseppe TI Characterization of Fibroblast Growth Factor Receptor 1 in Small-Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Small-cell lung cancer; FGFR1; Focal amplification; Copy number gain ID GENOME AB Introduction: There remains a significant therapeutic need for small-cell lung cancer (SCLC). We and others have reported high frequency of copy number gains in cytogenetic bands encoding fibroblast growth factor receptor 1 (FGFR1) in SCLC tumors and cell lines. Methods: Thirteen SCLC cell lines and 68 SCLC patient tumor samples were studied for FGFR1 amplification. Growth inhibition assays were performed using PD173074, a pan-FGFR inhibitor to determine the correlation between FGFR1 expression and drug sensitivity. Results: We did not detect FGFR1 mutations in SCLC cell lines. Focal amplification of FGFR1 gene was found in five tumor samples (7%), with high-level focal amplification in only one tumor sample (1%). Amplification owing to polysomy of chromosome 8, where FGFR1 locates, was observed in 22 tumor samples (32%). There was no correlation between FGFR1 gene copy number and messenger RNA expression or protein expression in SCLC cells. FGFR inhibitor sensitivity correlated with FGFR1 copy number determined by real-time polymerase chain reaction assay (r= -0.79; p = 0.01). Conclusion:FGFR1 gene mutations and focal amplification are rare in SCLC, but polysomy of chromosome 8 is relatively common. FGFR1 copy number gain predicts sensitivity to FGFR inhibition, and FGFR expression correlates inversely with chemosensitivity. C1 [Thomas, Anish; Lee, Jih-Hsiang; Park, Kang-Seo; Wang, Yisong; Giaccone, Giuseppe] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Abdullaev, Zied; Saidkhodjaeva, Lola; Miettinen, Markku; Pack, Svetlana D.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Pineda, Marbin] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Giaccone, G (reprint author), Georgetown Univ, Lombardi Canc Ctr, Res Bldg Room W503,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM gg496@georgetown.edu RI Pack, Svetlana/C-2020-2014; Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Thomas, Anish/0000-0003-3293-3115 FU National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institutes of Health. NR 12 TC 10 Z9 10 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD APR PY 2014 VL 9 IS 4 BP 567 EP 571 DI 10.1097/JTO.0000000000000089 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AD3MO UT WOS:000333145300026 PM 24736083 ER PT J AU Voller, B Lines, E McCrossin, G Artiles, A Tinaz, S Lungu, C Hallett, M Haubenberger, D AF Voller, Bernhard Lines, Emily McCrossin, Gayle Artiles, Aaron Tinaz, Sule Lungu, Codrin Hallett, Mark Haubenberger, Dietrich TI Alcohol challenge and sensitivity to change of the essential tremor rating assessment scale SO MOVEMENT DISORDERS LA English DT Article DE validation study; assessment scale; clinical rating; alcohol challenge; essential tremor ID RELIABILITY; AMPLITUDE AB Background The ability of the Essential Tremor (ET) Rating Assessment Scale (TETRAS) to detect changes in tremor severity is unknown. Methods Fifteen adult ET patients received a single oral ethanol dose calculated to reach 0.05 g/dL breath alcohol content (brAC). Effects were investigated independently with accelerometry and TETRAS. Results Accelerometry data were log-transformed and a cumulative score logACC(R+L) was calculated. Correlation between logACC(R+L) and TETRAS was significant. TETRAS and accelerometry showed a significant effect of time point using repeated-measures analysis of variance. The difference between baseline and each of the following six time points as well as the correlation of TETRAS with brAC were significant. The calculated minimum detectable change of TETRAS was 8.9% and the effect size was d = 4.75 (95% confidence interval: 3.60-5.90). Conclusion We demonstrated sensitivity to change of the TETRAS performance scale after a therapeutic intervention, which further establishes its potential for use in both clinical and research settings. (c) 2013 International Parkinson and Movement Disorder Society C1 [Voller, Bernhard; Lines, Emily; McCrossin, Gayle; Artiles, Aaron; Tinaz, Sule; Lungu, Codrin; Hallett, Mark; Haubenberger, Dietrich] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Voller, Bernhard; Haubenberger, Dietrich] Med Univ Vienna, Dept Neurol, Vienna, Austria. RP Haubenberger, D (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10-7D37,10 Ctr Dr, Bethesda, MD 20892 USA. EM haubenbergerd@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke Intramural Research Program FX This work was funded by the National Institute of Neurological Disorders and Stroke Intramural Research Program. NR 17 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2014 VL 29 IS 4 BP 555 EP 558 DI 10.1002/mds.25667 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AE6TC UT WOS:000334128100020 PM 24123358 ER PT J AU Albanese, A Bhatia, K Bressman, SB DeLong, MR Fahn, S Fung, VSC Hallett, M Jankovic, J Jinnah, HA Klein, C Lang, AE Mink, JW Teller, JK AF Albanese, Alberto Bhatia, Kailash Bressman, Susan B. DeLong, Mahlon R. Fahn, Stanley Fung, Victor S. C. Hallett, Mark Jankovic, Joseph Jinnah, H. A. Klein, Christine Lang, Anthony E. Mink, Jonathan W. Teller, Jan K. TI Dystonia after severe brain injuries SO MOVEMENT DISORDERS LA English DT Letter ID MOVEMENT-DISORDERS; PHENOMENOLOGY C1 [Albanese, Alberto] Univ Cattolica Sacro Cuore, Dept Neurol, I-20123 Milan, Italy. [Albanese, Alberto] Ist Nazl Neurol Carlo Besta, Milan, Italy. [Bhatia, Kailash] UCL Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London, England. [Bressman, Susan B.] Beth Israel Deaconess Med Ctr, Dept Neurol, New York, NY 10003 USA. [Bressman, Susan B.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [DeLong, Mahlon R.; Jinnah, H. A.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Fahn, Stanley] Columbia Univ, Dept Neurol, New York, NY USA. [Fung, Victor S. C.] Westmead Hosp, Dept Neurol, Movement Disorders Unit, Sydney, NSW, Australia. [Fung, Victor S. C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Parkinsons Dis Ctr, Houston, TX 77030 USA. [Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA. [Jinnah, H. A.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. [Jinnah, H. A.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Klein, Christine] Med Univ Lubeck, Dept Neurol, Sect Clin & Mol Neurogenet, D-23538 Lubeck, Germany. [Lang, Anthony E.] Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Clin, Toronto, ON M5T 2S8, Canada. [Lang, Anthony E.] Toronto Western Hosp, Edmond J Safra Program Parkinsons Dis, Toronto, ON M5T 2S8, Canada. [Lang, Anthony E.] Univ Toronto, Toronto, ON, Canada. [Mink, Jonathan W.] Univ Rochester, Dept Neurol, Rochester, NY USA. [Mink, Jonathan W.] Univ Rochester, Dept Neurobiol & Anat, Rochester, NY USA. [Mink, Jonathan W.] Univ Rochester, Dept Brain & Cognit Sci, Rochester, NY USA. [Mink, Jonathan W.] Univ Rochester, Dept Pediat, Rochester, NY USA. [Teller, Jan K.] Dystonia Med Res Fdn, Chicago, IL USA. RP Albanese, A (reprint author), Ist Neurol Carlo Besta, Via Celoria 11, I-20133 Milan, Italy. RI Bagnato, Sergio/H-6842-2013 OI Bagnato, Sergio/0000-0002-6289-1887 FU NCATS NIH HHS [U54 TR001456] NR 5 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2014 VL 29 IS 4 BP 578 EP 579 DI 10.1002/mds.25840 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AE6TC UT WOS:000334128100028 PM 24590449 ER PT J AU Miyazaki, Y Shimizu, A Pastan, I Taguchi, K Naganuma, E Suzuki, T Hosoya, T Yokoo, T Saito, A Miyata, T Yamamoto, M Matsusaka, T AF Miyazaki, Yoichi Shimizu, Akihiro Pastan, Ira Taguchi, Keiko Naganuma, Eriko Suzuki, Takafumi Hosoya, Tatsuo Yokoo, Takashi Saito, Akihiko Miyata, Toshio Yamamoto, Masayuki Matsusaka, Taiji TI Keap1 inhibition attenuates glomerulosclerosis SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE antioxidant genes; glomerulosclerosis; hypomorphic allele; oxidative stress ID TRANSCRIPTION FACTOR NRF2; INDUCED DIABETIC-NEPHROPATHY; ENHANCES SUSCEPTIBILITY; BARDOXOLONE METHYL; CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; KIDNEY-DISEASE; ACTIVATES NRF2; IN-VIVO; PODOCYTE AB NFE2-related factor 2 (Nrf2) is a master regulatory transcription factor for antioxidant genes. Inhibition of its adaptor protein, Kelch-like ECH-associated protein 1 (Keap1), activates Nrf2. Podocyte injury triggers the progressive deterioration of glomerular damage toward glomerulosclerosis. We examined whether modulation of the Keap1-Nrf2 system has an impact on this process. Methods. Nrf2 null-mutant (KO) and Keap1 hypomorphic knockdown (KD) mice were crossed with NEP25 mice, in which podocyte-specific injury can be induced by an immunotoxin. Results. Thiobarbituric acid reactive substances, 8-hydroxy-deoxyguanosine and phosphorylated JNK were increased in the injured NEP25 kidney. Real-time PCR revealed that Keap1 KD upregulated Nrf2 target genes, including Gclc, Gclm, Gstp1, Gstp2 and Nqo1 in the glomerulus. However, podocyte injury did not upregulate these genes in Keap1 wild-type mice, nor did it further increase the expression of those genes in Keap1 KD mice. Three weeks after the induction of podocyte injury, glomerulosclerosis was considerably more attenuated in Keap1 KD mice than in control mice (median sclerosis index, 0.27 versus 3.03, on a 0-4 scale). Keap1 KD mice also showed considerably preserved nephrin staining (median index, 6.76 versus 0.91, on a 0-8 scale) and decreased glomeruli containing desmin-positive injured podocytes (median percentage, 24.5% versus 85.8%), along with a decrease in mRNAs for Fn1, Tgfb1, Col4a4 and Col1a2. Conclusions. Thus, podocyte injury cannot effectively activate Nrf2, but Nrf2 activation by Keap1 knockdown attenuates glomerulosclerosis. These results indicate that the Nrf2-Keap1 system is a promising drug target for the treatment of chronic kidney diseases. C1 [Miyazaki, Yoichi; Shimizu, Akihiro; Yokoo, Takashi] Jikei Univ, Sch Med, Dept Internal Med, Div Kidney & Hypertens, Tokyo, Japan. [Shimizu, Akihiro; Matsusaka, Taiji] Tokai Univ, Sch Med, Dept Internal Med, Isehara, Kanagawa 25911, Japan. [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Taguchi, Keiko; Naganuma, Eriko; Suzuki, Takafumi; Yamamoto, Masayuki] Tohoku Univ, Grad Sch Med, Dept Med Biochem, Sendai, Miyagi 980, Japan. [Hosoya, Tatsuo] Jikei Univ, Sch Med, Dept Pathophysiol & Therapy Chron Kidney Dis, Tokyo, Japan. [Saito, Akihiko] Niigata Univ, Grad Sch Med & Dent Sci, Dept Appl Mol Med, Niigata, Japan. [Miyata, Toshio] Tohoku Univ, Grad Sch Med, United Ctr Adv Res & Translat Med ART, Sendai, Miyagi 980, Japan. [Matsusaka, Taiji] Tokai Univ, Sch Med, Inst Med Sci, Isehara, Kanagawa 25911, Japan. RP Matsusaka, T (reprint author), Tokai Univ, Sch Med, Dept Internal Med, Isehara, Kanagawa 25911, Japan. EM taijim@is.icc.u-tokai.ac.jp RI Miyata, Toshio/A-4872-2010; Yamamoto, Masayuki/A-4873-2010 FU Japan Society for the Promotion of Science, MEXT, MEXT; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX We acknowledge Ms Shiho Imai, Ms Chika Sato and Ms Chie Sakurai for excellent technical assistance, Ms Yukiko Tanaka for administrative assistance, Dr Susumu Takekoshi for help with TBARS assay, Dr Takamasa Ishii for help with 8-OHdG staining and pJNK assay. We also thank Dr Reiko Inagi for helpful discussions. Parts of this study were presented in abstract form at the annual meetings of the Japanese Society of Nephrology in 2011. This study was supported by Grant-in-Aid for Scientific Research of Japan Society for the Promotion of Science, MEXT, MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2009-2013), and in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 58 TC 5 Z9 5 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD APR PY 2014 VL 29 IS 4 BP 783 EP 791 DI 10.1093/ndt/gfu002 PG 9 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA AH4JR UT WOS:000336093700015 PM 24523358 ER PT J AU Wing, MR Devaney, JM Joffe, MM Xie, DW Feldman, HI Dominic, EA Guzman, NJ Ramezani, A Susztak, K Herman, JG Cope, L Harmon, B Kwabi-Addo, B Gordish-Dressman, H Go, AS He, J Lash, JP Kusek, JW Raj, DS AF Wing, Maria R. Devaney, Joseph M. Joffe, Marshall M. Xie, Dawei Feldman, Harold I. Dominic, Elizabeth A. Guzman, Nicolas J. Ramezani, Ali Susztak, Katalin Herman, James G. Cope, Leslie Harmon, Brennan Kwabi-Addo, Bernard Gordish-Dressman, Heather Go, Alan S. He, Jiang Lash, James P. Kusek, John W. Raj, Dominic S. CA Chronic Renal Insufficiency Cohort TI DNA methylation profile associated with rapid decline in kidney function: findings from the CRIC Study SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE chronic renal disease; chronic renal disease progression; DNA methylation; epigenetics ID EPITHELIAL-MESENCHYMAL TRANSITION; CHRONIC RENAL-INSUFFICIENCY; I-KAPPA-B; DIABETIC-NEPHROPATHY; DISEASE; BETA; INFLAMMATION; EPIGENETICS; 5-HYDROXYMETHYLCYTOSINE; FIBROGENESIS AB Background. Epigenetic mechanisms may be important in the progression of chronic kidney disease (CKD). Methods. We studied the genome-wide DNA methylation pattern associated with rapid loss of kidney function using the Infinium Human Methylation 450 K BeadChip in 40 Chronic Renal Insufficiency (CRIC) study participants (n = 3939) with the highest and lowest rates of decline in estimated glomerular filtration rate. Results. The mean eGFR slope was 2.2 (1.4) and -5.1 (1.2) mL/min/1.73 m(2) in the stable kidney function group and the rapid progression group, respectively. CpG islands in NPHP4, IQSEC1 and TCF3 were hypermethylated to a larger extent in subjects with stable kidney function (P-values of 7.8E-05 to 9.5E-05). These genes are involved in pathways known to promote the epithelial to mesenchymal transition and renal fibrosis. Other CKD-related genes that were differentially methylated are NOS3, NFKBIL2, CLU, NFKBIB, TGFB3 and TGFBI, which are involved in oxidative stress and inflammatory pathways (P-values of 4.5E-03 to 0.046). Pathway analysis using Ingenuity Pathway Analysis showed that gene networks related to cell signaling, carbohydrate metabolism and human behavior are epigenetically regulated in CKD. Conclusions. Epigenetic modifications may be important in determining the rate of loss of kidney function in patients with established CKD. C1 [Wing, Maria R.; Devaney, Joseph M.; Guzman, Nicolas J.; Ramezani, Ali; Raj, Dominic S.] George Washington Univ, Sch Med, Divis Renal Dis & Hypertens, Washington, DC 20052 USA. [Devaney, Joseph M.; Harmon, Brennan; Gordish-Dressman, Heather] Childrens Natl Med Ctr, Ctr Genet Med Res, Washington, DC 20010 USA. [Joffe, Marshall M.; Xie, Dawei; Feldman, Harold I.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Dominic, Elizabeth A.] George Washington Univ, Sch Med, Washington, DC USA. [Susztak, Katalin] Albert Einstein Coll Med, Div Nephrol, Bronx, NY 10467 USA. [Herman, James G.; Cope, Leslie] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Kwabi-Addo, Bernard] Howard Univ, Dept Med, Washington, DC 20059 USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Lash, James P.] Univ Illinois, Div Nephrol, Chicago, IL USA. [Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA. RP Raj, DS (reprint author), George Washington Univ, Sch Med, Divis Renal Dis & Hypertens, Washington, DC 20052 USA. EM draj@mfa.gwu.edu RI Kwabi-Addo, Bernard/A-6993-2016 OI Kwabi-Addo, Bernard/0000-0003-3692-6350 FU National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK073665-01A1, 1U01DK099924-01, 1U01DK099914-01, 5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, 5U01DK060902]; National Institutes of Health [UL1RR024134, UL1RR025005, M01RR16500, UL1RR024989, M01RR000042, UL1RR024986, UL1RR029879, RR05096, UL1RR024131] FX This work is supported in part by grant R01 DK073665-01A1, 1U01DK099924-01 and 1U01DK099914-01 awarded to Dominic Raj from the National Institute of Diabetes and Digestive and Kidney Diseases. The CRIC Study is supported by cooperative agreement project grants 5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, and 5U01DK060902 from the National Institute of Diabetes and Digestive and Kidney Diseases, and by grants UL1RR024134, UL1RR025005, M01RR16500, UL1RR024989, M01RR000042, UL1RR024986, UL1RR029879, RR05096 and UL1RR024131 from the National Institutes of Health. NR 56 TC 20 Z9 20 U1 1 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD APR PY 2014 VL 29 IS 4 BP 864 EP 872 DI 10.1093/ndt/gft537 PG 10 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA AH4JR UT WOS:000336093700024 PM 24516231 ER PT J AU Zheng, XH Pedersen, LC Gabel, SA Mueller, GA Cuneo, MJ DeRose, EF Krahn, JM London, RE AF Zheng, Xunhai Pedersen, Lars C. Gabel, Scott A. Mueller, Geoffrey A. Cuneo, Matthew J. DeRose, Eugene F. Krahn, Juno M. London, Robert E. TI Selective unfolding of one Ribonuclease H domain of HIV reverse transcriptase is linked to homodimer formation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DYNAMICS IN-VIVO; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; CONFORMATIONAL-CHANGES; EFAVIRENZ BINDING; RECOMBINANT FORMS; DIMERIZATION; HETERODIMER; INHIBITORS AB HIV-1 reverse transcriptase (RT), a critical enzyme of the HIV life cycle and an important drug target, undergoes complex and largely uncharacterized conformational rearrangements that underlie its asymmetric folding, dimerization and subunit-selective ribonuclease H domain (RH) proteolysis. In the present article we have used a combination of NMR spectroscopy, small angle X-ray scattering and X-ray crystallography to characterize the p51 and p66 monomers and the conformational maturation of the p66/p66' homodimer. The p66 monomer exists as a loosely structured molecule in which the fingers/palm/connection, thumb and RH substructures are connected by flexible (disordered) linking segments. The initially observed homodimer is asymmetric and includes two fully folded RH domains, while exhibiting other conformational features similar to that of the RT heterodimer. The RH' domain of the p66' subunit undergoes selective unfolding with time constant similar to 6.5 h, consistent with destabilization due to residue transfer to the polymerase' domain on the p66' subunit. A simultaneous increase in the intensity of resonances near the random coil positions is characterized by a similar time constant. Consistent with the residue transfer hypothesis, a construct of the isolated RH domain lacking the two N-terminal residues is shown to exhibit reduced stability. These results demonstrate that RH' unfolding is coupled to homodimer formation. C1 [Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.; Mueller, Geoffrey A.; Cuneo, Matthew J.; DeRose, Eugene F.; Krahn, Juno M.; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM London@niehs.nih.gov RI Zheng, Xunhai/G-1187-2015; OI Zheng, Xunhai/0000-0003-0390-2491; Cuneo, Matthew/0000-0002-1475-6656 FU National Institute of Health; National Institute of Environmental Health Sciences [Z01-ES050147, Z1A ES102645]; National Institutes of Health, NIEHS [HHSN273200700046U] FX National Institute of Health (Intramural Research Program); National Institute of Environmental Health Sciences [Research Project Number Z01-ES050147 to R. E. L., and Research Project Number Z1A ES102645 to L. C. P.]; National Institutes of Health, NIEHS (Delivery Order HHSN273200700046U to E. F. D.). Funding for Open Access charge: Funding from Intramural Research Project [Number Z01-ES050147]. NR 56 TC 9 Z9 9 U1 4 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2014 VL 42 IS 8 BP 5361 EP 5377 DI 10.1093/nar/gku143 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH4JD UT WOS:000336092300059 PM 24574528 ER PT J AU Ghayee, HK Isaacson, B Farley, M Click, A Pacak, K Shay, JW AF Ghayee, Hans K. Isaacson, Brandon Farley, Megan Click, Arielle Pacak, Karel Shay, Jerry W. TI Unusual Case of a Hormone-Secreting SDHC Head and Neck Paraganglioma SO PANCREAS LA English DT Meeting Abstract C1 [Ghayee, Hans K.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Isaacson, Brandon] Univ Texas SW Med Ctr Dallas, Dept Otolaryngol, Dallas, TX 75390 USA. [Farley, Megan] Univ Texas SW Med Ctr Dallas, Dept Canc Genet, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Click, Arielle; Shay, Jerry W.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. [Pacak, Karel] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD APR PY 2014 VL 43 IS 3 BP 496 EP 496 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD3SQ UT WOS:000333166800046 ER PT J AU King, KS Martucci, V Wesley, R Adams, KT Raygada, M Stratakis, CA Huynh, TT Pacak, K AF King, Kathryn S. Martucci, Victoria Wesley, Robert Adams, Karen T. Raygada, Margarita Stratakis, Constantine A. Thanh-Truc Huynh Pacak, Karel TI SDHB Pheochromocytoma and Paraganglioma Penetrance in a United States Population: An NIH Study SO PANCREAS LA English DT Meeting Abstract C1 [King, Kathryn S.; Martucci, Victoria; Adams, Karen T.; Thanh-Truc Huynh; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Wesley, Robert] NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Raygada, Margarita] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genet, NIH, Bethesda, MD USA. [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet PDEGEN, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD APR PY 2014 VL 43 IS 3 BP 496 EP 497 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD3SQ UT WOS:000333166800049 ER PT J AU Martucci, V Lorenzo, ZG Weintraub, M del Rivero, J Ling, A Merino, M Siddiqui, M Shuch, B Vourganti, S Linehan, WM Agarwal, PK Pacak, K AF Martucci, Victoria Lorenzo, Zarina G. Weintraub, Michael del Rivero, Jaydira Ling, Alexander Merino, Maria Siddiqui, Minhaj Shuch, Brian Vourganti, Srinivas Linehan, W. Marston Agarwal, Piyush K. Pacak, Karel TI Association of Urinary Bladder Paragangliomas with Germline Mutations in the SDHB and VHL Genes SO PANCREAS LA English DT Meeting Abstract C1 [Martucci, Victoria; Lorenzo, Zarina G.; del Rivero, Jaydira; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Ling, Alexander] NIH, Radiol & Imaging Sci Dept, Warren Magnuson Clin Ctr, Bethesda, MD USA. [Merino, Maria] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Weintraub, Michael; Siddiqui, Minhaj; Shuch, Brian; Vourganti, Srinivas; Linehan, W. Marston; Agarwal, Piyush K.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Lorenzo, Zarina G.] Univ Santo Tomas Hosp, Dept Med, Sect Endocrinol & Metab, Manila, Philippines. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD APR PY 2014 VL 43 IS 3 BP 499 EP 499 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD3SQ UT WOS:000333166800055 ER PT J AU Benoit, JB Attardo, GM Michalkova, V Krause, TB Bohova, J Zhang, QR Baumann, AA Mireji, PO Takac, P Denlinger, DL Ribeiro, JM Aksoy, S AF Benoit, Joshua B. Attardo, Geoffrey M. Michalkova, Veronika Krause, Tyler B. Bohova, Jana Zhang, Qirui Baumann, Aaron A. Mireji, Paul O. Takac, Peter Denlinger, David L. Ribeiro, Jose M. Aksoy, Serap TI A Novel Highly Divergent Protein Family Identified from a Viviparous Insect by RNA-seq Analysis: A Potential Target for Tsetse Fly-Specific Abortifacients SO PLOS GENETICS LA English DT Article ID GLOSSINA-MORSITANS-MORSITANS; EVOLUTIONARY GENETICS ANALYSIS; MILK-FAT-GLOBULE; ODORANT-BINDING PROTEINS; DROSOPHILA-MELANOGASTER; MOLECULAR CHARACTERIZATION; SEQUENCE ALIGNMENT; PROTEOMIC ANALYSIS; MASS-SPECTROMETRY; PREGNANCY CYCLE AB In tsetse flies, nutrients for intrauterine larval development are synthesized by the modified accessory gland (milk gland) and provided in mother's milk during lactation. Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity. The goal of this study was to perform a comprehensive characterization of tsetse milk proteins using lactation-specific transcriptome/milk proteome analyses and to define functional role(s) for the milk proteins during lactation. Differential analysis of RNA-seq data from lactating and dry (non-lactating) females revealed enrichment of transcripts coding for protein synthesis machinery, lipid metabolism and secretory proteins during lactation. Among the genes induced during lactation were those encoding the previously identified milk proteins (milk gland proteins 1-3, transferrin and acid sphingomyelinase 1) and seven new genes (mgp4-10). The genes encoding mgp2-10 are organized on a 40 kb syntenic block in the tsetse genome, have similar exon-intron arrangements, and share regions of amino acid sequence similarity. Expression of mgp2-10 is female-specific and high during milk secretion. While knockdown of a single mgp failed to reduce fecundity, simultaneous knockdown of multiple variants reduced milk protein levels and lowered fecundity. The genomic localization, gene structure similarities, and functional redundancy of MGP2-10 suggest that they constitute a novel highly divergent protein family. Our data indicates that MGP2-10 function both as the primary amino acid resource for the developing larva and in the maintenance of milk homeostasis, similar to the function of the mammalian casein family of milk proteins. This study underscores the dynamic nature of the lactation cycle and identifies a novel family of lactation-specific proteins, unique to Glossina sp., that are essential to larval development. The specificity of MGP2-10 to tsetse and their critical role during lactation suggests that these proteins may be an excellent target for tsetse-specific population control approaches. C1 [Benoit, Joshua B.; Attardo, Geoffrey M.; Michalkova, Veronika; Krause, Tyler B.; Aksoy, Serap] Yale Univ, Sch Publ Hlth, Div Epidemiol Microbial Dis, New Haven, CT 06520 USA. [Michalkova, Veronika; Bohova, Jana; Takac, Peter] Slovak Acad Sci, Inst Zool, Sect Mol & Appl Zool, Bratislava, Slovakia. [Zhang, Qirui; Denlinger, David L.] Ohio State Univ, Dept Entomol, Columbus, OH 43210 USA. [Zhang, Qirui; Denlinger, David L.] Ohio State Univ, Dept Evolut Ecol & Organismal Biol, Columbus, OH 43210 USA. [Baumann, Aaron A.] Howard Hughes Med Inst, Ashburn, VA USA. [Mireji, Paul O.] Egerton Univ, Dept Biochem & Mol Biol, Njoro, Kenya. [Ribeiro, Jose M.] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Benoit, JB (reprint author), Yale Univ, Sch Publ Hlth, Div Epidemiol Microbial Dis, New Haven, CT 06520 USA. EM joshua.benoit@yale.edu RI Zhang, Qirui/C-6579-2011; Ribeiro, Jose/J-7011-2015; OI Zhang, Qirui/0000-0002-2749-9740; Baumann, Aaron/0000-0002-7410-8482; Aksoy, Serap/0000-0001-9941-143X; Ribeiro, Jose/0000-0002-9107-0818 FU National Institutes of Health [AI081774, F32AI093023]; Ambrose Monell Foundation; Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; NIH [2R56 AI058279] FX Funding was provided by the National Institutes of Health awards AI081774 (SA and GMA) and F32AI093023 (JBB), and Ambrose Monell Foundation Award. JMR was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. DLD and QZ were supported by a NIH Bridge Grant (2R56 AI058279). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 131 TC 14 Z9 14 U1 0 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2014 VL 10 IS 4 AR e1003874 DI 10.1371/journal.pgen.1003874 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA AG6AB UT WOS:000335499600012 PM 24763277 ER PT J AU Chang, YC Lamichhane, AK Garraffo, HM Walter, PJ Leerkes, M Kwon-Chung, KJ AF Chang, Yun C. Lamichhane, Ami Khanal Garraffo, H. Martin Walter, Peter J. Leerkes, Maarten Kwon-Chung, Kyung J. TI Molecular Mechanisms of Hypoxic Responses via Unique Roles of Ras1, Cdc24 and Ptp3 in a Human Fungal Pathogen Cryptococcus neoformans SO PLOS GENETICS LA English DT Article ID PROTEIN-TYROSINE PHOSPHATASES; RHO-GTPASES; ACTIN CYTOSKELETON; SACCHAROMYCES-CEREVISIAE; STRESS-RESPONSE; FISSION YEAST; DRUG-SENSITIVITY; HIGH-TEMPERATURE; GENE-EXPRESSION; KINASE PATHWAY AB Cryptococcus neoformans encounters a low oxygen environment when it enters the human host. Here, we show that the conserved Ras1 (a small GTPase) and Cdc24 (the guanine nucleotide exchange factor for Cdc42) play an essential role in cryptococcal growth in hypoxia. Suppressor studies indicate that PTP3 functions epistatically downstream of both RAS1 and CDC24 in regulating hypoxic growth. Ptp3 shares sequence similarity to the family of phosphotyrosine-specific protein phosphatases and the ptp3D strain failed to grow in 1% O-2. We demonstrate that RAS1, CDC24 and PTP3 function in parallel to regulate thermal tolerance but RAS1 and CDC24 function linearly in regulating hypoxic growth while CDC24 and PTP3 reside in compensatory pathways. The ras1 Delta and cdc24 Delta strains ceased to grow at 1% O2 and became enlarged but viable single cells. Actin polarization in these cells, however, was normal for up to eight hours after transferring to hypoxic conditions. Double deletions of the genes encoding Rho GTPase Cdc42 and Cdc420, but not of the genes encoding Rac1 and Rac2, caused a slight growth retardation in hypoxia. Furthermore, growth in hypoxia was not affected by the deletion of several central genes functioning in the pathways of cAMP, Hog1, or the two-component like phosphorylation system that are critical in the cryptococcal response to osmotic and genotoxic stresses. Interestingly, although deletion of HOG1 rescued the hypoxic growth defect of ras1 Delta, cdc24 Delta, and ptp3 Delta, Hog1 was not hyperphosphorylated in these three mutants in hypoxic conditions. RNA sequencing analysis indicated that RAS1, CDC24 and PTP3 acted upon the expression of genes involved in ergosterol biosynthesis, chromosome organization, RNA processing and protein translation. Moreover, growth of the wild-type strain under low oxygen conditions was affected by sub-inhibitory concentrations of the compounds that inhibit these biological processes, demonstrating the importance of these biological processes in the cryptococcal hypoxia response. C1 [Chang, Yun C.; Lamichhane, Ami Khanal; Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Garraffo, H. Martin; Walter, Peter J.] NIDDK, Clin Mass Spectrometry Core, NIH, Bethesda, MD 20892 USA. [Leerkes, Maarten] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA. RP Chang, YC (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ychang@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Diseases, NIH FX This study was supported by funds from the intramural program of the National Institute of Allergy and Infectious Diseases, and the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 68 TC 3 Z9 3 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2014 VL 10 IS 4 AR e1004292 DI 10.1371/journal.pgen.1004292 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA AG6AB UT WOS:000335499600043 PM 24762475 ER PT J AU Cotton, LA Kuang, XMT Le, AQ Carlson, JM Chan, B Chopera, DR Brumme, CJ Markle, TJ Martin, E Shahid, A Anmole, G Mwimanzi, P Nassab, P Penney, KA Rahman, MA Milloy, MJ Schechter, MT Markowitz, M Carrington, M Walker, BD Wagner, T Buchbinder, S Fuchs, J Koblin, B Mayer, KH Harrigan, PR Brockman, MA Poon, AFY Brumme, ZL AF Cotton, Laura A. Kuang, Xiaomei T. Le, Anh Q. Carlson, Jonathan M. Chan, Benjamin Chopera, Denis R. Brumme, Chanson J. Markle, Tristan J. Martin, Eric Shahid, Aniqa Anmole, Gursev Mwimanzi, Philip Nassab, Pauline Penney, Kali A. Rahman, Manal A. Milloy, M-J Schechter, Martin T. Markowitz, Martin Carrington, Mary Walker, Bruce D. Wagner, Theresa Buchbinder, Susan Fuchs, Jonathan Koblin, Beryl Mayer, Kenneth H. Harrigan, P. Richard Brockman, Mark A. Poon, Art F. Y. Brumme, Zabrina L. TI Genotypic and Functional Impact of HIV-1 Adaptation to Its Host Population during the North American Epidemic SO PLOS GENETICS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; REPLICATION CAPACITY; ESCAPE MUTATIONS; CLASS-I; VANCOUVER LYMPHADENOPATHY; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; LYMPHOCYTE ESCAPE; SAN-FRANCISCO AB HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979-1989) and 382 modern (2000-2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a "consensus-like" founder virus, the median "background" frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were similar to 2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e. g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were "pre-adapted" to the average host HLA profile was only similar to 2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins. C1 [Cotton, Laura A.; Le, Anh Q.; Chan, Benjamin; Chopera, Denis R.; Shahid, Aniqa; Mwimanzi, Philip; Nassab, Pauline; Penney, Kali A.; Rahman, Manal A.; Brockman, Mark A.; Poon, Art F. Y.; Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Kuang, Xiaomei T.; Markle, Tristan J.; Martin, Eric; Anmole, Gursev; Brockman, Mark A.] Simon Fraser Univ, Dept Mol Biol & Biochem, Fac Sci, Burnaby, BC V5A 1S6, Canada. [Carlson, Jonathan M.] Microsoft Res, Los Angeles, CA USA. [Chopera, Denis R.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, KwaZulu Natal Res Inst TB & HIV, Durban, Kwazulu Natal, South Africa. [Brumme, Chanson J.; Martin, Eric; Milloy, M-J; Harrigan, P. Richard; Brockman, Mark A.; Poon, Art F. Y.; Brumme, Zabrina L.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Milloy, M-J; Schechter, Martin T.; Harrigan, P. Richard; Poon, Art F. Y.] Univ British Columbia, Fac Med, Vancouver, BC, Canada. [Markowitz, Martin] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA. [Carrington, Mary] Leidos Biomed Res Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA. [Carrington, Mary; Walker, Bruce D.] Ragon Inst MGH MIT & Harvard Univ, Cambridge, MA USA. [Wagner, Theresa; Buchbinder, Susan; Fuchs, Jonathan] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Koblin, Beryl] New York Blood Ctr, New York, NY 10021 USA. [Mayer, Kenneth H.] Fenway Community Hlth, Boston, MA USA. [Mayer, Kenneth H.] Harvard Univ, Sch Med, Boston, MA USA. RP Cotton, LA (reprint author), Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. EM zbrumme@sfu.ca OI Brumme, Chanson/0000-0003-2722-5288; Schechter, Martin/0000-0001-6063-2155; Poon, Art/0000-0003-3779-154X; Brockman, Mark/0000-0001-6432-1426 FU Canadian Institutes for Health Research (CIHR) [MOP-93536, HOP-115700]; National Institute on Drug Abuse, NIH [RO1DA011591, RO1DA021525]; Frederick National Laboratory for Cancer Research [HHSN261200800001E]; Intramural Research Program of the NIH; Frederick National Lab; Center for Cancer Research; CAHR/BMS Master's Scholarship in Basic Science; CIHR; Canada-HOPE fellowship from CIHR; Sanofi-Aventis; Clinical Infectious Diseases Research Initiative (CIDRI) fellowship; Claude Leon Foundation fellowship; Canadian Association of HIV Research; Abbott Virology; Michael Smith Foundation for Health Research (MSFHR); CIHR/GSK research chair in Clinical Virology; MSFHR/St. Paul's Hospital Foundation - Providence Health Care Research Institute Career Investigator program; CIHR New Investigator Award; MSFHR; Vanier Canada Graduate Scholarship from the CIHR FX This work was supported by operating grants from the Canadian Institutes for Health Research (CIHR) MOP-93536 to ZLB/MAB and HOP-115700 to ZLB/MAB/AFYP. The VIDUS and ACCESS projects were funded by the National Institute on Drug Abuse, NIH (RO1DA011591 and RO1DA021525). This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. XTK was funded by a CAHR/BMS Master's Scholarship in Basic Science. AQL was funded by a CIHR Frederick Banting and Charles Best Masters Award. JMC was an employee of Microsoft Corporation. DRC was a recipient of the Canada-HOPE fellowship from CIHR and Sanofi-Aventis, the Clinical Infectious Diseases Research Initiative (CIDRI) fellowship and the Claude Leon Foundation fellowship. CJB was supported by a Vanier Canada Graduate Scholarship from the CIHR. EM was supported by a Master's Scholarship from the Canadian Association of HIV Research and Abbott Virology. PM is the recipient of a Postdoctoral fellowship from the Michael Smith Foundation for Health Research (MSFHR). PRH was supported by a CIHR/GSK research chair in Clinical Virology. MAB holds a Canada Research Chair, Tier 2, in Viral Pathogenesis and Immunity. AFYP was the recipient of a Scholar Award from the MSFHR/St. Paul's Hospital Foundation - Providence Health Care Research Institute Career Investigator program, and a CIHR New Investigator Award. ZLB is the recipient of a CIHR New Investigator Award and a scholar award from the MSFHR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 108 TC 15 Z9 17 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2014 VL 10 IS 4 AR e1004295 DI 10.1371/journal.pgen.1004295 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA AG6AB UT WOS:000335499600046 PM 24762668 ER PT J AU Figueiredo, JC Hsu, L Hutter, CM Lin, Y Campbell, PT Baron, JA Berndt, SI Jiao, S Casey, G Fortini, B Chan, AT Cotterchio, M Lemire, M Gallinger, S Harrison, TA Le Marchand, L Newcomb, PA Slattery, ML Caan, BJ Carlson, CS Zanke, BW Rosse, SA Brenner, H Giovannucci, EL Wu, KN Chang-Claude, J Chanock, SJ Curtis, KR Duggan, D Gong, J Haile, RW Hayes, RB Hoffmeister, M Hopper, JL Jenkins, MA Kolonel, LN Qu, CH Rudolph, A Schoen, RE Schumacher, FR Seminara, D Stelling, DL Thibodeau, SN Thornquist, M Warnick, GS Henderson, BE Ulrich, C Gauderman, WJ Potter, JD White, E Peters, U AF Figueiredo, Jane C. Hsu, Li Hutter, Carolyn M. Lin, Yi Campbell, Peter T. Baron, John A. Berndt, Sonja I. Jiao, Shuo Casey, Graham Fortini, Barbara Chan, Andrew T. Cotterchio, Michelle Lemire, Mathieu Gallinger, Steven Harrison, Tabitha A. Le Marchand, Loic Newcomb, Polly A. Slattery, Martha L. Caan, Bette J. Carlson, Christopher S. Zanke, Brent W. Rosse, Stephanie A. Brenner, Hermann Giovannucci, Edward L. Wu, Kana Chang-Claude, Jenny Chanock, Stephen J. Curtis, Keith R. Duggan, David Gong, Jian Haile, Robert W. Hayes, Richard B. Hoffmeister, Michael Hopper, John L. Jenkins, Mark A. Kolonel, Laurence N. Qu, Conghui Rudolph, Anja Schoen, Robert E. Schumacher, Fredrick R. Seminara, Daniela Stelling, Deanna L. Thibodeau, Stephen N. Thornquist, Mark Warnick, Greg S. Henderson, Brian E. Ulrich, CorneliaM. Gauderman, W. James Potter, John D. White, Emily Peters, Ulrike CA CCFR GECCO TI Genome-Wide Diet-Gene Interaction Analyses for Risk of Colorectal Cancer SO PLOS GENETICS LA English DT Article ID SUSCEPTIBILITY LOCI; ENVIRONMENT INTERACTION; ASSOCIATION SCAN; COLON-CANCER; RED MEAT; ULCERATIVE-COLITIS; MULTIETHNIC COHORT; METAANALYSIS; FIBER; PROGRESSION AB Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention. C1 [Figueiredo, Jane C.; Casey, Graham; Fortini, Barbara; Schumacher, Fredrick R.; Henderson, Brian E.; Gauderman, W. James] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Hsu, Li; Lin, Yi; Jiao, Shuo; Harrison, Tabitha A.; Newcomb, Polly A.; Carlson, Christopher S.; Rosse, Stephanie A.; Curtis, Keith R.; Gong, Jian; Qu, Conghui; Stelling, Deanna L.; Thornquist, Mark; Warnick, Greg S.; Ulrich, CorneliaM.; Potter, John D.; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Hutter, Carolyn M.; Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Cotterchio, Michelle] Canc Care Ontario, Toronto, ON, Canada. [Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada. [Gallinger, Steven] Toronto Gen Hosp, Dept Surg, Univ Hlth Network, Toronto, ON, Canada. [Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Caan, Bette J.] Kaiser Permanente, Med Care Program, Div Res, Oakland, CA USA. [Zanke, Brent W.] Univ Ottawa, Fac Med, Div Hematol, Ottawa, ON, Canada. [Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA. [Haile, Robert W.] Stanford Canc Inst, Palo Alto, CA USA. [Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, New York, NY USA. [Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic, Australia. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Genet, Rochester, MN USA. [Ulrich, CorneliaM.] Natl Ctr Tumor Dis, Div Prevent Oncol, Heidelberg, Germany. [Ulrich, CorneliaM.] German Canc Res Ctr, Heidelberg, Germany. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. RP Figueiredo, JC (reprint author), Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. EM janefigu@usc.edu; upeters@fhcrc.org RI Hoffmeister, Michael/B-5745-2012; Jenkins, Mark/P-7803-2015; Brenner, Hermann/B-4627-2017; OI Hoffmeister, Michael/0000-0002-8307-3197; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X FU GECCO: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045, R01 CA120582]; CCFR: National Institutes of Health (RFA) [CA-95-011]; National Cancer Institute, National Institutes of Health [U01 CA122839]; National Institutes of Health: Australasian Colorectal Cancer Family Registry [U01 CA097735]; National Institutes of Health: Seattle Colorectal Cancer Family Registry [U01 CA074794]; National Institutes of Health: Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; DACHS: German Research Council (Deutsche Forschungsgemeinschaft [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; DALS: National Institutes of Health [R01 CA48998]; National Institutes of Health [P01 CA 055075, UM1 CA167552, R01 137178, P50 CA 127003]; NHS by the National Institutes of Health [R01 137178, P50 CA 127003, P01 CA 087969]; OFCCR: National Institutes of Health [U01 CA074783]; Ontario Research Fund; Canadian Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute; Ontario Institute for Cancer Research through Ontario Ministry of Research and Innovation. PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS FX This work was supported by, GECCO: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088; R01 CA059045; R01 CA120582). CCFR: National Institutes of Health (RFA # CA-95-011) and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. This genome wide scan was supported by the National Cancer Institute, National Institutes of Health by U01 CA122839. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CFR. The following Colon CFR centers contributed data to this manuscript and were supported by National Institutes of Health: Australasian Colorectal Cancer Family Registry (U01 CA097735), Seattle Colorectal Cancer Family Registry (U01 CA074794) and Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783). DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). DALS: National Institutes of Health (R01 CA48998 to MLS); HPFS was supported by the National Institutes of Health (P01 CA 055075, UM1 CA167552, R01 137178, and P50 CA 127003), and NHS by the National Institutes of Health (R01 137178, P01 CA 087969 and P50 CA 127003,). OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. Genetic analyses have been supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation. PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Additionally, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager, M et al. Nat Genet 2007 May; 39(5): 645-9), Colon CGEMS pancreatic cancer scan (PanScan) (Amundadottir, L et al. Nat Genet. 2009 Sep; 41(9): 986-90 and Petersen, GM et al Nat Genet. 2010 Mar; 42(3): 224-8), and the Lung Cancer and Smoking study. The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/)accession numbers 000207v.1p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093 v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping. PMH: National Institutes of Health (R01 CA076366 to PAN). VITAL: National Institutes of Health (K05 CA154337).; WHI: The WHI program was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U. S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 18 Z9 21 U1 5 U2 22 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2014 VL 10 IS 4 AR e1004228 DI 10.1371/journal.pgen.1004228 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AG6AB UT WOS:000335499600015 PM 24743840 ER PT J AU Osorio, A Milne, RL Kuchenbaecker, K Vaclova, T Pita, G Alonso, R Peterlongo, P Blanco, I de la Hoya, M Duran, M Diez, O Cajal, TRY Konstantopoulou, I Martinez-Bouzas, C Conejero, RA Soucy, P McGuffog, L Barrowdale, D Lee, A Arver, B Rantala, J Loman, N Ehrencrona, H Olopade, OI Beattie, MS Domchek, SM Nathanson, K Rebbeck, TR Arun, BK Karlan, BY Walsh, C Lester, J John, EM Whittemore, AS Daly, MB Southey, M Hopper, J Terry, MB Buys, SS Janavicius, R Dorfling, CM van Rensburg, EJ Steele, L Neuhausen, SL Ding, YC Hansen, TVO Jonson, L Ejlertsen, B Gerdes, AM Infante, M Herraez, B Moreno, LT Weitzel, JN Herzog, J Weeman, K Manoukian, S Peissel, B Zaffaroni, D Scuvera, G Bonanni, B Mariette, F Volorio, S Viel, A Varesco, L Papi, L Ottini, L Tibiletti, MG Radice, P Yannoukakos, D Garber, J Ellis, S Frost, D Platte, R Fineberg, E Evans, G Lalloo, F Izatt, L Eeles, R Adlard, J Davidson, R Cole, T Eccles, D Cook, J Hodgson, S Brewer, C Tischkowitz, M Douglas, F Porteous, M Side, L Walker, L Morrison, P Donaldson, A Kennedy, J Foo, C Godwin, AK Schmutzler, RK Wappenschmidt, B Rhiem, K Engel, C Meindl, A Ditsch, N Arnold, N Plendl, HJ Niederacher, D Sutter, C Wang-Gohrke, S Steinemann, D Preisler-Adams, S Kast, K Varon-Mateeva, R Gehrig, A Stoppa-Lyonnet, D Sinilnikova, OM Mazoyer, S Damiola, F Poppe, B Claes, K Piedmonte, M Tucker, K Backes, F Rodriguez, G Brewster, W Wakeley, K Rutherford, T Caldes, T Nevanlinna, H Aittomaki, K Rookus, MA van Os, TAM van der Kolk, L de Lange, JL Meijers-Heijboer, HEJ van der Hout, AH van Asperen, CJ Garcia, EBG Hoogerbrugge, N Collee, JM van Deurzen, CHM van der Luijt, RB Devilee, P Olah, E Lazaro, C Teule, A Menendez, M Jakubowska, A Cybulski, C Gronwald, J Lubinski, J Durda, K Jaworska-Bieniek, K Johannsson, OT Maugard, C Montagna, M Tognazzo, S Teixeira, MR Healey, S Olswold, C Guidugli, L Lindor, N Slager, S Szabo, CI Vijai, J Robson, M Kauff, N Zhang, LY Rau-Murthy, R Fink-Retter, A Singer, CF Rappaport, C Kaulich, DG Pfeiler, G Tea, MK Berger, A Phelan, CM Greene, MH Mai, PL Lejbkowicz, F Andrulis, I Mulligan, AM Glendon, G Toland, AE Bojesen, A Pedersen, IS Sunde, L Thomassen, M Kruse, TA Jensen, UB Friedman, E Laitman, Y Shimon, SP Simard, J Easton, DF Offit, K Couch, FJ Chenevix-Trench, G Antoniou, AC Benitez, J AF Osorio, Ana Milne, Roger L. Kuchenbaecker, Karoline Vaclova, Tereza Pita, Guillermo Alonso, Rosario Peterlongo, Paolo Blanco, Ignacio de la Hoya, Miguel Duran, Mercedes Diez, Orland Ramon y Cajal, Teresa Konstantopoulou, Irene Martinez-Bouzas, Cristina Conejero, Raquel Andres Soucy, Penny McGuffog, Lesley Barrowdale, Daniel Lee, Andrew Arver, Brita Rantala, Johanna Loman, Niklas Ehrencrona, Hans Olopade, Olufunmilayo I. Beattie, Mary S. Domchek, Susan M. Nathanson, Katherine Rebbeck, Timothy R. Arun, Banu K. Karlan, Beth Y. Walsh, Christine Lester, Jenny John, Esther M. Whittemore, Alice S. Daly, Mary B. Southey, Melissa Hopper, John Terry, Mary B. Buys, Saundra S. Janavicius, Ramunas Dorfling, Cecilia M. van Rensburg, Elizabeth J. Steele, Linda Neuhausen, Susan L. Ding, Yuan Chun Hansen, Thomas V. O. Jonson, Lars Ejlertsen, Bent Gerdes, Anne-Marie Infante, Mar Herraez, Belen Moreno, Leticia Thais Weitzel, Jeffrey N. Herzog, Josef Weeman, Kisa Manoukian, Siranoush Peissel, Bernard Zaffaroni, Daniela Scuvera, Giulietta Bonanni, Bernardo Mariette, Frederique Volorio, Sara Viel, Alessandra Varesco, Liliana Papi, Laura Ottini, Laura Tibiletti, Maria Grazia Radice, Paolo Yannoukakos, Drakoulis Garber, Judy Ellis, Steve Frost, Debra Platte, Radka Fineberg, Elena Evans, Gareth Lalloo, Fiona Izatt, Louise Eeles, Ros Adlard, Julian Davidson, Rosemarie Cole, Trevor Eccles, Diana Cook, Jackie Hodgson, Shirley Brewer, Carole Tischkowitz, Marc Douglas, Fiona Porteous, Mary Side, Lucy Walker, Lisa Morrison, Patrick Donaldson, Alan Kennedy, John Foo, Claire Godwin, Andrew K. Schmutzler, Rita Katharina Wappenschmidt, Barbara Rhiem, Kerstin Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Plendl, Hans Joerg Niederacher, Dieter Sutter, Christian Wang-Gohrke, Shan Steinemann, Doris Preisler-Adams, Sabine Kast, Karin Varon-Mateeva, Raymonda Gehrig, Andrea Stoppa-Lyonnet, Dominique Sinilnikova, Olga M. Mazoyer, Sylvie Damiola, Francesca Poppe, Bruce Claes, Kathleen Piedmonte, Marion Tucker, Kathy Backes, Floor Rodriguez, Gustavo Brewster, Wendy Wakeley, Katie Rutherford, Thomas Caldes, Trinidad Nevanlinna, Heli Aittomaki, Kristiina Rookus, Matti A. van Os, Theo A. M. van der Kolk, Lizet de Lange, J. L. Meijers-Heijboer, Hanne E. J. van der Hout, A. H. van Asperen, Christi J. Gomez Garcia, Encarna B. Hoogerbrugge, Nicoline Collee, J. Margriet van Deurzen, Carolien H. M. van der Luijt, Rob B. Devilee, Peter Olah, Edith Lazaro, Conxi Teule, Alex Menendez, Mireia Jakubowska, Anna Cybulski, Cezary Gronwald, Jacek Lubinski, Jan Durda, Katarzyna Jaworska-Bieniek, Katarzyna Johannsson, Oskar Th Maugard, Christine Montagna, Marco Tognazzo, Silvia Teixeira, Manuel R. Healey, Sue Olswold, Curtis Guidugli, Lucia Lindor, Noralane Slager, Susan Szabo, Csilla I. Vijai, Joseph Robson, Mark Kauff, Noah Zhang, Liying Rau-Murthy, Rohini Fink-Retter, Anneliese Singer, Christian F. Rappaport, Christine Kaulich, Daphne Geschwantler Pfeiler, Georg Tea, Muy-Kheng Berger, Andreas Phelan, Catherine M. Greene, Mark H. Mai, Phuong L. Lejbkowicz, Flavio Andrulis, Irene Mulligan, Anna Marie Glendon, Gord Toland, Amanda Ewart Bojesen, Anders Pedersen, Inge Sokilde Sunde, Lone Thomassen, Mads Kruse, Torben A. Jensen, Uffe Birk Friedman, Eitan Laitman, Yael Shimon, Shani Paluch Simard, Jacques Easton, Douglas F. Offit, Kenneth Couch, Fergus J. Chenevix-Trench, Georgia Antoniou, Antonis C. Benitez, Javier CA SWE-BRCA HEBON KConFab Investigators TI DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers SO PLOS GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; BREAST-CANCER; OVARIAN-CANCER; GENETIC MODIFIERS; COMMON VARIANTS; NEIL2; OGG1; INVESTIGATORS; CONSORTIUM; DAMAGE AB Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7x10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95% CI: 1.03-1.21, p = 4.8x10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied. C1 [Osorio, Ana; Vaclova, Tereza; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid, Spain. [Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Kuchenbaecker, Karoline; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Ellis, Steve; Frost, Debra; Platte, Radka; Fineberg, Elena; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Pita, Guillermo; Alonso, Rosario; Herraez, Belen; Moreno, Leticia Thais; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Genotyping Unit CeGen, Madrid, Spain. [Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. 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[Healey, Sue; Chenevix-Trench, Georgia] Queensland Inst Med Res, Dept Genet & Computat Biol, Brisbane, Qld 4006, Australia. [KConFab Investigators] Peter MacCallum Canc Ctr, Kathleen Cuningham Consortium Res Familial Breast, Melbourne, Vic, Australia. [Olswold, Curtis; Couch, Fergus J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Guidugli, Lucia; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Lindor, Noralane] Mayo Clin, Ctr Individualized Med, Scottsdale, AZ USA. [Slager, Susan] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Szabo, Csilla I.] Univ Delaware, Dept Biol Sci, Ctr Translat Canc Res, Newark, DE USA. [Vijai, Joseph; Robson, Mark; Kauff, Noah; Rau-Murthy, Rohini; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA. [Vijai, Joseph; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. [Zhang, Liying] Mem Sloan Kettering Canc Ctr, Diagnost Mol Genet Lab, New York, NY 10021 USA. [Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng; Berger, Andreas] Med Univ Vienna, Dept OB GYN, Vienna, Austria. [Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng; Berger, Andreas] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Phelan, Catherine M.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA. [Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Lejbkowicz, Flavio] Clalit Natl Israeli Canc Control Ctr, Haifa, Israel. [Andrulis, Irene] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene] Univ Toronto, Canc Care Ontario, Dept Mol Genet, Toronto, ON, Canada. [Andrulis, Irene] Univ Toronto, Canc Care Ontario, Dept Lab Med, Toronto, ON, Canada. [Andrulis, Irene] Univ Toronto, Canc Care Ontario, Dept Pathobiol, Toronto, ON, Canada. [van der Hout, A. H.; Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada. [Glendon, Gord] Mt Sinai Hosp, Ontario Canc Genet Network Samuel Lunenfeld Res I, Toronto, ON M5G 1X5, Canada. [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Dept Internal Med & Mol Virol, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Dept Immunol, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Dept Med Genet, Columbus, OH 43210 USA. [van der Hout, A. H.; Bojesen, Anders] Vejle Hosp, Dept Clin Genet, Vejle, Denmark. [Pedersen, Inge Sokilde] Aalborg Univ Hosp, Dept Clin Biochem, Sect Mol Diagnost, Aalborg, Denmark. [Sunde, Lone; Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Thomassen, Mads; Kruse, Torben A.] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Friedman, Eitan; Laitman, Yael; Shimon, Shani Paluch] Sheba Med Ctr, Tel Aviv, Israel. [Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Canada Res Chair Oncogenet, Quebec City, PQ, Canada. [Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. RP Osorio, A (reprint author), Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain. RI Arnold, Norbert/E-3012-2010; Peissel, Bernard/E-8187-2017; Whittemore, Alice/F-9925-2014; Menendez Vila, Mireia/H-9981-2015; Gronwald, Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Ditsch, Nina/F-6267-2014; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Osorio, Ana/I-4324-2014; Ehrencrona, Hans/M-5619-2014; Jakubowska, Anna/O-8050-2014; Andrulis, Irene/E-7267-2013; montagna, marco/E-2225-2012; Hoogerbrugge, Nicoline/O-1016-2013; Teixeira, Manuel/E-4885-2011 OI Arnold, Norbert/0000-0003-4523-8808; Sunde, Lone/0000-0002-8479-165X; Kauff, Noah/0000-0001-7242-6156; Joseph, Vijai/0000-0002-7933-151X; Yannoukakos, Drakoulis/0000-0001-7509-3510; Evans, Gareth/0000-0002-8482-5784; Peissel, Bernard/0000-0001-9233-3571; Nevanlinna, Heli/0000-0002-0916-2976; Rappaport-Fuerhauser, Christine/0000-0002-6820-0020; Devilee, Peter/0000-0002-8023-2009; Papi, Laura/0000-0003-4552-9517; Robson, Mark/0000-0002-3109-1692; Barrowdale, Daniel/0000-0003-1661-3939; Eeles, Rosalind/0000-0002-3698-6241; Backes, Floor/0000-0002-9225-6913; Blanco, Ignacio/0000-0002-7414-7481; Menendez Vila, Mireia/0000-0001-8050-0803; Gronwald, Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562; Osorio, Ana/0000-0001-8124-3984; Ehrencrona, Hans/0000-0002-5589-3622; montagna, marco/0000-0002-4929-2150; Teixeira, Manuel/0000-0002-4896-5982 FU Mutua Madrilena Foundation (FMMA); Spanish Association against Cancer [AECC08]; RTICC [06/0020/1060]; European Community [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK [C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692, C1287/A11990, C5047/A8385]; National Institutes of Health [CA128978]; Post-Cancer GWAS initiative [1 U19 CA 148537]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR); Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund; Swedish Cancer Society; Cancer Association of South Africa (CANSA); NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA125183, R01 CA142996, 1U01CA161032, CA116201]; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Women's Cancer Research Alliance; Basser Research Center; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; National Cancer Institute [UM1 CA164920, CA 27469, CA 101165, CA 37517]; Lithuania (BFBOCC-LT): Research Council of Lithuania [LIG-07/2012]; Hereditary Cancer Association (Paveldimo vezio asociacija); LSC [10.0010.08]; ESF [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Liepaja's municipal council; Morris and Horowitz Families Professorship; NEYE Foundation; City of Hope Clinical Cancer Genetics Community Research Network, National Cancer Institute [RC4A153828]; Office of the Director, National Institutes of Health; Italian Association for Cancer Research (AIRC); FiorGen Foundation for Pharmacogenomics; Associazione CAOS Varese; European Union (European Social Fund - ESF); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA; NIHR; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlons-en!" Award; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Intramural Research Program, NCI; RTICC (ISCIII), Spanish Ministry of Economy and Competitivity [RD06/0020/0021]; Helsinki University Central Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon grant [110005]; BBMRI [NWO 184.021.007/CP46]; Hungarian Research Grant KTIA-OTKA [CK-80745]; Polish Foundation of Science; Nordic Cancer Union, Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital Research Fund; Canadian Institutes of Health Research; Canadian Breast Cancer Research Alliance-grant [019511]; Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]; Ministero dell'Istruzione, dell'Universitae della Ricerca and Ministero della Salute; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria; NIH [CA128978]; U.S. Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; Sharon Levine Corzine Fund; Niehaus Clinical Cancer Genetics Initiative; Andrew Sabin Family Foundation; Lymphoma Foundation; US National Cancer Institute, NIH; Westat, Inc, Rockville, MD [NO2-CP-11019-50, N02-CP-65504]; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), NY; Ohio State University Comprehensive Cancer Center; [FISPI12/00070]; [5U01CA113916]; [R01CA140323] FX The CNIO study was supported by Mutua Madrilena Foundation (FMMA), Spanish Association against Cancer (AECC08), RTICC 06/0020/1060 and FISPI12/00070. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (No. 1 U19 CA 148537 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. SWE-BRCA collaborators are supported by the Swedish Cancer Society. BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to EJvR. UCHICAGO is supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer research Foundation. OIO is an ACS Clinical Research Professor. UPENN study is supported by Basser Research Center (SMD, KN, TRR), Breast Cancer Research Foundation (KN), Komen Foundation for the Cure (SMD). The Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). BCFR study: This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC is supported by: Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012 and Hereditary Cancer Association (Paveldimo vezio asociacija); Latvia (BFBOCC-LV) is partly supported by LSC grant 10.0010.08 and in part by a grant from the ESF Nr. 2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016 and Liepaja's municipal council. BRICOH study: NIH R01CA74415 and P30 CA033752. SLN was partially supported by the Morris and Horowitz Families Professorship. CBCS work was supported by the NEYE Foundation. The City of Hope Clinical Cancer Genetics Community Research Network is supported by Award Number RC4A153828 (PI: JNW) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The members of CONSIT TEAM were funded by grants from the Italian Association for Cancer Research (AIRC) to PP, LO and PR; FiorGen Foundation for Pharmacogenomics to LP; Associazione CAOS Varese to MGT and by funds from Italian citizens who allocated the 561000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000') to SMan and PR.; Demokritos: This research has been co-financed by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA. Investing in knowledge society through the European Social Fund. We wish to thank Hellenic Cooperative Oncology Group (HeCOG) and the Hellenic Foundation for Cancer Research (HFCR). EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. GE and FLa are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. RE and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. FCCC study: The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. AKG was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, RKS) and by the Center for Molecular Medicine Cologne (CMMC). This study was kindly supported by the German Cancer Aid to RKS (grant no 109076) and by the Center for Molecular Medicine Cologne (CMMC). GEMO study: The study was supported by the Ligue National Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award; and the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program. GOG study: This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and GOG's Cancer Prevention and Control Committee (CA 101165). MHG, PLM and Sharon A. Savage were supported by funding from the Intramural Research Program, NCI. This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) CA 27469, CA 37517, and CA 101165. HCSC study was supported by a grant RD06/0020/0021 from RTICC (ISCIII), Spanish Ministry of Economy and Competitivity. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society and the Sigrid Juselius Foundation. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.007/CP46. Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grant KTIA-OTKA CK-80745. IHCC study: KJB is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science. The ILUH group was supported by the Nordic Cancer Union, Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund.; INHERIT: This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer'' program, the Canadian Breast Cancer Research Alliance-grant #019511 and the Ministry of Economic Development, Innovation and Export Trade - grant # PSR-SIIRI-701. IOVHBOCS study was supported by Ministero dell'Istruzione, dell'Universitae della Ricerca and Ministero della Salute. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. GCT and Amanda B. Spurdle are NHMRC Senior Research Fellows. MAYO is supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. MSKCC was supported by the Sharon Levine Corzine Fund, Breast Cancer Research Foundation, Niehaus Clinical Cancer Genetics Initiative, Andrew Sabin Family Foundation and Lymphoma Foundation. NCI study: The research of MHG, PLM and Sharon A. Savage was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD. NICCC is supported by Clalit Health Services in Israel. Some of its activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. SMC study: This project was partially funded through a grant by the Israel cancer association and the funding for the Israeli Inherited breast cancer consortium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 8 Z9 8 U1 2 U2 28 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2014 VL 10 IS 4 AR e1004256 DI 10.1371/journal.pgen.1004256 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AG6AB UT WOS:000335499600026 PM 24698998 ER PT J AU Sawyer, E Roylance, R Petridis, C Brook, MN Nowinski, S Papouli, E Fletcher, O Pinder, S Hanby, A Kohut, K Gorman, P Caneppele, M Peto, J Silva, ID Johnson, N Swann, R Dwek, M Perkins, KA Gillett, C Houlston, R Ross, G De Ieso, P Southey, MC Hopper, JL Provenzano, E Apicella, C Wesseling, J Cornelissen, S Keeman, R Fasching, PA Jud, SM Ekici, AB Beckmann, MW Kerin, MJ Marme, F Schneeweiss, A Sohn, C Burwinkel, B Guenel, P Truong, T Laurent-Puig, P Kerbrat, P Bojesen, SE Nordestgaard, BG Nielsen, SF Flyger, H Milne, RL Perez, JIA Menendez, P Benitez, J Brenner, H Dieffenbach, AK Arndt, V Stegmaier, C Meindl, A Lichtner, P Schmutzler, RK Lochmann, M Brauch, H Fischer, HP Ko, YD Nevanlinna, H Muranen, TA Aittomaki, K Blomqvist, C Bogdanova, NV Dork, T Lindblom, A Margolin, S Mannermaa, A Kataja, V Kosma, VM Hartikainen, JM Chenevix-Trench, G Lambrechts, D Weltens, C Van Limbergen, E Hatse, S Chang-Claude, J Rudolph, A Seibold, P Flesch-Janys, D Radice, P Peterlongo, P Bonanni, B Volorio, S Giles, GG Severi, G Baglietto, L Mclean, CA Haiman, CA Henderson, BE Schumacher, F Le Marchand, L Simard, J Goldberg, MS Labreche, F Dumont, M Kristensen, V Winqvist, R Pylkas, K Jukkola-Vuorinen, A Kauppila, S Andrulis, IL Knight, JA Glendon, G Mulligan, AM Devillee, P Tollenaar, RAEM Seynaeve, CM Kriege, M Figueroa, J Chanock, SJ Sherman, ME Hooning, MJ Hollestelle, A van den Ouweland, AMW van Deurzen, CHM Li, JM Czene, K Humphreys, K Cox, A Cross, SS Reed, MWR Shah, M Jakubowska, A Lubinski, J Jaworska-Bieniek, K Durda, K Swerdlow, A Ashworth, A Orr, N Schoemaker, M Couch, FJ Hallberg, E Gonzalez-Neira, A Pita, G Alonso, MR Tessier, DC Vincent, D Bacot, F Bolla, MK Wang, Q Dennis, J Michailidou, K Dunning, AM Hall, P Easton, D Pharoah, P Schmidt, MK Tomlinson, I Garcia-Closas, M AF Sawyer, Elinor Roylance, Rebecca Petridis, Christos Brook, Mark N. Nowinski, Salpie Papouli, Efterpi Fletcher, Olivia Pinder, Sarah Hanby, Andrew Kohut, Kelly Gorman, Patricia Caneppele, Michele Peto, Julian Silva, Isabel dos Santos Johnson, Nichola Swann, Ruth Dwek, Miriam Perkins, Katherine-Anne Gillett, Cheryl Houlston, Richard Ross, Gillian De Ieso, Paolo Southey, Melissa C. Hopper, John L. Provenzano, Elena Apicella, Carmel Wesseling, Jelle Cornelissen, Sten Keeman, Renske Fasching, Peter A. Jud, Sebastian M. Ekici, Arif B. Beckmann, Matthias W. Kerin, Michael J. Marme, Federick Schneeweiss, Andreas Sohn, Christof Burwinkel, Barbara Guenel, Pascal Truong, Therese Laurent-Puig, Pierre Kerbrat, Pierre Bojesen, Stig E. Nordestgaard, Borge G. Nielsen, Sune F. Flyger, Henrik Milne, Roger L. Perez, Jose Ignacio Arias Menendez, Primitiva Benitez, Javier Brenner, Hermann Dieffenbach, Aida Karina Arndt, Volker Stegmaier, Christa Meindl, Alfons Lichtner, Peter Schmutzler, Rita K. Lochmann, Magdalena Brauch, Hiltrud Fischer, Hans-Peter Ko, Yon-Dschun Nevanlinna, Heli Muranen, Taru A. Aittomaki, Kristiina Blomqvist, Carl Bogdanova, Natalia V. Dork, Thilo Lindblom, Annika Margolin, Sara Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M. Chenevix-Trench, Georgia Lambrechts, Diether Weltens, Caroline Van Limbergen, Erik Hatse, Sigrid Chang-Claude, Jenny Rudolph, Anja Seibold, Petra Flesch-Janys, Dieter Radice, Paolo Peterlongo, Paolo Bonanni, Bernardo Volorio, Sara Giles, Graham G. Severi, Gianluca Baglietto, Laura Mclean, Catriona A. Haiman, Christopher A. Henderson, Brian E. Schumacher, Fredrick Le Marchand, Loic Simard, Jacques Goldberg, Mark S. Labreche, France Dumont, Martine Kristensen, Vessela Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Kauppila, Saila Andrulis, Irene L. Knight, Julia A. Glendon, Gord Mulligan, Anna Marie Devillee, Peter Tollenaar, Rob A. E. M. Seynaeve, Caroline M. Kriege, Mieke Figueroa, Jonine Chanock, Stephen J. Sherman, Mark E. Hooning, Maartje J. Hollestelle, Antoinette van den Ouweland, Ans M. W. van Deurzen, Carolien H. M. Li, Jingmei Czene, Kamila Humphreys, Keith Cox, Angela Cross, Simon S. Reed, Malcolm W. R. Shah, Mitul Jakubowska, Anna Lubinski, Jan Jaworska-Bieniek, Katarzyna Durda, Katarzyna Swerdlow, Anthony Ashworth, Alan Orr, Nicholas Schoemaker, Minouk Couch, Fergus J. Hallberg, Emily Gonzalez-Neira, Anna Pita, Guillermo Alonso, M. Rosario Tessier, Daniel C. Vincent, Daniel Bacot, Francois Bolla, Manjeet K. Wang, Qin Dennis, Joe Michailidou, Kyriaki Dunning, Alison M. Hall, Per Easton, Doug Pharoah, Paul Schmidt, Marjanka K. Tomlinson, Ian Garcia-Closas, Montserrat CA GENICA Network KConFab Investigators TI Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CANCER SUSCEPTIBILITY LOCI; COMMON VARIANTS; CONFER SUSCEPTIBILITY; MUTATION CARRIERS; 14Q24.1 RAD51L1; IDENTIFIES 3; RISK; METAANALYSIS; CHEMOTHERAPY AB Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95% CI) for ILC = 1.13 (1.09-1.18), P = 6.0x10(-10); P-het for ILC vs IDC ER+ tumors = 1.8x10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes. C1 [Sawyer, Elinor; Petridis, Christos; Nowinski, Salpie; Pinder, Sarah; Gillett, Cheryl] Kings Coll London, Guys Hosp, Div Canc Studies, London WC2R 2LS, England. [Roylance, Rebecca; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele] Queen Mary Univ London, Ctr Mol Oncol, Barts Canc Inst, London, England. [Brook, Mark N.; Houlston, Richard; Schoemaker, Minouk; Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England. [Papouli, Efterpi] Kings Coll London, Guys Hosp, Biomed Res Ctr, London WC2R 2LS, England. [Fletcher, Olivia; Johnson, Nichola; Garcia-Closas, Montserrat] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Hanby, Andrew] St James Univ Hosp, Leeds Inst Mol Med, Leeds, W Yorkshire, England. [Peto, Julian; Silva, Isabel dos Santos] London Sch Hyg & Trop Med, London WC1, England. [Swann, Ruth; Dwek, Miriam; Perkins, Katherine-Anne] Univ Westminster, Dept Mol & Appl Biosci, London W1R 8AL, England. [Ross, Gillian; De Ieso, Paolo] Royal Marsden NHS Fdn Trust, London, England. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Hopper, John L.; Apicella, Carmel] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Provenzano, Elena] Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Cambridge, England. [Wesseling, Jelle; Cornelissen, Sten; Keeman, Renske; Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Fasching, Peter A.; Jud, Sebastian M.; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Dept Obstet & Gynecol, Univ Hosp Erlangen, D-91054 Erlangen, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany. [Kerin, Michael J.] Natl Univ Ireland, Inst Clin Sci, Galway, Ireland. [Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany. [Marme, Federick; Schneeweiss, Andreas] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany. [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany. [Guenel, Pascal; Truong, Therese] CESP Ctr Res Epidemiol & Populat Hlth, INSERM, U1018, Villejuif, France. [Guenel, Pascal; Truong, Therese] Univ Paris 11, UMRS 1018, Villejuif, France. [Laurent-Puig, Pierre] Univ Paris, Sorbonne Cite, INSERM, UMR S775, F-75252 Paris, France. [Kerbrat, Pierre] Ctr Eugene Marquis, Dept Med Oncol, Rennes, France. [Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Univ Copenhagen, Copenhagen Univ Hosp, Copenhagen Gen Populat Study, Herlev Hosp, Copenhagen, Denmark. [Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Univ Copenhagen, Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, Copenhagen, Denmark. [Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Copenhagen, Denmark. [Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Genet & Mol Epidemiol Grp, Madrid, Spain. [Perez, Jose Ignacio Arias] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain. [Menendez, Primitiva] Hosp Monte Naranco, Serv Anat Patol, Oviedo, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genet Grp, Madrid, Spain. [Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany. [Meindl, Alfons; Lochmann, Magdalena] Tech Univ Munich, Div Gynaecol & Obstet, D-80290 Munich, Germany. [Lichtner, Peter] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany. [Fischer, Hans-Peter] Univ Bonn, Inst Pathol, Fac Med, Bonn, Germany. [Ko, Yon-Dschun] Johanniter Krankenhaus, Evangel Kliniken Bonn gGmbH, Dept Internal Med, Bonn, Germany. Univ Med Ctr Hamburg Eppendorf, Inst Occupat Med & Maritime Med, Hamburg, Germany. Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany. [GENICA Network] Inst Ruhr Univ Bochum IPA, Inst Prevent & Occupat Med German Social Accident, Bochum, Germany. [Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. [Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. [Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany. [Dork, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, Joensuu, Finland. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland. [Chenevix-Trench, Georgia] QIMR Berghofer Inst Med Res, Dept Genet, Brisbane, Qld, Australia. [KConFab Investigators] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Lambrechts, Diether] VIB, VRC, Louvain, Belgium. [Lambrechts, Diether] Univ Louvain, Dept Oncol, Louvain, Belgium. [Weltens, Caroline; Van Limbergen, Erik; Hatse, Sigrid] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing Prevent, Milan, Italy. [Radice, Paolo; Peterlongo, Paolo; Volorio, Sara] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Bonanni, Bernardo] IEO, Div Canc Prevent & Genet, Milan, Italy. [Volorio, Sara] Cogentech Canc Genet Test Lab, Milan, Italy. [Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Mclean, Catriona A.] Alfred Hosp, Dept Pathol, Prahran, Vic 3181, Australia. [Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Simard, Jacques; Dumont, Martine] Ctr Hosp Univ Quebec, Canc Genom Lab, Res Ctr, Quebec City, PQ, Canada. [Simard, Jacques; Dumont, Martine] Univ Laval, Quebec City, PQ, Canada. [Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ, Canada. [Goldberg, Mark S.] Royal Victoria Hosp, McGill Univ Hlth Ctr, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada. [Labreche, France] Univ Montreal, Dept Sante Environm & Sante Travail, Dept Med Sociale & Prevent, Montreal, PQ, Canada. [Kristensen, Vessela] Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Genet, Oslo, Norway. [Kristensen, Vessela] UiO, Fac Div Ahus, Fac Med, Oslo, Norway. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, Dept Clin Chem, Lab Canc Genet & Tumor Biol, NordLab,Oulu Univ Hosp, Oulu, Finland. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, Bioctr Oulu, NordLab, Oulu Univ Hosp, Oulu, Finland. [Jukkola-Vuorinen, Arja; Kauppila, Saila] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland. [Andrulis, Irene L.; Glendon, Gord] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada. [Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada. [Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Devillee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Devillee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands. [Tollenaar, Rob A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, Leiden, Netherlands. [Seynaeve, Caroline M.; Kriege, Mieke] Dr Daniel Den Hoed Canc Ctr, Erasmus MC, Dept Med Oncol, Family Canc Clin, NL-3008 AE Rotterdam, Netherlands. [Figueroa, Jonine; Chanock, Stephen J.; Sherman, Mark E.] NCI, Div Canc Prevent, Bethesda, MD 20892 USA. [Hooning, Maartje J.; Hollestelle, Antoinette] Erasmus MC Canc Inst, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [van den Ouweland, Ans M. W.] Erasmus Univ, Med Ctr, Dept Clin Genet, Rotterdam, Netherlands. [van Deurzen, Carolien H. M.] Erasmus Univ, Dept Pathol, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Li, Jingmei] Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [Czene, Kamila; Humphreys, Keith; Hall, Per] Karolinska Inst, Stockholm, Sweden. [Cox, Angela; Reed, Malcolm W. R.] Univ Sheffield, Dept Oncol, CRUK YCR Sheffield Canc Res Ctr, Sheffield, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England. [Shah, Mitul; Dunning, Alison M.; Pharoah, Paul] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England. [Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Jaworska-Bieniek, Katarzyna] Med Univ Warsaw, Postgrad Sch Mol Med, Warsaw, Poland. [Swerdlow, Anthony] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England. [Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, Sutton, Surrey, England. [Ashworth, Alan; Orr, Nicholas] Inst Canc Res, Div Breast Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Hallberg, Emily] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Gonzalez-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid, Spain. [Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois] McGill Univ, Montreal, PQ, Canada. [Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Easton, Doug; Pharoah, Paul] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England. RP Sawyer, E (reprint author), Kings Coll London, Guys Hosp, Div Canc Studies, London WC2R 2LS, England. RI Garcia-Closas, Montserrat /F-3871-2015; Dork, Thilo/J-8620-2012; laurent-puig, pierre/B-2226-2013; Brenner, Hermann/B-4627-2017; Knight, Julia/A-6843-2012; Jakubowska, Anna/O-8050-2014; Li, Jingmei/I-2904-2012; Andrulis, Irene/E-7267-2013; Gonzalez-Neira, Anna/C-5791-2015; Hartikainen, Jaana/E-6256-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; laurent-puig, pierre/0000-0001-8475-5459; Brenner, Hermann/0000-0002-6129-1572; Czene, Kamila/0000-0002-3233-5695; Schoemaker, Minouk/0000-0001-8403-2234; Li, Jingmei/0000-0001-8587-7511; Nevanlinna, Heli/0000-0002-0916-2976; Cross, Simon/0000-0003-2044-1754; Arias Perez, Jose Ignacio/0000-0003-4500-397X; Dunning, Alison Margaret/0000-0001-6651-7166; Brook, Mark/0000-0002-8969-2378; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099; Muranen, Taru/0000-0002-5895-1808; Houlston, Richard/0000-0002-5268-0242 FU Breast Cancer Campaign [2010NovPR61]; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust and King's College London; Wellcome Trust Centre for Human Genetics (Wellcome Trust) [090532/Z/09/Z]; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Ministry of Economic Development, Innovation and Export Trade of Quebec [PSR-SIIRI-701]; European Community [223175, HEALTH-F2-2009-223175]; United States National Cancer Institute, National Institutes of Health (NIH) [RFA-CA-06-503]; Cancer Care Ontario [U01 CA69467]; Northern California Cancer Center [U01 CA69417]; University of Melbourne [U01 CA69638]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; Dutch Cancer Society [NKI 2007-3839, 2009-4363, RUL 1997-1505, DDHK 2004-3124, DDHK 2009-4318]; ELAN-Fond of the University Hospital of Erlangen; Cancer Research UK; Breakthrough Breast Cancer; NHS; National Cancer Research Network (NCRN); CR-UK [C1287/A10118, C1287/A12014]; European Union COST programme [BM0606]; Oxford Biomedical Research Centre; Dietmar-Hopp Foundation; Helmholtz Society; German Cancer Research Center (DKFZ); Fondation de France; Institut National du Cancer (INCa); Ligue Nationale contre le Cancer; Ligue contre le Cancer Grand Ouest; Agence Nationale de Securite Sanitaire (ANSES); Agence Nationale de la Recherche (ANR); Lise Boserup Fund; Danish Medical Research Council; Herlev Hospital; Genome Spain Foundation; Red Tematica de Investigacion Cooperativa en Cancer; Asociacion Espanola Contra el Cancer; Fondo de Investigacion Sanitario [PI11/00923, PI081120]; charity Against Breast Cancer [1121258]; Baden Wurttemberg Ministry of Science, Research and Arts; German Cancer Aid (Deutsche Krebshilfe); Deutsche Krebshilfe [107 352]; Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation; Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum; Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH; Johanniter Krankenhaus, Bonn, Germany; Helsinki University Central Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer Society; Nordic Cancer Union; Sigrid Juselius Foundation; Friends of Hannover Medical School; Rudolf Bartling Foundation; Stockholm County Council; Karolinska Institutet; Swedish Cancer Society; Bert von Kantzow foundation; Kuopio University Hospital grants; Cancer Fund of North Savo; Finnish Cancer Organizations; Academy of Finland; University of Eastern Finland; National Breast Cancer Foundation; NHMRC; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; NHMRC [145684, 288704, 454508, 199600]; United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council of Tasmania; Stichting tegen Kanker [232-2008, 196-2010]; FWO; Deutsche Krebshilfe e.V. [70-2892-BR I]; Hamburg Cancer Society; German Cancer Research Center; Italian Association for Cancer Research (AIRC); Fondazione IRCCS Istituto Nazionale Tumori [561000]; NIH [CA128978, CA63464, CA54281, CA098758, CA132839]; NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; Breast Cancer Research Foundation; VicHealth and Cancer Council Victoria; Australian NHMRC [209057, 251553, 504711]; MTLGEBCS: The Quebec Breast Cancer Foundation; Norwegian Research council [FUGE-NFR 181600/V11]; Finnish Cancer Foundation; University of Oulu; Oulu University Hospital; Canadian Institutes of Health Research "CIHR Team in Familial Risks of Breast Cancer" program; National Cancer Institute/NIH (USA) [UM1 CA164920]; Biobanking and Biomolecular Resources Research Infrastructure [BBMRI-NL CP16]; Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA; Agency for Science, Technology and Research of Singapore (A*STAR); US National Institute of Health (NIH); Susan G. Komen Breast Cancer Foundation; Yorkshire Cancer Research [S295, S299, S305PA]; Cancer Research UK [C490/A10124]; UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge; DKFZ, Heidelberg, Germany; Polish Foundation of Science; Institute of Cancer Research (ICR); [KULPFV/10/016-SymBioSysII] FX GLACIER: Genotyping was funded by the Breast Cancer Campaign (grant number 2010NovPR61, www.breastcancercampaign.org). Sample and data collection by Cancer Research UK. Core funding came from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust and King's College London and the Wellcome Trust Centre for Human Genetics (provided by the Wellcome Trust, 090532/Z/09/Z). The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR or the Department of Health. iCOGs was partly supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program (JS & DE), and the Ministry of Economic Development, Innovation and Export Trade of Quebec - grant # PSR-SIIRI-701 (JS, DE, PH). JS is chair holder of the Canada Research Chair in Oncogenetics. Part of this work was supported by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The ABCFS, NC-BCFR and OFBCR work was supported by the United States National Cancer Institute, National Institutes of Health (NIH) under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638). Samples from the NC-BCFR were processed and distributed by the Coriell Institute for Medical Research. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. JLH is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. MCS is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. The ABCS study was supported by the Dutch Cancer Society grants number NKI 2007-3839 and 2009-4363. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCAC is funded by CR-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). DE is a Principal Research Fellow of CR-UK. BIGGS: IT is supported by the Oxford Biomedical Research Centre. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CECILE study was funded by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Ligue contre le Cancer Grand Ouest, Agence Nationale de Securite Sanitaire (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital.; The CNIO-BCS was supported by the Genome Spain Foundation, the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI11/00923 and PI081120). DietCompLyf: The University of Westminster's ABC Research Unit acknowledges funding from the charity Against Breast Cancer (Registered Charity Number 1121258). The ESTHER study was supported by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The GC-HBOC was supported by Deutsche Krebshilfe (107 352). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, The Swedish Cancer Society and Bert von Kantzow foundation. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, the Academy of Finland and by the strategic funding of the University of Eastern Finland. kConFab is supported by grants from the National Breast Cancer Foundation, the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study was funded by the NHMRC [145684, 288704, 454508]. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], the Cancer Council of Tasmania and Cancer Foundation of Western Australia and the NHMRC [199600]. GCT is supported by the NHMRC. LMBC is supported by the 'Stichting tegen Kanker' (232-2008 and 196-2010). DL is supported by the FWO and the KULPFV/10/016-SymBioSysII. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I], the Hamburg Cancer Society, the German Cancer Research Center and the genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "561000"). MCBCS investigators were supported by the NIH grant CA128978, an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201] and the Breast Cancer Research Foundation, and generous gifts from the David F. and Margaret T.; Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. The MEC was supported by NIH grants CA63464, CA54281, CA098758 and CA132839. MTLGEBCS: The Quebec Breast Cancer Foundation supported the case-control study. The NBCS was supported by grants from the Norwegian Research council FUGE-NFR 181600/V11 to VK. The OBCS was supported by the Finnish Cancer Foundation, the Academy of Finland, the University of Oulu, and the Oulu University Hospital. OFBCR: This work was supported by the Canadian Institutes of Health Research "CIHR Team in Familial Risks of Breast Cancer" program, and grant UM1 CA164920 from the National Cancer Institute/NIH (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCS was supported by Yorkshire Cancer Research S295, S299, S305PA. SEARCH is funded by a programme grant from Cancer Research UK [C490/A10124] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. SKKDKFZS is supported by the DKFZ, Heidelberg, Germany. SZBCS:KJB is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science. The UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR). ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 16 Z9 16 U1 1 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2014 VL 10 IS 4 AR e1004285 DI 10.1371/journal.pgen.1004285 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA AG6AB UT WOS:000335499600037 PM 24743323 ER PT J AU Nie, LM Wang, SJ Wang, XY Rong, PF Bhirde, A Ma, Y Liu, G Huang, P Lu, GM Chen, XY AF Nie, Liming Wang, Shouju Wang, Xiaoyong Rong, Pengfei Bhirde, Ashwinkumar Ma, Ying Liu, Gang Huang, Peng Lu, Guangming Chen, Xiaoyuan TI In Vivo Volumetric Photoacoustic Molecular Angiography and Therapeutic Monitoring with Targeted Plasmonic Nanostars SO SMALL LA English DT Article DE tumor angiogenesis; plasmonic nanostars; photoacoustic imaging; photothermal therapy; therapy monitoring ID MULTISPECTRAL OPTOACOUSTIC TOMOGRAPHY; CANCER; ANGIOGENESIS; NANOCAGES; NANORODS; INTEGRIN; DELIVERY; GROWTH AB Photoacoustic (PA) imaging promises deeper tissue penetration while maintaining rich optical contrast as compared to other high resolution optical imaging techniques. In this report, a near-infrared pulse laser serves as the excitation source, and 128 ultrasonic transducers are spirally distributed on a hemispherical surface to receive PA signals for three-dimensional (3D) image reconstruction. With these attributes, the unique modality produces an isotropic and homogeneous spatial resolution (approximate to 200 m) with penetration depth of centimeters. Cyclic Arg-Gly-Asp (RGD) peptides conjugated plasmonic gold nanostars (RGD-GNS) are designed to specifically target over-expressed integrin (v3) on tumor neovasculature, enabling highly sensitive angiography and photothermal therapy (PTT). After the administration of RGD-GNS, tumor angiogenesis is clearly imaged with enhanced contrast, and the growth of tumor is effectively inhibited by PTT after laser irradiation. This study suggest that the PA angiography with plasmonic RGD-GNS can be applied as a triple functional platform for tumor diagnosis, PTT, and treatment monitoring. This PA technique offers deeper imaging depth with homogeneous resolution over existing optical imaging techniques for early diagnosis of tumor angiogenesis as well as on-the-spot nanotherapeutic evaluation. C1 [Nie, Liming; Rong, Pengfei; Bhirde, Ashwinkumar; Ma, Ying; Huang, Peng; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Nie, Liming; Wang, Xiaoyong; Liu, Gang] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361005, Peoples R China. [Wang, Shouju; Lu, Guangming] Nanjing Univ, Dept Med Imaging, Jinling Hosp, Clin Sch Med Coll, Nanjing 210002, Jiangsu, Peoples R China. RP Lu, GM (reprint author), Nanjing Univ, Dept Med Imaging, Jinling Hosp, Clin Sch Med Coll, Nanjing 210002, Jiangsu, Peoples R China. EM cjr.luguangming@vip.163.com; shawn.chen@nih.gov RI Huang, Peng/H-9985-2013; Nie, Liming/F-7718-2016; Huang, Peng/R-2480-2016 OI Huang, Peng/0000-0003-3651-7813 FU National Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH; National Key Basic Research Program (973 project) [2014CB744503, 2014CB744504, 2013CB733802]; National Natural Science Foundation of China [81301257, 81371596, 51273165, 81101101] FX This work was supported by National Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH, and the National Key Basic Research Program (973 project) (2014CB744503, 2014CB744504, 2013CB733802) as well as National Natural Science Foundation of China (81301257, 81371596, 51273165, 81101101). The authors acknowledge National Cancer Institute (NCI) fellows editorial board for editorial assistance. We also thank Ms. Verma Walker for close reading of the manuscript. NR 30 TC 64 Z9 64 U1 6 U2 78 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1613-6810 EI 1613-6829 J9 SMALL JI Small PD APR PY 2014 VL 10 IS 8 BP 1585 EP 1593 DI 10.1002/smll.201302924 PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA AE8VH UT WOS:000334280500019 PM 24150920 ER PT J AU Milman, G Bergamaschi, MM Lee, D Mendu, DR Barnes, AJ Vandrey, R Huestis, MA AF Milman, Garry Bergamaschi, Mateus M. Lee, Dayong Mendu, Damodara R. Barnes, Allan J. Vandrey, Ryan Huestis, Marilyn A. TI Plasma Cannabinoid Concentrations During Dronabinol Pharmacotherapy for Cannabis Dependence SO THERAPEUTIC DRUG MONITORING LA English DT Article DE dronabinol; plasma; cannabinoids; smoking; oral administration ID ORAL THC; DELTA-9-TETRAHYDROCANNABINOL CONCENTRATIONS; TOBACCO WITHDRAWAL; MARIJUANA; SMOKING; BLOOD; DELTA(9)-TETRAHYDROCANNABINOL; ABSORPTION; THCCOOH; IMPACT AB Background:Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic, daily cannabis smokers who received high-dose oral THC pharmacotherapy and later a smoked cannabis challenge.Methods:Eleven daily cannabis smokers received 0, 30, 60, or 120 mg/d THC for four 5-day medication sessions, each separated by 9 days of ad libitum cannabis smoking. On the fifth day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the first and fifth days was quantified by two-dimensional gas chromatography mass spectrometer for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5-100 for THC, 1-50 for 11-OH-THC, and 0.5-200 for THCCOOH.Results:During placebo dosing, THC, 11-OH-THC, and THCCOOH concentrations consistently decreased, whereas all cannabinoids increased dose dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during the 60- and 120-mg/d doses, and THCCOOH increased significantly only during the 120-mg/d dose. THC, 11-OH-THC, and THCCOOH concentrations peaked within 0.25 hours after cannabis smoking, except after 120 mg/d THC when THCCOOH peaked 0.5 hours before smoking.Conclusions:The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 hour, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 hours after overnight oral dronabinol abstinence but cannot distinguish oral THC dosing from the smoked cannabis intake. C1 [Milman, Garry; Bergamaschi, Mateus M.; Lee, Dayong; Mendu, Damodara R.; Barnes, Allan J.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, Biomed Res Ctr,NIH, Baltimore, MD 21224 USA. [Vandrey, Ryan] Johns Hopkins Bayview Med Ctr, Behav Pharmacol Res Unit, Baltimore, MD USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, Intramural Res Program, Biomed Res Ctr,NIH, 251 Bayview Blvd,Rm 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU US National Institute on Drug Abuse [R01-DA025044]; National Institutes of Health, Intramural Research Program of the National Institute on Drug Abuse FX Supported by grant R01-DA025044 from the US National Institute on Drug Abuse and the National Institutes of Health, Intramural Research Program of the National Institute on Drug Abuse. NR 25 TC 7 Z9 7 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 EI 1536-3694 J9 THER DRUG MONIT JI Ther. Drug Monit. PD APR PY 2014 VL 36 IS 2 BP 218 EP 224 DI 10.1097/FTD.0b013e3182a5c446 PG 7 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA AD4ET UT WOS:000333200900013 PM 24067260 ER PT J AU Barnes, AJ Scheidweiler, KB Huestis, MA AF Barnes, Allan J. Scheidweiler, Karl B. Huestis, Marilyn A. TI Quantification of 11-Nor-9-Carboxy-D9-Tetrahydrocannabinol in Human Oral Fluid by Gas Chromatography-Tandem Mass Spectrometry SO THERAPEUTIC DRUG MONITORING LA English DT Article DE cannabinoids; THCCOOH; oral fluid; GC-MS; MS ID CONTROLLED SMOKED CANNABIS; 11-NOR-DELTA(9)-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID; LIQUID-CHROMATOGRAPHY; METABOLITES; DRUGS; ABUSE; DISPOSITION; SPECIMENS; EXPOSURE AB A sensitive and specific method for the quantification of 11-nor-9-carboxy-9-tetrahydrocannabinol (THCCOOH) in oral fluid collected with the Quantisal and Oral-Eze devices was developed and fully validated. Extracted analytes were derivatized with hexafluoroisopropanol and trifluoroacetic anhydride and quantified by gas chromatography-tandem mass spectrometry with negative chemical ionization. Standard curves, using linear least-squares regression with 1/x(2) weighting were linear from 10 to 1000 ng/L with coefficients of determination >0.998 for both collection devices. Bias was 89.2%-112.6%, total imprecision 4.0%-5.1% coefficient of variation, and extraction efficiency >79.8% across the linear range for Quantisal-collected specimens. Bias was 84.6%-109.3%, total imprecision 3.6%-7.3% coefficient of variation, and extraction efficiency >92.6% for specimens collected with the Oral-Eze device at all 3 quality control concentrations (10, 120, and 750 ng/L). This effective high-throughput method reduces analysis time by 9 minutes per sample compared with our current 2-dimensional gas chromatography-mass spectrometry method and extends the capability of quantifying this important oral fluid analyte to gas chromatography-tandem mass spectrometry. This method was applied to the analysis of oral fluid specimens collected from individuals participating in controlled cannabis studies and will be effective for distinguishing passive environmental contamination from active cannabis smoking. C1 [Barnes, Allan J.; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, National Institutes of Health FX Supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 26 TC 2 Z9 2 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 EI 1536-3694 J9 THER DRUG MONIT JI Ther. Drug Monit. PD APR PY 2014 VL 36 IS 2 BP 225 EP 233 DI 10.1097/01.ftd.0000443071.30662.01 PG 9 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA AD4ET UT WOS:000333200900014 PM 24622724 ER PT J AU Li, H Deng, XW Kim, DY Smith, EP AF Li, Han Deng, Xinwei Kim, Dong-Yun Smith, Eric P. TI Modeling maximum daily temperature using a varying coefficient regression model SO WATER RESOURCES RESEARCH LA English DT Article DE varying coefficients; stream temperature; nonparametric ID STREAM TEMPERATURE; WATER TEMPERATURE; AIR-TEMPERATURE; ECOLOGICAL-SYSTEM; RIVER; CLIMATE; CANADA; BROOK; TROUT AB Relationships between stream water and air temperatures are often modeled using linear or nonlinear regression methods. Despite a strong relationship between water and air temperatures and a variety of models that are effective for data summarized on a weekly basis, such models did not yield consistently good predictions for summaries such as daily maximum temperature. A good predictive model for daily maximum temperature is required because daily maximum temperature is an important measure for predicting survival of temperature sensitive fish. To appropriately model the strong relationship between water and air temperatures at a daily time step, it is important to incorporate information related to the time of the year into the modeling. In this work, a time-varying coefficient model is used to study the relationship between air temperature and water temperature. The time-varying coefficient model enables dynamic modeling of the relationship, and can be used to understand how the air-water temperature relationship varies over time. The proposed model is applied to 10 streams in Maryland, West Virginia, Virginia, North Carolina, and Georgia using daily maximum temperatures. It provides a better fit and better predictions than those produced by a simple linear regression model or a nonlinear logistic model. C1 [Li, Han; Deng, Xinwei; Smith, Eric P.] Virginia Tech, Dept Stat, Blacksburg, VA 24060 USA. [Kim, Dong-Yun] Virginia Tech, Caril Sch Med, Dept Psychiat & Behav Med, Blacksburg, VA USA. [Kim, Dong-Yun] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Smith, EP (reprint author), Virginia Tech, Dept Stat, Blacksburg, VA 24060 USA. EM epsmith@vt.edu FU US Forest Service FX We thank Mark Hudy and Andy Dolloff for access to the data and comments on the analysis. Our research was partially supported by a grant from the US Forest Service. NR 48 TC 3 Z9 3 U1 1 U2 18 PU AMER GEOPHYSICAL UNION PI WASHINGTON PA 2000 FLORIDA AVE NW, WASHINGTON, DC 20009 USA SN 0043-1397 EI 1944-7973 J9 WATER RESOUR RES JI Water Resour. Res. PD APR PY 2014 VL 50 IS 4 BP 3073 EP 3087 DI 10.1002/2013WR014243 PG 15 WC Environmental Sciences; Limnology; Water Resources SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Water Resources GA AH3LV UT WOS:000336026000019 ER PT J AU Newman, JD AF Newman, John D. TI Vocal coordination and vocal imitation: A role for mirror neurons? SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB Some birds and mammals have vocal communication systems in which coordination between individuals is important. Examples would include duetting or antiphonal calling in some birds and mammals, rapid exchanges of the same vocalization, and vocal exchanges between paired individuals and other nearby pairs. Mirror neurons may play a role in such systems but become functional only after experience. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. RP Newman, JD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. EM jn1g@nih.gov FU Intramural NIH HHS NR 0 TC 0 Z9 0 U1 2 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD APR PY 2014 VL 37 IS 2 BP 211 EP 212 DI 10.1017/S0140525X13002410 PG 2 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA AH0QV UT WOS:000335826100050 PM 24775169 ER PT J AU Simpson, EA Fox, NA Tramacere, A Ferrari, PF AF Simpson, Elizabeth A. Fox, Nathan A. Tramacere, Antonella Ferrari, Pier F. TI Neonatal imitation and an epigenetic account of mirror neuron development SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB Neonatal imitation should not exclusively be considered at the population-level; instead, we propose that inconsistent findings regarding its occurrence result from important individual differences in imitative responses. We also highlight what we consider to be a false dichotomy of genetic versus learning accounts of the development of mirror neurons, and instead suggest a more parsimonious epigenetic perspective. C1 [Simpson, Elizabeth A.; Tramacere, Antonella; Ferrari, Pier F.] Univ Parma, Dipartimento Biol Evolut & Funz, I-43100 Parma, Italy. [Simpson, Elizabeth A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Comparat Ethol, Anim Ctr, Dickerson, MD 20842 USA. [Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA. RP Simpson, EA (reprint author), Univ Parma, Dipartimento Biol Evolut & Funz, I-43100 Parma, Italy. EM simpsonea@mail.nih.gov; fox@umd.edu; a.tramacere@gmail.com; pierfrancesco.ferrari@unipr.it OI Simpson, Elizabeth/0000-0003-2715-2533 FU Intramural NIH HHS; NICHD NIH HHS [P01 HD064653, P01HD064653] NR 0 TC 1 Z9 1 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD APR PY 2014 VL 37 IS 2 BP 220 EP 220 DI 10.1017/S0140525X13002495 PG 1 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA AH0QV UT WOS:000335826100058 PM 24775177 ER PT J AU Hoffman, DA AF Hoffman, Dax A. TI Dendrites and Disease SO BRAIN RESEARCH BULLETIN LA English DT Editorial Material C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Sect, NIH, Rockville, MD USA. RP Hoffman, DA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Sect, NIH, Rockville, MD USA. EM hoffmand@mail.nih.gov RI Hoffman, Dax/E-5155-2011 OI Hoffman, Dax/0000-0001-6999-2157 FU Intramural NIH HHS [Z99 HD999999] NR 5 TC 0 Z9 0 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 EI 1873-2747 J9 BRAIN RES BULL JI Brain Res. Bull. PD APR PY 2014 VL 103 SI SI BP 1 EP 1 DI 10.1016/j.brainresbull.2014.02.001 PG 1 WC Neurosciences SC Neurosciences & Neurology GA AH0JV UT WOS:000335806100001 PM 24513428 ER PT J AU Meder, B Ruhle, F Weis, T Homuth, G Keller, A Franke, J Peil, B Bermejo, JL Frese, K Huge, A Witten, A Vogel, B Haas, J Volker, U Ernst, F Teumer, A Ehlermann, P Zugck, C Friedrichs, F Kroemer, H Dorr, M Hoffmann, W Maisch, B Pankuweit, S Ruppert, V Scheffold, T Kuhl, U Schultheiss, HP Kreutz, R Ertl, G Angermann, C Charron, P Villard, E Gary, F Isnard, R Komajda, M Lutz, M Meitinger, T Sinner, MF Wichmann, HE Krawczak, M Ivandic, B Weichenhan, D Gelbrich, G El-Mokhtari, NE Schreiber, S Felix, SB Hasenfuss, G Pfeufer, A Hubner, N Kaab, S Arbustini, E Rottbauer, W Frey, N Stoll, M Katus, HA AF Meder, Benjamin Ruehle, Frank Weis, Tanja Homuth, Georg Keller, Andreas Franke, Jennifer Peil, Barbara Bermejo, Justo Lorenzo Frese, Karen Huge, Andreas Witten, Anika Vogel, Britta Haas, Jan Voelker, Uwe Ernst, Florian Teumer, Alexander Ehlermann, Philipp Zugck, Christian Friedrichs, Frauke Kroemer, Heyo Doerr, Marcus Hoffmann, Wolfgang Maisch, Bernhard Pankuweit, Sabine Ruppert, Volker Scheffold, Thomas Kuehl, Uwe Schultheiss, Hans-Peter Kreutz, Reinhold Ertl, Georg Angermann, Christiane Charron, Philippe Villard, Eric Gary, Francoise Isnard, Richard Komajda, Michel Lutz, Matthias Meitinger, Thomas Sinner, Moritz F. Wichmann, H. -Erich Krawczak, Michael Ivandic, Boris Weichenhan, Dieter Gelbrich, Goetz El-Mokhtari, Nour-Eddine Schreiber, Stefan Felix, Stephan B. Hasenfuss, Gerd Pfeufer, Arne Huebner, Norbert Kaeaeb, Stefan Arbustini, Eloisa Rottbauer, Wolfgang Frey, Norbert Stoll, Monika Katus, Hugo A. TI A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy SO EUROPEAN HEART JOURNAL LA English DT Article DE Dilated cardiomyopathy; DCM; Genome-wide association study ID CORONARY-ARTERY-DISEASE; HEART-FAILURE; HLA-C; SUSCEPTIBILITY LOCI; MYOCARDITIS; CARDIOLOGY; VARIANTS; SOCIETY; HEALTH; GENE AB Aims Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM. Methods and reuslts Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 x 10(-9)) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors. Conclusion The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM. C1 [Meder, Benjamin; Weis, Tanja; Franke, Jennifer; Frese, Karen; Vogel, Britta; Haas, Jan; Ehlermann, Philipp; Zugck, Christian; Ivandic, Boris; Rottbauer, Wolfgang; Frey, Norbert; Katus, Hugo A.] Heidelberg Univ, Dept Internal Med 3, D-69120 Heidelberg, Germany. [Meder, Benjamin; Weis, Tanja; Frese, Karen; Haas, Jan; Katus, Hugo A.] DZHK German Ctr Cardiovasc Res, Lubeck, Germany. [Ruehle, Frank; Huge, Andreas; Witten, Anika; Friedrichs, Frauke; Stoll, Monika] Univ Munster, Leibniz Inst Arteriosclerosis Res, D-48149 Munster, Germany. [Homuth, Georg; Voelker, Uwe; Ernst, Florian; Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Keller, Andreas] Univ Saarland, Dept Human Genet, Homburg, Germany. [Peil, Barbara; Bermejo, Justo Lorenzo] Univ Heidelberg Hosp, IMBI, Heidelberg, Germany. [Kroemer, Heyo] Univ Med Greifswald, Dept Pharmacol, Greifswald, Germany. [Doerr, Marcus; Felix, Stephan B.] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany. [Hoffmann, Wolfgang] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Maisch, Bernhard; Pankuweit, Sabine; Ruppert, Volker] Univ Hosp Marburg, Dept Cardiol, Marburg, Germany. [Scheffold, Thomas] Univ Witten Herdecke, Inst Heart & Circulat Res, Dortmund, Germany. [Kuehl, Uwe; Schultheiss, Hans-Peter] Charite, Charite Ctr Cardiovasc Med 11, Dept Cardiol & Pneumonol, D-13353 Berlin, Germany. [Kreutz, Reinhold] Charite, Dept Clin Pharmacol, D-13353 Berlin, Germany. [Ertl, Georg; Angermann, Christiane] Univ & Univ Hosp Wurzburg, Dept Internal Med 1, Wurzburg, Germany. [Ertl, Georg; Angermann, Christiane] Univ & Univ Hosp Wurzburg, Comprehens Heart Failure Ctr, Wurzburg, Germany. [Charron, Philippe; Villard, Eric; Gary, Francoise; Isnard, Richard] Univ Paris 06, Hop La Pitie Salpetriere, AP HP, INSERM UMRS956, Paris, France. [Lutz, Matthias; Frey, Norbert] Univ Kiel, Dept Internal Med, Kiel, Germany. [Meitinger, Thomas] Helmholtz Ctr Munich, Inst Human Genet, Munich, Germany. [Sinner, Moritz F.; Kaeaeb, Stefan] Univ Munich, Univ Hosp Munich, Dept Med 1, Munich, Germany. [Sinner, Moritz F.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Sinner, Moritz F.] NHLBI, Framingham, MA USA. [Sinner, Moritz F.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Wichmann, H. -Erich] Helmholtz Ctr Munich, Inst Epidemiol 1, Munich, Germany. [Wichmann, H. -Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Krawczak, Michael] Univ Kiel, Inst Med Informat & Stat, Kiel, Germany. [Weichenhan, Dieter] German Canc Res Ctr, Heidelberg, Germany. [Gelbrich, Goetz] Coordinat Ctr Clin Trials Leipzig, Leipzig, Germany. [El-Mokhtari, Nour-Eddine; Schreiber, Stefan] Univ Kiel, Kiel, Germany. [Hasenfuss, Gerd] Univ Gottingen, Dept Cardiol & Pneumol, D-37073 Gottingen, Germany. [Pfeufer, Arne] Tech Univ Munich, Genome Res Ctr Environm Hlth, Inst Human Genet, D-80290 Munich, Germany. [Pfeufer, Arne] Helmholtz Ctr Munich, Munich, Germany. [Huebner, Norbert] Max Delbruck Ctr Mol Med, Berlin, Germany. [Kaeaeb, Stefan] Munich Heart Alliance, Munich, Germany. [Arbustini, Eloisa] Fdn IRCCS Policlin San Matteo, Ctr Inherited Cardiovasc Dis, Pavia, Italy. [Rottbauer, Wolfgang] Univ Ulm, Dept Internal Med 2, D-89069 Ulm, Germany. RP Katus, HA (reprint author), Heidelberg Univ, Dept Internal Med 3, Neuenheimer Feld 410, D-69120 Heidelberg, Germany. EM hugo.katus@med.uni-heidelberg.de RI Krawczak, Michael/A-8964-2010; Frey, Norbert/A-9695-2010; Pfeufer, Arne/B-6634-2013; Meitinger, Thomas/O-1318-2015; Katus, Hugo/P-1712-2016; OI Krawczak, Michael/0000-0003-2603-1502; Arbustini, Eloisa/0000-0003-2948-7994; , Andreas/0000-0002-5361-0895 FU Bndesministerium fur Bildung und Forschung' (BMBF) FX This work was supported by grants from the 'Bndesministerium fur Bildung und Forschung' (BMBF): German Center for Cardiovascular Research (GCCR), NGFN II, NGFN- plus, and NGFN- transfer, the medical faculty of the University of Heidelberg, INSIGHT DCM( BMBF & Agence nationale pour la recherche '), the European Union ( FP7 INHERITANCE and BestAgeing), and Deutsche Forschungsgemeinschaft ( SFB TR 19). SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research ( 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg- West Pomerania. Genome- wide data have been supported by the Federal Ministry of Education and Research ( 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg West Pomerania. The Competence Network Heart Failure was funded by the German Federal Ministry of Education and Research ( BMBF, grant number 01GI0205). NR 35 TC 27 Z9 28 U1 0 U2 11 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 APR PY 2014 VL 35 IS 16 BP 1069 EP + DI 10.1093/eurheartj/eht251 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH0MH UT WOS:000335813500015 PM 23853074 ER PT J AU Zeidner, JF Karp, JE Blackford, AL Smith, BD Gojo, I Gore, SD Levis, MJ Carraway, HE Greer, JM Ivy, SP Pratz, KW McDevitt, MA AF Zeidner, Joshua F. Karp, Judith E. Blackford, Amanda L. Smith, B. Douglas Gojo, Ivana Gore, Steven D. Levis, Mark J. Carraway, Hetty E. Greer, Jacqueline M. Ivy, S. Percy Pratz, Keith W. McDevitt, Michael A. TI A phase II trial of sequential ribonucleotide reductase inhibition in aggressive myeloproliferative neoplasms SO HAEMATOLOGICA LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW-TRANSPLANTATION; INTERNATIONAL WORKING GROUP; NERVOUS-SYSTEM TOXICITY; FLUDARABINE PHOSPHATE; POLYCYTHEMIA-VERA; INDUCTION THERAPY; RESPONSE CRITERIA; ALLELE BURDEN AB Myeloproliferative neoplasms are a varied group of disorders that can have prolonged chronic phases, but eventually accelerate and can transform into a secondary acute myeloid leukemia that is ultimately fatal. Triapine is a novel inhibitor of the M2 subunit of ribonucleotide reductase. Sequential inhibition of ribonucleotide reductase with triapine and an M1 ribonucleotide reductase inhibitor (fludarabine) was noted to be safe, and led to a 29% complete plus partial response rate in myeloproliferative neoplasms. This article reports the findings of a phase II trial of triapine (105 mg/m(2)/day) followed by fludarabine (30 mg/m(2)/day) daily for 5 consecutive days in 37 patients with accelerated myeloproliferative neoplasms and secondary acute myeloid leukemia. The overall response rate was 49% (18/37), with a complete remission rate of 24% (9/37). Overall response rates and complete remissions were seen in all disease subsets, including secondary acute myeloid leukemia, in which the overall response rate and complete remission rate were 48% and 33%, respectively. All patients with known JAK2 V617F mutations (6/6) responded. The median overall survival of the entire cohort was 6.9 months, with a median overall survival of both overall responders and complete responders of 10.6 months. These data further demonstrate the promise of sequential inhibition of ribonucleotide reductase in patients with accelerated myeloproliferative neoplasms and secondary acute myeloid leukemia. C1 [Zeidner, Joshua F.; Karp, Judith E.; Smith, B. Douglas; Gojo, Ivana; Gore, Steven D.; Levis, Mark J.; Carraway, Hetty E.; Greer, Jacqueline M.; Pratz, Keith W.; McDevitt, Michael A.] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Hematol Malignancies, Baltimore, MD 21205 USA. [Blackford, Amanda L.] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol Biostat, Baltimore, MD USA. [Ivy, S. Percy] NCI, Bethesda, MD 20892 USA. [McDevitt, Michael A.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. RP Zeidner, JF (reprint author), Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Hematol Malignancies, Baltimore, MD 21205 USA. EM jzeidner@jhmi.edu; mmcdevi1@jhmi.edu FU NCI [U01 CA70095]; NCI Cancer Center [2P30 CA06973-46] FX This trial was supported in part by NCI Cooperative Agreement U01 CA70095 and NCI Cancer Center Support Grant 2P30 CA06973-46. NR 45 TC 11 Z9 11 U1 0 U2 6 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD APR PY 2014 VL 99 IS 4 BP 672 EP 678 DI 10.3324/haematol.2013.097246 PG 7 WC Hematology SC Hematology GA AH6QQ UT WOS:000336256100018 PM 24362550 ER PT J AU Sonnega, A Faul, JD Ofstedal, MB Langa, KM Phillips, JWR Weir, DR AF Sonnega, Amanda Faul, Jessica D. Ofstedal, Mary Beth Langa, Kenneth M. Phillips, John W. R. Weir, David R. TI Cohort Profile: the Health and Retirement Study (HRS) SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID UNITED-STATES; COGNITIVE IMPAIRMENT; DEMENTIA; WORK; DEMOGRAPHICS; INNOVATIONS; PREVALENCE; MEMORY AB The Health and Retirement Study (HRS) is a nationally representative longitudinal survey of more than 37 000 individuals over age 50 in 23 000 households in the USA. The survey, which has been fielded every 2 years since 1992, was established to provide a national resource for data on the changing health and economic circumstances associated with ageing at both individual and population levels. Its multidisciplinary approach is focused on four broad topics-income and wealth; health, cognition and use of healthcare services; work and retirement; and family connections. HRS data are also linked at the individual level to administrative records from Social Security and Medicare, Veteran's Administration, the National Death Index and employer-provided pension plan information. Since 2006, data collection has expanded to include biomarkers and genetics as well as much greater depth in psychology and social context. This blend of economic, health and psychosocial information provides unprecedented potential to study increasingly complex questions about ageing and retirement. The HRS has been a leading force for rapid release of data while simultaneously protecting the confidentiality of respondents. Three categories of data-public, sensitive and restricted-can be accessed through procedures described on the HRS website ( ext-link-type="uri" xlink:href="http://hrsonline.isr.umich.edu/" xlink:type="simple">hrsonline.isr.umich.edu). C1 [Sonnega, Amanda; Faul, Jessica D.; Ofstedal, Mary Beth; Langa, Kenneth M.; Weir, David R.] Univ Michigan, Hlth & Retirement Study, Survey Res Ctr, Inst Social Res, Ann Arbor, MI 48106 USA. [Langa, Kenneth M.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48106 USA. [Langa, Kenneth M.] Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA. [Phillips, John W. R.] NIA, Div Behav & Social Res, Bethesda, MD 20892 USA. RP Sonnega, A (reprint author), Univ Michigan, Hlth & Retirement Study, Survey Res Ctr, Inst Social Res, POB 1248,426 Thompson St, Ann Arbor, MI 48106 USA. EM asonnega@umich.edu FU Division of Behavioral and Social Research of the National Institute on Aging of the National Institutes of Health [U01 AG009740]; Social Security Administration FX HRS is grateful to the Division of Behavioral and Social Research of the National Institute on Aging of the National Institutes of Health for primary support of this project (U01 AG009740) and to the Social Security Administration for substantial co-funding. NR 37 TC 57 Z9 57 U1 3 U2 18 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 APR PY 2014 VL 43 IS 2 BP 576 EP 585 DI 10.1093/ije/dyu067 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AH1ZD UT WOS:000335919500027 PM 24671021 ER PT J AU Shekhawat, N Mkocha, H Munoz, B Gaydos, C Dize, L Quinn, TC West, SK AF Shekhawat, Nakul Mkocha, Harran Munoz, Beatriz Gaydos, Charlotte Dize, Laura Quinn, Thomas C. West, Sheila K. TI Cohort and Age Effects of Mass Drug Administration on Prevalence of Trachoma: A Longitudinal Study in Rural Tanzania SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE trachoma; mass drug administration (MDA); Tanzania; cohort study; population-based study ID OCULAR CHLAMYDIA-TRACHOMATIS AB PURPOSE. Mass drug administration (MDA) is part of the SAFE strategy for trachoma elimination. This study examined the effect of three annual MDAs on prevalence of trachoma among 13 longitudinal cohorts of Tanzanian children. METHODS. Children younger than 10 years were assigned to cohorts based on age at baseline and followed annually for 3 years, with newborns assigned to new cohorts over time. Annual MDA consisted of topical tetracycline for children younger than 6 months and oral azithromycin for those 6 months and older. Follicular trachoma (TF) and Chlamydia trachomatis infection status were assessed annually before the next MDA. Prevalence and risk factors for TF and infection at each age were compared across cohorts. RESULTS. At each survey, most age groups and cohorts had MDA coverage of more than 80% and showed decreased TF prevalence after every MDA. One cohort had consistently lower coverage, higher-than-expected TF and infection at ages 6 and 7, and elevated risk of TF at age 7 relative to the preceding cohort in spite of receiving one additional MDA (odds ratio 2.3, 95% confidence interval 1.0-5.2). Cohorts aged 1 or older at baseline generally showed reductions in TF and infection after each MDA, whereas younger cohorts showed decreased infection but increased TF over time. Successive cohorts of never-treated children younger than 1 year showed sequential TF and infection reductions with each MDA (P < 0.001). CONCLUSIONS. Multiple MDAs significantly reduce trachoma prevalence and appear to increasingly protect children born into these communities. The youngest children show declining/stable rates of infection but increasing rates of trachoma, which may reflect longer duration of clinical signs. C1 [Shekhawat, Nakul; Munoz, Beatriz; West, Sheila K.] Johns Hopkins Univ, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21218 USA. [Mkocha, Harran] Kongwa Trachoma Project, Kongwa, Tanzania. [Gaydos, Charlotte; Dize, Laura; Quinn, Thomas C.] Johns Hopkins Univ, Dept Med, Div Infect Dis, Int Chlamydia Res Lab, Baltimore, MD USA. [Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Shekhawat, N (reprint author), Johns Hopkins Univ, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21218 USA. EM nakul.shekhawat@vanderbilt.edu FU Bill and Melinda Gates Foundation; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX Supported by a grant from the Bill and Melinda Gates Foundation and by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 11 TC 3 Z9 3 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 APR PY 2014 VL 55 IS 4 BP 2307 EP 2314 DI 10.1167/iovs.13-12701 PG 8 WC Ophthalmology SC Ophthalmology GA AH1WS UT WOS:000335913100038 PM 24448262 ER PT J AU Wright, CB Chrenek, MA Feng, W Getz, SE Duncan, T Pardue, MT Feng, Y Redmond, TM Boatright, JH Nickerson, JM AF Wright, Charles B. Chrenek, Micah A. Feng, Wei Getz, Shannon E. Duncan, Todd Pardue, Machelle T. Feng, Yue Redmond, T. Michael Boatright, Jeffrey H. Nickerson, John M. TI The Rpe65(rd12) Allele Exerts a Semidominant Negative Effect on Vision in Mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE RPE65; rd12; visual cycle ID LEBER CONGENITAL AMAUROSIS; PERFORMANCE LIQUID-CHROMATOGRAPHY; GENE-THERAPY; MOUSE MODEL; RETINITIS-PIGMENTOSA; RPE65 MUTATIONS; ISOMEROHYDROLASE ACTIVITY; ADENOASSOCIATED VIRUS; MACULAR DEGENERATION; RETINAL DYSTROPHY AB PURPOSE. The rd12 mouse was reported as a recessively inherited Rpe65 mutation. We asked if the rd12 mutation resides in Rpe65 and how the mutation manifests itself. METHODS. A complementation test was performed by mating Rpe65(KO) (KO/KO) and rd12 mice together to determine if the rd12 mutation is in the Rpe65 gene. Visual function of wildtype (+/+), KO/+, rd12/+, KO/KO, rd12/rd12, and KO/rd12 mice was measured by optokinetic tracking (OKT) and ERG. Morphology was assessed by retinal cross section. qRT-PCR quantified Rpe65 mRNA levels. Immunoblotting measured the size and level of RPE65 protein. Rpe65 mRNA localization was visualized with RNA fluorescence in situ hybridization (FISH). Fractions of Rpe65 mRNA-bound proteins were separated by linear sucrose gradient fractionation. RESULTS. The KO and rd12 alleles did not complement. The rd12 allele induced a negative semidominant effect on visual function; OKT responses became undetectable 120 days earlier in rd12/rd12 mice compared with KO/KO mice. rd12/+ mice lost approximately 21% visual acuity by P210. rd12/rd12 mice had fewer cone photoreceptor nuclei than KO/KO mice at P60. rd12/rd12 mice expressed 71% +/+ levels of Rpe65 mRNA, but protein was undetectable. Mutant mRNA was appropriately spliced, exported to the cytoplasm, trafficked, and contained no other coding mutation aside from the known nonsense mutation. Mutant mRNA was enriched on ribosome-free messenger ribonucleoproteins (mRNPs), whereas wildtype mRNA was enriched on actively translating polyribosomes. CONCLUSIONS. The rd12 lesion is in Rpe65. The rd12 mutant phenotype inherits in a semidominant manner. The effects of the mutant mRNA on visual function may result from inefficient binding to ribosomes for translation. C1 [Wright, Charles B.; Chrenek, Micah A.; Getz, Shannon E.; Pardue, Machelle T.; Boatright, Jeffrey H.; Nickerson, John M.] Emory Univ, Dept Ophthalmol, Sch Med, Atlanta, GA 30322 USA. [Feng, Wei; Feng, Yue] Emory Univ, Dept Pharmacol, Sch Med, Atlanta, GA 30322 USA. [Duncan, Todd; Redmond, T. Michael] NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Pardue, Machelle T.] Atlanta VA Med Ctr, Rehabil Res & Dev Ctr Excellence, Decatur, GA USA. RP Nickerson, JM (reprint author), Emory Univ, Dept Ophthalmol, B5602,1365B Clifton Rd NE, Atlanta, GA 30322 USA. EM litjn@emory.edu FU National Institutes of Health [P30EY006360, R01EY016470, T32EY007092, R01EY014026, R01EY016435, R01EY021592, R01NS070526, Z01EY000444]; Intramural Research Program of the National Eye Institute; Phyllis Katz Foundation FX Supported by National Institutes of Health Grants P30EY006360, R01EY016470, T32EY007092, R01EY014026, R01EY016435, R01EY021592, R01NS070526, and Z01EY000444; an unrestricted Departmental Award from Research to Prevent Blindness; the Intramural Research Program of the National Eye Institute; and a grant from the Abraham J. and Phyllis Katz Foundation. The authors alone are responsible for the content and writing of the paper. NR 75 TC 4 Z9 4 U1 0 U2 4 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 APR PY 2014 VL 55 IS 4 BP 2500 EP 2515 DI 10.1167/iovs.13-13574 PG 16 WC Ophthalmology SC Ophthalmology GA AH1WS UT WOS:000335913100068 PM 24644049 ER PT J AU Song, H Bush, RA Vijayasarathy, C Fariss, RN Kjellstrom, S Sieving, PA AF Song, Hongman Bush, Ronald A. Vijayasarathy, Camasamudram Fariss, Robert N. Kjellstrom, Sten Sieving, Paul A. TI Transgenic Expression of Constitutively Active RAC1 Disrupts Mouse Rod Morphogenesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE RAC1; mouse rod morphogenesis; lamination; positioning and polarity; photoreceptor degeneration ID PROTEIN-KINASE-C; RETINAL DEGENERATION; CELL-POLARITY; RHO-GTPASES; PHOTORECEPTOR MORPHOGENESIS; OUTER SEGMENTS; DROSOPHILA; GENE; COMPLEX; CRUMBS AB PURPOSE. Dominant-active RAC1 rescues photoreceptor structure in Drosophila rhodopsinnull mutants, indicating an important role in morphogenesis. This report assesses the morphogenetic effect of activated RAC1 during mammalian rod photoreceptor development using transgenic mice that express constitutively active (CA) RAC1. METHODS. Transgenic mice were generated by expressing CA RAC1 under control of the Rhodopsin promoter, and morphological features of the photoreceptors were evaluated by histology, immunohistochemistry, and transmission electron microscopy. Function was evaluated by electroretinography. Potential protein partners of CA RAC1 were identified by co-immunoprecipitation of retinal extracts. RESULTS. Constitutively active RAC1 expression in differentiating rods disrupted outer retinal lamination as early as postnatal day ( P) 6, and many photoreceptor cell nuclei were displaced apically into the presumptive subretinal space. These photoreceptors did not develop normal inner and outer segments and had abnormal placement of synaptic elements. Some photoreceptor nuclei were also mislocalized into the inner nuclear layer. Extensive photoreceptor degeneration was subsequently observed in the adult animal. Constitutively active RAC1 formed a complex with the polarity protein PAR6 and with microtubule motor dynein in mouse retina. The normal localization of the PAR6 complex was disrupted in CA RAC1-expressing rod photoreceptors. CONCLUSIONS. Constitutively active RAC1 had a profound negative effect on mouse rod cell viability and development. Rod photoreceptors in the CA RAC1 retina exhibited a defect in polarity and migration. Constitutively active RAC1 disrupted rod morphogenesis and gave a phenotype resembling that found in the Crumbs mutant. PAR6 and dynein are two potential downstream effectors that may be involved in CA RAC1-mediated defective mouse photoreceptor morphogenesis. C1 [Song, Hongman; Bush, Ronald A.; Vijayasarathy, Camasamudram; Kjellstrom, Sten; Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD USA. [Fariss, Robert N.] NEI, Biol Imaging Core Facil, NIH, Bethesda, MD 20892 USA. [Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. RP Sieving, PA (reprint author), BG 31,RM6A03,31 Ctr Dr, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov FU National Institutes of Health Intramural Research Programs of the National Institute on Deafness and Other Communication Disorders; National Eye Institute FX Supported by the National Institutes of Health Intramural Research Programs of the National Institute on Deafness and Other Communication Disorders and the National Eye Institute. The authors alone are responsible for the content and writing of the paper. NR 57 TC 7 Z9 7 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2014 VL 55 IS 4 BP 2659 EP 2668 DI 10.1167/iovs.13-13649 PG 10 WC Ophthalmology SC Ophthalmology GA AH1WS UT WOS:000335913100087 PM 24651551 ER PT J AU Toazza, R Salum, GA Flores, SM Jarros, RB Pine, DS de Salles, JF Manfro, GG AF Toazza, Rudineia Salum, Giovanni Abrahao Flores, Suzielle Menezes Jarros, Rafaela Behs Pine, Daniel S. de Salles, Jerusa Fumagalli Manfro, Gisele Gus TI Phonemic Verbal Fluency Is Associated with Pediatric Anxiety Disorders: Evidence from a Community Study SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT-HYPERACTIVITY; LEXICAL ACCESS; NORMATIVE DATA; CHILDREN; ADOLESCENTS; PERFORMANCE; MEMORY; RISK; DEPRESSION; AGE AB Background: Anxiety disorders typically begin in childhood and adolescence and predict risk for many problems throughout life. Although some neuropsychological correlates have been described, more research is needed, particularly in adolescents. This study compares neurocognitive characteristics of anxious adolescents with and without comorbidity to externalizing disorders to those of typically developing comparison (TDC) adolescents and adolescents with externalizing disorders alone. Methods: The study included 57 adolescents 12-18 years of age (TDC, n = 23; anxiety, n = 16; externalizing, n = 11; comorbid, n = 7). We used a neuropsychological battery to assess eight domains: Orientation, attention, visual perception, memory, arithmetic, language, praxis, and executive function. Results: Multivariate analysis of variance revealed amain effect of group in the neurocognitive domains evaluated (F-8,F-48 = 2.32, p = 0.034, eta(2)(p) = 0.279). Post-hoc analysis revealed that executive functions score differed among groups, specifically in the task of verbal fluency (FLeft perpendiculardf = 3right perpendicular = 5.01, p = 0.004, eta(2)(p) = 0.221), with both the anxious groups (anxiety and comorbid) presenting a lower score than the TDC and externalizing groups. This effect was independent of age, intelligence, and levels of education. Conclusions: Verbal fluency is specifically impaired in adolescents with anxiety disorders. This extends results from neuroimaging research implicating prefrontal areas in pediatric anxiety disorder neurobiology, and has potential implications to new therapeutics. C1 [Toazza, Rudineia; Salum, Giovanni Abrahao; Flores, Suzielle Menezes; Jarros, Rafaela Behs; Manfro, Gisele Gus] Univ Fed Rio Grande do Sul, Anxiety Disorders Program Child & Adolescent Psyc, Porto Alegre, RS, Brazil. [Toazza, Rudineia; Manfro, Gisele Gus] Univ Fed Rio Grande do Sul, Postgrad Program Neurosci, Porto Alegre, RS, Brazil. [Salum, Giovanni Abrahao; Jarros, Rafaela Behs; Manfro, Gisele Gus] Univ Fed Rio Grande do Sul, Postgrad Program Med Sci Psychiat, Hosp Clin Porto Alegre, Inst Basic Sci Hlth ICBS, Porto Alegre, RS, Brazil. [de Salles, Jerusa Fumagalli] Univ Fed Rio Grande do Sul, Cognit Neuropsychol Res Ctr Neurocog, Dept Dev & Personal Psychol, Inst Psychol, Porto Alegre, RS, Brazil. [Salum, Giovanni Abrahao; Manfro, Gisele Gus] Natl Inst Child & Adolescent Psychiat CNPq Brazil, Porto Alegre, RS, Brazil. [Pine, Daniel S.] NIMH, Intramural Res Program, Emot & Dev Branch, Bethesda, MD 20892 USA. RP Toazza, R (reprint author), Hosp Clin Porto Alegre, Ramiro Barcelos 2350,Room 2202, BR-90035003 Porto Alegre, RS, Brazil. EM rudineiatoazza@yahoo.com.br RI Salum, Giovanni/A-7849-2010 OI Salum, Giovanni/0000-0002-7537-7289 FU CAPES; FAPERGS/CAPES; CNPq; FIPE-HCPA; FAPERGS [10/0018.3] FX Rudineia Toazza receives a CAPES doctoral scholarship. Giovanni Abrahao Salum receives a FAPERGS/CAPES scholarship. Jerusa Fumagalli de Salles receives a CNPq senior researcher scholarship. Gisele Gus Manfro receives a CNPq senior researcher scholarship. This research was supported by FIPE-HCPA, CNPq and FAPERGS 10/0018.3. NR 58 TC 0 Z9 3 U1 2 U2 11 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 EI 1557-8992 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD APR PY 2014 VL 24 IS 3 BP 149 EP 157 DI 10.1089/cap.2013.0086 PG 9 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AH6HC UT WOS:000336230300006 PM 24725199 ER PT J AU Crank, MC Grossman, JK Moir, S Pittaluga, S Buckner, CM Kardava, L Agharahimi, A Meuwissen, H Stoddard, J Niemela, J Kuehn, H Rosenzweig, SD AF Crank, M. C. Grossman, J. K. Moir, S. Pittaluga, S. Buckner, C. M. Kardava, L. Agharahimi, A. Meuwissen, H. Stoddard, J. Niemela, J. Kuehn, H. Rosenzweig, S. D. TI Mutations in PIK3CD Can Cause Hyper IgM Syndrome (HIGM) Associated with Increased Cancer Susceptibility SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Immunodeficiency; hyper IgM; PI3K; lymphoma; cancer susceptibility; epstein-barr virus AB Autosomal dominant gain of function mutations in the gene encoding PI3K p110 delta were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, CMV and/or EBV viremia and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM. Here we describe three patients in two families who were diagnosed with HIGM at a young age and were recently found to carry heterozygous mutations in PIK3CD. These patients had an abnormal circulating B cell distribution featuring a preponderance of early transitional (T1) B cells and plasmablasts. When stimulated in vitro, PIK3CD mutated B cells were able to secrete class-switched immunoglobulins. This finding implies that the patients' elevated serum IgM levels were unlikely a product of an intrinsic B cell functional inability to class switch. All three patients developed malignant lymphoproliferative syndromes that were not associated with EBV. Thus, we identified a novel subset of patients with PIK3CD mutations associated with HIGM, despite indications of preserved in vitro B cell class switch recombination, as well as susceptibility to non-EBV-associated malignancies. C1 [Crank, M. C.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Grossman, J. K.] Alberta Hlth Serv, Div Hematol & Hematol Malignancies, Calgary, AB, Canada. [Moir, S.; Buckner, C. M.; Kardava, L.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Pittaluga, S.] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Agharahimi, A.; Rosenzweig, S. D.] NIAID, Primary Immune Deficiency Clin, NIH, Bethesda, MD 20892 USA. RP Rosenzweig, SD (reprint author), NIH, Serv Immunol, Dept Lab Med, 10 Ctr Dr,Bldg 10,2C410F, Bethesda, MD 20892 USA. EM srosenzweig@cc.nih.gov OI Niemela, Julie/0000-0003-4197-3792 FU Intramural NIH HHS [Z99 CL999999] NR 10 TC 45 Z9 47 U1 0 U2 10 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 APR PY 2014 VL 34 IS 3 BP 272 EP 276 DI 10.1007/s10875-014-0012-9 PG 5 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800003 PM 24610295 ER PT J AU Buchbinder, D Baker, R Lee, YN Ravell, J Zhang, Y McElwee, J Nugent, D Su, HL Notarangelo, LD AF Buchbinder, David Baker, Rebecca Lee, Yu Nee Ravell, Juan Zhang, Yu McElwee, Joshua Nugent, Diane Su, Helen Notarangelo, Luigi D. TI Compound Heterozygous Rag1 Mutations in a Patient with Common Variable Immunodeficiency SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Buchbinder, David; Nugent, Diane] CHOC Childrens Hosp UC Irvine, Orange, CA USA. [Baker, Rebecca; Ravell, Juan] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Lee, Yu Nee] Harvard Univ, Sch Med, Div Immunol, Boston Childrens Hosp, Boston, MA USA. [Zhang, Yu; Su, Helen] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [McElwee, Joshua] Merck & Co Inc, Merck Res Labs, Boston, MA USA. [Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 0 TC 0 Z9 0 U1 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 APR PY 2014 VL 34 IS 3 BP 350 EP 350 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800018 ER PT J AU Yu, XM Almeida, J Darko, S van der Burg, M DeRavin, SS Malech, H Gennery, A Chinn, I Markert, ML Perales, MA Pamer, EG Douek, DC Milner, JD AF Yu, Xiaomin Almeida, Jorge Darko, Sam van der Burg, Mirjam DeRavin, Suk See Malech, Harry Gennery, Andrew Chinn, Ivan Markert, Mary Louise Perales, Miguel-Angel Pamer, Eric G. Douek, Daniel C. Milner, Joshua D. TI Human Syndromes of Immune Deficiency and Dysregulation are Characterized by Distinct Defects in T-Cell Receptor Repertoire Development SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Yu, Xiaomin; Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Almeida, Jorge; Darko, Sam; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [van der Burg, Mirjam] Univ Med Ctr Rotterdam, Dept Immunol, Erasmus MC, Rotterdam, Netherlands. [DeRavin, Suk See; Malech, Harry] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Gennery, Andrew] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Chinn, Ivan] Duke Univ Med Ctr, Div Allergy & Immunol, Dept Pediat, Durham, NC USA. [Markert, Mary Louise] Duke Univ Med Ctr, Div Allergy & Immunol, Dept Pediat, Durham, NC USA. [Markert, Mary Louise] Duke Univ Med Ctr, Dept Immunol, Durham, NC USA. [Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplantat Serv, New York, NY 10021 USA. [Perales, Miguel-Angel; Pamer, Eric G.] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA. [Pamer, Eric G.] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Immunol Program, New York, NY 10021 USA. [Pamer, Eric G.] Mem Sloan Kettering Canc Ctr, Lucille Castori Ctr, Mol Microbiol Core Facil, New York, NY 10021 USA. [Pamer, Eric G.] Mem Sloan Kettering Canc Ctr, Dept Med, Infect Dis Serv, New York, NY 10021 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 350 EP 351 PG 2 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800020 ER PT J AU Grossman, JK Moir, S Pittaluga, S Rosenzweig, S Crank, MC AF Grossman, Jennifer K. Moir, Susan Pittaluga, Stefania Rosenzweig, Sergio Crank, Michelle C. TI Hyper IGM Syndrome and EBV Independent Hematologic Malignancy Associated with gain of function mutations in PIK3CD SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Grossman, Jennifer K.] Alberta Hlth Serv, Dept Med, Div Hematol & Hematol Malignancies, Calgary, AB, Canada. [Moir, Susan] NIAID, NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NIH, Hematopathol Sect, Bethesda, MD 20892 USA. [Rosenzweig, Sergio] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Crank, Michelle C.] NIAID, Immunol Lab, Cytokine Biol Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR PY 2014 VL 34 IS 3 BP 351 EP 351 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800021 ER PT J AU Walter, JE Rosen, LB Chen, K Lee, YN Tirosh, I Csomos, K Ujhazi, B Al-Herz, W Cowan, MJ Puck, J Bleesing, JJ Malech, H DeRavin, SS Gennery, AR Abraham, RS Butte, MJ Nadeau, KC Sullivan, KE Giliani, S Niehues, T Schuetz, C Kuijpers, T Holland, SM Browne, SK Notarangelo, LD AF Walter, Jolan E. Rosen, Lindsey B. Chen, Karin Lee, Yu Nee Tirosh, Irit Csomos, Krisztian Ujhazi, Boglarka Al-Herz, Waleed Cowan, Morton J. Puck, Jennifer Bleesing, Jack J. Malech, Harry DeRavin, Suk See Gennery, Andrew R. Abraham, Roshini Sarah Butte, Manish J. Nadeau, Kari C. Sullivan, Kathleen E. Giliani, Silvia Niehues, Tim Schuetz, Catharina Kuijpers, Taco Holland, Steven M. Browne, Sarah K. Notarangelo, Luigi D. TI Distinct Anti-Cytokine Autoantibody Profile is Likely Driven by Innate Hyperinflammation Among Patients with Primary Immunodeficiency Secondary To Rag Mutations SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Walter, Jolan E.] Harvard Univ, Sch Med, Boston, MA USA. [Walter, Jolan E.] Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Boston, MA USA. [Walter, Jolan E.; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Rosen, Lindsey B.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Chen, Karin] Univ Utah, Dept Pediat, Div Allergy Immunol & Rheumatol, Salt Lake City, UT USA. [Lee, Yu Nee] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Tirosh, Irit] Boston Childrens Hosp, Boston, MA USA. [Csomos, Krisztian] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA USA. [Ujhazi, Boglarka] Univ Debrecen, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. [Al-Herz, Waleed] Kuwait Univ, Fac Med, Dept Pediat, Kuwait, Kuwait. [Cowan, Morton J.; Puck, Jennifer] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bleesing, Jack J.] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immunodeficiency, Cincinnati, OH 45229 USA. [Malech, Harry; DeRavin, Suk See] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Gennery, Andrew R.] Newcastle Upon Tyne Hosp, Dept Paediat Immunol, Newcastle Upon Tyne, Tyne & Wear, England. [Abraham, Roshini Sarah] Mayo Clin, Rochester, MN USA. [Butte, Manish J.] Stanford Univ, Dept Pediat, Div Immunol, Stanford, CA 94305 USA. [Nadeau, Kari C.] Stanford Univ, Dept Pediat, Div Immunol, Sch Med, Stanford, CA 94305 USA. [Sullivan, Kathleen E.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Giliani, Silvia] Clin Pediat Azienda Osped Spedali Civili Brescia, Ist Med Mol Angelo Nocivelli, Brescia, Italy. [Niehues, Tim] Acad Hosp, Helios Klinikum Krefeld, Ctr Child Hlth & Adolescence, Dusseldorf, Germany. [Schuetz, Catharina] Univ Hosp, Dept Pediat & Adolescent Med, Ulm, Germany. [Kuijpers, Taco] Emma Childrens Hosp, AMC, Amsterdam, Netherlands. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RI Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Butte, Manish/0000-0002-4490-5595 NR 0 TC 0 Z9 0 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 APR PY 2014 VL 34 IS 3 BP 353 EP 354 PG 2 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800030 ER PT J AU Niemela, JE Lucas, CL Kuehn, H Biancalana, M Stoddard, JL Oliveira, JB Fleisher, TA Uzel, G AF Niemela, Julie E. Lucas, Carrie L. Kuehn, Hyesun Biancalana, Matthew Stoddard, Jennifer L. Oliveira, Joao Bosco Fleisher, Thomas A. Uzel, Gulbu TI Protein Modeling Led to the Discovery that Mutations in the Gene Encoding PI(3) K Catalytic Subunit p110 delta (PIK3CD) Cause PASLI (p110 delta Activating Mutation Causing Senescent T Cells, Lymphadenopathy, and Immunodeficiency) Disease SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Niemela, Julie E.; Kuehn, Hyesun; Stoddard, Jennifer L.; Fleisher, Thomas A.] NIH, Dept Lab Med, CC, Bethesda, MD 20892 USA. [Lucas, Carrie L.; Biancalana, Matthew] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Oliveira, Joao Bosco] Inst Med Integral Prof Fernando Figueira, Recife, PE, Brazil. [Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 APR PY 2014 VL 34 IS 3 BP 358 EP 359 PG 2 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800048 ER PT J AU Zhang, Y Yu, XM Ichikawa, M Lyons, JJ Datta, S Jing, H Lamborn, IT Biancalana, M Wolfe, LA Matthews, HF Kranick, SM Stone, K Holland, SM Reich, DS McElwee, J Mehmet, H Freeman, AF Freeze, HH Su, HL Milner, J AF Zhang, Yu Yu, Xiaomin Ichikawa, Mie Lyons, Jonathan J. Datta, Shrimati Jing, Huie Lamborn, Ian T. Biancalana, Matthew Wolfe, Lynne A. Matthews, Helen F. Kranick, Sarah M. Stone, Kelly Holland, Steven M. Reich, Daniel S. McElwee, Joshua Mehmet, Huseyin Freeman, Alexandra F. Freeze, Hudson H. Su, Helen Milner, Joshua TI Autosomal Recessive PGM3 Mutations Link Glycosylation Defects to Atopy, Immune Deficiency, Autoimmunity, and Neurocognitive Impairment SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Zhang, Yu; Jing, Huie; Lamborn, Ian T.; Su, Helen] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Yu, Xiaomin; Lyons, Jonathan J.; Datta, Shrimati; Stone, Kelly; Milner, Joshua] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Ichikawa, Mie; Freeze, Hudson H.] Sanford Burnham Med Res Inst, La Jolla, CA USA. [Biancalana, Matthew; Matthews, Helen F.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wolfe, Lynne A.] NIH, NIH Undiagnosed Dis Program, Common Fund, Bethesda, MD 20892 USA. [Kranick, Sarah M.] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Reich, Daniel S.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [McElwee, Joshua; Mehmet, Huseyin] Merck & Co Inc, Merck Res Labs, Boston, MA USA. [Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 358 EP 358 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800047 ER PT J AU Crestani, E Volpi, S Pai, SY Giliani, S Candotti, F Notarangelo, LD AF Crestani, Elena Volpi, Stefano Pai, Sung-Yun Giliani, Silvia Candotti, Fabio Notarangelo, Luigi D. TI Intermediate/High Avidity of Anti-dsDNA and Anti-ssDNA Autoantibodies in Patients with XLTand Was SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Crestani, Elena] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Volpi, Stefano; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Pai, Sung-Yun] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Giliani, Silvia] Univ Brescia, I-25121 Brescia, Italy. [Candotti, Fabio] NHGRI, NIH, Bethesda, MD USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 359 EP 359 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800050 ER PT J AU Komarow, H Sokolic, R Young, M Garabedian, E Olivier, KN Hershfield, MS Metcalfe, DD Candotti, F AF Komarow, Hirsh Sokolic, Robert Young, Michael Garabedian, Elizabeth Olivier, Kenneth N. Hershfield, Michael S. Metcalfe, Dean D. Candotti, Fabio TI Impulse Oscillometry (IOS) Reveals Increased Pulmonary Impedence in Children with Adenosine Deaminase-Deficient Severe Combined Immunodeficiency (ADA-SCID) SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Komarow, Hirsh; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. [Sokolic, Robert; Garabedian, Elizabeth; Candotti, Fabio] NHGRI, Disorders Immun Sect, Bethesda, MD 20892 USA. [Young, Michael] Leidos Biomed Res Inc, Clin Res Directorate CMRP, Frederick Natl Lab Canc Res, Frederick, MD USA. [Olivier, Kenneth N.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Hershfield, Michael S.] Duke Univ Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 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 APR PY 2014 VL 34 IS 3 BP 359 EP 359 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800049 ER PT J AU Tangye, SG Stoddard, JL Ma, CS Wong, N Hsu, AP Fleisher, TA Pittaluga, S Holland, SM Uzel, G AF Tangye, Stuart G. Stoddard, Jennifer L. Ma, Cindy S. Wong, Natalie Hsu, Amy P. Fleisher, Thomas A. Pittaluga, Stefania Holland, Steven M. Uzel, Gulbu TI Primary Immune Deficiencies Help to Reveal Molecular Requirements for Human T Follicular Helper Cells SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Tangye, Stuart G.; Ma, Cindy S.] Garvan Inst Med Res, Immunol Program, Sydney, NSW, Australia. [Stoddard, Jennifer L.; Fleisher, Thomas A.] NIH, Dept Lab Med, CC, Bethesda, MD 20892 USA. [Wong, Natalie] Garvan Inst Med Res, Immunol Program, Sydney, NS, Australia. [Hsu, Amy P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NIH, Hematopathol Sect, Bethesda, MD 20892 USA. [Uzel, Gulbu] NIAID, Lab Clin Infect Dis, 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 360 EP 360 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800055 ER PT J AU Jing, HE Zhang, Q Zhang, Y Hill, BJ Dove, C Gelfand, EW Atkinson, TP Uzel, G Matthews, HF Mustillo, PJ Lewis, DB Kavadas, FD Hanson, IC Kumar, AR Geha, RS Douek, DC Holland, SM Freeman, AF Su, HL AF Jing, Huie Zhang, Qian Zhang, Yu Hill, Brenna J. Dove, Christopher Gelfand, Erwin W. Atkinson, Thomas Prescott Uzel, Gulbu Matthews, Helen F. Mustillo, Peter J. Lewis, David B. Kavadas, Fotini D. Hanson, Imelda Celine Kumar, Ashish R. Geha, Raif S. Douek, Daniel C. Holland, Steven M. Freeman, Alexandra F. Su, Helen TI Somatic Reversion in Dock8 Immunodeficiency Modulates Disease Phenotype SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Jing, Huie; Zhang, Qian; Zhang, Yu; Dove, Christopher; Su, Helen] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Hill, Brenna J.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Gelfand, Erwin W.] Natl Jewish Hlth, Div Allergy & Immunol, Dept Pediat, Div Cell Biol, Denver, CO USA. [Atkinson, Thomas Prescott] Univ Alabama Birmingham, Birmingham, AL USA. [Uzel, Gulbu; Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Matthews, Helen F.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Mustillo, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA. [Lewis, David B.] Stanford Univ, Dept Pediat, Div Immunol Allergy & Rheumatol, Stanford, CA 94305 USA. [Kavadas, Fotini D.] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada. [Hanson, Imelda Celine] Baylor Coll Med, Dept Pediat, Sect Immunol Allergy & Rheumatol, Houston, TX 77030 USA. [Hanson, Imelda Celine] Texas Childrens Hosp, Houston, TX 77030 USA. [Kumar, Ashish R.] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immunodeficiency, Cincinnati, OH 45229 USA. [Geha, Raif S.] Harvard Univ, Childrens Hosp, Sch Med, Immunol Div, Boston, MA 02115 USA. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, 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 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 APR PY 2014 VL 34 IS 3 BP 361 EP 361 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800056 ER PT J AU Lamborn, IT Zhang, Y Jing, HE McElwee, J Matthews, HF Choi, U Mustillo, PJ Lenardo, MJ Su, HL AF Lamborn, Ian T. Zhang, Yu Jing, Huie McElwee, Joshua Matthews, Helen F. Choi, Uimook Mustillo, Peter J. Lenardo, Michael J. Su, Helen TI Novel Immunodysregulation Disorder Associated with a Gain-Of-Function Mutation in an Ubiquitous G-Protein Coupled Receptor Regulator SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Lamborn, Ian T.; Zhang, Yu; Jing, Huie; Choi, Uimook; Su, Helen] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [McElwee, Joshua] Merck & Co Inc, Merck Res Labs, Boston, MA USA. [Matthews, Helen F.; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Mustillo, Peter J.] Nationwide Childrens Hosp, Columbus, OH 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 361 EP 362 PG 2 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800059 ER PT J AU Murdock, HM Zhang, Q Garcia, J Su, HL AF Murdock, Heardley M. Zhang, Qian Garcia, Jordan Su, Helen TI Diverse Regulators Influence T Cell Migration Through Dense Tissues SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Murdock, Heardley M.] NIAID, Host Def Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Zhang, Qian; Garcia, Jordan; Su, Helen] NIAID, Host Def Lab, NIH, 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 361 EP 361 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800058 ER PT J AU Zerbe, CS Zelazny, A Holland, SM AF Zerbe, Christa S. Zelazny, Adrian Holland, Steven M. TI Trichosporon Inkin Pneumonia and Osteomyelitis in a Lyonized Carrier of X-Linked Chronic Granulomatous Disease SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Zerbe, Christa S.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Zelazny, Adrian] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR PY 2014 VL 34 IS 3 BP 361 EP 361 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800057 ER PT J AU Rosen, LB Pereira, NR Figueiredo, C Fiske, LC Ressner, RA Hong, JC Holland, SM Browne, SK AF Rosen, Lindsey B. Pereira, Nuno Rocha Figueiredo, Cristovao Fiske, Lauren C. Ressner, Roseanne A. Hong, Julie C. Holland, Steven M. Browne, Sarah K. TI Anti-GM-CSF Autoantibodies in Patients with Nocardiosis of the Central Nervous System SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Rosen, Lindsey B.; Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Pereira, Nuno Rocha] Univ Porto, Nephrol & Infect Dis Res & Dev Grp, INEB I3S, P-4100 Oporto, Portugal. [Pereira, Nuno Rocha; Figueiredo, Cristovao] Sao Joao Hosp Ctr, EPE, Dept Infect Dis, Oporto, Portugal. [Fiske, Lauren C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Ressner, Roseanne A.] Walter Reed Natl Mil Med Ctr, Infect Dis Clin OIC, Bethesda, MD USA. [Hong, Julie C.] Kaiser Permanente, Clackamas, OR USA. NR 0 TC 0 Z9 0 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 APR PY 2014 VL 34 IS 3 BP 362 EP 363 PG 2 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800063 ER PT J AU Szymanski, EP Leung, JM Fowler, CJ Liu, XY Devine, SE Fraser, CM Tettelin, H Olivier, KN Holland, SM AF Szymanski, Eva P. Leung, Janice M. Fowler, Cedar J. Liu, Xinyue Devine, Scott E. Fraser, Claire M. Tettelin, Herve Olivier, Kenneth N. Holland, Steven M. TI STAT1 Gain of Function Mutations are Infrequent in Pulmonary Nontuberculous Mycobacterial Infection SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Szymanski, Eva P.; Leung, Janice M.; Fowler, Cedar J.; Olivier, Kenneth N.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Liu, Xinyue; Devine, Scott E.; Fraser, Claire M.; Tettelin, Herve] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2014 VL 34 IS 3 BP 362 EP 362 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800062 ER PT J AU Kapnick, S Schwartzberg, P AF Kapnick, Senta Schwartzberg, Pamela TI Investigating the Role of Inducible T-Cell Kinase in CD8+T-Lymphocyte Cytolytic Effector Function SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Kapnick, Senta; Schwartzberg, Pamela] NHGRI, NIH, Bethesda, MD 20892 USA. [Kapnick, Senta] JHU, Baltimore, MD 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 364 EP 364 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800069 ER PT J AU Stoddard, JL Hsu, AP Hussey, AA Agharahimi, A Holland, SM Fleisher, TA Tangye, SG Uzel, G AF Stoddard, Jennifer L. Hsu, Amy P. Hussey, Ashleigh A. Agharahimi, Anahita Holland, Steven M. Fleisher, Thomas A. Tangye, Stuart G. Uzel, Gulbu TI Beyond T, B, and NK Flow: An Extended Analytical Panel for the Flow Cytometric Evaluation of Primary Immune Deficiencies SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Stoddard, Jennifer L.; Fleisher, Thomas A.] NIH, Dept Lab Med, CC, Bethesda, MD 20892 USA. [Hsu, Amy P.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hussey, Ashleigh A.; Agharahimi, Anahita] NIAID, Bethesda, MD 20892 USA. [Tangye, Stuart G.] Garvan Inst Med Res, Immunol Program, Sydney, NSW, Australia. [Uzel, Gulbu] NIAID, Lab Clin Infect Dis, 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 366 EP 366 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800076 ER PT J AU Milligan, KL Williams, KW Sharma, HP Keller, MD Loechelt, BJ AF Milligan, Ki Lee Williams, Kelli W. Sharma, Hemant P. Keller, Michael D. Loechelt, Brett J. TI EBV-Negative Lymphoproliferative Disease in Severe Combined Immunodeficiency SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Milligan, Ki Lee] NIH, Bethesda, MD 20892 USA. [Williams, Kelli W.] NIAID, NIH, Bethesda, MD 20892 USA. [Sharma, Hemant P.; Keller, Michael D.] Childrens Natl Hlth Syst, Div Allergy & Immunol, Washington, DC USA. [Loechelt, Brett J.] Childrens Natl Hlth Syst, CCIR, Washington, DC 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 367 EP 367 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800078 ER PT J AU Anvari, S Uzel, G Jara, D Jones, B AF Anvari, Sara Uzel, Gulbu Jara, David Jones, Bridgette TI Combined Primary Immunodeficiency Caused by Gain-Of-Function Mutations in PIK3CD and Alternatives for Long-Term Treatment SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Anvari, Sara; Jara, David; Jones, Bridgette] Childrens Mercy Hosp & Clin, Div Allergy Asthma & Immunol, Kansas City, MO USA. [Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Jones, Bridgette] Childrens Mercy Hosp & Clin, Kansas City, MO USA. NR 0 TC 0 Z9 0 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 APR PY 2014 VL 34 IS 3 BP 368 EP 368 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800083 ER PT J AU Freeman, AF Grossman, J Sowerwine, K Heimall, J Welch, P Daub, J Marciano, B Leiding, JW Holland, SM AF Freeman, Alexandra F. Grossman, Jennifer Sowerwine, Kathryn Heimall, Jennifer Welch, Pamela Daub, Janine Marciano, Betty Leiding, Jennifer W. Holland, Steven M. TI Clinical Phenotype of Idiopathic CD4 Lymphopenia (ICL) SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Grossman, Jennifer; Sowerwine, Kathryn; Daub, Janine; Marciano, Betty] NIAID, Bethesda, MD USA. [Heimall, Jennifer] Childrens Hosp Philadelphia, Div Allergy & Immunol, Philadelphia, PA 19104 USA. [Welch, Pamela] NIAID, DCR, ICMOB, NIH, Bethesda, MD 20892 USA. [Leiding, Jennifer W.] Univ S Florida, Tampa, FL USA. NR 0 TC 0 Z9 0 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 APR PY 2014 VL 34 IS 3 BP 368 EP 368 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800081 ER PT J AU Lyons, JJ Yu, XM Ma, CA Hughes, JD Mehmet, H McElwee, J McDonnell, NB Freeman, AF Milner, J AF Lyons, Jonathan J. Yu, Xiaomin Ma, Chi A. Hughes, Jason D. Mehmet, Huseyin McElwee, Joshua McDonnell, Nazli B. Freeman, Alexandra F. Milner, Joshua TI ERBB2IP Mutations Disrupt TGF-beta Pathway Signaling in Syndromic Atopy in Humans SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Lyons, Jonathan J.; Yu, Xiaomin; Ma, Chi A.; Milner, Joshua] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. [Hughes, Jason D.; Mehmet, Huseyin; McElwee, Joshua] Merck & Co Inc, Merck Res Labs, Boston, MA USA. [McDonnell, Nazli B.] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. [Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2014 VL 34 IS 3 BP 369 EP 369 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800087 ER PT J AU Pozos, TC Abraham, RS Smith, M Leidal, K Hsu, A Bagatikar, J McCormick, S Hinde, S Austin, A Dinauer, M Holland, SM Nauseef, W AF Pozos, Tamara C. Abraham, Roshini Sarah Smith, Mathew Leidal, Kevin Hsu, Amy Bagatikar, Juhi McCormick, Sally Hinde, Sara Austin, Anthony Dinauer, Mary Holland, Steven M. Nauseef, William TI Novel Clinical Presentation of Complete Myeloperoxidase (MPO) Deficiency: Should MPO Deficiency be Re-Instated as a Primary Immunodeficiency? SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Pozos, Tamara C.] Childrens Hosp & Clin Minnesota, St Paul, MN USA. [Abraham, Roshini Sarah; Smith, Mathew] Mayo Clin, Dept Lab Med & Pathol, Cellular & Mol Immunol Lab, Rochester, MN USA. [Leidal, Kevin; McCormick, Sally; Hinde, Sara; Nauseef, William] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Med & Microbiol, Coralville, IA USA. [Hsu, Amy; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Bagatikar, Juhi; Austin, Anthony; Dinauer, Mary] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2014 VL 34 IS 3 BP 369 EP 369 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800086 ER PT J AU Lopez, DB Milner, JD AF Lopez, Diego B. Milner, Joshua D. TI Gain of STAT1 Signaling Associated with Overlapping Pathophysiology in STAT3, IL21R and STAT1 Mutant Patients SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Lopez, Diego B.; Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 370 EP 370 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800089 ER PT J AU Falcone, EL Lionakis, MS Abusleme, L Hsu, AP Ding, L Kuhns, DB Moutsopoulos, N Holland, SM AF Falcone, Emilia Liana Lionakis, Michail S. Abusleme, Loreto Hsu, Amy P. Ding, Li Kuhns, Douglas B. Moutsopoulos, Niki Holland, Steven M. TI Susceptibility to DSS Colitis in CGD Mice Varies by Genotype and is Mediated by the Intestinal Stroma SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Falcone, Emilia Liana; Hsu, Amy P.; Ding, Li; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Abusleme, Loreto; Moutsopoulos, Niki] Natl Inst Dent & Craniofacial Res, Clin Res Core, NIH, Bethesda, MD USA. [Kuhns, Douglas B.] NCI, Leidos Biomed Res Inc, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 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 APR PY 2014 VL 34 IS 3 BP 374 EP 374 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800106 ER PT J AU Aderibigbe, OM Cowen, EW Milner, JD AF Aderibigbe, Oyinade M. Cowen, Edward W. Milner, Joshua D. TI Distinct Leukocyte Activation States Uniquely Contribute to the Manifestations of Both Plaid and Aplaid SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Aderibigbe, Oyinade M.; Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Cowen, Edward W.] NCI, Dermatol Branch, 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 375 EP 375 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800109 ER PT J AU Gupta, M Sindher, S Sullivan, KE Uzel, G AF Gupta, Malika Sindher, Sayantani Sullivan, Kathleen E. Uzel, Gulbu TI Large Granular Lymphocytic (LGL) Expansion in X-Linked Agamma-globulinemia (XLA): A Case Report SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Gupta, Malika; Sindher, Sayantani; Sullivan, Kathleen E.] Childrens Hosp Philadelophia, Philadelphia, PA USA. [Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 375 EP 375 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800111 ER PT J AU Hsu, AP Freeman, AF Holland, SM AF Hsu, Amy P. Freeman, Alexandra F. Holland, Steven M. TI IL2RG Reversion Event in a Common Lymphoid Progenitor Leads to Delayed Diagnosis and Milder Phenotype SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Hsu, Amy P.; Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 376 EP 376 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800113 ER PT J AU Hanks, ME Hsu, AP Choi, U Sickel, B Chandrasekaran, P Wu, UI Spalding, C Uzel, G Freeman, AF Malech, H Zerbe, CS Holland, SM Sampaio, EP AF Hanks, Mary E. Hsu, Amy P. Choi, Uimook Sickel, Brandon Chandrasekaran, Prabha Wu, Un-In Spalding, Christine Uzel, Gulbu Freeman, Alexandra F. Malech, Harry Zerbe, Christa S. Holland, Steven M. Sampaio, Elizabeth P. TI Novel IL-12R beta 2 Mutation Associated with Disseminated Coccidioidomycosis SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Hanks, Mary E.; Hsu, Amy P.; Sickel, Brandon; Chandrasekaran, Prabha; Wu, Un-In; Uzel, Gulbu; Freeman, Alexandra F.; Zerbe, Christa S.; Sampaio, Elizabeth P.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Choi, Uimook; Malech, Harry] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Spalding, Christine] CC NIH, Bethesda, MD USA. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR PY 2014 VL 34 IS 3 BP 377 EP 377 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800117 ER PT J AU Rudman, AK Marquesen, M DeCastro, R Qin, J DeRavin, SS Kang, E Malech, HL AF Rudman, Amanda K. Marquesen, Martha DeCastro, Rosamma Qin, Jing DeRavin, Suk See Kang, Elizabeth Malech, Harry L. TI Infection Prophylaxis Compliance in a Chronic Granulomatous Disease Population SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Rudman, Amanda K.; Marquesen, Martha; DeCastro, Rosamma; DeRavin, Suk See; Kang, Elizabeth; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Qin, Jing] NIAID, Biostat Res Branch, NIH, 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 378 EP 378 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800121 ER PT J AU Schwartzberg, PL Kapnick, S Zhao, R Cannons, J Uzel, G AF Schwartzberg, Pamela L. Kapnick, Senta Zhao, Roseanne Cannons, Jennifer Uzel, Gulbu TI Signaling Defects in Immunodeficiencies with Impaired CD8 Cytolysis SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Schwartzberg, Pamela L.; Zhao, Roseanne; Cannons, Jennifer] NHGRI, Bethesda, MD 20892 USA. [Kapnick, Senta] NHGRI, NIH, Bethesda, MD 20892 USA. [Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 382 EP 382 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800135 ER PT J AU Freeman, AF Olivier, KN Jancel, T Kwak, EJ Holland, SM Bermudez, C McDyer, J AF Freeman, Alexandra F. Olivier, Kenneth N. Jancel, Timothy Kwak, Eun Jeong Holland, Steven M. Bermudez, Christian McDyer, John TI Successful Bilateral Lung Transplant in Autosomal Dominant Hyper IgE Syndrome SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Olivier, Kenneth N.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Jancel, Timothy] NIH, Bethesda, MD USA. [Kwak, Eun Jeong; Bermudez, Christian; McDyer, John] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 386 EP 386 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800152 ER PT J AU Odio, CD Holland, SM AF Odio, Camila D. Holland, Steven M. TI Disseminated Coccidioidomycosis: Risk Factors and Review of the Literature SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Odio, Camila D.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 388 EP 388 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800160 ER PT J AU Zhang, Q Dove, C Strauss-Albee, D Garcia, J Mandl, J Grodick, R Jing, H Chandler-Brown, D Kim, E Murdock, HM Crawford, GH Matthews, H Freeman, AF Cornall, R Germain, R Mueller, SN Su, H AF Zhang, Qian Dove, Christopher Strauss-Albee, Dara Garcia, Jordan Mandl, Judith Grodick, Rachael Jing, Huie Chandler-Brown, Devon Kim, Emily Murdock, Heardley M. Crawford, Greg H. Matthews, Helen Freeman, Alexandra F. Cornall, Richard Germain, Ronald Mueller, Scott Norman Su, Helen TI Dock8 Regulates Lymphocyte Shape Integrity For Skin Antiviral Responses SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Zhang, Qian; Dove, Christopher; Strauss-Albee, Dara; Garcia, Jordan; Grodick, Rachael; Jing, Huie; Chandler-Brown, Devon; Kim, Emily; Murdock, Heardley M.; Su, Helen] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA. [Mandl, Judith; Germain, Ronald] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Crawford, Greg H.; Cornall, Richard] Univ Oxford, Oxford OX1 2JD, England. [Matthews, Helen] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Mueller, Scott Norman] Univ Melbourne, Melbourne, Vic 3010, Australia. RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 392 EP 392 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800176 ER PT J AU Liu, WL Dogan, RI Kim, S Comeau, DC Kim, W Yeganova, L Lu, ZY Wilbur, WJ AF Liu, Wanli Dogan, Rezarta Islamaj Kim, Sun Comeau, Donald C. Kim, Won Yeganova, Lana Lu, Zhiyong Wilbur, W. John TI Author Name Disambiguation for PubMed SO JOURNAL OF THE ASSOCIATION FOR INFORMATION SCIENCE AND TECHNOLOGY LA English DT Article ID ENTITY RESOLUTION; MODEL; SIMILARITY; ARTICLES AB Log analysis shows that PubMed users frequently use author names in queries for retrieving scientific literature. However, author name ambiguity may lead to irrelevant retrieval results. To improve the PubMed user experience with author name queries, we designed an author name disambiguation system consisting of similarity estimation and agglomerative clustering. A machine-learning method was employed to score the features for disambiguating a pair of papers with ambiguous names. These features enable the computation of pairwise similarity scores to estimate the probability of a pair of papers belonging to the same author, which drives an agglomerative clustering algorithm regulated by 2 factors: name compatibility and probability level. With transitivity violation correction, high precision author clustering is achieved by focusing on minimizing false-positive pairing. Disambiguation performance is evaluated with manual verification of random samples of pairs from clustering results. When compared with a state-of-the-art system, our evaluation shows that among all the pairs the lumping error rate drops from 10.1% to 2.2% for our system, while the splitting error rises from 1.8% to 7.7%. This results in an overall error rate of 9.9%, compared with 11.9% for the state-of-the-art method. Other evaluations based on gold standard data also show the increase in accuracy of our clustering. We attribute the performance improvement to the machine-learning method driven by a large-scale training set and the clustering algorithm regulated by a name compatibility scheme preferring precision. With integration of the author name disambiguation system into the PubMed search engine, the overall click-through-rate of PubMed users on author name query results improved from 34.9% to 36.9%. C1 [Liu, Wanli; Dogan, Rezarta Islamaj; Kim, Sun; Comeau, Donald C.; Kim, Won; Yeganova, Lana; Lu, Zhiyong; Wilbur, W. John] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Liu, WL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM liu15@ncbi.nlm.nih.gov; islamaj@ncbi.nlm.nih.gov; sun.kim@ncbi.nlm.nih.gov; comeau@ncbi.nlm.nih.gov; wonkim@ncbi.nlm.nih.gov; yeganova@ncbi.nlm.nih.gov; luzh@ncbi.nlm.nih.gov; wilbur@ncbi.nlm.nih.gov RI Lu, Zhiyong/H-3622-2016 OI Lu, Zhiyong/0000-0001-9998-916X FU Intramural Research Program of the NIH, National Library of Medicine FX This research was supported by the Intramural Research Program of the NIH, National Library of Medicine. We thank the anonymous reviewers for valuable suggestions, which improved this paper. NR 41 TC 9 Z9 9 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2330-1635 EI 2330-1643 J9 J ASSOC INF SCI TECH PD APR PY 2014 VL 65 IS 4 BP 765 EP 781 DI 10.1002/asi.23063 PG 17 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA AG7FI UT WOS:000335583300012 ER PT J AU Raffel, SJ Battisti, JM Fischer, RJ Schwan, TG AF Raffel, Sandra J. Battisti, James M. Fischer, Robert J. Schwan, Tom G. TI Inactivation of Genes for Antigenic Variation in the Relapsing Fever Spirochete Borrelia hermsii Reduces Infectivity in Mice and Transmission by Ticks SO PLOS PATHOGENS LA English DT Article ID LYME-DISEASE SPIROCHETE; OUTER-SURFACE PROTEIN; VARIABLE MAJOR PROTEINS; WHITE-FOOTED MICE; LINEAR PLASMIDS; ORNITHODOROS-HERMSI; EXPRESSION SITE; B1B LYMPHOCYTES; PURINE SALVAGE; VLSE LOCUS AB Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host's acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream Vmp and produce a different outer surface protein, the variable tick protein (Vtp), during persistent infection in the tick salivary glands. Thus the production of Vmps in mammalian blood versus Vtp in ticks is a dominant feature of the spirochete's alternating life cycle. We constructed two mutants, one which was unable to produce a Vmp and the other was unable to produce Vtp. The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia. This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes. The mutant lacking Vtp also colonized ticks but produced neither Vtp nor a Vmp in tick salivary glands, which rendered the spirochete noninfectious by tick bite. Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector. Author SummaryBorrelia hermsii, an agent of tick-borne relapsing fever when infecting humans, employs antigenic variation of the variable major proteins (Vmps) to escape the host immune response. This mechanism allows the bacteria to persist in the blood of a mammal, which increases their potential for acquisition by their tick vector Ornithodoros hermsi. Once in the tick, the bacteria move from the midgut to salivary glands where the Vmps are replaced with another major surface protein, the variable tick protein (Vtp). We constructed two mutants, one that was unable to produce a Vmp (Vmp(-)) and another that was unable to produce Vtp (vtp). The Vmp(-) mutant could not reach as high bacterial levels in the blood of mice when infected by needle-inoculation and tick bite compared to the parent strain, and was incapable of relapsing. The vtp mutant was able to colonize ticks, but was non-infectious by tick bite. Our study provides insight into the roles of the Vmps and Vtp in the infectivity of B. hermsii by showing the importance of antigenic variation for prolonging bacteria levels in the host as well as the requirement of Vtp for mammalian infection by the bite of its tick vector. C1 [Raffel, Sandra J.; Battisti, James M.; Fischer, Robert J.; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Battisti, James M.] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. RP Raffel, SJ (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM tschwan@niaid.nih.gov OI Fischer, Robert/0000-0002-1816-472X FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 84 TC 14 Z9 14 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2014 VL 10 IS 4 DI 10.1371/journal.ppat.1004056 PG 17 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AG6AZ UT WOS:000335502100021 ER PT J AU Wei, DG Chiang, V Fyne, E Balakrishnan, M Barnes, T Graupe, M Hesselgesser, J Irrinki, A Murry, JP Stepan, G Stray, KM Tsai, A Yu, H Spindler, J Kearney, M Spina, CA McMahon, D Lalezari, J Sloan, D Mellors, J Geleziunas, R Cihlar, T AF Wei, Datsen George Chiang, Vicki Fyne, Elizabeth Balakrishnan, Mini Barnes, Tiffany Graupe, Michael Hesselgesser, Joseph Irrinki, Alivelu Murry, Jeffrey P. Stepan, George Stray, Kirsten M. Tsai, Angela Yu, Helen Spindler, Jonathan Kearney, Mary Spina, Celsa A. McMahon, Deborah Lalezari, Jacob Sloan, Derek Mellors, John Geleziunas, Romas Cihlar, Tomas TI Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing SO PLOS PATHOGENS LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; LATENT RESERVOIR; HDAC INHIBITORS; VIRAL RESERVOIRS; DOUBLE-BLIND; INFECTION; DEPSIPEPTIDE; ERADICATION; ACTIVATION; MEMORY AB Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50=4.5 nM) compared with vorinostat (VOR; EC50=3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50=10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 mu M VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART. Author Summary Combination antiretroviral therapy has greatly improved the clinical outcome of HIV infection treatment. However, latent viral reservoirs established primarily in memory CD4 T cells persist even after long periods of suppressive antiretroviral therapy, which hinders the ability to achieve a prolonged drug-free remission or a cure of the HIV infection. Activation of HIV expression from latent reservoirs is a part of proposed strategies that may potentially lead to virus elimination and ultimately cure of the infection. In this study, we show that romidepsin, a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, is a potent activator of HIV expression in an in vitro model of viral latency as well as ex vivo in resting and memory CD4 T cells isolated from HIV-infected patients with suppressed viremia. Importantly, the ex vivo activation of latent HIV occurred at romidepsin concentrations lower than those achieved in drug-treated lymphoma patients. In addition, romidepsin exhibited a more potent effect than other drugs in the same class that have already been shown to activate HIV expression in vivo. Together, these results support the clinical assessment of romidepsin in HIV-infected patients on suppressive antiretroviral therapy. C1 [Wei, Datsen George; Chiang, Vicki; Balakrishnan, Mini; Barnes, Tiffany; Graupe, Michael; Hesselgesser, Joseph; Irrinki, Alivelu; Murry, Jeffrey P.; Stepan, George; Stray, Kirsten M.; Tsai, Angela; Yu, Helen; Sloan, Derek; Geleziunas, Romas; Cihlar, Tomas] Gilead Sci, Foster City, CA 94404 USA. [Fyne, Elizabeth; McMahon, Deborah; Mellors, John] Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA 15213 USA. [Spindler, Jonathan; Kearney, Mary] NCI, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA. [Spina, Celsa A.] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA. [Lalezari, Jacob] Quest Clin Res, San Francisco, CA USA. RP Wei, DG (reprint author), Gilead Sci, Foster City, CA 94404 USA. EM tomas.cihlar@gilead.com OI Murry, Jeffrey/0000-0002-3716-1460 FU National Institutes of Health [UL1 RR024153, UL1TR000005]; Gilead Sciences, Inc. FX The project described was supported in part by the National Institutes of Health through Grant Numbers UL1 RR024153 and UL1TR000005. The study was also funded by Gilead Sciences, Inc. Employees of the company were involved in study design, data collection and analysis, and writing the manuscript. However, none of the therapeutics characterized in this study are products of Gilead Sciences, and studies were designed, executed, and objectively interpreted purely with a purpose to advance basic research in the field of HIV latency and cure. NR 59 TC 90 Z9 90 U1 0 U2 17 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 APR PY 2014 VL 10 IS 4 DI 10.1371/journal.ppat.1004071 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AG6AZ UT WOS:000335502100019 ER PT J AU Burroughs, AM Aravind, L AF Burroughs, A. Maxwell Aravind, L. TI A highly conserved family of domains related to the DNA-glycosylase fold helps predict multiple novel pathways for RNA modifications SO RNA BIOLOGY LA English DT Article DE DNA glycosylase; NEMF; Tae2; caliban; FbpA; fibronectin-binding; tRNA 4-thiouridylation; IscS; TusA; base modification ID FIBRONECTIN-BINDING PROTEIN; IRES-MEDIATED TRANSLATION; COLI ENDONUCLEASE-VIII; ESCHERICHIA-COLI; PSEUDOURIDINE SYNTHASES; CRYSTAL-STRUCTURE; GUANINE TRANSGLYCOSYLASE; CLOSTRIDIUM-DIFFICILE; CATALYTIC MECHANISM; LESION RECOGNITION AB A protein family including mammalian NEMF, Drosophila caliban, yeast Tae2, and bacterial FpbA-like proteins was first defined over a decade ago and found to be universally distributed across the three domains/superkingdoms of life. Since its initial characterization, this family of proteins has been tantalizingly linked to a wide range of biochemical functions. Tapping the enormous wealth of genome information that has accumulated since the initial characterization of these proteins, we perform a detailed computational analysis of the family, identifying multiple conserved domains. Domains identified include an enzymatic domain related to the formamidopyrimidine (Fpg), MutM, and Nei/EndoVIII family of DNA glycosylases, a novel, predicted RNA-binding domain, and a domain potentially mediating protein-protein interactions. Through this characterization, we predict that the DNA glycosylase-like domain catalytically operates on double-stranded RNA, as part of a hitherto unknown base modification mechanism that probably targets rRNAs. At least in archaea, and possibly eukaryotes, this pathway might additionally include the AMMECR1 family of proteins. The predicted RNA-binding domain associated with this family is also observed in distinct architectural contexts in other proteins across phylogenetically diverse prokaryotes. Here it is predicted to play a key role in a new pathway for tRNA 4-thiouridylation along with TusA-like sulfur transfer proteins. C1 [Burroughs, A. Maxwell; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Burroughs, AM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM max.burroughs@nih.gov FU funds of the Intramural Research Program of the NIH, National Library of Medicine FX Burroughs AM and Aravind L's research is supported by the funds of the Intramural Research Program of the NIH, National Library of Medicine. NR 89 TC 4 Z9 4 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1547-6286 EI 1555-8584 J9 RNA BIOL JI RNA Biol. PD APR PY 2014 VL 11 IS 4 BP 360 EP 372 DI 10.4161/rna.28302 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH5CB UT WOS:000336144900010 PM 24646681 ER PT J AU Camargo, MC Garcia, A Riquelme, A Otero, W Camargo, CA Hernandez-Garcia, T Candia, R Bruce, MG Rabkin, CS AF Camargo, M. Constanza Garcia, Apolinaria Riquelme, Arnoldo Otero, William Camargo, Claudia A. Hernandez-Garcia, Tomas Candia, Roberto Bruce, Michael G. Rabkin, Charles S. TI The Problem of Helicobacter pylori Resistance to Antibiotics: A Systematic Review in Latin America SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID AGAR DILUTION; INFECTION; METAANALYSIS; ERADICATION; MANAGEMENT; AGENTS; EVOLUTION; STRAINS; BIAS AB OBJECTIVES: Latin America has a high prevalence of Helicobacter pylori infection and associated diseases, including gastric cancer. Antibiotic therapy can eradicate the bacterial infection and decrease associated morbidity and mortality. To tailor recommendations for optimal treatments, we summarized published literature and calculated region-and country-specific prevalences of antibiotic resistance. METHODS: Searches of PubMed and regional databases for observational studies evaluating H. pylori antibiotic resistance yielded a total of 59 independent studies (56 in adults, 2 in children, and 1 in both groups) published up to October 2013 regarding H. pylori isolates collected between 1988 and 2011. Study-specifi c prevalences of primary resistance to commonly prescribed antibiotics were summarized using random-effects models. Between-study heterogeneity was assessed by meta-regression. As a sensitivity analysis, we extended our research to studies of patients with prior H. pylori-eradication therapy. RESULTS: Summary prevalences of antimicrobial primary resistance among adults varied by antibiotic, including 12% for clarithromycin (n=35 studies), 53% for metronidazole (n=34), 4% for amoxicillin (n=28), 6% for tetracycline (n=20), 3% for furazolidone (n=6), 15% for fluoroquinolones (n=5), and 8% for dual clarithromycin and metronidazole (n=10). Resistance prevalence varied significantly by country, but not by year of sample collection. Analyses including studies of patients with prior therapy yielded similar estimates. Pediatric reports were too few to be summarized by meta-analysis. CONCLUSIONS: Resistance to first-line anti-H. pylori antibiotics is high in Latin American populations. In some countries, the empirical use of clarithromycin without susceptibility testing may not be appropriate. These findings stress the need for appropriate surveillance programs, improved antimicrobial regulations, and increased public awareness. C1 [Camargo, M. Constanza; Rabkin, Charles S.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Garcia, Apolinaria; Hernandez-Garcia, Tomas] Univ Concepcion, Dept Microbiol, Concepcion, Chile. [Riquelme, Arnoldo; Candia, Roberto] Pontificia Univ Catolica, Sch Med, Dept Gastroenterol, Santiago, Chile. [Otero, William] Univ Nacl Colombia, Sch Med, Dept Gastroenterol, Bogota, Colombia. [Otero, William] Clin Fundadores, Bogota, Colombia. [Camargo, Claudia A.] Secretaria Salud Mexico, Mexico City, DF, Mexico. [Bruce, Michael G.] Ctr Dis Control & Prevent, Div Preparedness & Emerging Infect, Art Investigat Program, Anchorage, AK USA. RP Camargo, MC (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,BG 9609-6E206, Rockville, MD 20850 USA. EM camargomc@mail.nih.gov RI Camargo, M. Constanza/R-9891-2016; OI Candia, Roberto/0000-0003-1856-7737 FU Intramural Research Program of the United States National Institutes of Health; National Cancer Institute FX This work was supported by the Intramural Research Program of the United States National Institutes of Health, National Cancer Institute. NR 44 TC 30 Z9 36 U1 0 U2 12 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 APR PY 2014 VL 109 IS 4 BP 485 EP 495 DI 10.1038/ajg.2014.24 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AG5HO UT WOS:000335450300004 PM 24589670 ER PT J AU Altekruse, SF Henley, SJ Cucinelli, JE McGlynn, KA AF Altekruse, Sean F. Henley, S. Jane Cucinelli, James E. McGlynn, Katherine A. TI Changing Hepatocellular Carcinoma Incidence and Liver Cancer Mortality Rates in the United States SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID C VIRUS-INFECTION; US ADULTS; TRENDS; EPIDEMIOLOGY; PREVALENCE; HEPATITIS; OBESITY; JAPAN; DISEASE; FUTURE AB OBJECTIVES: The objectives were to describe Surveillance, Epidemiology and End Results (SEER) hepatocellular carcinoma (HCC) incidence trends and the US liver cancer mortality trends by geography, age, race /ethnicity, and gender. METHODS: HCC incidence data from SEER 18 registries and liver cancer mortality data from the National Center for Health Statistics were analyzed. Rates and joinpoint trends were calculated by demographic subgroup. State-level liver cancer mortality rates and trends were mapped. RESULTS: HCC incidence rates in SEER registries did not signifi cantly increase during 2007-2010; however, the US liver cancer mortality rates did increase. HCC incidence and liver cancer mortality rates increased among black, Hispanic, and white men aged 50 + years and decreased among 35-49-year-old men in all racial /ethnic groups including Asians /Pacifi c Islanders. Signifi cantly increasing incidence and mortality rates among women were restricted to blacks, Hispanics, and whites aged 50 + years. Asian /Pacifi c Islander liver cancer mortality rates decreased during 2000 -2010 with decreasing rates among women aged 50-64 years and men aged 35-49 years and stable rates in other groups. During 2006 -2010, among individuals 50-64 years of age, blacks and Hispanics had higher incidence and mortality rates than Asians /Pacifi c Islanders. Liver cancer mortality rates were highest in Louisiana, Mississippi, Texas, and Washington, DC. CONCLUSIONS: Decreasing HCC incidence and liver cancer mortality rates among Asians /Pacifi c Islanders, men aged 35-49 years, and the nonsignifi cant increase in overall HCC incidence rates suggest that the peak of the epidemic may be near or have passed. Findings of geographic variation in mortality rates can inform control efforts. C1 [Altekruse, Sean F.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Henley, S. Jane] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. [Cucinelli, James E.] Informat Management Serv Inc, Silver Spring, MD USA. [McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Altekruse, SF (reprint author), NCI, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 504, Rockville, MD 20852 USA. EM altekrusesf@mail.nih.gov OI Henley, S Jane/0000-0002-2420-306X FU Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention FX This study was supported by Division of Cancer Control and Population Sciences; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; and Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. NR 35 TC 76 Z9 76 U1 0 U2 10 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 APR PY 2014 VL 109 IS 4 BP 542 EP 553 DI 10.1038/ajg.2014.11 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AG5HO UT WOS:000335450300011 PM 24513805 ER PT J AU Villasenor, A Ramamoorthy, A dos Santos, MS Lorenzo, MP Laje, G Zarate, C Barbas, C Wainer, IW AF Villasenor, A. Ramamoorthy, A. Silva dos Santos, M. Lorenzo, M. P. Laje, G. Zarate, C., Jr. Barbas, C. Wainer, I. W. TI A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response-related difference in mitochondrial networks SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE mitochondrial function; fatty acid metabolism; pharmacometabolomics; lithium; valproate ID GLOBAL BIOCHEMICAL APPROACH; D-ASPARTATE ANTAGONIST; MAJOR DEPRESSION; FATTY-ACID; GERIATRIC DEPRESSION; IN-VITRO; DISORDER; CARNITINE; DISEASE; PHARMACOMETABOLOMICS AB Background and Purpose(R,S)-ketamine produces rapid and significant antidepressant effects in approximately 65% of patients suffering from treatment-resistant bipolar depression (BD). The genetic, pharmacological and biochemical differences between ketamine responders and non-responders have not been identified. The purpose of this study was to employ a metabolomics approach, a global, non-targeted determination of endogenous metabolic patterns, to identify potential markers of ketamine response and non-response. Experimental ApproachPlasma samples from 22 BD patients were analyzed to produce metabolomic patterns. The patients had received ketamine in a placebo-controlled crossover study and the samples were obtained 230min post-administration at which time the patients were categorized as responders or non-responders. Matching plasma samples from the placebo arm of the study were also analysed. During the study, the patients were maintained on either lithium or valproate. Key ResultsThe metabolomic patterns were significantly different between the patients maintained on lithium and those maintained on valproate, irrespective of response to ketamine. In the patients maintained on lithium, 18 biomarkers were identified. In responders, lysophosphatidylethanolamines (4) and lysophosphatidylcholines (9) were increased relative to non-responders. Conclusions and ImplicationsThe results indicate that the differences between patients who respond to ketamine and those who do not are due to alterations in the mitochondrial -oxidation of fatty acids. These differences were not produced by ketamine administration. The data indicate that pretreatment metabolomics screening may be a guide to the prediction of response and a potential approach to the individualization of ketamine therapy. Linked ArticlesThis article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit C1 [Villasenor, A.; Silva dos Santos, M.; Lorenzo, M. P.; Barbas, C.] Univ CEU San Pablo, Fac Farm, Ctr Metabol & Bioanal CEMBIO, Madrid, Spain. [Ramamoorthy, A.; Wainer, I. W.] NIA, Lab Clin Invest, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Silva dos Santos, M.] Univ Fed Minas Gerais, Fac Pharm, Belo Horizonte, MG, Brazil. [Laje, G.; Zarate, C., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD USA. [Laje, G.] NIMH, Human Genet Branch, NIH, Bethesda, MD USA. [Laje, G.] NIMH, Genet Basis Mood & Anxiety Disorders Sect, Intramural Res Program, NIH, Bethesda, MD USA. [Laje, G.] MIND, Bethesda, MD USA. RP Wainer, IW (reprint author), NIA, Lab Clin Invest, NIH, 251 Bayview Blvd,08B133, Baltimore, MD 21224 USA. EM wainerir@grc.nia.nih.gov RI Lorenzo, Maria /K-4497-2014; Laje, Gonzalo/L-2654-2014; Barbas, Coral/K-3871-2014; Santos, Mariana/A-6410-2015 OI Laje, Gonzalo/0000-0003-2763-3329; Barbas, Coral/0000-0003-4722-491X; FU Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH); National Institute of Mental Health, NIH; Spanish Ministerio de Economia y Competitividad (MEC) [CTQ2011-23562]; EADS CASA FX This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH) and the National Institute of Mental Health, NIH. The authors also acknowledge the funding from Spanish Ministerio de Economia y Competitividad (MEC) grant CTQ2011-23562 and A. V. acknowledges her fellowship to EADS CASA. NR 35 TC 20 Z9 20 U1 3 U2 33 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1188 EI 1476-5381 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD APR PY 2014 VL 171 IS 8 SI SI BP 2230 EP 2242 DI 10.1111/bph.12494 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AD7XZ UT WOS:000333482100028 PM 24684390 ER PT J AU Wood, D Wesselschmidt, R Hematti, P Gee, AP Rooney, C Silberstein, L Armant, M Couture, L Wagner, JE McKenna, DH Hei, D Mondoro, TH Welniak, L Lindblad, R AF Wood, Deborah Wesselschmidt, Robin Hematti, Peiman Gee, Adrian P. Rooney, Cliona Silberstein, Leslie Armant, Myriam Couture, Larry Wagner, John E. McKenna, David H., Jr. Hei, Derek Mondoro, Traci Heath Welniak, Lisbeth Lindblad, Robert TI An Update from the United States National Heart, Lung, and Blood Institute- funded Production Assistance for Cellular Therapies ( PACT) Program: A Decade of Cell Therapy SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Editorial Material ID CYTOTOXIC T-LYMPHOCYTES; ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR FUNCTION; ANTIGEN-PRESENTING CELLS; WISKOTT-ALDRICH SYNDROME; MESENCHYMAL STEM-CELLS; NATURAL-KILLER-CELLS; EPSTEIN-BARR-VIRUS; VIRAL-INFECTIONS; TRANSPLANT RECIPIENTS C1 [Wood, Deborah; Lindblad, Robert] EMMES Corp, Rockville, MD 20850 USA. [Wesselschmidt, Robin; Couture, Larry] City Hope Natl Med Ctr, Ctr Appl Technol Dev, Duarte, CA USA. [Hematti, Peiman; Hei, Derek] Univ Wisconsin, Waisman BioMfg, Madison, WI USA. [Gee, Adrian P.; Rooney, Cliona] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Silberstein, Leslie; Armant, Myriam] Boston Childrens Hosp, Ctr Human Cell Therapy, Boston, MA USA. [Wagner, John E.; McKenna, David H., Jr.] Univ Minnesota, Minneapolis, MN USA. [Mondoro, Traci Heath; Welniak, Lisbeth] NHLBI, Bethesda, MD 20892 USA. RP Wood, D (reprint author), EMMES Corp, Rockville, MD 20850 USA. EM dwood@emmes.com FU NHLBI NIH HHS [HHSN268201000009C, HHSN268201000006C, HHSN268201000007C, HHSN268201000011C, HHSN268201000008C, HHSN268201000010C]; PHS HHS [HHSN268201000011C, HHSN268201000006C, HHSN268201000008C, HHSN268201000009C, HHSN268201000010C, HHSN268201000007C] NR 52 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1752-8054 EI 1752-8062 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD APR PY 2014 VL 7 IS 2 BP 93 EP 99 DI 10.1111/cts.12148 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AF9UJ UT WOS:000335059900007 PM 24655892 ER PT J AU Ciencewicki, JM Wang, XT Marzec, J Serra, ME Bell, DA Polack, FP Kleeberger, SR AF Ciencewicki, Jonathan M. Wang, Xuting Marzec, Jacqui Elina Serra, M. Bell, Douglas A. Polack, Fernando P. Kleeberger, Steven R. TI A genetic model of differential susceptibility to human respiratory syncytial virus (RSV) infection SO FASEB JOURNAL LA English DT Article DE gene expression; infant lung disease; bronchiolitis; lymphoblastoid cell lines; MX1; HapMap ID HUMAN MXA PROTEIN; INFLUENZA-VIRUS; LYMPHOBLASTOID-CELLS; EPITHELIAL-CELLS; DISEASE SEVERITY; EXPRESSION; RESISTANCE; INTERFERON; MICE; POLYMORPHISMS AB Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract infection during childhood and causes severe symptoms in some patients, which may cause hospitalization and death. Mechanisms for differential responses to RSV are unknown. Our objective was to develop an in vitro model of RSV infection to evaluate interindividual variation in response to RSV and identify susceptibility genes. Populations of human-derived HapMap lymphoblastoid cell lines (LCLs) were infected with RSV. Compared with controls, RSV-G mRNA expression varied from similar to 1- to 400-fold between LCLs. Basal expression of a number of gene transcripts, including myxovirus (influenza virus) resistance 1 (MX1), significantly correlated with RSV-G expression in HapMap LCLs. Individuals in a case-control population of RSV-infected children who were homozygous (n=94) or heterozygous (n=172) for the predicted deleterious A allele in a missense G/A SNP in MX1 had significantly greater risk for developing severe RSV disease relative to those with the major allele (n=108) (chi(2)=5.305, P=0.021; OR: 1.750, 95% CI: 1.110, 2.758, P=0.021). We conclude that genetically diverse human LCLs enable identification of susceptibility genes (e.g., MX1) for RSV disease severity in children, providing insight for disease risk.-Ciencewicki, J. M., Wang, X., Marzec, J., Serra, M. E., Bell, D. A., Polack, F. P., Kleeberger, S. R. A genetic model of differential susceptibility to human respiratory syncytial virus (RSV) infection. C1 [Ciencewicki, Jonathan M.; Wang, Xuting; Marzec, Jacqui; Bell, Douglas A.; Kleeberger, Steven R.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Elina Serra, M.; Polack, Fernando P.] Fdn INFANT, Buenos Aires, DF, Argentina. [Polack, Fernando P.] Vanderbilt Univ, Dept Pediat, Nashville, TN USA. RP Ciencewicki, JM (reprint author), NIEHS, Lab Resp Biol, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA. EM ciencewickij@niehs.nih.gov OI Wang, Xuting/0000-0001-6781-8008 FU Director's Challenge Program; National Institutes of Health, National Institute of Environmental Health Sciences, U.S. Department of Health and Human Services FX This research was supported (in part) by a Director's Challenge Program and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences, U.S. Department of Health and Human Services. The authors thank Dr. Patricio Acosta for all of his work to obtain the second population of RSV-infected children and his genotyping analyses. The authors also thank Dr. Michael Fessler and Dr. Donald Cook for thoughtful comments on the manuscript. NR 52 TC 7 Z9 7 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 4 BP 1947 EP 1956 DI 10.1096/fj.13-239855 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AG3UC UT WOS:000335344300038 PM 24421397 ER PT J AU Cimino, JJ Frisse, ME Halamka, J Sweeney, L Yasnoff, W AF Cimino, James J. Frisse, Mark E. Halamka, John Sweeney, Latanya Yasnoff, William TI Consumer-mediated health information exchanges: The 2012 ACMI debate SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Health information exchange; Personal health record AB The American College of Medical Informatics (ACMI) sponsors periodic debates during the American Medical Informatics Fall Symposium to highlight important informatics issues of broad interest. In 2012, a panel debated the following topic: "Resolved: Health Information Exchange Organizations Should Shift Their Principal Focus to Consumer-Mediated Exchange in Order to Facilitate the Rapid Development of Effective, Scalable, and Sustainable Health Information Infrastructure." Those supporting the proposition emphasized the need for consumer-controlled community repositories of electronic health records (health record banks) to address privacy, stakeholder cooperation, scalability, and sustainability. Those opposing the proposition emphasized that the current healthcare environment is so complex that development of consumer control will take time and that even then, consumers may not be able to mediate their information effectively. While privately each discussant recognizes that there are many sides to this complex issue, each followed the debater's tradition of taking an extreme position in order emphasize some of the polarizing aspects in the short time allotted them. In preparing this summary, we sought to convey the substance and spirit of the debate in printed form. Transcripts of the actual debate were edited for clarity, and appropriate supporting citations were added for the further edification of the reader. Published by Elsevier Inc. C1 [Cimino, James J.] NIH, Ctr Clin, Lab Informat Dev, Bethesda, MD 20892 USA. [Frisse, Mark E.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37235 USA. [Halamka, John] Beth Israel Deaconess Med Ctr, Dept Informat Syst, Boston, MA 02215 USA. [Sweeney, Latanya] Harvard Univ, Cambridge, MA 02138 USA. [Yasnoff, William] Natl Hlth Informat Infrastruct Advisors, Arlington, VA USA. RP Cimino, JJ (reprint author), NIH, Ctr Clin, Lab Informat Dev, Bethesda, MD 20892 USA. EM ciminoj@mail.nih.gov RI Frisse, Mark/B-3824-2016; OI Frisse, Mark/0000-0003-0382-6222; Cimino, James/0000-0003-4101-1622 FU NIH Clinical Center; National Library of Medicine FX The authors thank Dr. Ted Shortliffe for developing the concept for this debate, securing an excellent panel of debaters, and helping to edit the transcript. Dr. Cimino is supported in part by intramural research funds from the NIH Clinical Center and the National Library of Medicine. NR 13 TC 1 Z9 1 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD APR PY 2014 VL 48 BP 5 EP 15 DI 10.1016/j.jbi.2014.02.009 PG 11 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA AG4ZP UT WOS:000335429200002 PM 24561078 ER PT J AU Millum, J Sina, B AF Millum, Joseph Sina, Barbara TI INTRODUCTION: INTERNATIONAL RESEARCH ETHICS EDUCATION SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Editorial Material DE research ethics; education; Fogarty International Center AB NIH's FOGARTY INTERNATIONAL Center has provided grants for the development of training programs in international research ethics for low- and middle-income (LMIC) professionals since 2000. Drawing on 12 years of research ethics training experience, a group of Fogarty grantees, trainees, and other ethics experts sought to map the current capacity and need for research ethics in LMICs, analyze the lessons learned about teaching bioethics, and chart a way forward for research ethics training in a rapidly changing health research landscape. This collection of papers is the result. C1 [Millum, Joseph] NIH, Bethesda, MD 20892 USA. [Sina, Barbara] NIH, Int Res Eth Educ & Curriculum Dev Program, Div Int Training & Res, Fogarty Int Ctr, Bethesda, MD USA. RP Millum, J (reprint author), NIH, Bethesda, MD 20892 USA. EM joseph.millum@nih.gov; sinab@mail.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 0 TC 3 Z9 3 U1 0 U2 1 PU UNIV CALIFORNIA PRESS PI OAKLAND PA 155 GRAND AVE, SUITE 400, OAKLAND, CA 94612-3758 USA SN 1556-2646 EI 1556-2654 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD APR PY 2014 VL 9 IS 2 BP 1 EP 2 DI 10.1525/jer.2014.9.2.1 PG 2 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA AG6RN UT WOS:000335546200001 PM 24782067 ER PT J AU Matar, A Garner, S Millum, J Sina, B Silverman, H AF Matar, Amal Garner, Sam Millum, Joseph Sina, Barbara Silverman, Henry TI CURRICULAR ASPECTS OF THE FOGARTY BIOETHICS INTERNATIONAL TRAINING PROGRAMS SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Article DE curriculum; research ethics; National Institutes of Health; low- and middle-income countries ID RESEARCH ETHICS AB THE CURRICULUM DESIGN, FACULTY characteristics, and experience of implementing masters' level international research ethics training programs supported by the Fogarty International Center was investigated. Multiple pedagogical approaches were employed to adapt to the learning needs of the trainees. While no generally agreed set of core competencies exists for advanced research ethics training, more than 75% of the curricula examined included international issues in research ethics, responsible conduct of research, human rights, philosophical foundations of research ethics, and research regulation and ethical review process. Common skills taught included critical thinking, research methodology and statistics, writing, and presentation proficiency. Curricula also addressed the cultural, social, and religious context of the trainees related to research ethics. Programs surveyed noted trainee interest in Western concepts of research ethics and the value of the transnational exchange of ideas. Similar faculty expertise profiles existed in all programs. Approximately 40% of faculty were female. Collaboration between faculty from low- and middle-income countries (LMICs) and high-income countries (HICs) occurred in most programs and at least 50% of HIC faculty had previous LMIC experience. This paper is part of a collection of papers analyzing the Fogarty International Research Ethics Education and Curriculum Development program. C1 [Matar, Amal] Uppsala Univ, Doctoral Bioeth Program, Uppsala, Sweden. [Garner, Sam] Henry M Jackson Fdn, Bethesda, MD USA. [Millum, Joseph] NIH, Bethesda, MD USA. [Sina, Barbara] NIH, Int Res Eth Educ & Curriculum Dev Program, Div Int Training & Res, Fogarty Int Ctr, Bethesda, MD USA. [Silverman, Henry] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Silverman, H (reprint author), Univ Maryland, Sch Med, 110 South Paca St,2nd Floor, Baltimore, MD 21201 USA. EM hsilverm@medicine.umaryland.edu FU Fogarty International Center, National Institutes of Health [R25TW007090]; National Institute of Allergy and Infectious Diseases, National Institutes of Health [HHSN272200800014C] FX The authors thank Mili Ferreira, Jonathan Fix, Elizabeth Heitman, and the program directors of the Fogarty International Center's International Research Ethics Education and Curriculum Development program. This project was supported by the Fogarty International Center, National Institutes of Health, Grant R25TW007090 and National Institute of Allergy and Infectious Diseases, National Institutes of Health, Grant HHSN272200800014C. NR 10 TC 6 Z9 6 U1 2 U2 8 PU UNIV CALIFORNIA PRESS PI OAKLAND PA 155 GRAND AVE, SUITE 400, OAKLAND, CA 94612-3758 USA SN 1556-2646 EI 1556-2654 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD APR PY 2014 VL 9 IS 2 BP 12 EP 23 DI 10.1525/jer.2014.9.2.12 PG 12 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA AG6RN UT WOS:000335546200003 PM 24782069 ER PT J AU Prasanna, A Ahmed, MM Mohiuddin, M Coleman, CN AF Prasanna, Anish Ahmed, Mansoor M. Mohiuddin, Mohammed Coleman, C. Norman TI Exploiting sensitization windows of opportunity in hyper and hypo-fractionated radiation therapy SO JOURNAL OF THORACIC DISEASE LA English DT Review DE Low Doses Fractionated Radiation Therapy (LDFRT); hyper-radiation sensitivity (HRS); induced radiation resistance (IRR); hyperfractionation; chemopotentiation; stereotactic body radiation therapy (SBRT); stereotactic ablative radiosurgery (SARS); stereotactic ablative radiotherapy (SABR); stereotactic radiosurgery (SRS); spatially fractionated GRID radiotherapy (SFGRT); lattice ID STEREOTACTIC ABLATIVE RADIOTHERAPY; LOW-DOSE HYPERSENSITIVITY; SQUAMOUS-CELL CARCINOMA; HUMAN-MALIGNANT GLIOMA; PROSPECTIVE PHASE-II; CLASSICAL RADIOBIOLOGY RESPONSE; NECROSIS-FACTOR-ALPHA; IONIZING-RADIATION; GLIOBLASTOMA-MULTIFORME; GRID RADIATION AB In contrast to the conventional radiotherapy/chemoradiotherapy paradigms used in the treatment of majority of cancer types, this review will describe two areas of radiobiology, hyperfractionated and hypofractionated radiation therapy, for cancer treatment focusing on application of novel concepts underlying these treatment modalities. The initial part of the review discusses the phenomenon of hyper-radiation sensitivity (HRS) at lower doses (0.1 to 0.6 Gy), describing the underlying mechanisms and how this could enhance the effects of chemotherapy, particularly, in hyperfractionated settings. The second part examines the radiobiological/physiological mechanisms underlying the effects of high-dose hypofractionated radiation therapy that can be exploited for tumor cure. These include abscopal/bystander effects, activation of immune system, endothelial cell death and effect of hypoxia with re-oxygenation. These biological properties along with targeted dose delivery and distribution to reduce normal tissue toxicity may make high-dose hypofractionation more effective than conventional radiation therapy for treatment of advanced cancers. The novel radiation physics based methods that take into consideration the tumor volume to be irradiated and normal tissue avoidance/tolerance can further improve treatment outcome and post-treatment quality of life. In conclusion, there is enough evidence to further explore novel avenues to exploit biological mechanisms from hyper-fractionation by enhancing the efficacy of chemotherapy and hypo-fractionated radiation therapy that could enhance tumor control and use imaging and technological advances to reduce toxicity. C1 [Prasanna, Anish; Ahmed, Mansoor M.; Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, NIH, Rockville, MD 20850 USA. [Mohiuddin, Mohammed] King Faisal Specialist Hosp & Res Ctr, Oncol Ctr, Riyadh 11211, Saudi Arabia. RP Ahmed, MM (reprint author), NCI, RDB, RRP, DCTD,NIH, 9609 Med Ctr Dr,Rm 3W224, Rockville, MD 20850 USA. EM ahmedmm@mail.nih.gov NR 101 TC 17 Z9 17 U1 2 U2 11 PU PIONEER BIOSCIENCE PUBL CO PI HONG KONG PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG, 00000, PEOPLES R CHINA SN 2072-1439 EI 2077-6624 J9 J THORAC DIS JI J. Thorac. Dis. PD APR PY 2014 VL 6 IS 4 BP 287 EP 302 DI 10.3978/j.issn.2072-1439.2014.01.14 PG 16 WC Respiratory System SC Respiratory System GA AG8CS UT WOS:000335647000003 PM 24688774 ER PT J AU Fedota, JR Hardee, JE Perez-Edgar, K Thompson, JC AF Fedota, John R. Hardee, Jillian E. Perez-Edgar, Koraly Thompson, James C. TI Representation of response alternatives in human presupplementary motor area: Multi-voxel pattern analysis in a go/no-go task SO NEUROPSYCHOLOGIA LA English DT Article DE preSMA; Response inhibition; Multi-voxel pattern analysis; Cognitive control ID MEDIAL FRONTAL-CORTEX; ANTERIOR CINGULATE CORTEX; TOP-DOWN CONTROL; COGNITIVE CONTROL; FUNCTIONAL CONNECTIVITY; NEURAL BASIS; HUMAN BRAIN; INHIBITION; CONFLICT; FMRI AB A debate exists as to the role of the presupplementary motor area (preSMA) in cognitive control. Recent findings suggest that preSMA plays a central role in conflict resolution and encodes response alternatives as opposed to simply the presence of conflict. Evidence of neuronal heterogeneity within preSMA of non-human primates suggests that univariate analysis of functional MRI data may not provide adequate resolution to fully characterize cognitive control-related responses. Here, multi-voxel pattern analysis (MVPA) is employed to examine the distributed patterns of activity in preSMA associated with both successful go responses and no-go inhibitions. In a go/no-go task, univariate analysis showed undifferentiated activation of preSMA in response to both go and no-go stimuli. However, when an anatomically-defined preSMA ROI was subjected to MVPA, a significant difference in the activation pattern encoded by go as compared to no-go stimuli was observed. These differences in preSMA activation are consistent with the ongoing maintenance and manipulation of stimulus-action C1 [Fedota, John R.; Thompson, James C.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Hardee, Jillian E.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Perez-Edgar, Koraly] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. RP Fedota, JR (reprint author), NIDA IRP, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM john.fedota@nih.gov OI Perez-Edgar, Koraly/0000-0003-4051-9563; Hardee, Jillian/0000-0001-8230-3045 FU NIH [U01 MH074454]; AFOSR/AFRL [FA9550-10-1-0385]; Center of Excellence in Neuroergonomics, Technology, and Cognition (CENTEC) FX This work was completed with the assistance of NIH Grant U01 MH074454 (J.E.H. and K.P-E.), and AFOSR/AFRL Grant FA9550-10-1-0385, the Center of Excellence in Neuroergonomics, Technology, and Cognition (CENTEC) (J.R.F, J.E.H., and J.C.T.). NR 62 TC 0 Z9 0 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD APR PY 2014 VL 56 BP 110 EP 118 DI 10.1016/j.neuropsychologia.2013.12.022 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA AG5VM UT WOS:000335486800013 PM 24440411 ER PT J AU Li, KG Simons-Morton, BG Vaca, FE Hingson, R AF Li, Kaigang Simons-Morton, Bruce G. Vaca, Federico E. Hingson, Ralph TI Association Between Riding With an Impaired Driver and Driving While Impaired SO PEDIATRICS LA English DT Article DE impaired driving; riding with impaired drivers; adolescents; heavy episodic drinking; driving licensure timing ID RISK BEHAVIOR SURVEILLANCE; MOTOR-VEHICLE CRASHES; UNITED-STATES; PARENTING PRACTICES; YOUNG-ADULTS; ALCOHOL-USE; DRINKING; INVOLVEMENT; STUDENTS; PREDICTORS AB OBJECTIVE:To examine the association between driving while alcohol/drug impaired (DWI) and the timing and amount of exposure to others' alcohol/drug-impaired driving (riding while impaired [RWI]) and driving licensure timing among teenage drivers.METHODS:The data were from waves 1, 2, and 3 (W1, W2, and W3, respectively) of the NEXT Generation Study, with longitudinal assessment of a nationally representative sample of 10th graders starting in 2009-2010. Multivariate logistic regression was used for the analyses.RESULTS:Teenagers exposed to RWI at W1 (adjusted odds ratio [AOR] = 21.12, P < .001), W2 (AOR = 19.97, P < .001), and W3 (AOR = 30.52, P < .001) were substantially more likely to DWI compared with those reporting never RWI. Those who reported RWI at 1 wave (AOR = 10.89, P < .001), 2 waves (AOR = 34.34, P < .001), and all 3 waves (AOR = 127.43, P < .001) were more likely to DWI compared with those who never RWI. Teenagers who reported driving licensure at W1 were more likely to DWI compared with those who were licensed at W3 (AOR = 1.83, P < .05).CONCLUSIONS:The experience of riding in a vehicle with an impaired driver increased the likelihood of future DWI among teenagers after licensure. There was a strong, positive dose-response association between RWI and DWI. Early licensure was an independent risk factor for DWI. The findings suggest that RWI and early licensure could be important prevention targets. C1 [Li, Kaigang; Simons-Morton, Bruce G.] NICHD, Hlth Behav Branch, Bethesda, MD 20892 USA. [Vaca, Federico E.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. [Hingson, Ralph] NIAAA, Epidemiol & Prevent Res Div, Bethesda, MD USA. RP Li, KG (reprint author), NICHD, Hlth Behav Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd,7B13B, Bethesda, MD 20892 USA. EM kaigang.li@nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200800009C]; National Heart, Lung, and Blood Institute; National Institute on Alcohol Abuse and Alcoholism; Maternal and Child Health Bureau of the Health Resources and Services Administration; National Institutes of Health (NIH) FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract HHSN267200800009C) and the National Heart, Lung, and Blood Institute, the National Institute on Alcohol Abuse and Alcoholism, and the Maternal and Child Health Bureau of the Health Resources and Services Administration, with supplemental support from the National Institute on Drug Abuse. Funded by the National Institutes of Health (NIH). NR 42 TC 5 Z9 5 U1 2 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD APR PY 2014 VL 133 IS 4 BP 620 EP 626 DI 10.1542/peds.2013-2786 PG 7 WC Pediatrics SC Pediatrics GA AG3TU UT WOS:000335343500008 PM 24639277 ER PT J AU Bukowski, R Hansen, NI Willinger, M Reddy, UM Parker, CB Pinar, H Silver, RM Dudley, DJ Stoll, BJ Saade, GR Koch, MA Hogue, CJR Varner, MW Conway, DL Coustan, D Goldenberg, RL AF Bukowski, Radek Hansen, Nellie I. Willinger, Marian Reddy, Uma M. Parker, Corette B. Pinar, Halit Silver, Robert M. Dudley, Donald J. Stoll, Barbara J. Saade, George R. Koch, Matthew A. Hogue, Carol J. Rowland Varner, Michael W. Conway, Deborah L. Coustan, Donald Goldenberg, Robert L. CA Eunice Kennedy Shriver Natl Inst C TI Fetal Growth and Risk of Stillbirth: A Population-Based Case-Control Study SO PLOS MEDICINE LA English DT Article ID BIRTH-WEIGHT STANDARDS; GESTATIONAL-AGE; STILLBORN FETUSES; HISTOLOGIC EVALUATION; PERINATAL-MORTALITY; DEATH; PREGNANCY; TIME; ASSOCIATION; PREDICTORS AB Editors' Summary Background Pregnancy is usually a happy time, when the parents-to-be anticipate the arrival of a new baby. But, sadly, about 20% of pregnancies end in miscarriage-the early loss of a fetus (developing baby) that is unable to survive independently. Other pregnancies end in stillbirth-fetal death after 20 weeks of pregnancy (in the US; after 24 weeks in the UK). Stillbirths, like miscarriages, are common. In the US, for example, one in every 160 pregnancies ends in stillbirth. How women discover that their unborn baby has died varies. Some women simply know something is wrong and go to hospital to have their fears confirmed. Others find out when a routine check-up detects no fetal heartbeat. Most women give birth naturally after their baby has died, but if the mother's health is at risk, labor may be induced. Common causes of stillbirth include birth defects and infections. Risk factors for stillbirth include being overweight and smoking during pregnancy. Why Was This Study Done? ? Stillbirths are often associated with having a "small for gestational age" (SGA) fetus. Gestation is the period during which a baby develops in its mother's womb. Gestational age is estimated from the date of the woman's last menstrual period and/or from ultrasound scans. An SGA fetus is lighter than expected for its age based on observed distributions (norms) of fetal weights for gestational age. Although stillbirth is clearly associated with impaired fetal growth, the exact relationship between fetal growth and stillbirth remains unclear for two reasons. First, studies investigating this relationship have used gestational age at delivery rather than gestational age at death as an estimate of fetal age, which overestimates the gestational age of stillbirths and leads to errors in estimates of the proportions of SGA and "large for gestational age" (LGA) stillbirths. Second, many characteristics that affect normal fetal growth are also associated with the risk of stillbirth, and this has not been allowed for in previous studies. In this population-based case-control study, the researchers investigate the fetal growth abnormalities associated with stillbirth using a new approach to estimate gestational age and accounting for the effect of characteristics that affect both fetal growth and stillbirth. A population-based case-control study compares the characteristics of patients with a condition in a population with those of unaffected people in the same population. What Did the Researchers Do and Find? ? The researchers investigated all the stillbirths and a sample of live births that occurred over 2.5 years at 59 hospitals in five US regions. They used a formula developed by the Stillbirth Collaborative Research Network to calculate the gestational age at death of the stillbirths. They categorized fetuses as SGA if they had a weight for gestational age within the bottom 10% (below the 10th percentile) of the population and as LGA if they had a weight for gestational age above the 90th percentile at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms of fetal weight for gestational age. Population norms incorporate weights for gestational age from normal pregnancies and from pregnancies complicated by growth abnormalities, whereas the other two norms include weights for gestational age from normal pregnancies only. Having an SGA fetus was associated with a 3- to 4-fold increased risk of stillbirth compared to having a fetus with "appropriate" weight for gestational age based on all three norms. LGA was associated with an increased risk of stillbirth based on the ultrasound and individualized norms but not the population norms. Being more severely SGA or LGA (below the 5th percentile or above the 95th percentile) was associated with an increased risk of stillbirth. What Do These Findings Mean? ? These findings indicate that, when the time of death is accounted for and norms for weight for gestational age only from uncomplicated pregnancies are used, stillbirth is associated with both restricted and excessive fetal growth. Overall, abnormal fetal growth was identified in 25% of stillbirths using population norms and in about 50% of stillbirths using ultrasound or individualized norms. Although the accuracy of these findings is likely to be affected by aspects of the study design, these findings suggest that, contrary to current practices, strategies designed to prevent stillbirth should focus on identifying both severely SGA and severely LGA fetuses and should use norms for the calculation of weight for gestational age based on normal pregnancies only. Such an approach has the potential to identify almost half of the pregnancies likely to result in stillbirth. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001633. The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on stillbirth Tommy's, a UK nonprofit organization that funds research into stillbirth, premature birth, and miscarriage and provides information for parents-to-be, also provides information on stillbirth (including personal stories) The UK National Health Service Choices website provides information about stillbirth (including a video about dealing with grief after a stillbirth) MedlinePlus provides links to other resources about stillbirth (in English and Spanish) Information about the Stillbirth Collaborative Research Network is available Background Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth. Methods and Findings We conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings. Conclusions Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies. Please see later in the article for the Editors' Summary C1 [Bukowski, Radek; Saade, George R.] Univ Texas Med Branch, Galveston, TX 77555 USA. [Hansen, Nellie I.; Parker, Corette B.; Koch, Matthew A.] RTI Int, Res Triangle Pk, NC USA. [Willinger, Marian; Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. [Pinar, Halit; Coustan, Donald] Brown Univ, Sch Med, Providence, RI 02912 USA. [Silver, Robert M.; Varner, Michael W.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Silver, Robert M.; Varner, Michael W.] Intermt Hlth Care, Salt Lake City, UT USA. [Dudley, Donald J.; Conway, Deborah L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Stoll, Barbara J.] Emory Univ, Sch Med, Atlanta, GA USA. [Stoll, Barbara J.] Childrens Healthcare Atlanta, Atlanta, GA USA. [Hogue, Carol J. Rowland] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Goldenberg, Robert L.] Columbia Univ, Med Ctr, New York, NY USA. RP Bukowski, R (reprint author), Univ Texas Med Branch, Galveston, TX 77555 USA. EM rkbukows@utmb.edu RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development: Brown University, Rhode Island [U10-HD045953]; Eunice Kennedy Shriver National Institute of Child Health and Human Development: Emory University, Georgia [U10-HD045925]; Eunice Kennedy Shriver National Institute of Child Health and Human Development: University of Texas Medical Branch at Galveston, Texas [U10-HD045952]; Eunice Kennedy Shriver National Institute of Child Health and Human Development: University of Texas Health Sciences Center at San Antonio, Texas [U10-HDO45955]; Eunice Kennedy Shriver National Institute of Child Health and Human Development: University of Utah Health Sciences Center, Utah [U10-HD045944]; Eunice Kennedy Shriver National Institute of Child Health and Human Development: RTI International, RTP [U01-HD045954] FX This work, including the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review and approval of the manuscript, was supported by grant funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10-HD045953 Brown University, Rhode Island; U10-HD045925 Emory University, Georgia; U10-HD045952 University of Texas Medical Branch at Galveston, Texas; U10-HDO45955 University of Texas Health Sciences Center at San Antonio, Texas; U10-HD045944 University of Utah Health Sciences Center, Utah; and U01-HD045954 RTI International, RTP. Program officers from the funding agency (UMR and MW) were members of the Steering Committee of the study, and contributed to the study design, management, interpretation of the data, as well as preparation, review and approval of the manuscript. NR 42 TC 22 Z9 22 U1 1 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD APR PY 2014 VL 11 IS 4 DI 10.1371/journal.pmed.1001633 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA AG5NN UT WOS:000335465800003 ER PT J AU Mofenson, LM Watts, DH AF Mofenson, Lynne M. Watts, D. Heather TI Safety of Pediatric HIV Elimination: The Growing Population of HIV- and Antiretroviral-Exposed but Uninfected Infants SO PLOS MEDICINE LA English DT Editorial Material ID INFECTED WOMEN; BIRTH-DEFECTS; TRANSMISSION; PREGNANCY; BORN AB Lynne Mofenson and Heather Watts discuss the context and implications of the study by J. Sibuide and colleagues, which provides a detailed analysis of birth defects in infants with in utero antiretroviral drug exposure in the French Perinatal Cohort. Please see later in the article for the Editors' Summary C1 [Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Watts, D. Heather] US Dept State, Off Global AIDS Coordinator, Washington, DC 20520 USA. RP Mofenson, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. EM LM65D@nih.gov NR 14 TC 9 Z9 9 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD APR PY 2014 VL 11 IS 4 DI 10.1371/journal.pmed.1001636 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AG5NN UT WOS:000335465800004 ER PT J AU Voronin, Y Mofenson, LM Cunningham, CK Fowler, MG Kaleebu, P McFarland, EJ Safrit, JT Graham, BS Snow, W AF Voronin, Yegor Mofenson, Lynne M. Cunningham, Coleen K. Fowler, Mary G. Kaleebu, Pontiano McFarland, Elizabeth J. Safrit, Jeffrey T. Graham, Barney S. Snow, William TI HIV Monoclonal Antibodies: A New Opportunity to Further Reduce Mother-to-Child HIV Transmission SO PLOS MEDICINE LA English DT Article ID GP120 ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; POTENT NEUTRALIZATION; ANTIRETROVIRAL DRUGS; IN-VIVO; PREVENTION; BROAD; ZIDOVUDINE; INFECTION; PREGNANCY AB Yegor Voronin and colleagues explore how monoclonal antibodies against HIV could provide a new opportunity to further reduce mother-to-child transmission of HIV and propose that new interventions should consider issues related to implementation, feasibility, and access. Please see later in the article for the Editors' Summary C1 [Voronin, Yegor; Snow, William] Global HIV Vaccine Enterprise, New York, NY 10004 USA. [Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA. [Cunningham, Coleen K.] Duke Univ, Med Ctr, Durham, NC USA. [Fowler, Mary G.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kaleebu, Pontiano] MRC, Uganda Virus Res Inst, Uganda Res Unit AIDS, Entebbe, Uganda. [McFarland, Elizabeth J.] Univ Colorado, Sch Med, Denver, CO USA. [Safrit, Jeffrey T.] Elizabeth Glaser Pediat AIDS Fdn, Los Angeles, CA USA. [Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Voronin, Y (reprint author), Global HIV Vaccine Enterprise, New York, NY 10004 USA. EM yvoronin@vaccineenterprise.org FU Bill & Melinda Gates Foundation; National Institute of Allergy and Infectious Diseases, NIH, USA; Duke CFAR [5P30 AI064518-09] FX The work was supported by the Bill & Melinda Gates Foundation and by the National Institute of Allergy and Infectious Diseases, NIH, USA. CKC's contribution was supported, in part, by the Duke CFAR (5P30 AI064518-09). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 14 Z9 14 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD APR PY 2014 VL 11 IS 4 DI 10.1371/journal.pmed.1001616 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AG5NN UT WOS:000335465800006 ER PT J AU Zheng, W McLerran, DF Rolland, BA Fu, ZM Boffetta, P He, J Gupta, PC Ramadas, K Tsugane, S Irie, F Tamakoshi, A Gao, YT Koh, WP Shu, XO Ozasa, K Nishino, Y Tsuji, I Tanaka, H Chen, CJ Yuan, JM Ahn, YO Yoo, KY Ahsan, H Pan, WH Qiao, YL Gu, DF Pednekar, MS Sauvaget, C Sawada, N Sairenchi, T Yang, G Wang, RW Xiang, YB Ohishi, W Kakizaki, M Watanabe, T Oze, I You, SL Sugawara, Y Butler, LM Kim, DH Park, SK Parvez, F Chuang, SY Fan, JH Shen, CY Chen, Y Grant, EJ Lee, JE Sinha, R Matsuo, K Thornquist, M Inoue, M Feng, ZD Kang, D Potter, JD AF Zheng, Wei McLerran, Dale F. Rolland, Betsy A. Fu, Zhenming Boffetta, Paolo He, Jiang Gupta, Prakash Chandra Ramadas, Kunnambath Tsugane, Shoichiro Irie, Fujiko Tamakoshi, Akiko Gao, Yu-Tang Koh, Woon-Puay Shu, Xiao-Ou Ozasa, Kotaro Nishino, Yoshikazu Tsuji, Ichiro Tanaka, Hideo Chen, Chien-Jen Yuan, Jian-Min Ahn, Yoon-Ok Yoo, Keun-Young Ahsan, Habibul Pan, Wen-Harn Qiao, You-Lin Gu, Dongfeng Pednekar, Mangesh Suryakant Sauvaget, Catherine Sawada, Norie Sairenchi, Toshimi Yang, Gong Wang, Renwei Xiang, Yong-Bing Ohishi, Waka Kakizaki, Masako Watanabe, Takashi Oze, Isao You, San-Lin Sugawara, Yumi Butler, Lesley M. Kim, Dong-Hyun Park, Sue K. Parvez, Faruque Chuang, Shao-Yuan Fan, Jin-Hu Shen, Chen-Yang Chen, Yu Grant, Eric J. Lee, Jung Eun Sinha, Rashmi Matsuo, Keitaro Thornquist, Mark Inoue, Manami Feng, Ziding Kang, Daehee Potter, John D. TI Burden of Total and Cause-Specific Mortality Related to Tobacco Smoking among Adults Aged >= 45 Years in Asia: A Pooled Analysis of 21 Cohorts SO PLOS MEDICINE LA English DT Article ID BODY-MASS INDEX; CIGARETTE-SMOKING; GLOBAL MORTALITY; UNITED-STATES; COUNTRIES; DISEASE; DEATHS; CHINA; METAANALYSIS; HAZARDS AB Background Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest. Methods and Findings We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged >= 45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan-accounting for similar to 71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37-1.51) and 1.48-fold (1.38-1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%-17.2%) and 3.3% (2.6%-4.0%) of deaths, respectively, in men and women aged >= 45 y in the seven countries/regions combined, with a total number of estimated deaths of similar to 1,575,500 (95% CI = 1,398,000-1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged >= 45 y. Conclusions Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged >= 45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented. Please see later in the article for the Editors' Summary Editors' Summary Background Every year, more than 5 million smokers die from tobacco-related diseases. Tobacco smoking is a major risk factor for cardiovascular disease (conditions that affect the heart and the circulation), respiratory disease (conditions that affect breathing), lung cancer, and several other types of cancer. All told, tobacco smoking kills up to half its users. The ongoing global "epidemic" of tobacco smoking and tobacco-related diseases initially affected people living in the US and other Western countries, where the prevalence of smoking (the proportion of the population that smokes) in men began to rise in the early 1900s, peaking in the 1960s. A similar epidemic occurred in women about 40 years later. Smoking-related deaths began to increase in the second half of the 20th century, and by the 1990s, tobacco smoking accounted for a third of all deaths and about half of cancer deaths among men in the US and other Western countries. More recently, increased awareness of the risks of smoking and the introduction of various tobacco control measures has led to a steady decline in tobacco use and in smoking-related diseases in many developed countries. Why Was This Study Done? ? Unfortunately, less well-developed tobacco control programs, inadequate public awareness of smoking risks, and tobacco company marketing have recently led to sharp increases in the prevalence of smoking in many low- and middle-income countries, particularly in Asia. More than 50% of men in many Asian countries are now smokers, about twice the prevalence in many Western countries, and more women in some Asian countries are smoking than previously. More than half of the world's billion smokers now live in Asia. However, little is known about the burden of tobacco-related mortality (deaths) in this region. In this study, the researchers quantify the risk of total and cause-specific mortality associated with tobacco use among adults aged 45 years or older by undertaking a pooled statistical analysis of data collected from 21 Asian cohorts (groups) about their smoking history and health. What Did the Researchers Do and Find? ? For their study, the researchers used data from more than 1 million participants enrolled in studies undertaken in Bangladesh, India, mainland China, Japan, the Republic of Korea, Singapore, and Taiwan (which together account for 71% of Asia's total population). Smoking prevalences among male and female participants were 65.1% and 7.1%, respectively. Compared with never-smokers, ever-smokers had a higher risk of death from any cause in pooled analyses of all the cohorts (adjusted hazard ratios [HRs] of 1.44 and 1.48 for men and women, respectively; an adjusted HR indicates how often an event occurs in one group compared to another group after adjustment for other characteristics that affect an individual's risk of the event). Compared with never smoking, ever smoking was associated with a higher risk of death due to cardiovascular disease, cancer (particularly lung cancer), and respiratory disease among Asian men and among East Asian women. Moreover, the researchers estimate that, in the countries included in this study, tobacco smoking accounted for 15.8% of all deaths among men and 3.3% of deaths among women in 2004-a total of about 1.5 million deaths, which scales up to 2 million deaths for the population of the whole of Asia. Notably, in 2004, tobacco smoking accounted for 60.5% of lung-cancer deaths among Asian men and 16.7% of lung-cancer deaths among East Asian women. What Do These Findings Mean? ? These findings provide strong evidence that tobacco smoking is associated with a substantially raised risk of death among adults aged 45 years or older throughout Asia. The association between smoking and mortality risk in Asia reported here is weaker than that previously reported for Western countries, possibly because widespread tobacco smoking started several decades later in most Asian countries than in Europe and North America and the deleterious effects of smoking take some years to become evident. The researchers note that certain limitations of their analysis are likely to affect the accuracy of its findings. For example, because no data were available to estimate the impact of secondhand smoke, the estimate of deaths attributable to smoking is likely to be an underestimate. However, the finding that nearly 45% of the global deaths from active tobacco smoking occur in Asia highlights the urgent need to implement comprehensive tobacco control programs in Asia to reduce the burden of tobacco-related disease. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001631. The World Health Organization provides information about the dangers of tobacco (in several languages) and about the WHO Framework Convention on Tobacco Control, an international instrument for tobacco control that came into force in February 2005 and requires parties to implement a set of core tobacco control provisions including legislation to ban tobacco advertising and to increase tobacco taxes; its 2013 report on the global tobacco epidemic is available The US Centers for Disease Control and Prevention provides detailed information about all aspects of smoking and tobacco use The UK National Health Services Choices website provides information about the health risks associated with smoking MedlinePlus has links to further information about the dangers of smoking (in English and Spanish) SmokeFree, a website provided by the UK National Health Service, offers advice on quitting smoking and includes personal stories from people who have stopped smoking Smokefree. gov, from the US National Cancer Institute, offers online tools and resources to help people quit smoking C1 [Zheng, Wei; Fu, Zhenming; Shu, Xiao-Ou; Yang, Gong] Vanderbilt Univ, Dept Med, Div Epidemiol, Nashville, TN 37235 USA. [Zheng, Wei; Fu, Zhenming; Shu, Xiao-Ou; Yang, Gong] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Nashville, TN 37235 USA. [Zheng, Wei; Fu, Zhenming; Shu, Xiao-Ou; Yang, Gong] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA. [McLerran, Dale F.; Rolland, Betsy A.; Thornquist, Mark; Potter, John D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Fu, Zhenming] Wuhan Univ, Dept Radiat & Med Oncol, Zhongnan Hosp, Wuhan 430072, Peoples R China. [Boffetta, Paolo] Ichan Sch Med Mt Sinai, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Gupta, Prakash Chandra; Pednekar, Mangesh Suryakant] Healis Sekhsaria Inst Publ Hlth, Navi Mumbai, India. [Ramadas, Kunnambath] Reg Canc Ctr, Div Radiat Oncol, Trivandrum 695011, Kerala, India. [Tsugane, Shoichiro; Sawada, Norie] Natl Canc Ctr, Epidemiol & Prevent Div, Res Ctr Canc Prevent & Screening, Tokyo 104, Japan. [Irie, Fujiko] Ibaraki Prefectural Govt, Dept Hlth & Social Serv, Ibaraki, Japan. [Tamakoshi, Akiko] Aichi Med Univ, Dept Publ Hlth, Sch Med, Nagakute, Aichi, Japan. [Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Koh, Woon-Puay] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. [Koh, Woon-Puay] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Ozasa, Kotaro; Ohishi, Waka; Grant, Eric J.] Radiat Effects Res Fdn, Hiroshima, Japan. [Nishino, Yoshikazu] Miyagi Canc Ctr, Res Inst, Div Epidemiol, Natori, Miyagi, Japan. [Tsuji, Ichiro; Kakizaki, Masako; Watanabe, Takashi; Sugawara, Yumi] Tohoku Univ, Grad Sch Med, Sendai, Miyagi 980, Japan. [Tanaka, Hideo; Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan. [Chen, Chien-Jen; You, San-Lin] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan. [Chen, Chien-Jen; Pan, Wen-Harn] Natl Taiwan Univ, Grad Inst Epidemiol, Coll Publ Hlth, Taipei 10764, Taiwan. [Yuan, Jian-Min; Wang, Renwei; Butler, Lesley M.] Univ Pittsburgh, Div Canc Control & Populat Sci, Inst Canc, Pittsburgh, PA USA. [Yuan, Jian-Min; Wang, Renwei; Butler, Lesley M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Ahn, Yoon-Ok; Yoo, Keun-Young; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Ahsan, Habibul] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Ahsan, Habibul] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Ahsan, Habibul] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Ahsan, Habibul] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. [Pan, Wen-Harn] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. [Pan, Wen-Harn] Natl Taiwan Univ, Dept Biochem Sci & Technol, Taipei 10764, Taiwan. [Qiao, You-Lin; Fan, Jin-Hu] Chinese Acad Med Sci, Dept Canc Epidemiol, Canc Inst Hosp, Beijing 100730, Peoples R China. [Gu, Dongfeng] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100730, Peoples R China. [Gu, Dongfeng] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100730, Peoples R China. [Gu, Dongfeng] China Natl Ctr Cardiovasc Dis, Beijing, Peoples R China. [Sauvaget, Catherine] Int Agcy Res Canc, Screening Grp, Prevent & Early Detect Sect, F-69372 Lyon, France. [Sairenchi, Toshimi] Dokkyo Med Univ, Sch Med, Dept Publ Hlth, Mibu, Tochigi, Japan. [Oze, Isao] Nagoya City Univ, Dept Med Oncol & Immunol, Grad Sch Med Sci, Nagoya, Aichi, Japan. [Kim, Dong-Hyun] Hallym Univ, Coll Med, Dept Social & Prevent Med, Okcheon Dong, South Korea. [Park, Sue K.] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Parvez, Faruque] Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA. [Chuang, Shao-Yuan] Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Prevent Med & Hlth Serv Res, Miaoli, Taiwan. [Shen, Chen-Yang] Acad Sinica, Taiwan Biobank, Inst Biomed Sci, Taipei 115, Taiwan. [Shen, Chen-Yang] China Med Univ, Grad Inst Environm Sci, Taichung, Taiwan. [Chen, Yu; Thornquist, Mark] NYU, Sch Med, Dept Environm Med, New York, NY USA. [Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea. [Sinha, Rashmi] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. [Inoue, Manami] Univ Tokyo, Grad Sch Med, Tokyo, Japan. [Inoue, Manami] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Tokyo 104, Japan. [Feng, Ziding] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. RP Zheng, W (reprint author), Vanderbilt Univ, Dept Med, Div Epidemiol, Nashville, TN 37235 USA. EM wei.zheng@vanderbilt.edu RI Chuang, Shao-Yuan/B-3478-2011; Qiao, You-Lin/B-4139-2012; Tsugane, Shocichiro/A-2424-2015; Chen, Chien-Jen/C-6976-2008; Tanaka, Hideo/A-8145-2016; OI Qiao, You-Lin/0000-0001-6380-0871; Matsuo, Keitaro/0000-0003-1761-6314; Potter, John/0000-0001-5439-1500; Kakizaki, Masako/0000-0001-6030-8953; Yuan, Jian-Min/0000-0002-4620-3108; Sauvaget, Catherine/0000-0002-8053-4963 FU Mumbai Cohort Study (Mumbai); International Agency for Research on Cancer, Clinical Trials Service Unit/Oxford University, World Health Organization; Association for International Cancer Research, St Andrews, UK; Cancer Research UK; NIH [P42ES010349, R01CA102484, R01CA107431, R01CA0403092, R01CA144034, R01-CA82729, R37-CA70867, R01CA55069, R35CA53890, R01CA80205]; American Heart Association [9750612N]; NHLBI [U01-HL072507]; Chinese Academy of Medical Sciences; National Science Council and Department of Health, Taiwan; Department of Health, Taiwan [DOH80-27, DOH81-021, DOH8202-1027, DOH83-TD-015, DOH84-TD-006]; Ministry of Education, Science and Technology, Korea [2009-0087452]; National Research Foundation of Korea [2009-0087452]; Japanese Ministry of Health, Labour and Welfare (MHLW); U.S. Department of Energy (DOE); DOE [DE-HS0000031]; RERF Research Protocol [RP-A03-10]; Ministry of Health, Labour and Welfare, Japan; Ministry of Education, Culture, Sports, Science and Technology, Japan; National Cancer Center Research and Development Fund FX Participating cohort studies (funding sources) in the consortium are: Mumbai Cohort Study (Mumbai, funding sources: International Agency for Research on Cancer, Clinical Trials Service Unit/Oxford University, World Health Organization); Trivandrum Oral Cancer Screening (TOCS) Trial (funding sources: Association for International Cancer Research, St Andrews, UK; and Cancer Research UK); Health Effects of Arsenic Longitudinal Study [Bangladesh, funding sources: NIH (P42ES010349, R01CA102484, R01CA107431)]; China National Hypertension Survey Epidemiology Follow-up Study [CHEFS, funding sources: American Heart Association (9750612N), NHLBI (U01-HL072507), Chinese Academy of Medical Sciences]; Shanghai Cohort Study [SCS, funding sources: NIH (R01CA0403092, R01CA144034)]; Shanghai Men's Health Study [SMHS, funding sources: NIH (R01-CA82729)]; Shanghai Women's Health Study [SWHS, funding sources: NIH (R37-CA70867)]; Community-Based Cancer Screening Project [CBCSP, funding sources: National Science Council and Department of Health, Taiwan]; CardioVascular Disease risk FACtor Two-township Study [CVDFACTS, funding sources: Department of Health, Taiwan (DOH80-27, DOH81-021, DOH8202-1027, DOH83-TD-015, and DOH84-TD-006)]; Singapore Chinese Health Study [SCHS, funding sources: NIH (R01CA55069, R35CA53890, R01CA80205, R01CA144034)]; and Korea Multi-center Cancer Cohort [KMCC, funding sources: Ministry of Education, Science and Technology, Korea (2009-0087452), National Research Foundation of Korea (2009-0087452)]. The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan is a private, nonprofit foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the U.S. Department of Energy (DOE), the latter in part through DOE Award DE-HS0000031 to the National Academy of Sciences. This publication was supported by RERF Research Protocol RP-A03-10. Other Japanese cohorts: Three Prefecture Cohort Study Aichi (3-Prefecture Aichi); Ibaraki Prefectural Health Study (JACC); Japan Public Health Center-based Prospective Study (JPHC1, JPHC2); Three Prefecture Cohort Study Miyagi (3-Prefecture Miyagi); Miyagi Cohort Study (Miyagi); and Ohsaki National Health Insurance Cohort Study (Ohsaki), are supported by the Grantin-aid for Cancer Research, the Grant for the Third Term Comprehensive Control Research for Cancer, the Grant for Health Services, the Grant for Medical Services for Aged and Health Promotion, the Grant for Comprehensive Research on Cardiovascular and Life-style Related Diseases from the Ministry of Health, Labour and Welfare, Japan, and the Grant for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan. Japan Public Health Center-Based Prospective Study is also supported by the National Cancer Center Research and Development Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 24 Z9 24 U1 2 U2 28 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD APR PY 2014 VL 11 IS 4 DI 10.1371/journal.pmed.1001631 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA AG5NN UT WOS:000335465800016 ER PT J AU Lu, JH Marjon, KD Mold, C Marnell, L Du Clos, TW Sun, P AF Lu, Jinghua Marjon, Kristopher D. Mold, Carolyn Marnell, Lorraine Du Clos, Terry W. Sun, Peter TI Pentraxins and IgA share a binding hot-spot on Fc alpha RI SO PROTEIN SCIENCE LA English DT Article DE surface plasmon resonance; site-directed mutagenesis; competition ID C-REACTIVE PROTEIN; AMYLOID-P-COMPONENT; GAMMA RECEPTOR; SERUM; COMPLEXES; CHROMATIN; HISTONES; POLYSACCHARIDE; RECOGNITION; RESIDUES AB The pentraxins, C-reactive protein (CRP), and serum amyloid P component (SAP) have previously been shown to function as innate opsonins through interactions with Fc receptors. The molecular details of these interactions were elucidated by the crystal structure of SAP in complex with FcRIIA. More recently, pentraxins were shown to bind and activate FcRI (CD89), the receptor for IgA. Here, we used mutations of the receptor based on a docking model to further examine pentraxin recognition by FcRI. The solution binding of pentraxins to six FcRI alanine cluster mutants revealed that mutations Y35A and R82A, on the C-and F-strands of the D1 domain, respectively, markedly reduced receptor binding to CRP and SAP. These residues are in the IgA-binding site of the receptor, and thus, significantly affected receptor binding to IgA. The shared pentraxin and IgA-binding site on FcRI is further supported by the results of a solution binding competition assay. In addition to the IgA-binding site, pentraxins appear to interact with a broader region of the receptor as the mutation in the C-strand (R48A/E49A) enhanced pentraxin binding. Unlike Fc receptors, the H129A/I130A and R178A mutations on the BC- and FG-loops of D2 domain, respectively, had little effect on FcRI binding to the pentraxins. In conclusion, our data suggest that the pentraxins recognize a similar site on FcRI as IgA. C1 [Lu, Jinghua; Sun, Peter] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Marjon, Kristopher D.; Mold, Carolyn; Marnell, Lorraine; Du Clos, Terry W.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Marjon, Kristopher D.; Mold, Carolyn; Marnell, Lorraine] Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Du Clos, Terry W.] VA Med Ctr, Dept Med, Albuquerque, NM 87108 USA. RP Sun, P (reprint author), 12441 Parklawn Dr, Rockville, MD 20852 USA. EM psun@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases; National Research Service [F31AI080178]; National Institutes of Health [R21AI085414]; Department of Veterans Affairs Merit Review Award FX Grant sponsors: Division of Intramural Research, National Institute of Allergy and Infectious Diseases; National Research Service Award F31AI080178 (K. D. M.); National Institutes of Health Grant R21AI085414; Department of Veterans Affairs Merit Review Award. NR 31 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD APR PY 2014 VL 23 IS 4 BP 378 EP 386 DI 10.1002/pro.2419 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AD3MM UT WOS:000333143800005 PM 24407959 ER PT J AU Terracciano, A Strait, J Scuteri, A Meirelles, O Sutin, AR Tarasov, K Ding, J Marongiu, M Orru, M Pilia, MG Cucca, F Lakatta, E Schlessinger, D AF Terracciano, Antonio Strait, James Scuteri, Angelo Meirelles, Osorio Sutin, Angelina R. Tarasov, Kirill Ding, Jun Marongiu, Michele Orru, Marco Pilia, Maria Grazia Cucca, Francesco Lakatta, Edward Schlessinger, David TI Personality Traits and Circadian Blood Pressure Patterns: A 7-Year Prospective Study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE ambulatory blood pressure monitoring; circadian rhythm; dipping; impulsivity; conscientiousness; trust; personality; systolic blood pressure; cardiovascular ID CORONARY-HEART-DISEASE; 5-FACTOR MODEL; BIG 5; CONSCIENTIOUSNESS; MORTALITY; PREDICTORS; WOMEN; METAANALYSIS; ADHERENCE; EVENTS AB Objective: A nighttime dip in blood pressure is associated with decreased risk of cardiovascular morbidity and mortality. We examined whether personality traits predict nighttime dipping blood pressure. Methods: A community-based sample of 2848 adults from Sardinia (Italy) completed the Revised NEO Personality Inventory and 7 years later were examined with 24-hour ambulatory blood pressure monitoring. The primary analyses examined the associations of personality traits with continuous and categorical measures of mean arterial, systolic, and diastolic blood pressure nighttime dipping. Results: Agreeableness and conscientiousness were associated with more nocturnal blood pressure dipping (beta = .05 [p = .025] and beta = .07 [p < .001], respectively) and lower systolic blood pressure at night (beta = -.05 [p = .018] and beta = -.03 [p = .072], respectively). Nondippers were particularly more impulsive (p = .009), less trusting (p = .004), and less self-disciplined (p = .001), but there was no significant association between nocturnal dipping blood pressure and trait anxiety (p = .78) or depression (p = .59). The associations were stronger when comparing extreme dippers (nighttime drop >= 20%) to reverse dippers (nighttime increase in blood pressure). Indeed, scoring 1 standard deviation higher on conscientiousness was associated with approximately 40% reduced risk of reverse dipping (odds ratio = 1.43, confidence interval = 1.08-1.91). Conclusions: We found evidence that reduced nighttime blood pressure dipping is associated with antagonism and impulsivity-related traits but not with measures of emotional vulnerability. The strongest associations were found with conscientiousness, a trait that may have a broad impact on cardiovascular health. C1 [Terracciano, Antonio; Sutin, Angelina R.] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA. [Terracciano, Antonio; Strait, James; Meirelles, Osorio; Sutin, Angelina R.; Tarasov, Kirill; Ding, Jun; Lakatta, Edward; Schlessinger, David] NIA, NIH, Baltimore, MD 21224 USA. [Marongiu, Michele; Pilia, Maria Grazia; Cucca, Francesco] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. [Scuteri, Angelo] Hosp San Raffaele Pisana IRCCS, Rome, Italy. [Orru, Marco] Presidio Osped A Businco, Unita Operativa Complessa Cardiol, Cagliari, Italy. RP Terracciano, A (reprint author), Florida State Univ, Coll Med, Dept Geriatr, 1115 West Call St, Tallahassee, FL 32306 USA. EM antonio.terracciano@med.fsu.edu OI Marongiu, Michele/0000-0002-7289-9815 FU National Institutes of Health, National Institute on Aging FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. The authors have no financial or other conflict of interests to declare. NR 61 TC 3 Z9 3 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP 237 EP 243 DI 10.1097/PSY.0000000000000035 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100579 PM 24608035 ER PT J AU Ali, MK Mwendwa, DT O'Connor, MY Thoreson, CK Ricks, M Sumner, AE AF Ali, Mana K. Mwendwa, Denee T. O'Connor, Michelle Y. Thoreson, Caroline K. Ricks, Madia Sumner, Anne E. TI BEING POSITIVE IN THE OBESITY EPIDEMIC: OPTIMISM IS LINKED TO LOWER BMI IN OVERWEIGHT AND OBESE AFRICAN IMMIGRANTS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Ali, Mana K.] Howard Univ, Washington, DC 20059 USA. [Mwendwa, Denee T.] Univ Delaware, Newark, DE USA. [O'Connor, Michelle Y.; Thoreson, Caroline K.; Ricks, Madia; Sumner, Anne E.] NIDDKD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A73 EP A73 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100303 ER PT J AU Arguelles, W Llabre, MM Schwartz, SJ Penedo, FJ Talavera, GA Aviles-Santa, L Daviglus, ML Espinoza, RA Ostfeld, RJ Gonzalez, HM Rodriguez, CJ Schneiderman, N AF Arguelles, William Llabre, Maria M. Schwartz, Seth J. Penedo, Frank J. Talavera, Gregory A. Aviles-Santa, Larissa Daviglus, Martha L. Espinoza, Rebeca A. Ostfeld, Robert J. Gonzalez, Hector M. Rodriguez, Carlos J. Schneiderman, Neil TI DIFFERENT DOMAINS OF ACCULTURATION AND CULTURAL RETENTION AMONG US HISPANICS/LATINOS IN RELATION TO CARDIOVASCULAR RISK FACTORS: RESULTS FROM THE HISPANIC COMMUNITY HEALTH STUDY/STUDY OF LATINOS (HCHS/SOL) SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Arguelles, William; Llabre, Maria M.; Schwartz, Seth J.; Schneiderman, Neil] Univ Miami, Miami, FL USA. [Penedo, Frank J.] Northwester Univ, Feinberg Sch Med, Chicago, IL USA. [Talavera, Gregory A.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Aviles-Santa, Larissa] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Daviglus, Martha L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gonzalez, Hector M.] Michigan State Univ, E Lansing, MI 48824 USA. [Rodriguez, Carlos J.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A49 EP A49 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100207 ER PT J AU Graham-Engeland, J Slavish, D Munoz, L Song, SM Sliwinski, M AF Graham-Engeland, Jennifer Slavish, Danica Munoz, Liz Song, Sunmi Sliwinski, Martin TI SLEEP QUALITY AND PHYSICAL SYMPTOMATOLOGY AMONG DIVERSE MID-LIFE ADULTS IS PREDICTED BY DEPRESSED MOOD AND PAIN SEVERITY; THE ROLE OF PERCEIVED STRESS, ANXIETY, AND RUMINATION SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Graham-Engeland, Jennifer; Slavish, Danica; Munoz, Liz; Sliwinski, Martin] Penn State Univ, University Pk, PA 16802 USA. [Song, Sunmi] NHGRI, Social & Behav Res Branch, NIH, Bethesda, PA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A83 EP A83 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100347 ER PT J AU Hughes, S Jaremka, LM Alfano, CM Glaser, R Povoski, SP Lipari, AM Agnese, DM Farrar, WB Yee, LD Carson, WE Malarkey, WB Kiecolt-Glaser, JK AF Hughes, Spenser Jaremka, Lisa M. Alfano, Catherine M. Glaser, Ronald Povoski, Stephen P. Lipari, Adele M. Agnese, Doreen M. Farrar, William B. Yee, Lisa D. Carson, William E., III Malarkey, William B. Kiecolt-Glaser, Janice K. TI SOCIAL SUPPORT PREDICTS INFLAMMATION, PAIN, AND DEPRESSIVE SYMPTOMS: LONGITUDINAL RELATIONSHIPS AMONG BREAST CANCER SURVIVORS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Hughes, Spenser; Jaremka, Lisa M.; Glaser, Ronald; Povoski, Stephen P.; Lipari, Adele M.; Agnese, Doreen M.; Farrar, William B.; Yee, Lisa D.; Carson, William E., III; Malarkey, William B.; Kiecolt-Glaser, Janice K.] Ohio State Univ, Inst Behav Med Res, Columbus, OH 43210 USA. [Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. RI Carson, William/E-2846-2011 NR 0 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A46 EP A46 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100194 ER PT J AU Koenig, J Sonntag, D Windham, BG Ferrucci, L Fischer, JE Thayer, J Jarczok, MN AF Koenig, Julian Sonntag, Diana Windham, Beverly G. Ferrucci, Luigi Fischer, Joachim E. Thayer, Julian Jarczok, Marc N. TI ASSOCIATION STRENGTH OF THREE ADIPOSITY MEASURES WITH AUTONOMIC NERVOUS SYSTEM FUNCTION IN APPARENTLY HEALTHY EMPLOYEES SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Koenig, Julian] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Sonntag, Diana; Fischer, Joachim E.; Jarczok, Marc N.] Heidelberg Univ, Mannheim Med Fac, Mannheim Inst Publ Hlth Social & Prevent Med, Mannheim, BW, Germany. [Windham, Beverly G.] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, IRP, Baltimore, MD 21224 USA. [Thayer, Julian] Heidelberg Univ, Dept Psychol, Columbus, OH USA. RI Jarczok, Marc/A-2383-2014 OI Jarczok, Marc/0000-0002-6055-385X NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A24 EP A24 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100100 ER PT J AU Lovallo, WR Enoch, MA Yechiam, E Glahn, DC Acheson, A Sorocco, KH Reynolds, DW Hodgkinson, CA Bojeong, K Cohoon, AJ Vincent, AS Goldman, D AF Lovallo, William R. Enoch, Mary-Anne Yechiam, Eldad Glahn, David C. Acheson, Ashley Sorocco, Kristen H. Reynolds, Donald W. Hodgkinson, Colin A. Bojeong, Kim Cohoon, Andrew J. Vincent, Andrea S. Goldman, David TI DIFFERENTIAL IMPACT OF SEROTONIN TRANSPORTER ACTIVITY ON TEMPERAMENT AND BEHAVIOR IN PERSONS WITH A FAMILY HISTORY OF ALCOHOLISM IN THE OKLAHOMA FAMILY HEALTH PATTERNS PROJECT SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Lovallo, William R.] Unviers Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Lovallo, William R.] VA Med Ctr, Oklahoma City, OK USA. [Enoch, Mary-Anne; Bojeong, Kim; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. [Yechiam, Eldad] Techniol Univ, Haifa, Israel. [Glahn, David C.] Yale Univ, Hartford, CT USA. [Acheson, Ashley] UTHSCSA, San Antonio, TX USA. [Sorocco, Kristen H.] Univ Oklahoma, Hlth Sci Ctr, Donald W Reynolds Dept Geriatr Med, Oklahoma City, OK USA. [Cohoon, Andrew J.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Vincent, Andrea S.] Univ Oklahoma, Cognit Sci Res Ctr, Norman, OK 73019 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A77 EP A77 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100319 ER PT J AU McDonald, PAG Alfano, C Deeks, SG Jeste, DV Wolkowitz, OM Ness, KK Suls, J AF McDonald, Paige A. Green Alfano, Catherine Deeks, Steven G. Jeste, Dilip V. Wolkowitz, Owen M. Ness, Kirsten K. Suls, Jerry TI Aging in the Context of Chronic Disease: Premature, Accelerated, Normal, or Successful? SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [McDonald, Paige A. Green] NCI, Basic Biobehav & Psychol Sci Branch, Rockville, MD USA. [Alfano, Catherine] NCI, Off Canc Survivorship, Rockville, MD USA. [Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Jeste, Dilip V.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Wolkowitz, Owen M.] Univ Calif San Francisco, San Francisco, TN USA. [Ness, Kirsten K.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Suls, Jerry] NCI, Behav Res Program, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A16 EP A16 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100070 ER PT J AU Slavish, DC Graham-Engeland, JE Song, S AF Slavish, Danica C. Graham-Engeland, Jennifer E. Song, Sunmi TI DEPRESSED MOOD MEDIATES THE RELATIONSHIP BETWEEN RUMINATION AND SLEEP QUALITY SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Slavish, Danica C.; Graham-Engeland, Jennifer E.] Penn State Univ, University Pk, PA 16802 USA. [Song, Sunmi] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A119 EP A120 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100497 ER PT J AU Weimer, K Horing, B Colloca, L Gulewitsch, MD Schlarb, AA Sauer, H Enck, P AF Weimer, Katja Horing, Bjoern Colloca, Luana Gulewitsch, Marco D. Schlarb, Angelika A. Sauer, Helene Enck, Paul TI SOCIAL LEARNING OF PLACEBO EFFECTS IN CHILDREN AND THEIR PARENTS - A FEASIBILITY STUDY SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Weimer, Katja; Horing, Bjoern; Sauer, Helene; Enck, Paul] Univ Hosp Tubingen, Tubingen, BW, Germany. [Colloca, Luana] NIMH, Dept Bioeth, Bethesda, MD 20892 USA. [Gulewitsch, Marco D.] Univ Tubingen, Dept Psychol, Tubingen, BW, Germany. [Schlarb, Angelika A.] Univ Luxembourg, Fac Lettres Sci Humaines Arts & Sci Educ, Luxembourg, Luxembourg. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A135 EP A135 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100565 ER PT J AU Bhuvanendran, S Salka, K Rainey, K Sreetama, S Williams, E Leeker, M Prasad, V Boyd, J Patterson, GH Jaiswal, JK Colberg-Poley, AM AF Bhuvanendran, Shivaprasad Salka, Kyle Rainey, Kristin Sreetama, Sen Chandra Williams, Elizabeth Leeker, Margretha Prasad, Vidhya Boyd, Jonathan Patterson, George H. Jaiswal, Jyoti K. Colberg-Poley, Anamaris M. TI Superresolution Imaging of Human Cytomegalovirus vMIA Localization in Sub-Mitochondrial Compartments SO VIRUSES-BASEL LA English DT Article DE superresolution microscopy; mitochondria; MAM; MSIM; PALM; confocal microscopy; matrix; HCMV vMIA; GSTED; OMM ID ENDOPLASMIC-RETICULUM; UL37 PROTEINS; CELL-DEATH; FLUORESCENCE MICROSCOPY; STRUCTURED ILLUMINATION; MAMMALIAN-CELLS; ASSEMBLY SITES; LIVE CELLS; APOPTOSIS; MEMBRANES AB The human cytomegalovirus (HCMV) viral mitochondria-localized inhibitor of apoptosis (vMIA) protein, traffics to mitochondria-associated membranes (MAM), where the endoplasmic reticulum (ER) contacts the outer mitochondrial membrane (OMM). vMIA association with the MAM has not been visualized by imaging. Here, we have visualized this by using a combination of confocal and superresolution imaging. Deconvolution of confocal microscopy images shows vMIA localizes away from mitochondrial matrix at the Mitochondria-ER interface. By gated stimulated emission depletion (GSTED) imaging, we show that along this interface vMIA is distributed in clusters. Through multicolor, multifocal structured illumination microscopy (MSIM), we find vMIA clusters localize away from MitoTracker Red, indicating its OMM localization. GSTED and MSIM imaging show vMIA exists in clusters of ~100-150 nm, which is consistent with the cluster size determined by Photoactivated Localization Microscopy (PALM). With these diverse superresolution approaches, we have imaged the clustered distribution of vMIA at the OMM adjacent to the ER. Our findings directly compare the relative advantages of each of these superresolution imaging modalities for imaging components of the MAM and sub-mitochondrial compartments. These studies establish the ability of superresolution imaging to provide valuable insight into viral protein location, particularly in the sub-mitochondrial compartments, and into their clustered organization. C1 [Bhuvanendran, Shivaprasad; Salka, Kyle; Sreetama, Sen Chandra; Williams, Elizabeth; Leeker, Margretha; Prasad, Vidhya; Jaiswal, Jyoti K.; Colberg-Poley, Anamaris M.] Childrens Natl Hlth Syst, Childrens Res Inst, Med Genet Res Ctr, Washington, DC 20010 USA. [Rainey, Kristin; Patterson, George H.] Natl Inst Biomed Imaging & Bioengn, Sect Biophoton, NIH, Bethesda, MD 20892 USA. [Boyd, Jonathan] Leica Microsyst Inc, Div Life Sci, Buffalo Grove, IL 60089 USA. [Jaiswal, Jyoti K.; Colberg-Poley, Anamaris M.] George Washington Univ, Sch Med, Dept Integrat Syst Biol, Washington, DC 20037 USA. [Colberg-Poley, Anamaris M.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Med, Washington, DC 20037 USA. RP Patterson, GH (reprint author), Natl Inst Biomed Imaging & Bioengn, Sect Biophoton, NIH, Bethesda, MD 20892 USA. EM SBhuvanendran@childrensnational.org; kyle.salka@gmail.com; kristin.rainey@nih.gov; Sreetama.SenChandra@childrensnational.org; elizabeth.anne.williams.umd@gmail.com; maggie.leeker@gmail.com; VPrasad@childrensnational.org; Jonathan.Boyd@Leica-Microsystems.com; pattersg@mail.nih.gov; jkjaiswal@childrensnational.org; acolberg-poley@childrensnational.org RI Jaiswal, Jyoti/M-5891-2013 OI Jaiswal, Jyoti/0000-0002-5992-5185 FU NSF grant [MCB 1244509]; core grant [1P30HD40677]; Intramural Research Program of the National Institutes of Health, National Institute of Biomedical Imaging and Bioengineering FX This work was partially funded by the NSF grant (MCB 1244509) to ACP and JKJ. The confocal microscopy imaging was supported by a core grant (1P30HD40677) to the Children's Intellectual and Developmental Disabilities Research Center. This work was also supported by the Intramural Research Program of the National Institutes of Health including the National Institute of Biomedical Imaging and Bioengineering. NR 74 TC 5 Z9 5 U1 1 U2 14 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD APR PY 2014 VL 6 IS 4 BP 1612 EP 1636 DI 10.3390/v6041612 PG 25 WC Virology SC Virology GA AG9TB UT WOS:000335761600009 PM 24721787 ER PT J AU Vandergaast, R Hoover, LI Zheng, K Fredericksen, BL AF Vandergaast, Rianna Hoover, Lisa I. Zheng, Kang Fredericksen, Brenda L. TI Generation of West Nile Virus Infectious Clones Containing Amino Acid Insertions Between Capsid and Capsid Anchor SO VIRUSES-BASEL LA English DT Article DE infectious clone; West Nile virus; virus replication; WNV; reporter ID SMALL-MOLECULE INHIBITORS; NEW-YORK-CITY; GAUSSIA LUCIFERASE; REPLICON; PROTEIN; TRANSLATION; DISCOVERY; MOSQUITOS; EPIDEMIC; REPORTER AB West Nile virus (WNV) is a positive-sense RNA arbovirus responsible for recent outbreaks of severe neurological disease within the US and Europe. Large-scale analyses of antiviral compounds that inhibit virus replication have been limited due to the lack of an adequate WN reporter virus. Previous attempts to insert a reporter into the 3' untranslated region of WNV generated unstable viruses, suggesting that this region does not accommodate additional nucleotides. Here, we engineered two WNV infectious clones containing insertions at the Capsid (C)/Capsid Anchor (CA) junction of the viral polyprotein. Recombinant viruses containing a TAT(1-67) or Gaussia Luciferase (GLuc) gene at this location were successfully recovered. However, rapid loss of most, if not all, of the reporter sequence occurred for both viruses, indicating that the reporter viruses were not stable. While the GLuc viruses predominantly reverted back to wild-type WNV length, the TAT viruses retained up to 75 additional nucleotides of the reporter sequence. These additional nucleotides were stable over at least five passages and did not significantly alter WNV fitness. Thus, the C/CA junction of WNV can tolerate additional nucleotides, though insertions are subject to certain constraints. C1 Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA. Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Fredericksen, BL (reprint author), NIAID, Aids Review Branch, NIH, DHHS, Bethesda, MD 20817 USA. EM rvanderg@umd.edu; linjaian@umd.edu; kzheng@umd.edu; brenda.fredericksen@nih.gov FU National Institutes of Health [AI083397] FX We would like to thank Michael Gale for the kind gift of the WNV-TX infectious clone. This work was supported by a grant from the National Institutes of Health to B.L.F. (AI083397). NR 29 TC 7 Z9 7 U1 0 U2 7 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD APR PY 2014 VL 6 IS 4 BP 1637 EP 1653 DI 10.3390/v6041637 PG 17 WC Virology SC Virology GA AG9TB UT WOS:000335761600010 PM 24721788 ER PT J AU Lin, LS Cong, ZX Cao, JB Ke, KM Peng, QL Gao, JH Yang, HH Liu, G Chen, XY AF Lin, Li-Sen Cong, Zhong-Xiao Cao, Jian-Bo Ke, Kai-Mei Peng, Qiao-Li Gao, Jinhao Yang, Huang-Hao Liu, Gang Chen, Xiaoyuan TI Multifunctional Fe3O4@Polydopamine Core-Shell Nanocomposites for Intracellular mRNA Detection and Imaging-Guided Photothermal Therapy SO ACS NANO LA English DT Article DE polydopamine; multifunctional nanocomposites; mRNA recognition; magnetic resonance imaging; photoacoustic imaging; photothermal therapy ID MAGNETIC NANOPARTICLES; CANCER-THERAPY; LIVING CELLS; IN-VIVO; BREAST-CANCER; NANO-FLARES; IRON-OXIDE; PROBES; FUNCTIONALIZATION; POLYDOPAMINE AB Multifunctional nanocomposites have the potential to integrate sensing, diagnostic, and therapeutic functions into a single nanostructure. Herein, we synthesize Fe3O4@polydopamine core shell nanocomposites (Fe3O4@PDA NCs) through an in situ self-polymerization method. Dopamine, a melanin-like mimic of mussel adhesive proteins, can self-polymerize to form surface-adherent polydopamine (PDA) films onto a wide range of materials including Fe3O4 nanoparticles used here. In such nanocomposites, PDA provides a number of advantages, such as near-infrared absorption, high fluorescence quenching efficiency, and a surface for further functionalization with biomolecules. We demonstrate the ability of the Fe3O4@PDA NCs to act as theranostic agents for intracellular mRNA detection and multimodal imaging-guided photothermal therapy. This work would stimulate interest in the use of PDA as a useful material to construct multifunctional nanocomposites for biomedical applications. C1 [Lin, Li-Sen; Cong, Zhong-Xiao; Ke, Kai-Mei; Yang, Huang-Hao] Fuzhou Univ, Coll Chem, Key Lab Anal & Detect Technol Food Safety MOE, Fuzhou 350108, Peoples R China. [Cao, Jian-Bo; Peng, Qiao-Li; Gao, Jinhao; Liu, Gang] Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361005, Peoples R China. [Cao, Jian-Bo; Peng, Qiao-Li; Gao, Jinhao; Liu, Gang] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Yang, HH (reprint author), Fuzhou Univ, Coll Chem, Key Lab Anal & Detect Technol Food Safety MOE, Fuzhou 350108, Peoples R China. EM hhyang@fio.org.cn; gangliu.cmitm@xmu.edu.cn RI Gao, Jinhao/F-5092-2010 OI Gao, Jinhao/0000-0003-3215-7013 FU National Basic Research Program of China [2010CB732403, 2013CB733802, 2014CB744503]; National Natural Science Foundation of China [21125524, 51273165, 81101101]; Program for Changjiang Scholars and Innovative Research Team in University [IRT1116]; Program for New Century Excellent Talents in University [NCET-13-0502]; National Science Foundation of Fujian Province [2010J06003] FX This research was supported by the National Basic Research Program of China (Nos. 2010CB732403, 2013CB733802, 2014CB744503), the National Natural Science Foundation of China (Nos. 21125524, 51273165, 81101101), the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT1116), the Program for New Century Excellent Talents in University (NCET-13-0502), and the National Science Foundation of Fujian Province (No. 2010J06003). NR 41 TC 148 Z9 152 U1 106 U2 593 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 APR PY 2014 VL 8 IS 4 BP 3876 EP 3883 DI 10.1021/nn500722y PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA AF8UH UT WOS:000334990600085 PM 24654734 ER PT J AU Manoukis, NC Butail, S Diallo, M Ribeiro, JMC Paley, DA AF Manoukis, Nicholas C. Butail, Sachit Diallo, Moussa Ribeiro, Jose M. C. Paley, Derek A. TI Stereoscopic video analysis of Anopheles gambiae behavior in the field: Challenges and opportunities SO ACTA TROPICA LA English DT Article DE Anopheles gambiae; Swarming; Mating behavior; Computer vision ID MOTION CORRESPONDENCE; POPULATION-CONTROL; SWARMING BEHAVIOR; MATING-BEHAVIOR; MOSQUITOS; DIPTERA; CULICIDAE; DOMINANT; FITNESS; SYSTEMS AB Advances in our ability to localize and track individual swarming mosquitoes in the field via stereoscopic image analysis have enabled us to test long-standing ideas about individual male behavior and directly observe coupling. These studies further our fundamental understanding of the reproductive biology of mosquitoes. In addition, our analyses using stereoscopic video of swarms of the African malaria vector Anopheles gambiae have produced results that should be relevant to any "release-based" method of control including Sterile Insect Technique (SIT) and genetically modified male mosquitoes (GMM). The relevance of the results is primarily due to the fact that any mosquito vectors released for control are almost certainly going to be males; further, for SIT, GMM or similar approaches to be successful, the released males will have to successfully locate swarms and then mate with wild females. Thus, understanding and potentially manipulating the mating process could play a key role in future control programs. Our experience points to special challenges created by stereoscopic video of swarms. These include the expected technical difficulties of capturing usable images of mosquitoes in the field, and creating an automated tracking system to enable generation of large numbers of three dimensional tracks over many seconds of footage. Once the data are collected, visualization and application of appropriate statistical and analytic methods also are required. We discuss our recent progress on these problems, give an example of a statistical approach to quantify individual male movement in a swarm with some novel results, and suggest further studies incorporating experimental manipulation and three dimensional localization and tracking of individual mosquitoes in wild swarms. Copyright (C) International Atomic Energy Agency 2013. Published by Elsevier B.V. All rights reserved. C1 [Manoukis, Nicholas C.] USDA ARS, US Pacific Basin Agr Res Ctr, Hilo, HI 96720 USA. [Butail, Sachit] NYU, Polytech Inst, Brooklyn, NY 11201 USA. [Diallo, Moussa] Univ Bamako, Unit Mol Ecol, Malaria Res & Training Ctr, Bamako, Mali. [Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Paley, Derek A.] Univ Maryland, Dept Aerosp Engn, College Pk, MD 20742 USA. [Paley, Derek A.] Univ Maryland, Syst Res Inst, College Pk, MD 20742 USA. RP Manoukis, NC (reprint author), USDA ARS PBARC, 64 Nowelo St, Hilo, HI 96720 USA. EM nicholas.manoukis@ars.usda.gov; sb4304@nyu.edu; moussad@icermali.org; jribeiro@niaid.nih.gov; dpaley@umd.edu RI Butail, Sachit/O-2928-2013; OI Butail, Sachit/0000-0001-9785-7374; Manoukis, Nicholas/0000-0001-5062-7256; Ribeiro, Jose/0000-0002-9107-0818 FU NIH; NIAID; IAEA CRP [G34002] FX We would like to thank Adama Dao and our other collaborators at the Malaria Research and Training Center in Bamako, Mali for help capturing these data; Richard Sakai, Robert Gwadz and Sekou Traore provided essential support. We also acknowledge input from Tovi Lehmann and Abdouleye Diabate. Special thanks to the people of Doneguebougou for allowing us to work in their village and homes. This research was supported in part by the Intramural Research Program of the NIH, NIAID and by IAEA CRP G34002. NR 35 TC 6 Z9 6 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0001-706X EI 1873-6254 J9 ACTA TROP JI Acta Trop. PD APR PY 2014 VL 132 SU S SI SI BP S80 EP S85 DI 10.1016/j.actatropica.2013.06.021 PG 6 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA AG0NK UT WOS:000335112000011 PM 23850507 ER PT J AU Magnus, MC DeRoo, LA Haberg, SE Magnus, P Nafstad, P Nystad, W London, SJ AF Magnus, Maria C. DeRoo, Lisa A. Haberg, Siri E. Magnus, Per Nafstad, Per Nystad, Wenche London, Stephanie J. TI Prospective Study ofMaternal Alcohol Intake During Pregnancy or Lactation and Risk of Childhood Asthma: The NorwegianMother and Child Cohort Study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol; Asthma; Breastfeeding; Pregnancy; Respiratory Tract Infections ID UTERO ETHANOL EXPOSURE; ALVEOLAR MACROPHAGE; PULMONARY-FUNCTION; SELECTION BIAS; CONSUMPTION; LUNG; INFECTIONS; NEWBORNS; BIRTH; DRINK AB BackgroundMany women drink during pregnancy and lactation despite recommendations to abstain. In animals, alcohol exposure during pregnancy and lactation influences lung and immune development, plausibly increasing risk of asthma and lower respiratory tract infections (LRTIs). Studies in humans are few. MethodsIn the Norwegian Mother and Child Cohort Study, we examined maternal alcohol intake during pregnancy and lactation in relation to risk of current asthma at 36months (49,138 children), recurrent LRTIs by 36months (39,791 children), and current asthma at 7years (13,253 children). Mothers reported frequency and amount of alcohol intake each trimester and the first 3months following delivery. We calculated adjusted relative risk (aRR), comparing children of drinkers to nondrinkers, using Generalized Linear Models. ResultsA total of 31.8% of mothers consumed alcohol during first trimester, 9.7% during second trimester, and 15.6% during third trimester. Infrequent and low-dose prenatal alcohol exposure showed a modest statistically significant inverse association with current asthma at 36months (aRRs0.85). No association was seen with the highest alcohol intakes during the first trimester when alcohol consumption was most common. RRs of maternal alcohol intake during pregnancy with recurrent LRTIs were 1, with sporadic differences in risk for some metrics of intake, but without any consistent pattern. For current asthma at 7years, similar inverse associations were seen as with current asthma at 36months but were not statistically significant. Among children breastfed throughout the first 3months of life, maternal alcohol intake during this time was not significantly associated with any of the 3 outcomes. ConclusionsThe low levels of alcohol exposure during pregnancy or lactation observed in this cohort were not associated with increased risk of asthma or recurrent LRTIs. The slight inverse associations of infrequent or low-dose prenatal alcohol exposure with asthma may not be causal. C1 [Magnus, Maria C.; Haberg, Siri E.; Magnus, Per; Nafstad, Per; Nystad, Wenche] Norwegian Inst Publ Hlth, Dept Chron Dis, Div Epidemiol, N-0403 Oslo, Norway. [Magnus, Maria C.; DeRoo, Lisa A.; London, Stephanie J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [DeRoo, Lisa A.] Univ Bergen, Fac Med, Dept Global Publ Hlth & Primary Care, Bergen, Norway. [Nafstad, Per] Univ Oslo, Fac Med, Dept Community Med, Oslo, Norway. RP Magnus, MC (reprint author), Norwegian Inst Publ Hlth, Dept Chron Dis, Div Epidemiol, POB 4404 Nydalen, N-0403 Oslo, Norway. EM maria.christine.magnus@fhi.no OI London, Stephanie/0000-0003-4911-5290 FU NIH (NIH/NIEHS) [N01-ES-75558]; NIH/NINDS [1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1]; Norwegian Research Council/FUGE [151918/S10]; Norwegian Extra-Foundation for Health and Rehabilitation [2011.2.0218]; Intramural Program of the National Institutes of Health, National Institute of Environmental Health Sciences FX The authors are grateful to all the families participating in the ongoing Norwegian Mother and Child Cohort Study. The Norwegian Mother and Child Cohort Study is supported by NIH (NIH/NIEHS contract number N01-ES-75558, NIH/NINDS grant no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1) and the Norwegian Research Council/FUGE (grant number 151918/S10). MCM is also supported by the Norwegian Extra-Foundation for Health and Rehabilitation (grant number 2011.2.0218). This research was supported in part by the Intramural Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 45 TC 7 Z9 7 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2014 VL 38 IS 4 BP 1002 EP 1011 DI 10.1111/acer.12348 PG 10 WC Substance Abuse SC Substance Abuse GA AE4JJ UT WOS:000333948400012 PM 24460824 ER PT J AU Braithwaite, RS Nucifora, KA Kessler, J Toohey, C Mentor, SM Uhler, LM Roberts, MS Bryant, K AF Braithwaite, R. Scott Nucifora, Kimberly A. Kessler, Jason Toohey, Christopher Mentor, Sherry M. Uhler, Lauren M. Roberts, Mark S. Bryant, Kendall TI Impact of Interventions Targeting Unhealthy Alcohol Use in Kenya on HIV Transmission and AIDS-Related Deaths SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Unhealthy Alcohol Use; HIV Prevention; HIV; AIDS; Sub-Saharan Africa ID SUB-SAHARAN AFRICAN; FEMALE SEX WORKERS; ANTIRETROVIRAL THERAPY; NORTHERN TANZANIA; INFECTED PATIENTS; RANDOMIZED-TRIAL; HOTEL WORKERS; SOUTH-AFRICA; RISK-FACTORS; METAANALYSIS AB BackgroundHIV remains a major cause of preventable morbidity and mortality in Kenya. The effects of behaviors that accompany unhealthy alcohol consumption are a pervasive risk factor for HIV transmission and progression. Our objective was to estimate the portion of HIV infections attributable to unhealthy alcohol use and to evaluate the impact of hypothetical interventions directed at unhealthy alcohol use on HIV infections and deaths. MethodsWe estimated outcomes over a time horizon of 20years using a computer simulation of the Kenyan population. This computer simulation integrates a compartmental model of HIV transmission with a mechanistic model of HIV progression that was previously validated in sub-Saharan Africa. Integration of the transmission and progression models allows simultaneous consideration of alcohol's effects on HIV transmission and progression (e.g., lowering antiretroviral adherence may increase transmission risk by elevating viral load, and may simultaneously increase progression by increasing the likelihood of AIDS). The simulation considers important aspects of heterogeneous sexual mixing patterns, including assortativeness of partners by age and activity level, age-discordant relationships, and high activity subgroups. Outcomes included number of new HIV infections, number of AIDS deaths, and infectivity (number of new infections per infected person per year). ResultsOur model estimated that the effects of behaviors accompanying unhealthy alcohol consumption are responsible for 13.0% of new HIV infections in Kenya. An alcohol intervention with effectiveness similar to that observed in a published randomized controlled trial of a cognitive-behavioral therapy-based intervention in Kenya (45% reduction in unhealthy alcohol consumption) could prevent nearly half of these infections, reducing their number by 69,858 and reducing AIDS deaths by 17,824 over 20years. Estimates were sensitive to assumptions with respect to the magnitude of alcohol's underlying effects on condom use, antiretroviral therapy adherence, and sexually transmitted infection prevalence. ConclusionsA substantial number of new HIV infections in Kenya are attributable to unhealthy alcohol use. An alcohol intervention with the effectiveness observed in a published randomized controlled trial has the potential to reduce infections over 20years by nearly 5% and avert nearly 18,000 deaths related to HIV. C1 [Braithwaite, R. Scott; Nucifora, Kimberly A.; Kessler, Jason; Toohey, Christopher; Mentor, Sherry M.; Uhler, Lauren M.] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA. [Roberts, Mark S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA USA. [Bryant, Kendall] NIAAA, NIH, Bethesda, MD USA. RP Braithwaite, RS (reprint author), NYU, Sch Med, Dept Populat Hlth, 550 First Ave,VZ30 6th Floor,615, New York, NY 10016 USA. EM scott.braithwaite@nyumc.org FU National Institute of Alcohol Abuse and Alcoholism [R01 AA017385] FX This study has utilized computing resources at the High Performance Computing Facility of the Center for Health Informatics and Bioinformatics at New York University Langone Medical Center. This study is supported by the National Institute of Alcohol Abuse and Alcoholism award R01 AA017385. NR 41 TC 10 Z9 10 U1 4 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2014 VL 38 IS 4 BP 1059 EP 1067 DI 10.1111/acer.12332 PG 9 WC Substance Abuse SC Substance Abuse GA AE4JJ UT WOS:000333948400019 PM 24428236 ER PT J AU Rehm, J Dawson, D Frick, U Gmel, G Roerecke, M Shield, KD Grant, B AF Rehm, Juergen Dawson, Deborah Frick, Ulrich Gmel, Gerrit Roerecke, Michael Shield, Kevin D. Grant, Bridget TI Burden of Disease Associated with Alcohol Use Disorders in the United States SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Use Disorders; Mortality; Burden of Disease; Disability-Adjusted Life Years; United States ID NATIONAL EPIDEMIOLOGIC SURVEY; DISABILITY WEIGHTS; GLOBAL BURDEN; SYSTEMATIC ANALYSIS; SUBSTANCE-ABUSE; RISK-FACTORS; DEPENDENCE; MORTALITY; CONSUMPTION; INJURY AB BackgroundAlcohol use disorders (AUD) have long been considered to be some of the most disabling mental disorders; however, empirical data on the burden of disease associated with AUD have been sparse. The objective of this article is to quantify the burden of disease (in disability-adjusted life years [DALYs] lost), deaths, years of life lost due to premature mortality (YLL), and years of life lost due to disability (YLD) associated with AUD for the United States in 2005. MethodsStatistical modeling was based on epidemiological indicators derived from the National Epidemiologic Survey on Alcohol and Related Conditions. Formal consistency analyses were applied. Risk relations were taken from recent meta-analyses and the disability weights from the burden of disease study of the National Institutes of Health. Monte Carlo simulations were used to derive confidence intervals. All analyses were performed by sex and age. Sensitivity analyses were undertaken on key indicators. ResultsIn the United States in 2005, 65,000 deaths, 1,152,000 YLL, 2,443,000 YLD, and 3,595,000 DALYs were associated with AUD. For individuals 18years of age and older, AUD were associated with 3% of all deaths (5% for men and 1% for women), and 5% of all YLL (7% for men and 2% for women). The majority of the burden of disease associated with AUD stemmed from YLD, which accounted for 68% of DALYs associated with AUD (66% for men and 74% for women). The youngest age group had the largest proportion of DALYs associated with AUD stemming from YLD. ConclusionsUsing data from a large representative survey (checked for consistency) and by combining these data with the best available evidence, we found that AUD were associated with a larger burden of disease than previously estimated. To reduce this disease burden, implementation of prevention interventions and expansion of treatment are necessary. C1 [Rehm, Juergen] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, Dresden, Germany. [Rehm, Juergen] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Rehm, Juergen; Gmel, Gerrit; Roerecke, Michael; Shield, Kevin D.] Ctr Addict & Mental Hlth, Toronto, ON M5S 2S1, Canada. [Rehm, Juergen; Roerecke, Michael] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Rehm, Juergen; Shield, Kevin D.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. [Dawson, Deborah] Kelly Govt Serv, Rockville, MD USA. [Frick, Ulrich] Carinthia Univ Appl Sci, Feldkirchen, Austria. [Frick, Ulrich] Univ Regensburg, Psychiat Univ Hosp, D-93053 Regensburg, Germany. [Gmel, Gerrit] Univ New S Wales, Sch Elect Engn & Telecommun, Sydney, NSW 2052, Australia. [Grant, Bridget] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA. RP Roerecke, M (reprint author), Ctr Addict & Mental Hlth, Social & Epidemiol Res Dept, 33 Russell St, Toronto, ON M5S 2S1, Canada. EM m.roerecke@web.de FU National Institute of Alcohol Abuse and Alcoholism (NIAAA), Bethesda, MD [HHSN267200700041C]; Ontario Ministry of Health and Long-Term Care; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, U.S. Department of Health and Human Services; National Institute on Drug Abuse; National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism FX This work was financially supported by Contract No. HHSN267200700041C of the National Institute of Alcohol Abuse and Alcoholism (NIAAA), Bethesda, MD. The first author also acknowledges salary support from the Ontario Ministry of Health and Long-Term Care. The study on which this paper is based, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), is sponsored by the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, U.S. Department of Health and Human Services, with supplemental support from the National Institute on Drug Abuse. This research was supported in part by the Intramural Program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. NR 53 TC 36 Z9 36 U1 4 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2014 VL 38 IS 4 BP 1068 EP 1077 DI 10.1111/acer.12331 PG 10 WC Substance Abuse SC Substance Abuse GA AE4JJ UT WOS:000333948400020 PM 24428196 ER PT J AU Abramova, Z Choo, P Irvin, V Oh, M Hofstetter, R Hovell, M Huh, J AF Abramova, Zarina Choo, Peter Irvin, Veronica Oh, Minn Hofstetter, Richard Hovell, Mel Huh, Jimi TI DEPRESSION, ACCULTURATION, PERCEIVED BODY SHAPE/WEIGHT AMONG KOREAN AMERICAN WOMEN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Abramova, Zarina; Choo, Peter; Oh, Minn; Huh, Jimi] Univ So Calif, Los Angeles, CA 90032 USA. [Irvin, Veronica] NIH, OBSSR, Bethesda, MD 20892 USA. [Hofstetter, Richard; Hovell, Mel] San Diego State Univ, San Diego, CA 92182 USA. EM ms_abramova@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S114 EP S114 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300434 ER PT J AU Ali, MK Mwendwa, DT O'Connor, MY Thoreson, CK Ricks, M Sumner, AE AF Ali, Mana K. Mwendwa, Denee T. O'Connor, Michelle Y. Thoreson, Caroline K. Ricks, Madia Sumner, Anne E. TI THINKING OF FOOD IS ASSOCIATED WITH BODY MASS INDEX IN AFRICAN IMMIGRANTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ali, Mana K.] Howard Univ, Landover, MD 20785 USA. [Mwendwa, Denee T.] Univ Delaware, Dept Behav Hlth & Nutr, Newark, DE USA. [O'Connor, Michelle Y.; Thoreson, Caroline K.; Ricks, Madia; Sumner, Anne E.] NIDDK, NIH, Bethesda, MD 20892 USA. EM ms.manaali@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S25 EP S25 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300096 ER PT J AU Andersen, BL Redd, WH Dorfman, CS Lechner, SC Julia, RH AF Andersen, Barbara L. Redd, William H. Dorfman, Caroline S. Lechner, Suzanne C. Julia, Rowland H. TI DISSEMINATION OF EMPIRICALLY SUPPORTED PSYCHOLOGICAL TREATMENTS FOR CANCER PATIENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Andersen, Barbara L.; Dorfman, Caroline S.] Ohio State Univ, Columbus, OH 43210 USA. [Redd, William H.] Icahn Sch Med, New York, NY USA. [Julia, Rowland H.] NCI, Div Canc Control & Populat Sci, NIH, DHHS, Bethesda, MD 20892 USA. [Lechner, Suzanne C.] Univ Miami, Miami, FL USA. EM dorfman.12@osu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S165 EP S165 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300634 ER PT J AU Arora, NK Hesse, B Chawla, N Rutten, L Beckjord, E Hartigan, D Taplin, S Glasgow, R AF Arora, Neeraj K. Hesse, Bradford Chawla, Neetu Rutten, Lila Beckjord, Ellen Hartigan, Danielle Taplin, Stephen Glasgow, Russell TI IMPORTANCE OF PATIENT-CENTERED COMMUNICATION IN FACILITATING PATIENT ENGAGEMENT AMONG INDIVIDUALS WITH MULTIPLE CHRONIC CONDITIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Arora, Neeraj K.; Hesse, Bradford; Chawla, Neetu; Hartigan, Danielle; Taplin, Stephen] NCI, Bethesda, MD 20892 USA. [Rutten, Lila] Mayo Clin, Rochester, MN USA. [Beckjord, Ellen] Univ Pittsburgh, Pittsburgh, PA USA. [Glasgow, Russell] Univ Colorado, Denver, CO 80202 USA. EM aroran@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S214 EP S214 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408301069 ER PT J AU Augustson, E Hunt, Y Taylor, S Sanders, A AF Augustson, Erik Hunt, Yvonne Taylor, Shani Sanders, Amy TI SUPPORT FOR THE USE OF MHEALTH SMOKING CESSATION INTERVENTIONS: SELF-REPORTED QUIT RATES AND USER DATA FROM THE NATIONAL CANCER INSTITUTE'S SMOKEFREETXT PROGRAM SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Augustson, Erik; Hunt, Yvonne] NCI, Bethesda, MD 20892 USA. [Taylor, Shani; Sanders, Amy] MMG Inc, Rockville, MD USA. EM augustse@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S135 EP S135 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300521 ER PT J AU Beckjord, EB Rutten, LJ Arvey, SR Rechis, R Hartigan, D Chawla, N Arora, NK Hesse, BW AF Beckjord, Ellen B. Rutten, Lila J. Arvey, Sarah R. Rechis, Ruth Hartigan, Danielle Chawla, Neetu Arora, Neeraj K. Hesse, Bradford W. TI HEALTH SELF-EFFICACY AND INFORMATION EFFICACY AMONG ADULT CANCER SURVIVORS IN THE UNITED STATES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Beckjord, Ellen B.] Univ Pittsburgh, Pittsburgh, PA 15232 USA. [Rutten, Lila J.] Mayo Clin, Minneapolis, MN USA. [Hartigan, Danielle; Chawla, Neetu; Arora, Neeraj K.; Hesse, Bradford W.] NCI, Bethesda, MD 20892 USA. [Arvey, Sarah R.; Rechis, Ruth] LIVESTRONG, Austin, TX USA. EM beckjorde@upmc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S152 EP S152 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300584 ER PT J AU Biesecker, BB Klein, W Biesecker, L Han, P AF Biesecker, Barbara B. Klein, William Biesecker, Leslie Han, Paul TI PERCEPTIONS OF UNCERTAINTY IN GENOMIC SEQUENCING: THE ROLE OF EPISTEMOLOGICAL BELIEFS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Biesecker, Barbara B.; Klein, William; Han, Paul] NHGRI, NIH, Bethesda, MD 20892 USA. [Klein, William] NCI, NIH, Bethesda, MD 20892 USA. [Biesecker, Leslie] NHGRI, NIH, Genet Dis Branch, Bethesda, MD 20892 USA. [Han, Paul] Maine Med Ctr, Scarborough, ME USA. EM barbarab@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S92 EP S92 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300351 ER PT J AU Bluethmann, S Allen, JD Tom, L Chenoweth, M Leyva, B AF Bluethmann, Shirley Allen, Jennifer D. Tom, Laura Chenoweth, Matthew Leyva, Bryan TI WOMEN'S INVOLVEMENT IN SHARED DECISION MAKING FOR MAMMOGRAPHY: RESULTS FROM THE HEALTH AND RETIREMENT STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bluethmann, Shirley] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77030 USA. [Allen, Jennifer D.; Tom, Laura] Dana Farber Canc Inst, Boston, MA 02115 USA. [Allen, Jennifer D.] Harvard Univ, Sch Med, Boston, MA USA. [Chenoweth, Matthew] Tufts Univ, Community Hlth Program, Medford, MA 02155 USA. [Leyva, Bryan] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM shirley.m.bluethmann@uth.tmc.edu RI Allen, Jennifer/M-2113-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S193 EP S193 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300739 ER PT J AU Brooks, A Krumlauf, MC Whiting, B Clark, R Yang, L Ramchandani, VA Schwandt, ML George, DT Wallen, GR AF Brooks, Alyssa Krumlauf, Michael C. Whiting, Barbara Clark, Rosa Yang, Li Ramchandani, Vijay A. Schwandt, Melanie L. George, David T. Wallen, Gwenyth R. TI IMPROVED SLEEP DURING FOUR WEEKS OF AN INPATIENT ALCOHOL TREATMENT PROGRAM: CHARACTERIZING PATIENTS WHO MAY BENEFIT FROM TARGETED SLEEP INTERVENTIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Brooks, Alyssa; Krumlauf, Michael C.; Whiting, Barbara; Clark, Rosa; Yang, Li; Ramchandani, Vijay A.; Schwandt, Melanie L.; George, David T.; Wallen, Gwenyth R.] NIH, Ctr Clin, Bethesda, MD 20892 USA. EM todaroad@mail.nih.gov NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S139 EP S139 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300537 ER PT J AU Byrne, M Studts, J Hamaan, H Park, E Marcus, P Han, P AF Byrne, Margaret Studts, Jamie Hamaan, Heidi Park, Elyse Marcus, Pamela Han, Paul TI LUNG CANCER SCREENING: A NEW FRONTIER FOR BEHAVIORAL MEDICINE RESEARCH, PRACTICE, AND POLICY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Byrne, Margaret] Univ Miami, Miami, FL 33136 USA. [Studts, Jamie] Univ Kentucky, Lexington, KY USA. [Hamaan, Heidi] UT Southwestern Med Ctr, Dallas, TX USA. [Park, Elyse] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Marcus, Pamela] NCI, Bethesda, MD 20892 USA. [Han, Paul] Maine Med Ctr, Scarborough, ME USA. EM mbyrne2@med.miami.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S77 EP S77 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300294 ER PT J AU Caspi, CE Allen, JD Yang, M Tamers, S Stoddard, A Leyva, B Tucker-Seeley, R Sorensen, G AF Caspi, Caitlin E. Allen, Jennifer D. Yang, May Tamers, Sara Stoddard, Anne Leyva, Bryan Tucker-Seeley, Reginald Sorensen, Glorian TI PATHWAYS BETWEEN ACCULTURATION AND HEALTH BEHAVIORS AMONG LOW-INCOME HOUSING RESIDENTS: THE MEDIATING ROLE OF SOCIAL/CONTEXTUAL FACTORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Caspi, Caitlin E.] Univ Minnesota, Minneapolis, MN 55406 USA. [Allen, Jennifer D.; Tamers, Sara; Tucker-Seeley, Reginald; Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Allen, Jennifer D.; Tamers, Sara; Tucker-Seeley, Reginald; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Yang, May; Stoddard, Anne] New England Res Inst, Watertown, MA 02172 USA. [Leyva, Bryan] NCI, Bethesda, MD 20892 USA. EM cecaspi@umn.edu RI Allen, Jennifer/M-2113-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S82 EP S82 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300310 ER PT J AU Eggly, S Meert, K Kavanaugh, K Park, C AF Eggly, Susan Meert, Kathleen Kavanaugh, Karen Park, Crystal CA Coll Ped Crit Care Res Network TI PARENT MEANING MAKING DURING PHYSICIAN-PARENT FOLLOW-UP MEETINGS AFTER THE DEATH OF A CHILD IN THE PICU SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Eggly, Susan; Meert, Kathleen; Kavanaugh, Karen] Wayne State Univ, Detroit, MI 48201 USA. [Park, Crystal] Univ Connecticut, Storrs, CT USA. [Coll Ped Crit Care Res Network] NICHD, Bethesda, MD USA. EM egglys@karmanos.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S30 EP S30 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300117 ER PT J AU Elwood, WN Irvin, VL Sun, QK Breen, N AF Elwood, William N. Irvin, Veronica L. Sun, Qiankun Breen, Nancy TI FROM PERFECT PATIENTS TO UNCOVERED CHRONICALLY ILL: DISPARITIES IN HEALTH AND WELLBEING, HEALTHCARE, AND INSURANCE COVERAGE AMONG LGB ADULTS AND IMPLICATIONS TO RESOLVE THEM SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Elwood, William N.; Sun, Qiankun] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Irvin, Veronica L.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Breen, Nancy] NCI, NIH, Bethesda, MD 20892 USA. EM william.elwood@nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S271 EP S271 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408301291 ER PT J AU Elwood, WN Kagawa-Singer, M Szalacha, LA Guarnaccia, PJ AF Elwood, William N. Kagawa-Singer, Marjorie Szalacha, Laura A. Guarnaccia, Peter J. TI TRANSFORMING CULTURE AND RESEARCH: OPERATIONALIZING CULTURE AND ITS RELATIONSHIP TO HEALTH AND WELLBEING OUTCOMES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Elwood, William N.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Kagawa-Singer, Marjorie] Ohio State Univ, Coll Nursing, Columbus, OH 43210 USA. [Szalacha, Laura A.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Guarnaccia, Peter J.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging, Los Angeles, CA USA. EM william.elwood@nih.gov NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S202 EP S202 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408301023 ER PT J AU Estabrooks, P Gorin, SS AF Estabrooks, Paul Gorin, Sherri Sheinfeld TI INFLUENCING PHYSICAL ACTIVITY PROMOTION THROUGH INTEGRATED RESEARCH PRACTICE PARTNERSHIPS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gorin, Sherri Sheinfeld] NCI SAIC, DCCPS, NIH, New York, NY 10027 USA. [Estabrooks, Paul] Caril Clin, Roanoke, VA USA. [Estabrooks, Paul] Virginia Tech, Roanoke, VA USA. EM sherri.gorin@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S144 EP S144 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300552 ER PT J AU Fiore, MC Baker, TB Collins, LM Mermelstein, RJ Piper, ME Riley, W AF Fiore, Michael C. Baker, Timothy B. Collins, Linda M. Mermelstein, Robin J. Piper, Megan E. Riley, William TI MULTIPHASE OPTIMIZATION STRATEGY (MOST) FOR SMOKING INTERVENTION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Fiore, Michael C.; Baker, Timothy B.; Piper, Megan E.] Univ Wisconsin, Ctr Tobacco Res & Intervent, Madison, WI 53711 USA. [Collins, Linda M.] Penn State Univ, Methodol Ctr, State Coll, PA USA. [Mermelstein, Robin J.] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL USA. [Riley, William] NCI, Sci Res & Technol Branch, Bethesda, MD 20892 USA. EM mep@ctri.wisc.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S53 EP S53 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300205 ER PT J AU Galica, K Chou, WYS AF Galica, Kasia Chou, Wen-Ying Sylvia TI INSTAGRAM FOR HEALTH: PEER-TO-PEER FITNESS MOTIVATION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Galica, Kasia; Chou, Wen-Ying Sylvia] NCI, Washington, DC 20009 USA. EM kasia.galica@nih.gov NR 0 TC 0 Z9 0 U1 11 U2 68 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S89 EP S89 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300341 ER PT J AU Gaysynsky, A Romansky, K Arpadi, S AF Gaysynsky, Anna Romansky, Kathryn Arpadi, Stephen TI "MY YAP FAMILY": AN ANALYSIS OF A PRIVATE FACEBOOK PAGE FOR HIV-POSITIVE YOUNG ADULTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gaysynsky, Anna] NCI, Rockville, MD 20892 USA. [Romansky, Kathryn; Arpadi, Stephen] St Lukes Roosevelt Hosp, Spencer Cox Ctr Hlth, New York, NY 10025 USA. EM anna.gaysynsky@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S109 EP S109 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300416 ER PT J AU Glasgow, R Hayes, MS Krist, A Glenn, B Gorin, SS Heurtin-Roberts, S AF Glasgow, Russell Hayes, Melissa S. Krist, Alex Glenn, Beth Gorin, Sherri Sheinfeld Heurtin-Roberts, Suzanne CA MOHR Study Grp TI MY OWN HEALTH REPORT (MOHR): IMPLEMENTATION PROCESS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gorin, Sherri Sheinfeld] NCI SAIC, DCCPS, NIH, New York, NY 10027 USA. [Glasgow, Russell] Univ Colorado, Aurora, CO USA. [Hayes, Melissa S.; Krist, Alex] Virginia Commonwealth Univ, Richmond, VA USA. [Glenn, Beth] Univ Calif Los Angeles, Los Angeles, CA USA. [Heurtin-Roberts, Suzanne] DCCPS, Bethesda, MD USA. [MOHR Study Grp] MOHR Study Grp, Bethesda, MD USA. EM sherri.gorin@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S165 EP S165 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300631 ER PT J AU Gorin, SS Huber, A Joy, E Estabrooks, P Marcus, B Goodrich, D Craft, LL AF Gorin, Sherri Sheinfeld Huber, Adrian Joy, Elizabeth Estabrooks, Paul Marcus, Bess Goodrich, David Craft, Lynette L. TI EXERCISE IS MEDICINE: MULTILEVEL APPROACHES TO IMPLEMENTATION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gorin, Sherri Sheinfeld] NCI SAIC, DCCPS, NIH, New York, NY 10027 USA. [Huber, Adrian; Craft, Lynette L.] ACSM, Indianapolis, IN USA. [Joy, Elizabeth] Intermt Healthcare, Salt Lake City, UT USA. [Estabrooks, Paul] Fralin Translat Obes Res Ctr, Roanoke, VA USA. [Marcus, Bess] UCSD, La Jolla, CA USA. [Goodrich, David] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA. EM sherri.gorin@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S143 EP S143 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300549 ER PT J AU Hall, KL Vogel, AL Gehlert, S AF Hall, Kara L. Vogel, Amanda L. Gehlert, Sarah TI A CONCEPTUAL MODEL OF TRANSDISCIPLINARY TEAM RESEARCH: PLANNING, MANAGING, AND ENHANCING COLLABORATIVE SCIENCE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hall, Kara L.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Vogel, Amanda L.] SAIC Frederick Inc, Clin Res Directorate CMRP, Frederick Natl Lab Canc Res, Rockville, MD 20850 USA. [Gehlert, Sarah] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA. EM vogelal@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S63 EP S63 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300243 ER PT J AU Hamilton, JG Biesecker, BB AF Hamilton, Jada G. Biesecker, Barbara B. TI GENOMIC ADVANCES AND PATIENT DECISION MAKING: RECENT FINDINGS AND EMERGING ISSUES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hamilton, Jada G.] Mem Sloan Kettering Canc Ctr, New York, NY 10022 USA. [Biesecker, Barbara B.] NHGRI, Bethesda, MD 20892 USA. EM hamiltoj@mskcc.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S162 EP S162 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300621 ER PT J AU Hartigan, DB Forsythe, LP Alfano, CM Smith, T Nekhlyudov, L Ganz, PA Rowland, JH AF Hartigan, Danielle Blanch Forsythe, Laura P. Alfano, Catherine M. Smith, Tenbroeck Nekhlyudov, Larissa Ganz, Patricia A. Rowland, Julia H. TI PROVISION AND DISCUSSION OF SURVIVORSHIP CARE PLANS WITH CANCER SURVIVORS: RESULTS OF A NATIONALLY REPRESENTATIVE SURVEY OF ONCOLOGISTS AND PRIMARY CARE PHYSICIANS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hartigan, Danielle Blanch; Alfano, Catherine M.; Rowland, Julia H.] NCI, Off Canc Survivorship, Rockville, MD 20850 USA. [Forsythe, Laura P.] Patient Centered Outcomes Res Inst, Washington, DC USA. [Smith, Tenbroeck] Amer Canc Soc, Behav Res Ctr, Atlanta, GA 30329 USA. [Nekhlyudov, Larissa] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Nekhlyudov, Larissa] Harvard Vanguard Med Associates, Dept Med, Boston, MA USA. [Ganz, Patricia A.] UCLA Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA. EM danielleblanch@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S4 EP S4 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300013 ER PT J AU Hekler, EB Rivera, DE Riley, W Murray, T Spruijt-Metz, D AF Hekler, Eric B. Rivera, Daniel E. Riley, William Murray, Tylar Spruijt-Metz, Donna TI ADVANCES IN BEHAVIORAL THEORY SIMULATIONS - USING DYNAMICAL SYSTEMS MODELING TO IMPROVE THEORIES OF HEALTH-RELATED BEHAVIORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hekler, Eric B.] Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ 85004 USA. [Rivera, Daniel E.] Arizona State Univ, Tempe, AZ USA. [Riley, William] NCI, Bethesda, MD 20892 USA. [Murray, Tylar] Univ S Florida, Tampa, FL USA. [Spruijt-Metz, Donna] Univ So Calif, Los Angeles, CA USA. EM ehekler@asu.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S148 EP S148 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300570 ER PT J AU Heurtin-Roberts, SM Glasgow, R Glenn, B Krist, A AF Heurtin-Roberts, Suzanne M. Glasgow, Russ Glenn, Beth Krist, Alex TI COLLABORATIVELY CROWD-SOURCING A PRAGMATIC TRIAL: THE MY OWN HEALTH REPORT (MOHR) PROJECT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Heurtin-Roberts, Suzanne M.] NCI, Bethesda, MD 20892 USA. [Glasgow, Russ] Univ Colorado, Denver, CO 80202 USA. [Krist, Alex] Virginia Commonwealth Univ, Richmond, VA USA. [Glenn, Beth] Univ Calif Los Angeles, Los Angeles, CA USA. EM sheurtin@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S164 EP S164 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300630 ER PT J AU Huber, A Gorin, SS AF Huber, Adrian Gorin, Sherri Sheinfeld TI INTEGRATING AND IMPLEMENTING THE EXERCISE IS MEDICINE SOLUTION < (R) > WITHIN HEALTHCARE SYSTEMS AND SURROUNDING COMMUNITIES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gorin, Sherri Sheinfeld] NCI SAIC, DCCPS, NIH, New York, NY 10027 USA. [Huber, Adrian] Amer Coll Sports Med, Indianapolis, IN USA. EM sherri.gorin@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S143 EP S143 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300550 ER PT J AU Irvin, VL Kaplan, RM AF Irvin, Veronica L. Kaplan, Robert M. TI PRIMARY OUTCOMES IN LARGE BEHAVIORAL RANDOMIZED CONTROLLED TRIALS FUNDED BY NIH/NHLBI SINCE 1980 SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Irvin, Veronica L.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Irvin, Veronica L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. EM veronica.irvin@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S113 EP S113 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300433 ER PT J AU Johnson, SB Krist, A Glasgow, R Gorin, SS Heurtin-Roberts, S Hayes, MS Thompson, J Greenawald, M Estabrooks, P AF Johnson, Sallie Beth Krist, Alex Glasgow, Russell Gorin, Sherri Sheinfeld Heurtin-Roberts, Suzanne Hayes, Melissa S. Thompson, James Greenawald, Mark Estabrooks, Paul TI THE REACH OF A PATIENT REPORTED OUTCOMES TOOL FOR BEHAVIORAL AND PSYCHOSOCIAL FACTORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gorin, Sherri Sheinfeld] NCI SAIC, DCCPS, NIH, New York, NY 10027 USA. [Krist, Alex; Hayes, Melissa S.] VA Commonwealth Unvers, Richmond, VA USA. [Glasgow, Russell] U Colorado, Aurora, CO USA. [Heurtin-Roberts, Suzanne] DCCPS, Bethesda, MD USA. [Thompson, James] Caril Clin Southeast Family Med, Roanoke, VA USA. [Greenawald, Mark] VA Tech Caril SOM, Roanoke, VA USA. [Johnson, Sallie Beth; Estabrooks, Paul] Fralin Translat Obes Res Ctr, Roanoke, VA USA. EM sherri.gorin@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S165 EP S165 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300632 ER PT J AU Joy, E Gorin, SS AF Joy, Elizabeth Gorin, Sherri Sheinfeld TI IMPLEMENTING INTERMOUNTAIN HEALTHCARE'S LIFESTYLE AND WEIGHT MANAGEMENT CARE PROCESS MODEL SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gorin, Sherri Sheinfeld] NCI SAIC, DCCPS, NIH, New York, NY 10027 USA. [Joy, Elizabeth] Intermt Healthcare, Salt Lake City, UT USA. EM sherri.gorin@gmail.com NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S143 EP S143 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300551 ER PT J AU Kent, EE Prestin, A Galica, K Rinker, R Graff, K Gaysynksy, A Chou, WY AF Kent, Erin E. Prestin, Abby Galica, Kasia Rinker, Robin Graff, Kaitlin Gaysynksy, Anna Chou, Wen-Ying TI "I'D RATHER BE FAT AND ALONE THAN HAVE CANCER": CANCER AND OBESITY DISCUSSIONS IN FACEBOOK AND TWITTER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kent, Erin E.] NCI, Outcomes Res Branch, Rockville, MD 20850 USA. [Prestin, Abby; Galica, Kasia; Rinker, Robin; Graff, Kaitlin; Gaysynksy, Anna; Chou, Wen-Ying] NCI, Rockville, MD 20850 USA. EM Erin.Kent@nih.gov NR 0 TC 0 Z9 0 U1 3 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S9 EP S9 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300031 ER PT J AU Kessler, R Glasgow, R Krist, A Gorin, SS Heurtin-Roberts, S AF Kessler, Rodger Glasgow, Russell Krist, Alex Gorin, Sherri Sheinfeld Heurtin-Roberts, Suzanne CA MOHR Study Grp TI WHAT DOES MOHR HAVE TO TEACH US ABOUT PATIENT ENGAGEMENT? REFLECTIONS AND FUTURE DIRECTIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gorin, Sherri Sheinfeld] NCI SAIC, DCCPS, NIH, New York, NY 10027 USA. [Krist, Alex] VA Commonwealth U, Richmond, VA USA. [Glasgow, Russell] U Colorado, Aurora, CO USA. [Kessler, Rodger] U Vermont, Burlington, VT USA. [Heurtin-Roberts, Suzanne; MOHR Study Grp] DCCPS, Bethesda, MD USA. EM sherri.gorin@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S165 EP S165 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300633 ER PT J AU Kim, Y van Ryn, M Jensen, R Griffin, J Potosky, A Rowland, J AF Kim, Youngmee van Ryn, MIchelle Jensen, Roxanne Griffin, Joan Potosky, Arnold Rowland, Julia TI DYADIC EFFECTS OF GENDER AND DEPRESSIVE SYMPTOMS ON QUALITY OF LIFE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kim, Youngmee] Univ Miami, Coral Gables, FL 33124 USA. [van Ryn, MIchelle] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Jensen, Roxanne; Potosky, Arnold] Georgetown Univ, Med Ctr, Dc, DC USA. [Griffin, Joan] Minneapolis VA Med Ctr, Minneapolis, MN USA. [Rowland, Julia] NCI, Dc, DC USA. EM ykim@miami.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S60 EP S60 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300233 ER PT J AU Kobrin, S Suls, J AF Kobrin, Sarah Suls, Jerry TI WORKING TOGETHER: AN INTERACTIVE DISCUSSION WITH DIVERSE, SUCCESSFUL, BASIC AND APPLIED RESEARCH COLLABORATORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kobrin, Sarah; Suls, Jerry] NCI, Behav Res Program, Bethesda, MD 20850 USA. EM kobrins@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S65 EP S65 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300249 ER PT J AU Leyva, B Allen, JD Tom, L Rustan, S Torres, MI Ospino, H AF Leyva, Bryan Allen, Jennifer D. Tom, Laura Rustan, Sarah Torres, Maria I. Ospino, Hosffman TI ORGANIZATIONAL CHARACTERISTICS ASSOCIATED WITH HEALTH PROGRAM OFFERINGS AMONG CATHOLIC PARISHES: BASELINE RESULTS OF THE CRUZA STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Leyva, Bryan] NCI, Bethesda, MD 20892 USA. [Allen, Jennifer D.; Tom, Laura] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rustan, Sarah; Torres, Maria I.] Univ Massachusetts, Boston, MA 02125 USA. [Ospino, Hosffman] Boston Coll, Chestnut Hill, MA 02167 USA. EM leyvavengoechb@nih.gov RI Allen, Jennifer/M-2113-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S194 EP S194 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300742 ER PT J AU Leyva, B Allen, JD Rustan, S Tom, L Galeas, A Torres, MI Ospino, H AF Leyva, Bryan Allen, Jennifer D. Rustan, Sarah Tom, Laura Galeas, Ana Torres, Maria I. Ospino, Hosffman TI WORKING WITH PARISHES FOR CANCER CONTROL: RECRUITMENT AND ENGAGEMENT STRATEGIES IN THE CRUZA STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Leyva, Bryan] NCI, Gaithersburg, MD USA. [Allen, Jennifer D.; Tom, Laura; Galeas, Ana] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rustan, Sarah; Torres, Maria I.] Univ Massachusetts, Boston, MA 02125 USA. [Ospino, Hosffman] Boston Coll, Chestnut Hill, MA 02167 USA. EM leyvavengoechb@nih.gov RI Allen, Jennifer/M-2113-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S194 EP S194 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300741 ER PT J AU Manning, MA Eggly, S Slatcher, R Meert, K AF Manning, Mark A. Eggly, Susan Slatcher, Richard Meert, Kathleen CA Collab Pediat Critical Care Res Ne TI LINGUISTIC PATTERNS OF BEREAVED PARENTS DURING PARENT-PHYSICIAN FOLLOW UP MEETINGS: AN ACTOR-PARTNER INTERDEPENDENCE ANALYSIS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Manning, Mark A.; Eggly, Susan; Slatcher, Richard; Meert, Kathleen] Wayne State Univ, Detroit, MI 48201 USA. [Collab Pediat Critical Care Res Ne] NICHD, Bethesda, MD USA. EM manningm@karmanos.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S210 EP S210 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408301054 ER PT J AU Marcus, B Linke, S Gorin, SS AF Marcus, Bess Linke, Sarah Gorin, Sherri Sheinfeld TI LOW-COST INTERVENTIONS TO PROMOTE PHYSICAL ACTIVITY BEHAVIOR IN DIVERSE SETTINGS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gorin, Sherri Sheinfeld] NCI SAIC, DCCPS, NIH, New York, NY 10027 USA. [Marcus, Bess; Linke, Sarah] Univ Calif San Diego, San Diego, CA USA. EM sherri.gorin@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S144 EP S144 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300553 ER PT J AU Marcus, P AF Marcus, Pamela TI THE NATIONAL LUNG SCREENING TRIAL (NLST): ANSWERS AND QUESTIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Marcus, Pamela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM marcusp@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S78 EP S78 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300298 ER PT J AU Martin, MY Pisu, M Manne, S Basen-Engquist, K Alfano, C AF Martin, Michelle Y. Pisu, Maria Manne, Sharon Basen-Engquist, Karen Alfano, Catherine TI TO EVALUATE EFFICACY, WE NEED TO REACH: HOW DO WE RECRUIT CANCER SURVIVORS AND FAMILY MEMBERS TO PSYCHOSOCIAL RESEARCH STUDIES? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Martin, Michelle Y.; Pisu, Maria] Univ Alabama Birmingham, Birmingham, AL 35205 USA. [Martin, Michelle Y.; Pisu, Maria] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35205 USA. [Manne, Sharon] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Basen-Engquist, Karen] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Alfano, Catherine] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. EM mymartin@uab.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S63 EP S63 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300244 ER PT J AU Mauriello, L Evers, K Nilsen, W Patrick, K AF Mauriello, Leanne Evers, Kerry Nilsen, Wendy Patrick, Kevin TI THE USE OF MHEALTH WITH SPECIAL POPULATIONS: THEORY, RESEARCH AND PRACTICE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Mauriello, Leanne; Evers, Kerry] Prochange Behav Syst Inc, South Kingstown, RI 02879 USA. [Nilsen, Wendy] NIH, Bethesda, MD 20892 USA. [Patrick, Kevin] Univ Calif San Diego, La Jolla, CA 92093 USA. EM lmauriello@prochange.com NR 0 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S149 EP S149 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300574 ER PT J AU Moser, RP Ottenbacher, A Parker, J AF Moser, Richard P. Ottenbacher, Allison Parker, Jennifer TI HOW CAN 'BIG DATA' IN THE FEDERAL GOVERNMENT INFLUENCE THE IMPACT AND REACH OF BEHAVIORAL MEDICINE? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Moser, Richard P.; Ottenbacher, Allison] NCI, Rockville, MD 20850 USA. [Parker, Jennifer] Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. EM allison.ottenbacher@nih.gov NR 0 TC 0 Z9 0 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S62 EP S62 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300240 ER PT J AU Moser, R Hall, K Kobrin, S Parry, C Glasgow, R AF Moser, Rick Hall, Kara Kobrin, Sarah Parry, Carly Glasgow, Russell TI LEVERAGING GOVERNMENT-SUPPORTED TECHNOLOGY TO ADVANCE SCIENCE AND PRACTICE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Moser, Rick; Hall, Kara; Kobrin, Sarah; Parry, Carly] NCI, Behav Res Program, Bethesda, MD 20892 USA. [Glasgow, Russell] Univ Colorado, Sch Med, Denver, CO USA. EM moserr@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S154 EP S154 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300592 ER PT J AU Nahm, ES Murphy, J Ariosto, D Hesse, B Smith, T Wright, J AF Nahm, Eun-Shim Murphy, Judy Ariosto, Deborah Hesse, Bradford Smith, Tenbroeck Wright, Julie TI LEVERAGING MEANINGFUL USE REGULATIONS TO ACCELERATE PATIENT EMPOWERMENT AND HEALTH BEHAVIOR CHANGE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nahm, Eun-Shim] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Murphy, Judy] Off Natl Coordinator Hlth IT, Washington, DC USA. [Ariosto, Deborah] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Hesse, Bradford] NCI, Bethesda, MD 20892 USA. [Smith, Tenbroeck] Amer Canc Soc, Atlant, GA USA. [Wright, Julie] Univ Massachusetts, Boston, MA 02125 USA. EM enahm@son.umaryland.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S62 EP S62 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300238 ER PT J AU Nguyen, AB Patrick, H Oh, A AF Nguyen, Anh B. Patrick, Heather Oh, April TI PERCEPTIONS OF THE ROLES OF BEHAVIOR AND GENETICS IN DISEASE RISK: ARE THEYASSOCIATED WITH BEHAVIORAL CHANGE? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nguyen, Anh B.; Patrick, Heather; Oh, April] NCI, Rockville, MD 20912 USA. EM Anh.Nguyen3@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S222 EP S222 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408301103 ER PT J AU Nilsen, W AF Nilsen, Wendy TI NIH ADHERENCE RESEARCH NETWORK: A ROUNDTABLE DISCUSSION ON HOW TO ADVANCE THE SCIENCE AND PRACTICE OF ADHERENCE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nilsen, Wendy] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. EM nilsenwj@od.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S153 EP S153 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300586 ER PT J AU Nilsen, W AF Nilsen, Wendy TI MHEALTH IN TRADITIONALLY UNDERSERVED POPULATIONS: A VIEW FROM THE NATIONAL INSTITUTES OF HEALTH SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nilsen, Wendy] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. EM nilsenwj@od.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S149 EP S149 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300575 ER PT J AU Nilsen, W Bonafide, C Hekler, E Socklow, P AF Nilsen, Wendy Bonafide, Christopher Hekler, Eric Socklow, Paulina TI THE EVOLUTION OF MHEALTH SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nilsen, Wendy] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Socklow, Paulina] Drexel Univ, Philadelphia, PA 19104 USA. [Bonafide, Christopher] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Hekler, Eric] Arizona State Univ, Phoenix, AZ USA. EM nilsenwj@od.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S62 EP S62 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300239 ER PT J AU Nilsen, W Czajkowski, S Davidson, K Elwood, W Hillhouse, J Keefe, F Patrick, H Stirratt, M Szalacha, L AF Nilsen, Wendy Czajkowski, Susan Davidson, Karina Elwood, William Hillhouse, Joel Keefe, Francis Patrick, Heather Stirratt, Michael Szalacha, Laura TI NIH GRANT WRITING SEMINAR FOR EARLY CAREER RESEARCHERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nilsen, Wendy; Elwood, William] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Keefe, Francis] Duke Univ, Durham, NC USA. [Davidson, Karina] Columbia Univ, New York, NC USA. [Czajkowski, Susan] NHLBI, NIH, Bethesda, MD 20892 USA. [Stirratt, Michael] NIMH, NIH, Bethesda, MD 20892 USA. [Patrick, Heather] NCI, NIH, Bethesda, MD 20892 USA. [Hillhouse, Joel] E Tennessee State Univ, Johnson City, TN 37614 USA. [Szalacha, Laura] Ohio State Univ, Columbus, OH 43210 USA. EM nilsenwj@od.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S3 EP S3 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300009 ER PT J AU Pagoto, S Turner-McGrievy, G Evans, M Sepah, C Nilson, W AF Pagoto, Sherry Turner-McGrievy, Gabrielle Evans, Martinus Sepah, Cameron Nilson, Wendy TI WEIGHT LOSS IN THE AGE OF SOCIAL MEDIA: TWITTER, FACEBOOK, AND BLOGGING SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Pagoto, Sherry] Univ Massachusetts, Sch Med, Worcester, MA 01701 USA. [Turner-McGrievy, Gabrielle] Univ S Carolina, Columbia, SC 29208 USA. [Evans, Martinus] Univ Connecticut, Storr, CT USA. [Sepah, Cameron] Omada Hlth, San Francisco, CA USA. [Sepah, Cameron] UCSF, San Francisco, CA USA. [Nilson, Wendy] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. EM sherry.pagoto@umassmed.edu NR 0 TC 0 Z9 0 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S73 EP S73 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300279 ER PT J AU Phillips, SM Stampfer, MJ Chan, JM Giovannucci, EL Kenfield, SA AF Phillips, Siobhan M. Stampfer, Meir J. Chan, June M. Giovannucci, Edward L. Kenfield, Stacey A. TI PHYSICAL ACTIVITY, TV WATCHING AND HEALTH RELATED QUALITY OF LIFE IN PROSTATE CANCER SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Phillips, Siobhan M.] NCI, Rockville, MD 20850 USA. [Stampfer, Meir J.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Stampfer, Meir J.; Giovannucci, Edward L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Stampfer, Meir J.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, June M.; Kenfield, Stacey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. EM siobhan.white@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S131 EP S131 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300502 ER PT J AU Quintiliani, LM Turner-McGrievy, G Bennett, GG Hekler, EB Iyer, AK Nilsen, WJ AF Quintiliani, Lisa M. Turner-McGrievy, Gabrielle Bennett, Gary G. Hekler, Eric B. Iyer, Anand K. Nilsen, Wendy J. TI ACADEMIC-INDUSTRY PARTNERSHIPS IN EHEALTH ACROSS MULTIPLE BEHAVIORS: A PANEL DISCUSSION OF THE BENEFITS AND RISKS FOR YOUR RESEARCH PORTFOLIO SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Quintiliani, Lisa M.] Boston Univ, Boston, MA 02118 USA. [Turner-McGrievy, Gabrielle] Univ S Carolina, Columbia, SC 29208 USA. [Bennett, Gary G.] Duke Univ, Durham, NC USA. [Hekler, Eric B.] Arizona State Univ, Phoenix, AZ USA. [Iyer, Anand K.] WellDoc Inc, Baltimore, MD USA. [Nilsen, Wendy J.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. EM lmquinti@bu.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S153 EP S153 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300588 ER PT J AU Reese, JB Carpenter, KM Nelson, CJ Bober, SL Rowland, JH AF Reese, Jennifer B. Carpenter, Kristen M. Nelson, Christian J. Bober, Sharon L. Rowland, Julia H. TI NOVEL APPROACHES TO ADDRESSING SEXUAL CONCERNS FOR CANCER SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Reese, Jennifer B.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. [Carpenter, Kristen M.] Ohio State Univ, Columbus, OH 43210 USA. [Nelson, Christian J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bober, Sharon L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rowland, Julia H.] NCI, Bethesda, MD 20892 USA. EM jreese13@jhmi.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S76 EP S76 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300289 ER PT J AU Riddle, M Clark, D Weber, W Hesse, B AF Riddle, Melissa Clark, Dave Weber, Wendy Hesse, Bradford TI RIGOR AND REPRODUCIBILITY IN BEHAVIORAL MEDICINE RESEARCH: NIH PERSPECTIVES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Riddle, Melissa; Clark, Dave] NIDCR, NIH, Bethesda, MD 20892 USA. [Weber, Wendy] NIH, NCCAM, Bethesda, MD 20892 USA. [Hesse, Bradford] NCI, NIH, Bethesda, MD 20892 USA. EM riddleme@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S153 EP S153 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300587 ER PT J AU Riley, W Martin, C Rivera, D Hekler, E Buman, M Adams, M King, A Pavel, M AF Riley, William Martin, Cesar Rivera, Daniel Hekler, Eric Buman, Matthew Adams, Marc King, Abby Pavel, Misha TI THE DEVELOPMENT OF A CONTROL SYSTEMS MODEL OF SOCIAL COGNITIVE THEORY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Riley, William] NCI, Rockville, MD 20850 USA. [Martin, Cesar; Rivera, Daniel; Hekler, Eric; Buman, Matthew; Adams, Marc] Arizona State Univ, Tempe, AZ USA. [King, Abby] Stanford Univ, Stanford, CA 94305 USA. [Pavel, Misha] Natl Sci Fdn, Arlington, VA 22230 USA. EM wiriley@mail.nih.gov RI Adams, Marc/C-3513-2013 OI Adams, Marc/0000-0001-6310-1472 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S149 EP S149 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300572 ER PT J AU Ritterband, LM Shaikh, AR Strecher, VJ Krein, SH Tarini, P Riley, WT AF Ritterband, Lee M. Shaikh, Abdul R. Strecher, Victor J. Krein, Steven H. Tarini, Paul Riley, William T. TI FROM DEVELOPMENT TO EVALUATION & ANALYSIS TO DISSEMINATION: DEAD ON ARRIVAL SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ritterband, Lee M.] Univ Virginia, Charlottesville, VA 22903 USA. [Shaikh, Abdul R.] PricewaterhouseCoopers, Mclean, VA USA. [Strecher, Victor J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Krein, Steven H.] StartUp Hlth, New York, NY USA. [Tarini, Paul] RWJF, Princeton, NJ USA. [Riley, William T.] NCI, Bethesda, MD 20892 USA. EM leer@virginia.edu RI Ritterband, Lee/G-7810-2011 OI Ritterband, Lee/0000-0001-7624-5213 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S153 EP S153 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300589 ER PT J AU Ross, A Yang, L Wehrlen, L Klagholz, S Bevans, M AF Ross, Alyson Yang, Li Wehrlen, Leslie Klagholz, Stephen Bevans, Margaret TI DO HEALTHY BEHAVIORS HAVE A RELATIONSHIP WITH SLEEP DISTURBANCES AND FATIGUE IN TRANSPLANT CAREGIVERS? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ross, Alyson; Yang, Li; Wehrlen, Leslie; Klagholz, Stephen; Bevans, Margaret] NIH, Ctr Clin, Bethesda, MD 20892 USA. EM alyson.ross@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S178 EP S178 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300681 ER PT J AU Schindler-Ruwisch, J Augustson, E Patrick, H Sanders, A Taylor, S AF Schindler-Ruwisch, Jennifer Augustson, Erik Patrick, Heather Sanders, Amy Taylor, Shani TI EXPLORING BMI AND SMOKING STATUS AS INTERRELATED RISK FACTORS AMONG USERS OF WEB-BASED CESSATION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Schindler-Ruwisch, Jennifer; Augustson, Erik; Patrick, Heather; Sanders, Amy; Taylor, Shani] NCI, Rockville, MD 20850 USA. [Schindler-Ruwisch, Jennifer] BLH Technol Inc, Rockville, MD USA. [Sanders, Amy; Taylor, Shani] MMG Inc, Rockville, MD USA. EM jennifer.schindler@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S169 EP S169 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300645 ER PT J AU Starosta, AJ Martin, S Wolters, P Widemann, B AF Starosta, Amy J. Martin, Staci Wolters, Pam Widemann, Brigitte TI IMPACT OF SUSTAINED ATTENTION ON PAIN INTENSITY AND PAIN INTERFERENCE IN YOUTH WITH NEUROFIBROMATOSIS TYPE 1 (NF1) AND PLEXIFORM NEUROFIBROMAS (PNS) SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Starosta, Amy J.] SUNY Albany, Albany, NY 12222 USA. [Starosta, Amy J.; Martin, Staci; Wolters, Pam; Widemann, Brigitte] NCI, Bethesda, MD 20892 USA. EM as182232@albany.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S81 EP S81 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300308 ER PT J AU Steel, J Kim, Y Shaffer, KM Rowland, JH AF Steel, Jennifer Kim, Youngmee Shaffer, Kelly M. Rowland, Julia H. TI IT TAKES TWO TO CARE: INNOVATIVE DYADIC APPROACH TO CANCER CARE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kim, Youngmee; Shaffer, Kelly M.] Univ Miami, Coral Gables, FL 33124 USA. [Steel, Jennifer] Univ Pittsburgh, Pittsburgh, PA USA. [Rowland, Julia H.] NCI, Dc, DC USA. EM ykim@miami.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S59 EP S59 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300230 ER PT J AU Stokes, E Wiener, L Muriel, AC Loucas, C Pelletier, W Battles, H Zadeh, S AF Stokes, Elaina Wiener, Lori Muriel, Anna C. Loucas, Caitlyn Pelletier, Wendy Battles, Haven Zadeh, Sima TI PARENTS' USE OF DYADIC COPING STRATEGIES DURING ADJUSTMENT TO THEIR CHILD'S CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Stokes, Elaina; Wiener, Lori; Battles, Haven; Zadeh, Sima] NCI, NIH, Bethesda, MD 20892 USA. [Muriel, Anna C.; Loucas, Caitlyn] Dana Farber Canc Inst, Div Pediat Psychosocial Oncol, Boston, MA 02115 USA. [Pelletier, Wendy] Alberta Childrens Prov Gen Hosp, Hematol Oncol Transplant Program, Calgary, AB, Canada. EM evstokes@gmail.com NR 0 TC 0 Z9 0 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S103 EP S103 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300390 ER PT J AU Stoney, C Kaufmann, P Czajkowski, S AF Stoney, Catherine Kaufmann, Peter Czajkowski, Susan TI SCIENTIFIC PRIORITIES AT THE NATIONAL HEART, LUNG, AND BLOOD INSTITUTE, NIH SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Stoney, Catherine; Kaufmann, Peter; Czajkowski, Susan] NHLBI, NIH, Bethesda, MD 20892 USA. EM stoneyc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S154 EP S154 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300593 ER PT J AU Zarrett, N Czajkowski, SM Blanck, HM Yaroch, AL AF Zarrett, Nicole Czajkowski, Susan M. Blanck, Heidi Michels Yaroch, Amy Lazarus TI FUNDING OPPORTUNITIES AND STRATEGIES FOR DIET, PHYSICAL ACTIVITY, AND OBESITY PREVENTION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Zarrett, Nicole] Univ S Carolina, Columbia, SC 29208 USA. [Czajkowski, Susan M.] NIH, Div Cardiovasc Sci, Clin Applicat & Prevent Branch, Bethesda, MD 20892 USA. [Blanck, Heidi Michels] CDC, Div Nutr Phys Act & Obes, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Yaroch, Amy Lazarus] Gretchen Swanson Ctr Nutr, Omaha, NE USA. EM zarrettn@mailbox.sc.edu NR 0 TC 0 Z9 0 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S63 EP S63 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300242 ER PT J AU George, SM Ballard-Barbash, R Shikany, JM Caan, BJ Freudenheim, JL Kroenke, CH Vitolins, MZ Beresford, SA Neuhouser, ML AF George, Stephanie M. Ballard-Barbash, Rachel Shikany, James M. Caan, Bette J. Freudenheim, Jo L. Kroenke, Candyce H. Vitolins, Mara Z. Beresford, Shirley A. Neuhouser, Marian L. TI Better Postdiagnosis Diet Quality Is Associated with Reduced Risk of Death among Postmenopausal Women with Invasive Breast Cancer in the Women's Health Initiative SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID PHYSICAL-ACTIVITY; EATING INDEX-2005; SURVIVAL; PATTERNS; QUESTIONNAIRE; RECURRENCE; NUTRITION; DIAGNOSIS; BIOMARKER; INDEXES AB Background: Few studies have evaluated whether adherence to dietary recommendations is associated with mortality among cancer survivors. In breast cancer survivors, we examined how postdiagnosis Healthy Eating Index (HEI)-2005 scores were associated with all-cause and cause-specific mortality. Methods: Our prospective cohort study included 2,317 postmenopausal women, ages 50 to 79 years, in the Women's Health Initiative's Dietary Modification Trial (n = 1,205) and Observational Study (n = 1,112), who were diagnosed with invasive breast cancer and completed a food frequency questionnaire after being diagnosed. We followed women from this assessment forward. We used Cox proportional hazards models to estimate multivariate-adjusted HRs and 95% confidence intervals (CI) for death from any cause, breast cancer, and causes other than breast cancer, according to HEI-2005 quintiles. Results: Over 9.6 years, 415 deaths occurred. After adjustment for key covariates, women consuming better quality diets had a 26% lower risk of death from any cause (HRQ4:Q1, 0.74; 95% CI, 0.55-0.99; P-trend = 0.043) and a 42% lower risk of death from non-breast cancer causes (HRQ4:Q1, 0.58; 95% CI, 0.38-0.87; P-trend = 0.011). HEI-2005 score was not associated with breast cancer death (HRQ4:Q1, 0.91; 95% CI, 0.60-1.40; P-trend = 0.627). In analyses stratified by tumor estrogen receptor (ER) status, better diet quality was associated with a reduced risk of all-cause mortality among women with ER+ tumors (n = 1,758; HRQ4:Q1, 0.55; 95% CI, 0.38-0.79; P-trend = 0.0009). Conclusion: Better postdiagnosis diet quality was associated with reduced risk of death, particularly from non-breast cancer causes. Impact: Breast cancer survivors may experience improved survival by adhering to U. S. dietary guidelines. (C) 2014 AACR. C1 [George, Stephanie M.; Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Shikany, James M.] Univ Alabama Birmingham, Sch Med, Div Prevent Med, Birmingham, AL USA. [Caan, Bette J.; Kroenke, Candyce H.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Freudenheim, Jo L.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Vitolins, Mara Z.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Beresford, Shirley A.; Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP George, SM (reprint author), NCI, 9609 Med Ctr Dr,Room 3E408,MSC 9762, Bethesda, MD 20892 USA. EM stephanie.george@nih.gov FU Intramural NIH HHS [Z99 CA999999]; NHLBI NIH HHS [HHSN268201100046C, HHSN268201100004I, HHSN268201100001I, HHSN268201100002I]; NIA NIH HHS [HHSN271201100004C]; PHS HHS [HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C, HHSN268201100046C, HHSN268201100001C]; WHI NIH HHS [HHSN268201100004C, HHSN268201100002C, HHSN268201100001C, HHSN268201100003C] NR 42 TC 15 Z9 15 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2014 VL 23 IS 4 BP 575 EP 583 DI 10.1158/1055-9965.EPI-13-1162 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZR UT WOS:000335145000002 PM 24493629 ER PT J AU Brinton, LA Scoccia, B Moghissi, KS Westhoff, CL Niwa, S Ruggieri, D Trabert, B Lamb, EJ AF Brinton, Louise A. Scoccia, Bert Moghissi, Kamran S. Westhoff, Carolyn L. Niwa, Shelley Ruggieri, David Trabert, Britton Lamb, Emmet J. TI Long-term Relationship of Ovulation-Stimulating Drugs to Breast Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID IN-VITRO FERTILIZATION; FERTILITY DRUGS; INFERTILE WOMEN; OVARIAN-CANCER; POSSIBLE ASSOCIATION; POOLED ANALYSIS; FOLLOW-UP; COHORT; INDUCTION; EXPOSURE AB Background: Although fertility drugs stimulate ovulation and raise estradiol levels, their effect on breast cancer risk remains unresolved. Methods: An extended follow-up was conducted among a cohort of 12,193 women evaluated for infertility between 1965 and 1988 at five U. S. sites. Follow-up through 2010 was achieved for 9,892 women (81.1% of the eligible population) via passive as well as active (questionnaires) means. Cox regression determined HRs and 95% confidence intervals (CI) for fertility treatments adjusted for breast cancer risk factors and causes of infertility. Results: During 30.0 median years of follow-up (285,332 person-years), 749 breast cancers were observed. Ever use of clomiphene citrate among 38.1% of patients was not associated with risk (HR = 1.05; 95% CI, 0.90-1.22 vs. never use). However, somewhat higher risks were seen for patients who received multiple cycles, with the risk for invasive cancers confirmed by medical records being significantly elevated (HR = 1.69; 95% CI, 1.17-2.46). This risk remained relatively unchanged after adjustment for causes of infertility and multiple breast cancer predictors. Gonadotropins, used by 9.6% of patients, mainly in conjunction with clomiphene, showed inconsistent associations with risk, although a significant relationship of use with invasive cancers was seen among women who remained nulligravid (HR = 1.98; 95% CI, 1.04-3.60). Conclusions: Although the increased breast cancer risk among nulligravid women associated with gonadotropins most likely reflects an effect of underlying causes of infertility, reasons for the elevated risk associated with multiple clomiphene cycles are less clear. Impact: Given our focus on a relatively young population, additional evaluation of long-term fertility drug effects on breast cancer is warranted. (C) 2014 AACR. C1 [Brinton, Louise A.; Trabert, Britton] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Niwa, Shelley] Westat Corp, Rockville, MD USA. [Ruggieri, David] IMS Inc, Rockville, MD USA. [Scoccia, Bert] Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA. [Moghissi, Kamran S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Westhoff, Carolyn L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. [Lamb, Emmet J.] Stanford Univ, Stanford, CA 94305 USA. RP Brinton, LA (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, 9609 Med Ctr Dr,MSC 9774,7E-102, Rockville, MD 20892 USA. EM brintonl@mail.nih.gov RI Brinton, Louise/G-7486-2015; Trabert, Britton/F-8051-2015 OI Brinton, Louise/0000-0003-3853-8562; FU National Cancer Institute, National Institutes of Health FX Cancer incidence data have been provided by the following cancer registries and/or state departments of health: Arizona Cancer Registry; California Department of Public Health; State of Connecticut Department of Public Health; Florida Cancer Data System; Illinois Department of Public Health, Illinois State Cancer Registry; Indiana State Department of Health; Massachusetts Cancer Registry, Massachusetts Department of Public Health; Michigan Cancer Surveillance Program of the Michigan Department of Community Health; New Hampshire Department of Health and Human Services; New Jersey Cancer Registry; New York State Health Department; Ohio Cancer Incidence Surveillance System, Ohio Department of Health; Bureau of Health Statistics & Research, Pennsylvania Department of Health; Texas Cancer Registry, Texas Department of State Health Services. The authors assume full responsibility for the analyses, interpretations, and conclusions in this publication and endorsement by the state cancer registries is not intended nor should be inferred. This study was supported in part by funds from the intramural research component of the National Cancer Institute, National Institutes of Health.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 34 TC 9 Z9 9 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2014 VL 23 IS 4 BP 584 EP 593 DI 10.1158/1055-9965.EPI-13-0996 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZR UT WOS:000335145000003 PM 24700523 ER PT J AU Ahsan, H Halpern, J Kibriya, MG Pierce, BL Tong, L Gamazon, E McGuire, V Felberg, A Shi, JX Jasmine, F Roy, S Brutus, R Argos, M Melkonian, S Chang-Claude, J Andrulis, I Hopper, JL John, EM Malone, K Ursin, G Gammon, MD Thomas, DC Seminara, D Casey, G Knight, JA Southey, MC Giles, GG Santella, RM Lee, E Conti, D Duggan, D Gallinger, S Haile, R Jenkins, M Lindor, NM Newcomb, P Michailidou, K Apicella, C Park, DJ Peto, J Fletcher, O Silva, ID Lathrop, M Hunter, DJ Chanock, SJ Meindl, A Schmutzler, RK Muller-Myhsok, B Lochmann, M Beckmann, L Hein, R Makalic, E Schmidt, DF Bui, QM Stone, J Flesch-Janys, D Dahmen, N Nevanlinna, H Aittomaki, K Blomqvist, C Hall, P Czene, K Irwanto, A Liu, JJ Rahman, N Turnbull, C Dunning, AM Pharoah, P Waisfisz, Q Meijers-Heijboer, H Uitterlinden, AG Rivadeneira, F Nicolae, D Easton, DF Cox, NJ Whittemore, AS AF Ahsan, Habibul Halpern, Jerry Kibriya, Muhammad G. Pierce, Brandon L. Tong, Lin Gamazon, Eric McGuire, Valerie Felberg, Anna Shi, Jianxin Jasmine, Farzana Roy, Shantanu Brutus, Rachelle Argos, Maria Melkonian, Stephanie Chang-Claude, Jenny Andrulis, Irene Hopper, John L. John, Esther M. Malone, Kathi Ursin, Giske Gammon, Marilie D. Thomas, Duncan C. Seminara, Daniela Casey, Graham Knight, Julia A. Southey, Melissa C. Giles, Graham G. Santella, Regina M. Lee, Eunjung Conti, David Duggan, David Gallinger, Steve Haile, Robert Jenkins, Mark Lindor, Noralane M. Newcomb, Polly Michailidou, Kyriaki Apicella, Carmel Park, Daniel J. Peto, Julian Fletcher, Olivia Silva, Isabel dos Santos Lathrop, Mark Hunter, David J. Chanock, Stephen J. Meindl, Alfons Schmutzler, Rita K. Mueller-Myhsok, Bertram Lochmann, Magdalena Beckmann, Lars Hein, Rebecca Makalic, Enes Schmidt, Daniel F. Quang Minh Bui Stone, Jennifer Flesch-Janys, Dieter Dahmen, Norbert Nevanlinna, Heli Aittomaki, Kristiina Blomqvist, Carl Hall, Per Czene, Kamila Irwanto, Astrid Liu, Jianjun Rahman, Nazneen Turnbull, Clare Dunning, Alison M. Pharoah, Paul Waisfisz, Quinten Meijers-Heijboer, Hanne Uitterlinden, Andre G. Rivadeneira, Fernando Nicolae, Dan Easton, Douglas F. Cox, Nancy J. Whittemore, Alice S. CA Familial Breast Canc Study TI A Genome-wide Association Study of Early-Onset Breast Cancer Identifies PFKM as a Novel Breast Cancer Gene and Supports a Common Genetic Spectrum for Breast Cancer at Any Age SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SUSCEPTIBILITY LOCI; OVARIAN-CANCER; WHOLE-GENOME; CONFER SUSCEPTIBILITY; AFRICAN-AMERICAN; FAMILY REGISTRY; CHINESE WOMEN; RISK-FACTORS; FGFR2; POPULATION AB Early-onset breast cancer (EOBC) causes substantial loss of life and productivity, creating a major burden among women worldwide. We analyzed 1,265,548 Hapmap3 single-nucleotide polymorphisms (SNP) among a discovery set of 3,523 EOBC incident cases and 2,702 population control women ages <= 51 years. The SNPs with smallest P values were examined in a replication set of 3,470EOBC cases and 5,475 control women. We also tested EOBC association with 19,684 genes by annotating each gene with putative functional SNPs, and then combining their P values to obtain a gene-based P value. We examined the gene with smallest P value for replication in 1,145 breast cancer cases and 1,142 control women. The combined discovery and replication sets identified 72 new SNPs associated with EOBC(P < 4 x 10(-8)) located in six genomic regions previously reported to contain SNPs associated largely with later-onset breast cancer (LOBC). SNP rs2229882 and 10 other SNPs on chromosome 5q11.2 remained associated (P < 6 x 10(-4)) after adjustment for the strongest published SNPs in the region. Thirty-two of the 82 currently known LOBC SNPs were associated with EOBC (P < 0.05). Low power is likely responsible for the remaining 50 unassociated known LOBC SNPs. The gene-based analysis identified an association between breast cancer and the phosphofructokinase-muscle (PFKM) gene on chromosome 12q13.11 that met the genome-wide gene-based threshold of 2.5 x 10(-6). In conclusion, EOBC and LOBC seem to have similar genetic etiologies; the 5q11.2 region may contain multiple distinct breast cancer loci; and the PFKM gene region is worthy of further investigation. These findings should enhance our understanding of the etiology of breast cancer. (C)2014 AACR. C1 [Ahsan, Habibul; Kibriya, Muhammad G.; Pierce, Brandon L.; Tong, Lin; Jasmine, Farzana; Roy, Shantanu; Brutus, Rachelle; Argos, Maria; Melkonian, Stephanie] Univ Chicago, Ctr Canc Epidemiol & Prevent, Chicago, IL 60615 USA. [Ahsan, Habibul; Kibriya, Muhammad G.; Pierce, Brandon L.; Tong, Lin; Jasmine, Farzana; Roy, Shantanu; Brutus, Rachelle; Argos, Maria; Melkonian, Stephanie] Univ Chicago, Dept Hlth Studies, Chicago, IL 60615 USA. [Ahsan, Habibul; Gamazon, Eric; Nicolae, Dan; Cox, Nancy J.] Univ Chicago, Dept Med, Chicago, IL 60615 USA. [Ahsan, Habibul; Cox, Nancy J.] Univ Chicago, Dept Human Genet, Chicago, IL 60615 USA. [Ahsan, Habibul; Pierce, Brandon L.; Cox, Nancy J.] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60615 USA. [Halpern, Jerry; McGuire, Valerie; Felberg, Anna; John, Esther M.; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [John, Esther M.] Stanford Canc Inst, Stanford, CA USA. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [Thomas, Duncan C.; Casey, Graham; Lee, Eunjung; Conti, David; Haile, Robert] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Whittemore, Alice S.] Stanford Canc Inst, Palo Alto, CA USA. [Shi, Jianxin; Seminara, Daniela] NCI, Epidemiol & Genet Res Program, Rockville, MD USA. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Malone, Kathi; Newcomb, Polly] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Gammon, Marilie D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Santella, Regina M.] Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA. [Duggan, David] Translat Genom Res Inst, Integrated Canc Genom Div, Phoenix, AZ USA. [Lindor, Noralane M.] Mayo Clin Arizona, Dept Hlth Sci Res, Scottsdale, AZ USA. [Hunter, David J.] Harvard Univ, Sch Med, Program Mol & Genet Epidemiol, Boston, MA USA. [Chang-Claude, Jenny; Hein, Rebecca] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Meindl, Alfons; Lochmann, Magdalena] Tech Univ Munich, Div Gynaecol Tumor Genet, Clin Gynaecol & Obstet, Munich, Germany. [Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Schmutzler, Rita K.] Univ Cologne, Dept Obstet & Gynaecol, Div Mol Gynaecooncol, D-50931 Cologne, Germany. [Hein, Rebecca] Univ Cologne, Dept Child & Adolescent Psychiat & Psychotherapy, PMV Res Grp, D-50931 Cologne, Germany. [Beckmann, Lars] Fdn Qual & Efficiency Hlth Care, Cologne, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, Hamburg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany. [Dahmen, Norbert] Johannes Gutenberg Univ Mainz, Dept Psychiat, Mainz, Germany. [Andrulis, Irene; Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Gallinger, Steve] Mt Sinai Hosp, Zane Cohen Ctr Digest Dis, Toronto, ON M5G 1X5, Canada. [Hopper, John L.; Southey, Melissa C.; Giles, Graham G.; Apicella, Carmel; Makalic, Enes; Schmidt, Daniel F.; Quang Minh Bui; Stone, Jennifer] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Southey, Melissa C.; Park, Daniel J.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia. [Giles, Graham G.; Jenkins, Mark] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Michailidou, Kyriaki; Pharoah, Paul; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Dunning, Alison M.; Pharoah, Paul; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England. [Peto, Julian; Silva, Isabel dos Santos] London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Dept, London WC1, England. [Fletcher, Olivia] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Rahman, Nazneen; Turnbull, Clare] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England. [Lathrop, Mark] Ctr Natl Genotypage, Evry, France. [Lathrop, Mark] Fdn Jean Dausset CEPH, Paris, France. [Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Aittomaki, Kristiina] Univ Helsinki, Dept Clin Genet, Helsinki, Finland. [Blomqvist, Carl] Univ Helsinki, Dept Oncol, Helsinki, Finland. [Blomqvist, Carl] Univ Helsinki, Dept Oncol, Helsinki, Finland. [Hall, Per; Czene, Kamila] Karolinska Inst, Stockholm, Sweden. [Irwanto, Astrid; Liu, Jianjun] Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [Waisfisz, Quinten; Meijers-Heijboer, Hanne] Vrije Univ Amsterdam Med Ctr, Div Oncogenet, Dept Clin Genet, Amsterdam, Netherlands. [Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med & Epidemiol, Rotterdam, Netherlands. RP Ahsan, H (reprint author), Univ Chicago, Med Ctr, 5841 S Maryland Ave, Chicago, IL 60615 USA. EM habib@uchicago.edu RI Knight, Julia/A-6843-2012; Andrulis, Irene/E-7267-2013; Jenkins, Mark/P-7803-2015; Gallinger, Steven/E-4575-2013; Whittemore, Alice/F-9925-2014; Rahman, Nazneen/D-2802-2013; OI Jenkins, Mark/0000-0002-8964-6160; Rahman, Nazneen/0000-0003-4376-0440; Nevanlinna, Heli/0000-0002-0916-2976; Czene, Kamila/0000-0002-3233-5695; Dunning, Alison Margaret/0000-0001-6651-7166; Rivadeneira, Fernando/0000-0001-9435-9441; dos Santos Silva, Isabel/0000-0002-6596-8798; Pierce, Brandon/0000-0002-7829-952X; Park, Daniel/0000-0002-6354-0931; Gamazon, Eric/0000-0003-4204-8734; Giles, Graham/0000-0003-4946-9099 FU NIH [U01CA122171, RC1CA145506, R01CA094069, U19CA148065]; Cancer Care Ontario [U01 CA69467]; Cancer Prevention Institute of California (CPIC) [U01 CA69417]; University of Melbourne [U01 CA69638]; NCI, NIH [RFA-CA06-503, RFA-CA-95-011] FX This study was supported by NIH Grants U01CA122171, RC1CA145506, R01CA094069, and U19CA148065. The Breast Cancer Family Registry (BCFR) is supported by the NCI, NIH under RFA-CA06-503 and through cooperative agreements with members of the BCFR and principal investigators, including Cancer Care Ontario (U01 CA69467), Cancer Prevention Institute of California (CPIC; U01 CA69417), and University of Melbourne (U01 CA69638). Samples from the CPIC were processed and distributed by the Coriell Institute for Medical Research. The Colon Cancer Family Registry (CCFR) is supported by the NCI, NIH under RFA-CA-95-011. NR 68 TC 17 Z9 17 U1 4 U2 23 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2014 VL 23 IS 4 BP 658 EP 669 DI 10.1158/1055-9965.EPI-13-0340 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZR UT WOS:000335145000011 PM 24493630 ER PT J AU Nelson, DE Faupel-Badger, J Phillips, S Belcher, B Chang, S Abrams, DB Kramer, BS White, MC O'Malley, M Varanasi, AP Fabian, CJ Wiest, JS Colditz, GA Hall, K Shields, PG Weitzel, JN AF Nelson, David E. Faupel-Badger, Jessica Phillips, Siobhan Belcher, Britni Chang, Shine Abrams, David B. Kramer, Barnett S. White, Mary C. O'Malley, Michael Varanasi, Arti P. Fabian, Carol J. Wiest, Jonathan S. Colditz, Graham A. Hall, Kara Shields, Peter G. Weitzel, Jeffrey N. TI Future Directions for Postdoctoral Training in Cancer Prevention: Insights from a Panel of Experts SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID SYSTEMS SCIENCE; TEAM SCIENCE; HEALTH AB Cancer prevention postdoctoral fellowships have existed since the 1970s. The National Cancer Institute facilitated a meeting by a panel of experts in April 2013 to consider four important topics for future directions for cancer prevention postdoctoral training programs: (i) future research needs; (ii) underrepresented disciplines; (iii) curriculum; and (iv) career preparation. Panelists proffered several areas needing more research or emphasis, ranging from computational science to culture. Health care providers, along with persons from nontraditional disciplines in scientific training programs such as engineers and lawyers, were among those recognized as being underrepresented in training programs. Curriculum suggestions were that fellows receive training in topics such as leadership and human relations, in addition to learning the principles of epidemiology, cancer biologic mechanisms, and behavioral science. For career preparation, there was a clear recognition of the diversity of employment options available besides academic positions, and that programleaders should do more to help fellows identify and prepare for different career paths. The major topics and strategies covered at this meeting can help form the basis for cancer prevention training programleaders to consider modifications or new directions, and keep them updated with the changing scientific and employment climate for doctoral degree recipients and postdoctoral fellows. C1 [Nelson, David E.; Faupel-Badger, Jessica; Phillips, Siobhan; Belcher, Britni; Kramer, Barnett S.; Wiest, Jonathan S.; Hall, Kara] NCI, Bethesda, MD 20892 USA. [Varanasi, Arti P.] Advancing Synergy LLC, Baltimore, MD USA. [Chang, Shine] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Abrams, David B.] Legacy, Schroeder Inst Tobacco Res & Policy Studies, Washington, DC USA. [White, Mary C.] Ctr Dis Control & Prevent, Atlanta, GA USA. [O'Malley, Michael] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Fabian, Carol J.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Colditz, Graham A.] Washington Univ, Sch Med, St Louis, MO USA. [Shields, Peter G.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Duarte, CA USA. RP Nelson, DE (reprint author), NCI, 9609 Med Ctr Dr,Suite 2W-138,MSC 9712, Bethesda, MD 20892 USA. EM nelsonde@mail.nih.gov RI White, Mary /C-9242-2012; Colditz, Graham/A-3963-2009 OI White, Mary /0000-0002-9826-3962; Colditz, Graham/0000-0002-7307-0291 FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [R25 CA057726] NR 23 TC 2 Z9 2 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2014 VL 23 IS 4 BP 679 EP 683 DI 10.1158/1055-9965.EPI-13-1209 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZR UT WOS:000335145000016 PM 24604827 ER PT J AU Hirsch, D Barker, N McNeil, N Hu, Y Camps, J McKinnon, K Clevers, H Ried, T Gaiser, T AF Hirsch, Daniela Barker, Nick McNeil, Nicole Hu, Yue Camps, Jordi McKinnon, Katherine Clevers, Hans Ried, Thomas Gaiser, Timo TI LGR5 positivity defines stem-like cells in colorectal cancer SO CARCINOGENESIS LA English DT Article ID WNT/BETA-CATENIN PATHWAY; COUPLED RECEPTOR GPR49; COLON-CANCER; WNT ACTIVITY; TUMORS; REVEALS; MARKER; MODEL; GENE; DIFFERENTIATION AB Like normal colorectal epithelium, colorectal carcinomas (CRCs) are organized hierarchically and include populations of cells with stem-like properties. Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) is associated with these stem cells in normal colorectal epithelium; however, the precise function of LGR5 in CRC remains largely unknown. Here, we analyzed the functional and molecular consequences of short hairpin RNA-mediated silencing of LGR5 in CRC cell lines SW480 and HT-29. Additionally, we exposed Lgr5-EGFP-IRES-CreERT2 mice to azoxymethane/dextrane sodium sulfate (AOM/DSS), which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5 and were molecularly characterized using gene expression profiling and array comparative genomic hybridization. Silencing of LGR5 in SW480 CRC cells resulted in a depletion of spheres but did not affect adherently growing cells. Spheres expressed higher levels of several stem cell-associated genes than adherent cells, including LGR5. Silencing of LGR5 reduced proliferation, migration and colony formation in vitro and tumorigenicity in vivo. In accordance with these results, NOTCH signaling was downregulated upon LGR5 silencing. In AOM/DSS-induced colon tumors, Lgr5 high cells showed higher levels of several stem cell-associated genes and higher Wnt signaling than Lgr5 low tumor cells and Lgr5 high normal colon cells. Array comparative genomic hybridization revealed no genomic imbalances in either tumor cell fraction. Our data elucidate mechanisms that define the role of LGR5 as a marker for stem-like cells in CRC.Our functional and molecular findings link the intestinal stem cell marker LGR5 to stem-like colorectal cancer cells. LGR5 silencing reduced proliferation, migration and tumorigenicity, and NOTCH signaling. Primary mouse colon tumors maintained an Lgr5-based stem cell hierarchy. C1 [Hirsch, Daniela; McNeil, Nicole; Hu, Yue; Camps, Jordi; Ried, Thomas] NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Hirsch, Daniela] Univ Regensburg, D-93053 Regensburg, Germany. [Barker, Nick] Inst Med Biol, Singapore 138648, Singapore. [McKinnon, Katherine] NCI, FACS Core Facil, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Clevers, Hans] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands. [Gaiser, Timo] Univ Med Ctr Mannheim, Inst Pathol, D-68167 Mannheim, Germany. RP Ried, T (reprint author), NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM riedt@mail.nih.gov; timo.gaiser@umm.de FU National Institutes of Health, National Cancer Institute; German Academic Exchange Service FX Intramural Research Program, National Institutes of Health, National Cancer Institute; German Academic Exchange Service (D.H.). NR 49 TC 39 Z9 39 U1 2 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2014 VL 35 IS 4 BP 849 EP 858 DI 10.1093/carcin/bgt377 PG 10 WC Oncology SC Oncology GA AF8YL UT WOS:000335001800013 PM 24282287 ER PT J AU Lindahl, M Danilova, T Palm, E Lindholm, P Voikar, V Hakonen, E Ustinov, J Andressoo, JO Harvey, BK Otonkoski, T Rossi, J Saarma, M AF Lindahl, Maria Danilova, Tatiana Palm, Erik Lindholm, Paivi Voikar, Vootele Hakonen, Elina Ustinov, Jarkko Andressoo, Jaan-Olle Harvey, Brandon K. Otonkoski, Timo Rossi, Jari Saarma, Mart TI MANF Is Indispensable for the Proliferation and Survival of Pancreatic beta Cells SO CELL REPORTS LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; NEUROTROPHIC FACTOR; DOPAMINERGIC-NEURONS; GENE-EXPRESSION; ER STRESS; MECHANISM; APOPTOSIS; BRAIN; ARMET AB All forms of diabetes mellitus (DM) are characterized by the loss of functional pancreatic beta cell mass, leading to insufficient insulin secretion. Thus, identification of novel approaches to protect and restore b cells is essential for the development of DM therapies. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stressinducible protein, but its physiological role in mammals has remained obscure. We generated MANF-deficient mice that strikingly develop severe diabetes due to progressive postnatal reduction of beta cell mass, caused by decreased proliferation and increased apoptosis. Additionally, we show that lack of MANF in vivo in mouse leads to chronic unfolded protein response (UPR) activation in pancreatic islets. Importantly, MANF protein enhanced beta cell proliferation in vitro and overexpression of MANF in the pancreas of diabetic mice enhanced beta cell regeneration. We demonstrate that MANF specifically promotes beta cell proliferation and survival, thereby constituting a therapeutic candidate for beta cell protection and regeneration. C1 [Lindahl, Maria; Danilova, Tatiana; Palm, Erik; Lindholm, Paivi; Andressoo, Jaan-Olle; Saarma, Mart] Univ Helsinki, Inst Biotechnol, Helsinki 00014, Finland. [Voikar, Vootele] Univ Helsinki, Ctr Neurosci, FIN-00014 Helsinki, Finland. [Hakonen, Elina; Ustinov, Jarkko; Otonkoski, Timo] Univ Helsinki, Res Program Mol Neurol, FIN-00014 Helsinki, Finland. [Hakonen, Elina; Ustinov, Jarkko; Otonkoski, Timo] Univ Helsinki, Biomedicum Stem Cell Ctr, FIN-00014 Helsinki, Finland. [Harvey, Brandon K.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Otonkoski, Timo] Univ Helsinki, Cent Hosp, Childrens Hosp, Helsinki 00014, Finland. [Rossi, Jari] Univ Helsinki, Inst Biomed, FIN-00014 Helsinki, Finland. RP Lindahl, M (reprint author), Univ Helsinki, Inst Biotechnol, Viikinkaari 9, Helsinki 00014, Finland. EM maria.lindahl@helsinki.fi OI Rossi, Jari/0000-0002-3728-9800; Voikar, Vootele/0000-0003-4201-8666 FU Academy of Finland [117044, 260030]; Commission of the European Union [400752]; Lundbeck Foundation, personal price Mart Saarma [7519003]; Sigrid Juselius Foundation [4701537]; Juvenile Diabetes Research Foundation [17-2013-410] FX S.A kerberg, S. Wiss, and D. Howard are thanked for excellent technical assistance. We thank Frank Grosvelt for CAG-Flp mice and Edgar Kramer for Nestin-Cre mice. We acknowledge NIH KOMP for the MANF-targeted ESC clone. M. L. was supported by grant no. 117044 and J.R. by grant no. 260030 from the Academy of Finland. This work was supported by grants from the Commission of the European Union, collaborative project MOLPARK, no. 400752; The Lundbeck Foundation, personal price Mart Saarma, 2009, no. 7519003; Sigrid Juselius Foundation no. 4701537; and the Juvenile Diabetes Research Foundation no. 17-2013-410. University of Helsinki has filed a patent application based on these data with M.L., T.D., E.P., P.L., J.R., and M.S. as inventors. University of Helsinki owns intellectual property rights. NR 27 TC 23 Z9 24 U1 1 U2 15 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 APR PY 2014 VL 7 IS 2 BP 366 EP 375 DI 10.1016/j.celrep.2014.03.023 PG 10 WC Cell Biology SC Cell Biology GA AG5EO UT WOS:000335442300008 PM 24726366 ER PT J AU Goncharova, EA Goncharov, DA James, ML Atochina-Vasserman, EN Stepanova, V Hong, SB Li, H Gonzales, L Baba, M Linehan, WM Gow, AJ Margulies, S Guttentag, S Schmidt, LS Krymskaya, VP AF Goncharova, Elena A. Goncharov, Dmitry A. James, Melane L. Atochina-Vasserman, Elena N. Stepanova, Victoria Hong, Seung-Beom Li, Hua Gonzales, Linda Baba, Masaya Linehan, W. Marston Gow, Andrew J. Margulies, Susan Guttentag, Susan Schmidt, Laura S. Krymskaya, Vera P. TI Folliculin Controls Lung Alveolar Enlargement and Epithelial Cell Survival through E-Cadherin, LKB1, and AMPK SO CELL REPORTS LA English DT Article ID BIRT-HOGG-DUBE; ACTIVATED PROTEIN-KINASE; HERMANSKY-PUDLAK-SYNDROME; TUMOR-SUPPRESSOR FLCN; MOUSE MODEL; GENE; MIGRATION; GENODERMATOSIS; PROLIFERATION; LOCALIZATION AB Spontaneous pneumothoraces due to lung cyst rupture afflict patients with the rare disease Birt-Hogg- Dube (BHD) syndrome, which is caused by mutations of the tumor suppressor gene folliculin (FLCN). The underlying mechanism of the lung manifestations in BHD is unclear. We show that BHD lungs exhibit increased alveolar epithelial cell apoptosis and that Flcn deletion in mouse lung epithelium leads to cell apoptosis, alveolar enlargement, and an impairment of both epithelial barrier and overall lung function. We find that Flcn-null epithelial cell apoptosis is the result of impaired AMPK activation and increased cleaved caspase-3. AMPK activator LKB1 and E-cadherin are downregulated by Flcn loss and restored by its expression. Correspondingly, Flcn-null cell survival is rescued by the AMPK activator AICAR or constitutively active AMPK. AICAR also improves lung condition of Flcn(f/f) : SP-C-Cre mice. Our data suggest that lung cysts in BHD may result from an underlying defect in alveolar epithelial cell survival, attributable to FLCN regulation of the E-cadherin-LKB1-AMPK axis. C1 [Goncharova, Elena A.; Goncharov, Dmitry A.; James, Melane L.; Atochina-Vasserman, Elena N.; Hong, Seung-Beom; Li, Hua; Krymskaya, Vera P.] Perelman Sch Med, Dept Med, Airways Biol Initiat, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. [Stepanova, Victoria] Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Margulies, Susan] Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA. [Gonzales, Linda; Guttentag, Susan] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Goncharova, Elena A.; Goncharov, Dmitry A.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15261 USA. [Gow, Andrew J.] Rutgers State Univ, Dept Pharmacol & Toxicol, Piscataway, NJ 08854 USA. [Baba, Masaya; Linehan, W. Marston; Schmidt, Laura S.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Schmidt, Laura S.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 20892 USA. RP Krymskaya, VP (reprint author), Perelman Sch Med, Dept Med, Airways Biol Initiat, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. EM krymskay@mail.med.upenn.edu RI Baba, Masaya/L-7490-2013; Gow, Andrew/N-8566-2013; Guttentag, Susan/D-8705-2013 OI Baba, Masaya/0000-0002-5308-6683; Gow, Andrew/0000-0003-0876-5158; Guttentag, Susan/0000-0003-4420-5879 FU Frederick National Laboratory for Cancer Research; Intramural Research Program of NIH; Center for Cancer Research; Frederick National Laboratory for Cancer Research, NIH [HHSN261200800001E]; NIH/NHLBI [RO1 HL110551]; Myrovlytis Trust FX We thank Dr. Jeffrey A. Whitsett (Cincinnati Children's Hospital Medical Center) for generously providing SP-C-rtTA/tetO-Cre (line 2) mice and CCSP-rtTA/tetO-Cre (line 2) mice; Dr. Cheryl Walker (Texas A&M Health Science Center) for the generous gift of rat TSC2-null cells; Dr. Leslie A. Litzky (University of Pennsylvania) for help with tissue specimens from patients with BHD; Dr. Chang-Jiang Guo and Helen Abramova (Rutgers University) for excellent technical support; Ms. Sharmin Islam for preparing Figure S1A; and Mr. Nathan Tessema Ersumo for exceptional help with Figures 1 and 2, the graphical abstract, slider image, and technical assistance with the manuscript. This research was supported by the Intramural Research Program of NIH, Frederick National Laboratory for Cancer Research, and the Center for Cancer Research. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, NIH, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the DHHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This work was supported by NIH/NHLBI RO1 HL110551 (to V.P.K.) and the Myrovlytis Trust (to S.-B.H. and V. P. K.). NR 46 TC 14 Z9 14 U1 0 U2 6 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 APR PY 2014 VL 7 IS 2 BP 412 EP 423 DI 10.1016/j.celrep.2014.03.025 PG 12 WC Cell Biology SC Cell Biology GA AG5EO UT WOS:000335442300012 PM 24726356 ER PT J AU Sipe, HJ Lardinois, OM Mason, RP AF Sipe, Herbert J., Jr. Lardinois, Olivier M. Mason, Ronald P. TI Free Radical Metabolism of Methyleugenol and Related Compounds SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID EUGENOL-RELATED COMPOUNDS; SPIN-RESONANCE SPECTRA; ALKENYLBENZENE METHYLEUGENOL; HORSERADISH-PEROXIDASE; RAT-LIVER; OXIDATION; METHOXYBENZENES; DETOXIFICATION; BIOACTIVATION; CYTOTOXICITY AB Methyleugenol, the methyl ether of eugenol, both of which are flavorant constituents of spices, has been listed by the National Toxicology Program's Report on Carcinogens as reasonably anticipated to be a human carcinogen. This finding is based on the observation of increased incidence of malignant tumors at multiple tissue sites in experimental animals of different species. By contrast, eugenol is not listed. In this study, we show that both methyleugenol and eugenol readily undergo peroxidative metabolism in vitro to form free radicals with large hyperfine interactions of the methylene allylic hydrogen atoms. These large hyperfine splittings indicate large electron densities adjacent to those hydrogen atoms. Methyleugenol undergoes autoxidation such that the commercial product contains 10-30 mg/L hydroperoxide and is capable of activating peroxidases without the presence of added hydrogen peroxide. Additionally, the hydroperoxide is not a good substrate for catalase, which demonstrates that these antioxidant defenses will not be effective in protecting against methyleugenol exposure. C1 [Sipe, Herbert J., Jr.; Lardinois, Olivier M.; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. RP Sipe, HJ (reprint author), Hampden Sydney Coll, Dept Chem, Hampden Sydney, VA 23943 USA. EM hsipe@hsc.edu FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 44 TC 1 Z9 1 U1 4 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X EI 1520-5010 J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 2014 VL 27 IS 4 BP 483 EP 489 DI 10.1021/tx400256b PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA AF7NP UT WOS:000334902100005 PM 24564854 ER PT J AU Sinha, BK Leinisch, F Bhattacharjee, S Mason, RP AF Sinha, Birandra K. Leinisch, Fabian Bhattacharjee, Suchandra Mason, Ronald P. TI DNA Cleavage and Detection of DNA Radicals Formed from Hydralazine and Copper (II) by ESR and Immuno-Spin Trapping SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID NITROGEN-CENTERED RADICALS; HYDROGEN-PEROXIDE; HYDRAZINE DERIVATIVES; DAMAGE; SITE; ACTIVATION; METABOLISM; CANCER; INVIVO; BASES AB Metal ion-catalyzed oxidation of hydrazine and its derivatives leads to the formation of the hydrazyl radical and subsequently to oxy-radicals in the presence of molecular oxygen. Here, we have examined the role of Cu2+-catalyzed oxidation of hydralazine in the induction of DNA damage. Neither 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) nor dimethyl sulfoxide (DMSO) was effective in inhibiting hydralazine-Cu2+-induced DNA damage. Singlet oxygen did not appear to participate in this DNA cleavage. The one-electron oxidation of hydralazine also leads to the formation of DNA radicals as confirmed by immunospin trapping with 5,5-dimethyl-1-pyrroline-N-oxide. Electron spin resonance (ESR) and spin-trapping studies further confirmed the formation of DNA radicals; predominantly, 2'-deoxyadenosine radical adducts were detected, while some radicals were also detected with other nucleosides. Our results suggest that free hydroxyl radicals may not be the main damaging species causing DNA cleavage and that possibly Cu-peroxide complexes, formed from Cu+-H2O2, are responsible for this hydralazine-Cu2+-induced DNA cleavage. C1 [Sinha, Birandra K.; Leinisch, Fabian; Bhattacharjee, Suchandra; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. RP Sinha, BK (reprint author), NIEHS, Lab Toxicol & Pharmacol, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM sinha1@niehs.nih.gov FU 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 61 TC 6 Z9 6 U1 1 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X EI 1520-5010 J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 2014 VL 27 IS 4 BP 674 EP 682 DI 10.1021/tx500011m PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA AF7NP UT WOS:000334902100024 PM 24502259 ER PT J AU Gounden, V Soldin, SJ AF Gounden, Verena Soldin, Steven J. TI Tacrolimus Measurement: Building a Better Immunoassay SO CLINICAL CHEMISTRY LA English DT Editorial Material ID TANDEM MASS-SPECTROMETRY; IMMUNOSUPPRESSIVE DRUGS; TRANSPLANTATION; FK-506; PERFORMANCE; LIVER C1 [Gounden, Verena; Soldin, Steven J.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Soldin, Steven J.] Georgetown Univ, Dept Med, Washington, DC USA. RP Soldin, SJ (reprint author), NIH, Dept Lab Med, Ctr Clin, Bldg 10,Rm 2C-249, Bethesda, MD 20892 USA. EM soldinsj@cc.nih.gov NR 15 TC 1 Z9 2 U1 0 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2014 VL 60 IS 4 BP 575 EP 576 DI 10.1373/clinchem.2013.220012 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AG1AO UT WOS:000335147400002 PM 24415738 ER PT J AU Desrosiers, NA Himes, SK Scheidweiler, KB Concheiro-Guisan, M Gorelick, DA Huestis, MA AF Desrosiers, Nathalie A. Himes, Sarah K. Scheidweiler, Karl B. Concheiro-Guisan, Marta Gorelick, David A. Huestis, Marilyn A. TI Phase I and II Cannabinoid Disposition in Blood and Plasma of Occasional and Frequent Smokers Following Controlled Smoked Cannabis SO CLINICAL CHEMISTRY LA English DT Article ID SINGLE-DOSE KINETICS; ORAL FLUID; HEAVY USERS; WHOLE-BLOOD; SMOKING; METABOLISM; MARIJUANA; DELTA(9)-TETRAHYDROCANNABINOL; PHARMACOKINETICS; SERUM AB BACKGROUND: Delta(9)-Tetrahydrocannabinol (THC), 11-hydroxy- THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) have been reported in blood from frequent cannabis smokers for an extended time during abstinence. We compared THC, 11-OH-THC, THCCOOH, cannabidiol, cannabinol, THCglucuronide, and 11-nor-9-carboxy-THC-glucuronide (THCCOO-glucuronide) blood and plasma disposition in frequent and occasional cannabis smokers. METHODS: Frequent and occasional smokers resided on a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum. Blood and plasma cannabinoids were quantified on admission (approximately 19 h before), 1 h before, and up to 15 times (0.5-30 h) after smoking. RESULTS: Cannabinoid blood and plasma concentrations were significantly higher in frequent smokers compared with occasional smokers at most time points for THC and 11-OH-THC and at all time points for THCCOOH and THCCOO-glucuronide. Cannabidiol, cannabinol, and THC-glucuronide were not significantly different at any time point. Overall blood and plasma cannabinoid concentrations were significantly higher in frequent smokers for THC, 11-OH-THC, THCCOOH, and THCCOO-glucuronide, with and without accounting for baseline concentrations. For blood THC >5 mu g/L, median (range) time of last detection was 3.5 h (1.1->30 h) in frequent smokers and 1.0 h (0-2.1 h) in 11 occasional smokers; 2 individuals had no samples with THC >5 mu g/L. CONCLUSIONS: Cannabis smoking history plays a major role in cannabinoid detection. These differences may impact clinical and impaired driving drug detection. The presence of cannabidiol, cannabinol, or THCglucuronide indicates recent use, but their absence does not exclude it. (C) 2014 American Association for Clinical Chemistry C1 [Desrosiers, Nathalie A.; Himes, Sarah K.; Scheidweiler, Karl B.; Concheiro-Guisan, Marta; Gorelick, David A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Desrosiers, Nathalie A.; Himes, Sarah K.] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural Research Program, National Institute on Drug Abuse, NIH FX The Intramural Research Program, National Institute on Drug Abuse, NIH. NR 25 TC 28 Z9 28 U1 6 U2 24 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2014 VL 60 IS 4 BP 631 EP 643 DI 10.1373/clinchem.2013.216507 PG 13 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AG1AO UT WOS:000335147400014 PM 24563491 ER PT J AU Giguere, PM Kroeze, WK Roth, BL AF Giguere, Patrick M. Kroeze, Wesley K. Roth, Bryan L. TI Tuning up the right signal: chemical and genetic approaches to study GPCR functions SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; SEROTONIN RECEPTORS; SITE; PHARMACOLOGY; SELECTIVITY; ACTIVATION; TARGETS; DESIGN; LIGAND; KEY AB The G protein-coupled receptor (GPCR) family is among the most druggable families in the human proteome. GPCRs are involved in most physiological processes, and our ability to modulate their activity is a hallmark of modern pharmacology. The means by which the activity of GPCRs can be modulated have been expanded by emerging data and concepts in pharmacology, which has created new strategies for their control. These new approaches will lead to the generation of more potent, selective, and efficient pharmaceutics, while reducing inappropriate actions and adverse effects. Herein, we review and comment on some recent advances in chemical and genetic approaches to the profiling of GPCR function, as well as the validation of orphan GPCRs as potential therapeutic targets using engineered receptors. C1 [Giguere, Patrick M.] Univ N Carolina, Dept Pharmacol, Program Neurosci, Chapel Hill Med Sch, Chapel Hill, NC 27514 USA. Univ N Carolina, Chapel Hill Med Sch, Div Chem Biol & Med Chem, Chapel Hill, NC 27514 USA. Univ N Carolina, Chapel Hill Med Sch, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27514 USA. RP Giguere, PM (reprint author), Univ N Carolina, Dept Pharmacol, Program Neurosci, Chapel Hill Med Sch, 4072 Genet Med Bldg, Chapel Hill, NC 27514 USA. EM giguere.pm@gmail.com; bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010 FU NIDA NIH HHS [R01 DA017204]; NIMH NIH HHS [R01 MH061887, U19 MH082441] NR 28 TC 12 Z9 12 U1 0 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 EI 1879-0410 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD APR PY 2014 VL 27 BP 51 EP 55 DI 10.1016/j.ceb.2013.11.006 PG 5 WC Cell Biology SC Cell Biology GA AG0LD UT WOS:000335106100008 PM 24680430 ER PT J AU O'Hayre, M Degese, MS Gutkind, JS AF O'Hayre, Morgan Degese, Maria S. Gutkind, J. Silvio TI Novel insights into G protein and G protein-coupled receptor signaling in cancer SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID HIPPO-YAP PATHWAY; BREAST-CANCER; CELL-PROLIFERATION; 7-TRANSMEMBRANE RECEPTORS; CHEMOKINE RECEPTORS; ADENYLYL-CYCLASE; PITUITARY-TUMORS; APC(MIN/+) MICE; EXCHANGE FACTOR; COLON-CANCER AB G protein-coupled receptors (GPCRs) play a central role in signal transmission, thereby controlling many facets of cellular function. Overwhelming evidence now implicates GPCRs, G proteins and their downstream signaling targets in cancer initiation and progression, where they can influence aberrant cell growth and survival, largely through activation of AKT/mTOR, MAPKs, and Hippo signaling pathways. GPCRs also play critical roles in the invasion and metastasis of cancer cells via activation of Rho GTPases and cytoskeletal changes, and angiogenesis to supply the tumor with nutrients and provide routes for metastasis. Lastly, GPCRs contribute to the establishment and maintenance of a permissive tumor microenvironment. Understanding GPCR involvement in cancer malignancy may help identify novel therapeutic opportunities for cancer prevention and treatment. C1 [O'Hayre, Morgan; Degese, Maria S.; Gutkind, J. Silvio] NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), NIH, Oral & Pharyngeal Canc Branch, Bldg 10, Bethesda, MD 20892 USA. EM sg39v@nih.gov FU Intramural Research Program of the US National Institutes of Health; US National Institute of Dental and Craniofacial Research FX We truly regret that we could not cite the seminal work of many of our colleagues due to space limitations. This work was supported by the Intramural Research Program of the US National Institutes of Health and the US National Institute of Dental and Craniofacial Research. NR 91 TC 48 Z9 48 U1 3 U2 30 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 EI 1879-0410 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD APR PY 2014 VL 27 BP 126 EP 135 DI 10.1016/j.ceb.2014.01.005 PG 10 WC Cell Biology SC Cell Biology GA AG0LD UT WOS:000335106100018 PM 24508914 ER PT J AU Akbari, M Keijzers, G Maynard, S Scheibye-Knudsen, M Desler, C Hickson, ID Bohr, VA AF Akbari, Mansour Keijzers, Guido Maynard, Scott Scheibye-Knudsen, Morten Desler, Claus Hickson, Ian D. Bohr, Vilhelm A. TI Overexpression of DNA ligase III in mitochondria protects cells against oxidative stress and improves mitochondrial DNA base excision repair SO DNA REPAIR LA English DT Article DE Mitochondrial DNA repair intermediates; Oxidative stress; Autophagy; Cell survival ID SUBSTANTIA-NIGRA NEURONS; STRAND BREAKS; IN-VITRO; DAMAGE; MUTATIONS; NUCLEAR; DISEASE; REPLICATION; DELETIONS; GENOME AB Base excision repair (BER) is the most prominent DNA repair pathway in human mitochondria. BER also results in a temporary generation of AP-sites, single-strand breaks and nucleotide gaps. Thus, incomplete BER can result in the generation of DNA repair intermediates that can disrupt mitochondrial DNA replication and transcription and generate mutations. We carried out BER analysis in highly purified mitochondrial extracts from human cell lines U2OS and HeLa, and mouse brain using a circular DNA substrate containing a lesion at a specific position. We found that DNA ligation is significantly slower than the preceding mitochondrial BER steps. Overexpression of DNA ligase III in mitochondria improved the rate of overall BER, increased cell survival after menadione induced oxidative stress and reduced autophagy following the inhibition of the mitochondrial electron transport chain complex I by rotenone. Our results suggest that the amount of DNA ligase III in mitochondria may be critical for cell survival following prolonged oxidative stress, and demonstrate a functional link between mitochondrial DNA damage and repair, cell survival upon oxidative stress, and removal of dysfunctional mitochondria by autophagy. (C) 2014 Published by Elsevier B.V. C1 [Akbari, Mansour; Keijzers, Guido; Maynard, Scott; Desler, Claus; Hickson, Ian D.; Bohr, Vilhelm A.] Univ Copenhagen, Ctr Hlth Aging, SUND, DK-1168 Copenhagen, Denmark. [Scheibye-Knudsen, Morten; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd,Suite 100,Room 06B133, Baltimore, MD 21224 USA. EM vbohr@nih.gov OI Akbari, Mansour/0000-0002-6490-7766; desler, claus/0000-0002-0125-004X; Scheibye-Knudsen, Morten/0000-0002-6637-1280 FU NORDEA Foundation, Denmark FX We would like to thank Dr. Peter Sykora, Dr. Deborah L. Croteau, Dr. Tadokoro Takashi and Dr. Huiming Lu for critically reading of the manuscript. We thank Dr. Agla Jael Rubner Fridriksdottir for help with FACS cell sorting. Confocal and electron microscopy was carried out at the Core Facility of Integrated Microscopy, University of Copenhagen. This work was funded by the NORDEA Foundation, Denmark. NR 67 TC 8 Z9 9 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD APR PY 2014 VL 16 BP 44 EP 53 DI 10.1016/j.dnarep.2014.01.015 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA AG0KW UT WOS:000335105400006 PM 24674627 ER PT J AU Azevedo, MF Faucz, FR Bimpaki, E Horvath, A Levy, I de Alexandre, RB Ahmad, F Manganiello, V Stratakis, CA AF Azevedo, Monalisa F. Faucz, Fabio R. Bimpaki, Eirini Horvath, Anelia Levy, Isaac de Alexandre, Rodrigo B. Ahmad, Faiyaz Manganiello, Vincent Stratakis, Constantine A. TI Clinical and Molecular Genetics of the Phosphodiesterases (PDEs) SO ENDOCRINE REVIEWS LA English DT Review ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; CAMP-SPECIFIC PHOSPHODIESTERASE; PULMONARY ARTERIAL-HYPERTENSION; DEPENDENT PROTEIN-KINASE; CGMP-SPECIFIC PHOSPHODIESTERASE; ARYL-HYDROCARBON RECEPTOR; GMP-STIMULATED PHOSPHODIESTERASE; RECESSIVE RETINITIS-PIGMENTOSA; AMP-SPECIFIC PHOSPHODIESTERASE; STATIONARY NIGHT BLINDNESS AB Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that have the unique function of terminating cyclic nucleotide signaling by catalyzing the hydrolysis of cAMP and GMP. They are critical regulators of the intracellular concentrations of cAMP and cGMP as well as of their signaling pathways and downstream biological effects. PDEs have been exploited pharmacologically for more than half a century, and some of the most successful drugs worldwide today affect PDE function. Recently, mutations in PDE genes have been identified as causative of certain human genetic diseases; even more recently, functional variants of PDE genes have been suggested to play a potential role in predisposition to tumors and/ or cancer, especially in cAMP-sensitive tissues. Mouse models have been developed that point to wide developmental effects of PDEs from heart function to reproduction, to tumors, and beyond. This review brings together knowledge from a variety of disciplines (biochemistry and pharmacology, oncology, endocrinology, and reproductive sciences) with emphasis on recent research on PDEs, how PDEs affect cAMP and cGMP signaling in health and disease, and what pharmacological exploitations of PDEs may be useful in modulating cyclic nucleotide signaling in a way that prevents or treats certain human diseases. C1 [Azevedo, Monalisa F.; Faucz, Fabio R.; Bimpaki, Eirini; Horvath, Anelia; Levy, Isaac; de Alexandre, Rodrigo B.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Azevedo, Monalisa F.] Univ Brasilia, Fac Med, Univ Hosp Brasilia, Endocrinol Sect, BR-70840901 Brasilia, DF, Brazil. [Faucz, Fabio R.; de Alexandre, Rodrigo B.] Pontificia Univ Catolica Parana, Sch Med, Grad Program Hlth Sci, Grp Adv Mol Invest, BR-80215901 Curitiba, Parana, Brazil. [Ahmad, Faiyaz; Manganiello, Vincent] NHLBI, Cardiovasc Pulm Branch, NIH, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] NICHD, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH,CRC East Labs, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI de Alexandre, Rodrigo/H-9489-2013 OI de Alexandre, Rodrigo/0000-0002-1253-7716 FU Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (NIH) [HD008920]; intramural program of the National Heart,Lung, and Blood Institute, NIH; Department of Pediatrics, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece; Endocrinology Unit, Faculty of Medicine, University of Brasilia, Brasilia, Brazil; Graduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Parana, Curitiba, Brazil; Coordenacao de Aper-feicoamento de Pessoal de Nivel Superior, Brazil; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil FX This work was supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (NIH), protocol HD008920; and in part by the intramural program of the National Heart,Lung, and Blood Institute, NIH; the Department of Pediatrics, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece; the Endocrinology Unit, Faculty of Medicine, University of Brasilia, Brasilia, Brazil; Graduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Parana, Curitiba, Brazil; Coordenacao de Aper-feicoamento de Pessoal de Nivel Superior, Brazil; and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil. NR 483 TC 26 Z9 27 U1 5 U2 26 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD APR PY 2014 VL 35 IS 2 BP 195 EP 233 DI 10.1210/er.2013-1053 PG 39 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AG5FX UT WOS:000335446000002 PM 24311737 ER PT J AU Cheng, RYS Shang, Y Limjunyawong, N Dao, T Das, S Rabold, R Sham, JSK Mitzner, W Tang, WY AF Cheng, Robert Y. S. Shang, Yan Limjunyawong, Nathachit Dao, Tyna Das, Sandhya Rabold, Richard Sham, James S. K. Mitzner, Wayne Tang, Wan-Yee TI Alterations of the lung methylome in allergic airway hyper-responsiveness SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE asthma; next generation sequencing; DNA methylation; airway hyperresponsiveness; house dust mite ID POLYCYCLIC AROMATIC-HYDROCARBONS; ACTIVE DNA DEMETHYLATION; SMOOTH-MUSCLE-CELLS; TGF-BETA; EPIGENETIC MECHANISMS; PRENATAL EXPOSURE; CHILDHOOD ASTHMA; METHYLATION; INFLAMMATION; MICE AB Asthma is a chronic airway disorder characterized by recurrent attacks of breathlessness and wheezing, affecting 300 million people around the world (available at: ). To date, genetic factors associated with asthma susceptibility have been unable to explain the full etiology of asthma. Recent studies have demonstrated that the epigenetic disruption of gene expression plays an equally important role in the development of asthma through interaction with our environment. We sensitized 6-week-old C57BL/6J mice with house-dust-mite (HDM) extracts intraperitoneally followed by 5 weeks of exposure to HDM challenges (three times a week) intratracheally. HDM-exposed mice showed an increase in airway hyper-responsiveness (AHR) and inflammation together with structural remodeling of the airways. We applied methylated DNA immunoprecipitation-next generation sequencing (MeDIP-seq) for profiling of DNA methylation changes in the lungs in response to HDM. We observed about 20 million reads by a single-run of massive parallel sequencing. We performed bioinformatics and pathway analysis on the raw sequencing data to identify differentially methylated candidate genes in HDM-exposed mice. Specifically, we have revealed that the transforming growth factor beta signaling pathway is epigenetically modulated by chronic exposure to HDM. Here, we demonstrated that a specific allergen may play a role in AHR through an epigenetic mechanism by disrupting the expression of genes in lungs that might be involved in airway inflammation and remodeling. Our findings provide new insights into the potential mechanisms by which environmental allergens induce allergic asthma and such insights may assist in the development of novel preventive and therapeutic options for this debilitative disease. Environ. Mol. Mutagen. 55:244-255, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Cheng, Robert Y. S.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Shang, Yan; Limjunyawong, Nathachit; Dao, Tyna; Das, Sandhya; Rabold, Richard; Mitzner, Wayne; Tang, Wan-Yee] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21218 USA. [Shang, Yan] Second Mil Med Univ, Changhai Hosp, Dept Resp Dis, Shanghai, Peoples R China. [Sham, James S. K.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA. RP Tang, WY (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, 615 N Wolfe St,Room E7545, Baltimore, MD 21218 USA. EM wtang@jhsph.edu FU NIEHS [ES016887, P30ES03819-EHS]; NHLBI [HL10342]; National Natural Science Foundation of China [81000006] FX Grant sponsor: NIEHS; Grant number: ES016887 (to W.-Y.T.) and P30ES03819-EHS.; Grant sponsor: NHLBI; Grant number: HL10342 (to W.M.); Grant sponsor: National Natural Science Foundation of China; Grant number: 81000006 (to Y.S.). NR 59 TC 8 Z9 8 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR PY 2014 VL 55 IS 3 SI SI BP 244 EP 255 DI 10.1002/em.21851 PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA AG1FC UT WOS:000335159500009 PM 24446183 ER PT J AU Marzi, A Feldmann, H AF Marzi, Andrea Feldmann, Heinz TI Ebola virus vaccines: an overview of current approaches SO EXPERT REVIEW OF VACCINES LA English DT Review DE animal model; vaccine; prophylaxis; Ebola virus; filovirus ID PROTECTS NONHUMAN-PRIMATES; EQUINE ENCEPHALITIS-VIRUS; ADENOVIRUS-BASED VACCINE; RESPIRATORY-TRACT IMMUNIZATION; MARBURG VIRUS; HEMORRHAGIC-FEVER; GUINEA-PIGS; IMMUNE-RESPONSES; VECTORED VACCINE; DNA VACCINE AB Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible. C1 [Marzi, Andrea; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. RP Marzi, A (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. EM marzia@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH FX Ebola virus research is supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH. H Feldmann claims intellectual property regarding the vesicular stomatitis virus-based filovirus vaccines. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 76 TC 53 Z9 57 U1 13 U2 230 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD APR PY 2014 VL 13 IS 4 BP 521 EP 531 DI 10.1586/14760584.2014.885841 PG 11 WC Immunology SC Immunology GA AG3QI UT WOS:000335334100009 PM 24575870 ER PT J AU Konig, G Hudson, PS Boresch, S Woodcock, HL AF Koenig, Gerhard Hudson, Phillip S. Boresch, Stefan Woodcock, H. Lee TI Multiscale Free Energy Simulations: An Efficient Method for Connecting Classical MD Simulations to QM or QM/MM Free Energies Using Non-Boltzmann Bennett Reweighting Schemes SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID SOLVATION FREE-ENERGIES; HYDRATION FREE-ENERGIES; QUANTUM-MECHANICAL CALCULATIONS; ACCEPTANCE RATIO METHOD; BINDING FREE-ENERGIES; ACID SIDE-CHAINS; AQUEOUS-SOLUTION; THERMODYNAMIC INTEGRATION; PERTURBATION CALCULATIONS; MOLECULAR-DYNAMICS AB The reliability of free energy simulations (FES) is limited by two factors: (a) the need for correct sampling and (b) the accuracy of the computational method employed. Classical methods (e.g., force fields) are typically used for FES and present a myriad of challenges, with parametrization being a principle one. On the other hand, parameter-free quantum mechanical (QM) methods tend to be too computationally expensive for adequate sampling. One widely used approach is a combination of methods, where the free energy difference between the two end states is computed by, e.g., molecular mechanics (MM), and the end states are corrected by more accurate methods, such as QM or hybrid QM/MM techniques. Here we report two new approaches that significantly improve the aforementioned scheme; with a focus on how to compute corrections between, e.g., the MM and the more accurate QM calculations. First, a molecular dynamics trajectory that properly samples relevant conformational degrees of freedom is generated. Next, potential energies of each trajectory frame are generated with a QM or QM/MM Hamiltonian. Free energy differences are then calculated based on the QM or QM/MM energies using either a non-Boltzmann Bennett approach (QM-NBB) or non-Boltzmann free energy perturbation (NB-FEP). Both approaches are applied to calculate relative and absolute salvation free energies in explicit and implicit solvent environments. Solvation free energy differences (relative and absolute) between ethane and methanol in explicit solvent are used as the initial test case for QM-NBB. Next, implicit solvent methods are employed in conjunction with both QM-NBB and NB-FEP to compute absolute salvation free energies for 21 compounds. These compounds range from small molecules such as ethane and methanol to fairly large, flexible solutes, such as triacetyl glycerol. Several technical aspects were investigated. Ultimately some best practices are suggested for improving methods that seek to connect MM to QM (or QM/MM) levels of theory in FES. C1 [Koenig, Gerhard] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Hudson, Phillip S.; Woodcock, H. Lee] Univ S Florida, Dept Chem, Tampa, FL 33620 USA. [Boresch, Stefan] Univ Vienna, Fac Chem, Dept Computat Biol Chem, A-1090 Vienna, Austria. RP Boresch, S (reprint author), Univ Vienna, Fac Chem, Dept Computat Biol Chem, Wahringerstr 17, A-1090 Vienna, Austria. EM stefan@mdy.univie.ac.at; hlw@usf.edu RI Boresch, Stefan/F-3467-2014; OI Boresch, Stefan/0000-0002-2793-6656; Hudson, Phillip/0000-0002-1856-1135; Woodcock, Henry/0000-0003-3539-273X FU NIH [1K22HL088341-01A1]; University of South Florida; USF Research Computing Center (NSF Grant) [CHE-0722887]; XSEDE [MCB120133]; intramural research program of the National Heart, Lung and Blood Institute of the National Institutes of Health FX H.L.W. would like to acknowledge NIH (1K22HL088341-01A1) and the University of South Florida (start-up) for funding. Computations were performed at the USF Research Computing Center (NSF Grant CHE-0722887) and XSEDE (MCB120133); both centers are greatly appreciated. G.K. was supported by the intramural research program of the National Heart, Lung and Blood Institute of the National Institutes of Health and utilized the high-performance computational capabilities of the LoBoS and Biowulf Linux clusters at the National Institutes of Health (http://www.lobos.nih.gov/ and http://biowulf.nih.gov). NR 124 TC 36 Z9 36 U1 4 U2 52 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 EI 1549-9626 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD APR PY 2014 VL 10 IS 4 BP 1406 EP 1419 DI 10.1021/ct401118k PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AF2VZ UT WOS:000334571900006 PM 24803863 ER PT J AU Li, MH Petukh, M Alexov, E Panchenko, AR AF Li, Minghui Petukh, Marharyta Alexov, Emil Panchenko, Anna R. TI Predicting the Impact of Missense Mutations on Protein-Protein Binding Affinity SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISMS; ALANINE-SCANNING MUTAGENESIS; POISSON-BOLTZMANN EQUATION; FREE-ENERGY CHANGES; FORCE-FIELD; ELECTROSTATIC ENERGIES; COMPUTATIONAL DESIGN; MOLECULAR-DYNAMICS; MM-PBSA; COMPLEX AB The crucial prerequisite for proper biological function is the protein's ability to establish highly selective interactions with macromolecular partners. A missense mutation that alters the protein binding affinity may cause significant perturbations or complete abolishment of the function, potentially leading to diseases. The availability of computational methods to evaluate the impact of mutations on protein protein binding is critical for a wide range of biomedical applications. Here, we report an efficient computational approach for predicting the effect of single and multiple missense mutations on protein protein binding affinity. It is based on a well-tested simulation protocol for structure minimization, modified MM-PBSA and statistical scoring energy functions with parameters optimized on experimental sets of several thousands of mutations. Our simulation protocol yields very good agreement between predicted and experimental values with Pearson correlation coefficients of 0.69 and 0.63 and root-mean-square errors of 1.20 and 1.90 kcal mol(-1) for single and multiple mutations, respectively. Compared with other available methods, our approach achieves high speed and prediction accuracy and can be applied to large datasets generated by modern genomics initiatives. In addition, we report a crucial role of water model and the polar solvation energy in estimating the changes in binding affinity. Our analysis also reveals that prediction accuracy and effect of mutations on binding strongly depends on the type of mutation and its location in a protein complex.. C1 [Li, Minghui; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Petukh, Marharyta; Alexov, Emil] Clemson Univ, Dept Phys, Clemson, SC 29634 USA. RP Panchenko, AR (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM panch@ncbi.nlm.nih.gov RI Li, Minghui/M-9209-2014; Li, Minghui/E-4339-2016 OI Li, Minghui/0000-0002-2056-1249; FU Intramural Research Program of the National Library of Medicine at the U.S. National Institutes of Health; National Institutes of Health, National Institute of General Medical Sciences [R01GM093937] FX We thank Thomas Madej for insightful discussions. This work was supported by the Intramural Research Program of the National Library of Medicine at the U.S. National Institutes of Health. M.P. and E.A. were supported in part by National Institutes of Health, National Institute of General Medical Sciences, grant number R01GM093937. NR 65 TC 24 Z9 24 U1 0 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 EI 1549-9626 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD APR PY 2014 VL 10 IS 4 BP 1770 EP 1780 DI 10.1021/ct401022c PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AF2VZ UT WOS:000334571900039 PM 24803870 ER PT J AU Brown, GT Lee, CC AF Brown, G. T. Lee, Chyi-chia TI CUTANEOUS METASTASIS OF PROSTATE CANCER: A CASE REPORT AND BIOINFORMATICS ANALYSIS OF MULTIPLE HEALTHCARE DELIVERY NETWORKS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research (CSCTR) and Midwestern-Section-American-Federation-for-Medical-Research (MWAFMR) CY APR 24-25, 2014 CL Chicago, IL SP Cent Soc Clin & Translat Res, Midwestern Sect Amer Federat Med Res C1 [Brown, G. T.; Lee, Chyi-chia] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Lee, Chyi-Chia/I-1938-2013 OI Lee, Chyi-Chia/0000-0002-5306-7781 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2014 VL 62 IS 4 BP 764 EP 764 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE0ZQ UT WOS:000333695300172 ER PT J AU Lara-Otero, K Macias, CG Sanz, J Merino, MJ AF Lara-Otero, Karlena Garcia Macias, Carmen Sanz, Julian Merino, Maria J. TI MALE BREAST CANCER, IS THERE A CORRELATION BETWEEN PROGNOSTIC FACTORS AND MOLECULAR ANALYSIS? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research (CSCTR) and Midwestern-Section-American-Federation-for-Medical-Research (MWAFMR) CY APR 24-25, 2014 CL Chicago, IL SP Cent Soc Clin & Translat Res, Midwestern Sect Amer Federat Med Res C1 [Lara-Otero, Karlena; Merino, Maria J.] NCI, NIH, Bethesda, MD 20892 USA. [Garcia Macias, Carmen] Univ Salamanca, Inst Canc, E-37008 Salamanca, Spain. [Sanz, Julian] Hosp Clin Univ, Madrid, Spain. RI Sanz, Julian/G-5276-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2014 VL 62 IS 4 BP 770 EP 770 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE0ZQ UT WOS:000333695300189 ER PT J AU Lara-Otero, K Macias, CG Sanz, J Merino, MJ AF Lara-Otero, Karlena Garcia Macias, Carmen Sanz, Julian Merino, Maria J. TI DO MALE AND FEMALE BREAST CANCER SHARE SIMILAR MICRORNA EXPRESSION PATTERNS? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-and-Translational-Research (CSCTR) and Midwestern-Section-American-Federation-for-Medical-Research (MWAFMR) CY APR 24-25, 2014 CL Chicago, IL SP Cent Soc Clin & Translat Res, Midwestern Sect Amer Federat Med Res C1 [Lara-Otero, Karlena; Merino, Maria J.] NCI, NIH, Bethesda, MD 20892 USA. [Garcia Macias, Carmen] Univ Salamanca, Inst Canc, E-37008 Salamanca, Spain. [Sanz, Julian] Hosp Clin Univ, Madrid, Spain. RI Sanz, Julian/G-5276-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2014 VL 62 IS 4 BP 772 EP 772 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE0ZQ UT WOS:000333695300196 ER PT J AU Ravichandran, S Singh, N Donnelly, D Migliore, M Johnson, P Fishwick, C Luke, BT Martin, B Maudsley, S Fugmann, SD Moaddel, R AF Ravichandran, S. Singh, N. Donnelly, D. Migliore, M. Johnson, P. Fishwick, C. Luke, B. T. Martin, B. Maudsley, S. Fugmann, S. D. Moaddel, R. TI Pharmacophore model of the quercetin binding site of the SIRT6 protein SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article DE SIRT6; Pharmacophore modeling; Frontal displacement chromatography; HAT; HDAC ID MICE; GLUCOSE AB SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. We have previously reported on the identification of quercetin and vitexin as SIRT6 inhibitors, and studied structurally related flavonoids including luteolin, kaempferol, apigenin and naringenin. It was determined that the SIRT6 protein remained active after immobilization and that a single frontal displacement could correctly predict the functional activity of the immobilized enzyme. The previous study generated a preliminary pharmacophore for the quercetin binding site on SIRT6, containing 3 hydrogen bond donors and one hydrogen bond acceptor. In this study, we have generated a refined pharmacophore with an additional twelve quercetin analogs. The resulting model had a positive linear behavior between the experimental elution time verses the fit values obtained from the model with a correlation coefficient of 0.8456. Published by Elsevier Inc. C1 [Ravichandran, S.; Luke, B. T.] SAIC Frederick Inc, Adv Biomed Comp Ctr, Informat Syst Program, FNLCR, Frederick, MD 21702 USA. [Singh, N.; Martin, B.; Maudsley, S.; Moaddel, R.] NIA, Lab Clin Invest, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Donnelly, D.] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England. [Migliore, M.; Johnson, P.; Fishwick, C.] Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England. [Fugmann, S. D.] Chang Gung Univ, Dept Biomed Sci, Kwei Shan, Taiwan. RP Moaddel, R (reprint author), NIA, Lab Clin Invest, Biomed Res Ctr, NIH, 8B133,251 Bayview Blvd, Baltimore, MD 21224 USA. EM moaddelru@mail.nih.gov RI Donnelly, Dan/O-5374-2015; Singh, Nagendra/K-8966-2015 FU NIA Intramural Research Program; National Cancer Institute/National Institutes of Health [HHSN261200800001E] FX This work was supported in part by funds from the NIA Intramural Research Program (RM), and from the National Cancer Institute/National Institutes of Health contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 16 TC 9 Z9 10 U1 0 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1093-3263 EI 1873-4243 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD APR PY 2014 VL 49 BP 38 EP 46 DI 10.1016/j.jmgm.2014.01.004 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA AG0KX UT WOS:000335105500005 PM 24491483 ER PT J AU Correa-de-Araujo, R AF Correa-de-Araujo, Rosaly TI New Criteria for Clinically Relevant Weakness and Low Muscle Mass (LMM) in Older Women SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Correa-de-Araujo, Rosaly] NIA, NIH, Bethesda, MD 20892 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 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD APR 1 PY 2014 VL 23 IS 4 MA P66 BP 23 EP 24 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AE4EO UT WOS:000333934900067 ER PT J AU Reigstad, MM Larsen, IK Robsahm, T Oldereid, N Omland, AK Myklebust, TA Vangen, S Brinton, LA Storeng, R AF Reigstad, Marte Myhre Larsen, Inger Kristin Robsahm, Trude Oldereid, Nan Omland, Anne Katerine Myklebust, Tor Age Vangen, Siri Brinton, Louise A. Storeng, Ritsa TI Breast cancer risk among women giving birth following fertility treatment in Norway SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Reigstad, Marte Myhre; Vangen, Siri; Storeng, Ritsa] Natl Hosp Norway, Norwegian Resource Ctr Womens Hlth, Women & Childrens Div, Oslo Univ Hosp, Oslo, Norway. [Larsen, Inger Kristin; Robsahm, Trude; Myklebust, Tor Age] Canc Registry Norway, Oslo, Norway. [Oldereid, Nan; Omland, Anne Katerine] Natl Hosp Norway, Sect Reprod Med, Women & Childrens Div, Oslo Univ Hosp, Oslo, Norway. [Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD APR 1 PY 2014 VL 23 IS 4 MA P90 BP 32 EP 32 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AE4EO UT WOS:000333934900091 ER PT J AU Modi, M Heitmann, R Armstrong, A AF Modi, Monica Heitmann, Ryan Armstrong, Alicia TI Global Unintended Pregnancies and the Role of Long-Acting Reversible Contraception to prevent them SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Modi, Monica] Wayne State OB GYN, Detroit, MI USA. [Heitmann, Ryan; Armstrong, Alicia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, 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 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD APR 1 PY 2014 VL 23 IS 4 MA P101 BP 35 EP 35 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AE4EO UT WOS:000333934900102 ER PT J AU Caro, T Izzo, A Reiner, RC Walker, H Stankowich, T AF Caro, Tim Izzo, Amanda Reiner, Robert C., Jr. Walker, Hannah Stankowich, Theodore TI The function of zebra stripes SO NATURE COMMUNICATIONS LA English DT Article ID FLIES DIPTERA-TABANIDAE; BITING FLY CONTROL; LION PANTHERA-LEO; METEOROLOGICAL FACTORS; PREY PREFERENCES; SOCIAL-BEHAVIOR; BEEF-CATTLE; HORSE FLIES; TSETSE; GLOSSINIDAE AB Despite over a century of interest, the function of zebra stripes has never been examined systematically. Here we match variation in striping of equid species and subspecies to geographic range overlap of environmental variables in multifactor models controlling for phylogeny to simultaneously test the five major explanations for this infamous colouration. For subspecies, there are significant associations between our proxy for tabanid biting fly annoyance and most striping measures (facial and neck stripe number, flank and rump striping, leg stripe intensity and shadow striping), and between belly stripe number and tsetse fly distribution, several of which are replicated at the species level. Conversely, there is no consistent support for camouflage, predator avoidance, heat management or social interaction hypotheses. Susceptibility to ectoparasite attack is discussed in relation to short coat hair, disease transmission and blood loss. A solution to the riddle of zebra stripes, discussed by Wallace and Darwin, is at hand. C1 [Caro, Tim; Izzo, Amanda; Walker, Hannah] Univ Calif Davis, Dept Wildlife Fish & Conservat Biol, Davis, CA 95616 USA. [Caro, Tim] Univ Calif Davis, Ctr Populat Biol, Davis, CA 95616 USA. [Reiner, Robert C., Jr.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Reiner, Robert C., Jr.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Stankowich, Theodore] Calif State Univ Long Beach, Dept Biol Sci, Long Beach, CA 90840 USA. RP Caro, T (reprint author), Univ Calif Davis, Dept Wildlife Fish & Conservat Biol, 1 Shields Ave, Davis, CA 95616 USA. EM tmcaro@ucdavis.edu FU California Academy of Sciences; RAPIDD program of the Science and Technology Directorate; Department of Homeland Security; Fogarty International Center; National Institutes of Health; University of California FX We thank the Chicago Field Museum, Los Angeles Natural History Museum, California Academy of Sciences, and Museum of Vertebrate Zoology at Berkeley for access to pelts, University of California for funding, and R. C. R. acknowledges funding support from the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. We thank Rickesh Patel for drawings in Fig. 1, Martin Stevens for discussion, and Brenda Larison, Tom Sherratt, Martin Stevens for comments on the manuscript. NR 70 TC 16 Z9 18 U1 19 U2 149 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 APR PY 2014 VL 5 AR 3535 DI 10.1038/ncomms4535 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2BC UT WOS:000335219000002 PM 24691390 ER PT J AU Chagin, AS Vuppalapati, KK Kobayashi, T Guo, J Hirai, T Chen, M Offermanns, S Weinstein, LS Kronenberg, HM AF Chagin, Andrei S. Vuppalapati, Karuna K. Kobayashi, Tatsuya Guo, Jun Hirai, Takao Chen, Min Offermanns, Stefan Weinstein, Lee S. Kronenberg, Henry M. TI G-protein stimulatory subunit alpha and Gq/11 alpha G-proteins are both required to maintain quiescent stem-like chondrocytes SO NATURE COMMUNICATIONS LA English DT Article ID GROWTH-PLATE CHONDROGENESIS; PARATHYROID-HORMONE; IN-VIVO; ENDOCHONDRAL OSSIFICATION; SIGNALING PATHWAYS; PHOSPHOLIPASE-C; KINASE-A; RECEPTOR; DIFFERENTIATION; HYPERTROPHY AB Round chondrocytes in the resting zone of the growth plate provide precursors for columnar chondrocytes and have stem-like properties. Here we demonstrate that these stem-like chondrocytes undergo apoptosis in the absence of the receptor (PPR) for parathyroid hormone-related protein. We examine the possible roles of heterotrimeric G-proteins activated by the PPR. Inactivation of the G-protein stimulatory alpha-subunit (G(s)alpha) leads to accelerated differentiation of columnar chondrocytes, as seen in the PPR knockout, but a remnant of growth cartilage remains, in contrast to disappearance of the growth cartilage in the PPR knockout. Stem-like chondrocytes lose their quiescence and proliferate upon Gsa ablation. Inactivation of Gsa in mice with a mutant PPR that cannot activate G proteins, Gq and G11, leads to a PPR knockout-like phenotype. Thus, G(s)alpha is the major mediator of the anti-differentiation action of the PPR, while activation of both Gsa and Gq/11 alpha is required for quiescence of stem-like chondrocytes. C1 [Chagin, Andrei S.; Vuppalapati, Karuna K.] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden. [Chagin, Andrei S.; Kobayashi, Tatsuya; Guo, Jun; Hirai, Takao; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Chagin, Andrei S.; Kobayashi, Tatsuya; Guo, Jun; Hirai, Takao; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chen, Min; Weinstein, Lee S.] Natl Inst Diabet Digest & Kidney Dis, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Offermanns, Stefan] Max Planck Inst Heart & Lung Res, Dept Pharmacol, D-61231 Bad Nauheim, Germany. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM hkronenberg@partners.org RI Chagin, Andrei/F-4080-2014 OI Chagin, Andrei/0000-0002-2696-5850 FU National Institutes of Health [DK56246]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Disease; National Institutes of Health in Bethesda, Maryland; Sallskapet Barnavard Foundation in Stockholm; Swedish Research Council [2007-8037]; Swedish Society for Medical Research FX We thank Murat Bastepe and Shigeki Nishimori for helpful suggestions. This work was funded by National Institutes of Health Grant DK56246, the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health in Bethesda, Maryland, and the Sallskapet Barnavard Foundation in Stockholm. ASC was supported by postdoctoral fellowships from The Swedish Research Council (Dnr. 2007-8037) and The Swedish Society for Medical Research. NR 29 TC 10 Z9 10 U1 0 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 APR PY 2014 VL 5 AR 3673 DI 10.1038/ncomms4673 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2CA UT WOS:000335221800004 PM 24781502 ER PT J AU Lopez-Serra, P Marcilla, M Villanueva, A Ramos-Fernandez, A Palau, A Leal, L Wahi, JE Setien-Baranda, F Szczesna, K Moutinho, C Martinez-Cardus, A Heyn, H Sandoval, J Puertas, S Vidal, A Sanjuan, X Martinez-Balibrea, E Vinals, F Perales, JC Bramsem, JB Orntoft, TF Andersen, CL Tabernero, J McDermott, U Boxer, MB Vander Heiden, MG Albar, JP Esteller, M AF Lopez-Serra, Paula Marcilla, Miguel Villanueva, Alberto Ramos-Fernandez, Antonio Palau, Anna Leal, Lucia Wahi, Jessica E. Setien-Baranda, Fernando Szczesna, Karolina Moutinho, Catia Martinez-Cardus, Anna Heyn, Holger Sandoval, Juan Puertas, Sara Vidal, August Sanjuan, Xavier Martinez-Balibrea, Eva Vinals, Francesc Perales, Jose C. Bramsem, Jesper B. Orntoft, Torben F. Andersen, Claus L. Tabernero, Josep McDermott, Ultan Boxer, Matthew B. Vander Heiden, Matthew G. Pablo Albar, Juan Esteller, Manel TI A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect SO NATURE COMMUNICATIONS LA English DT Article ID PYRUVATE-KINASE M2; UNFOLDED PROTEIN RESPONSE; CANCER METABOLISM; GLUCOSE-TRANSPORTER; CELL-METABOLISM; TUMOR-GROWTH; METHYLATION; LACTATE; PKM2; ER AB Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis. C1 [Lopez-Serra, Paula; Palau, Anna; Leal, Lucia; Wahi, Jessica E.; Setien-Baranda, Fernando; Szczesna, Karolina; Moutinho, Catia; Martinez-Cardus, Anna; Heyn, Holger; Sandoval, Juan; Esteller, Manel] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona 08908, Catalonia, Spain. [Marcilla, Miguel; Pablo Albar, Juan] CSIC, Spanish Natl Biotechnol Ctr CNB, Prote Unit, E-28049 Madrid, Spain. [Villanueva, Alberto; Puertas, Sara; Vinals, Francesc] Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol ICO, Translat Res Lab, Barcelona 08908, Catalonia, Spain. [Ramos-Fernandez, Antonio] Proteobotics SL, Spanish Natl Biotechnol Ctr CNB, Madrid 28049, Spain. [Vidal, August; Sanjuan, Xavier] Bellvitge Univ Hosp, Dept Pathol, Bellvitge Biomed Res Inst IDIBELL, Barcelona 08908, Catalonia, Spain. [Martinez-Balibrea, Eva] Hosp Badalona Germans Trias & Pujol, Inst Invest Ciencies Salut Germans Trias & Pujol, Catalan Inst Oncol ICO, Med Oncol Serv, Barcelona 08916, Catalonia, Spain. [Vinals, Francesc; Perales, Jose C.; Esteller, Manel] Univ Barcelona, Sch Med, Dept Physiol Sci 2, E-08036 Barcelona, Spain. [Bramsem, Jesper B.; Orntoft, Torben F.; Andersen, Claus L.] Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark. [Tabernero, Josep] Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona 08035, Catalonia, Spain. [McDermott, Ultan] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. [Boxer, Matthew B.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20891 USA. [Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Esteller, Manel] Inst Catalana Recerca & Estudis Avancats, Barcelona 08010, Catalonia, Spain. RP Esteller, M (reprint author), Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona 08908, Catalonia, Spain. EM mesteller@idibell.cat RI Marcilla, Miguel/B-8430-2013; Andersen, Claus Lindbjerg/A-9217-2012; PERALES, JOSE C./D-5586-2012; Esteller, Manel/L-5956-2014; Lopez-Serra, Paula/M-6835-2015; Vidal, August/N-4662-2016; Andersen, Claus/C-1477-2017; OI Heyn, Holger/0000-0002-3276-1889; Marcilla, Miguel/0000-0001-9171-5076; McDermott, Ultan/0000-0001-9032-4700; Andersen, Claus Lindbjerg/0000-0002-7406-2103; PERALES, JOSE C./0000-0001-7363-2226; Esteller, Manel/0000-0003-4490-6093; Lopez-Serra, Paula/0000-0001-7231-3426; Vidal, August/0000-0001-5727-2099; Andersen, Claus/0000-0002-7406-2103; Martinez-Balibrea, Eva/0000-0002-4501-7100 FU European Community's Seventh Framework Programme [HEALTH-F2-2011-259015-COLTHERES, HEALTH-F5-2010-258236SYSCOL]; Cellex Foundation; Olga Torres Foundation; ERC grant [268626-EPINORC]; Spanish Ministry of Economy and Competitiveness (MINECO Project) [SAF2011-22803]; Institute of Health Carlos III (ISCIII) RTICC Grant [RD12/0036/0039]; Health and Science Departments of the Generalitat de Catalunya FX This work was supported by the European Community's Seventh Framework Programme HEALTH-F2-2011-259015-COLTHERES and HEALTH-F5-2010-258236SYSCOL Grants, Cellex Foundation, Olga Torres Foundation, ERC grant agreement no. 268626-EPINORC project, Spanish Ministry of Economy and Competitiveness (MINECO Project no. SAF2011-22803), the Institute of Health Carlos III (ISCIII) RTICC Grant RD12/0036/0039 and the Health and Science Departments of the Generalitat de Catalunya. We thank the Scientific and Technological Centre (CCiTUB) of the University of Barcelona for the cell cytometry and sorter technical support. NR 50 TC 10 Z9 10 U1 0 U2 13 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 APR PY 2014 VL 5 AR 3608 DI 10.1038/ncomms4608 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2BQ UT WOS:000335220700013 PM 24699711 ER PT J AU Sadatsuki, R Kaneko, H Futami, I Hada, S Culley, KL Otero, M Dragomir, C Kinoshita, M Goldring, MB Yamada, Y Arikawa-Hirasawa, E Kaneko, K Ishijima, M AF Sadatsuki, R. Kaneko, H. Futami, I. Hada, S. Culley, K. L. Otero, M. Dragomir, C. Kinoshita, M. Goldring, M. B. Yamada, Y. Arikawa-Hirasawa, E. Kaneko, K. Ishijima, M. TI ROLE OF PERLECAN IN CHONDROGENIC, OSTEOGENIC AND ADIPOGENIC DIFFERENTIATION OF SYNOVIAL MESENCHYMAL CALLS SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the Osteoarthritis-Research-Society-International (OARSI) CY APR 24-27, 2014 CL Paris, FRANCE SP Osteoarthritis Res Soc Int C1 [Sadatsuki, R.; Kaneko, H.; Futami, I.; Hada, S.; Kinoshita, M.; Kaneko, K.; Ishijima, M.] Juntendo Univ, Grad Sch Med, Dept Orthoped & Motor Organ, Tokyo, Japan. [Culley, K. L.; Otero, M.; Dragomir, C.; Goldring, M. B.] Weill Cornell Med, Hosp Special Surg, Div Res, Tissue Engn Regenerat & Repair Program, New York, NY USA. [Yamada, Y.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [Arikawa-Hirasawa, E.] Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2014 VL 22 SU S BP S439 EP S439 PG 1 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA AG4XX UT WOS:000335424800814 ER PT J AU Anuradha, R George, PJ Hanna, LE Kumaran, P Chandrasekaran, V Nutman, TB Babu, S AF Anuradha, Rajamanickam George, Parakkal Jovvian Hanna, Luke E. Kumaran, Paul Chandrasekaran, Vedachalam Nutman, Thomas B. Babu, Subash TI Expansion of Parasite-Specific CD4(+) and CD8(+) T Cells Expressing IL-10 Superfamily Cytokine Members and Their Regulation in Human Lymphatic Filariasis SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID HELMINTH-PARASITES; IMMUNE REGULATION; INFECTIONS; PSORIASIS; DISEASE; INTERLEUKIN-10; AUTOIMMUNE; MECHANISMS; RESPONSES; ALLERGY AB Author Summary Lymphatic filariasis afflicts over 120 million people worldwide. While the infection is mostly clinically asymptomatic, approximately 40 million people suffer from overt, morbid clinical pathology, characterized by swelling of the scrotal area and lower limbs (hydrocele and lymphedema). Host immunologic factors that influence the pathogenesis of disease in these individuals are not completely understood. CD4(+) and CD8(+) T cells are known to play a role in promoting pathogenesis through the secretion of pro-inflammatory cytokines, while IL-10 is known to play an important role in dampening inflammation. IL-10 belongs to a family of cytokines that include IL-19, IL-24 and IL-26, known as the IL-10 superfamily. We investigated whether these cytokines have a function similar to IL-10 in individuals with asymptomatic infection and no clinical pathology and those with overt, clinical pathology. We first identify that CD4(+) and CD8(+) T cells produce these cytokines. We next identify a significant association of IL-19 and IL-24 secreting T cells with asymptomatic infection. IL-26 secreting T cells, in contrast, appear to be significantly associated with the presence of lymphatic pathology in filarial infection. Therefore, we have uncovered a potentially new regulatory pathway involving the IL-10 superfamily cytokines in filarial infections. Background Lymphatic filariasis (LF) is known to be associated with an increased production of IL-10. The role of the other IL-10 family members in the pathogenesis of infection and/or disease is not known. Methodology/Principal Findings We examined the expression patterns of IL-10 family members - IL-19, IL-24 and IL-26 in LF. We demonstrate that both CD4(+) and CD8(+) T cells express IL-19, IL-24 and IL-26 and that the frequency of CD4(+) T cells expressing IL-19 and IL-24 (as well as IL-10) is significantly increased at baseline and following filarial antigen stimulation in patients with LF in comparison to individuals with filarial lymphedema and uninfected individuals. This CD4(+) T cell expression pattern was associated with increased production of IL-19 and IL-24 by filarial - antigen stimulated PBMC. Moreover, the frequency of CD4(+) and CD8(+) T cells expressing IL-26 was significantly increased following filarial antigen stimulation in filarial lymphedema individuals. Interestingly, IL-10 blockade resulted in diminished frequencies of IL-19(+) and IL-24(+) T cells, whereas the addition of recombinant IL-10 resulted in significantly increased frequency of IL-19(+) and IL-24(+) T cells as well as significantly up regulated IL-19 and IL-24 gene expression, suggesting that IL-10 regulates IL-19 and IL-24 expression in T cells. In addition, IL-1 beta and IL-23 blockade also induced a diminution in the frequency of IL-19(+) and IL-24(+) T cells, indicating a novel role for these cytokines in the induction of IL-19 and IL-24 expressing T cells. Finally, elimination of infection resulted in significantly decreased frequencies of antigen - specific CD4(+) T cells expressing IL-10, IL-19 and IL-24. Conclusions Our findings, therefore, suggest that IL-19 and IL-24 are associated with the regulation of immune responses in active filarial infection and potentially with protection against development of pathology, while IL-26 is predominantly associated with pathology in LF. C1 [Anuradha, Rajamanickam; George, Parakkal Jovvian; Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, Madras, Tamil Nadu, India. [Hanna, Luke E.; Kumaran, Paul; Chandrasekaran, Vedachalam] Natl Inst Res TB, Madras, Tamil Nadu, India. [Nutman, Thomas B.; Babu, Subash] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Anuradha, R (reprint author), Int Ctr Excellence Res, Natl Inst Hlth, Madras, Tamil Nadu, India. EM sbabu@mail.nih.gov FU Division of Intramural Research, NIAID, NIH FX This work was supported by the Division of Intramural Research, NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 5 Z9 5 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 APR PY 2014 VL 8 IS 4 DI 10.1371/journal.pntd.0002762 PG 13 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AG3TK UT WOS:000335342400058 PM 24699268 ER PT J AU Lee, JS Munoz, BE Mkocha, H Gaydos, CA Quinn, TC West, SK AF Lee, Jennifer S. Munoz, Beatriz E. Mkocha, Harran Gaydos, Charlotte A. Quinn, Thomas C. West, Sheila K. TI The Effect of Multiple Rounds of Mass Drug Administration on the Association between Ocular Chlamydia trachomatis Infection and Follicular Trachoma in Preschool-Aged Children SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID ANTIBIOTIC TREATMENTS; RANDOMIZED-TRIAL; ACTIVE TRACHOMA; NATURAL-HISTORY; TANZANIA; AZITHROMYCIN; GAMBIA; ELIMINATION; PREVALENCE; COMMUNITY AB Author Summary Trachoma, which is caused by infection by the bacterium Chlamydia trachomatis, is the leading preventable cause of blindness worldwide. Annual mass drug administration with azithromycin is recommended for trachoma control; however, monitoring the impact of azithromycin, which targets C. trachomatis, relies on the clinical assessment of follicular trachoma. If the relationship between chlamydial infection and the presence or absence of follicular trachoma were to remain unchanged with each round of treatment, we would be able to predict the level of residual infection, and the need for additional treatment, from the prevalence of follicular trachoma. In this study, we examined the association between infection and presence or absence of follicular trachoma in children prior to and following multiple rounds of treatment. Findings suggest that with increasing rounds of treatment, the prevalence of infection declines in children both with and without signs of follicular trachoma. Newer strategies, including tests that can rapidly detect infection under field conditions, may be needed to assess residual infection in treated communities. Purpose To examine the relationship between ocular Chlamydia trachomatis infection and follicular trachoma (TF) in children prior to and following multiple rounds of annual mass drug administration (MDA) with azithromycin. Methodology/principal findings Thirty-two communities with endemic trachoma in Kongwa District, Tanzania, were offered annual MDA as part of a district-wide trachoma control program. Presence of ocular C. trachomatis infection and TF were assessed in 3,200 randomly sampled children aged five years and younger, who were examined prior to each MDA. Infection was detected using the Amplicor CT/NG assay and TF was identified by clinical examination using the World Health Organization (WHO) simplified grading system. The association between chlamydial infection and TF in children was evaluated at baseline prior to any treatment, and 12 months after each of three annual rounds of mass treatment. Factors associated with infection were examined using generalized estimating equation models. At baseline, the overall prevalence of chlamydial infection and TF was 22% and 31%, respectively. Among children with clinical signs of TF, the proportion of those with infection was 49% prior to treatment and declined to 30% after three MDAs. The odds of infection positivity among children with clinical signs of TF decreased by 26% (OR 0.74, 95% CI 0.65 to 0.84, p = <0.01) with each MDA, after adjusting for age. For children aged under one year, who did not receive treatment, the relationship was unchanged. Conclusions/significance The association between ocular C. trachomatis infection and TF weakened in children with each MDA, as both infection and clinical disease prevalence declined. However, there was still a significant proportion of TF cases with infection after three rounds of MDA. New strategies are needed to assess this residual infection for optimal treatment distribution. C1 [Lee, Jennifer S.; Munoz, Beatriz E.; West, Sheila K.] Johns Hopkins Univ, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21218 USA. [Mkocha, Harran] Kongwa Trachoma Project, Kongwa, Tanzania. [Gaydos, Charlotte A.; Quinn, Thomas C.] Johns Hopkins Univ, Dept Med, Div Infect Dis, Baltimore, MD USA. [Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Lee, JS (reprint author), Johns Hopkins Univ, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21218 USA. EM jenleesf@gmail.com FU Bill and Melinda Gates Foundation [48027]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was supported by a grant from the Bill and Melinda Gates Foundation (Grant ID 48027) and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, 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 23 TC 2 Z9 2 U1 0 U2 2 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 APR PY 2014 VL 8 IS 4 DI 10.1371/journal.pntd.0002761 PG 6 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AG3TK UT WOS:000335342400044 PM 24722392 ER PT J AU Teixeira, C Gomes, R Oliveira, F Meneses, C Gilmore, DC Elnaiem, DEA Valenzuela, JG Kamhawi, S AF Teixeira, Clarissa Gomes, Regis Oliveira, Fabiano Meneses, Claudio Gilmore, Dana C. Elnaiem, Dia-Eldin A. Valenzuela, Jesus G. Kamhawi, Shaden TI Characterization of the Early Inflammatory Infiltrate at the Feeding Site of Infected Sand Flies in Mice Protected from Vector-Transmitted Leishmania major by Exposure to Uninfected Bites SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID NATURAL-KILLER-CELLS; LUTZOMYIA-LONGIPALPIS SALIVA; CUTANEOUS LEISHMANIASIS; DENDRITIC CELLS; VISCERAL LEISHMANIASIS; IMMUNE-RESPONSE; FLY SALIVA; NK CELLS; PROTEIN; MACROPHAGES AB Author Summary Sand flies transmit Leishmania parasites during bloodfeeding. Salivary molecules are deposited alongside parasites and can reshape the host's immune response to infection. Exposure to uninfected sand fly bites or immunization with salivary molecules protects the host against Leishmania infection. Here we show that mice exposed to bites of uninfected Phlebotomus duboscqi sand flies are protected against P. duboscqi-transmitted L. major and characterize the formerly unknown early cellular infiltrate at the bite site following L.major vector-transmission. The kinetics and nature of the inflammatory response at the bite site of exposed mice were notably different from those of naive mice showing an amplified expression of cytokines and chemokines after parasite transmission. The transcripts reflected a faster and more robust infiltrate of immune cells to the bite site of exposed mice composed of neutrophils, macrophages, monocytes, NK cells and CD4+ T cells. In addition, there was an increased influx of activated IFN-gamma producing CD4+ T cells and Granzyme B-producing mature NK cells in exposed animals. These findings suggest that the observed robust and persistent proinflammatory response in exposed animals restrict parasite multiplication. Background Mice exposed to sand fly saliva are protected against vector-transmitted Leishmania major. Although protection has been related to IFN- gamma producing T cells, the early inflammatory response orchestrating this outcome has not been defined. Methodology/Principal findings Mice exposed to uninfected P. duboscqi bites and naive mice were challenged with L. major-infected flies to characterize their early immune response at the bite site. Mostly, chemokine and cytokine transcript expression post-infected bites was amplified in exposed compared to naive mice. In exposed mice, induced chemokines were mostly involved in leukocyte recruitment and T cell and NK cell activation; IL-4 was expressed at 6 h followed by IFN-gamma and iNOS2 as well as IL-5 and IL-10 expression. In naive animals, the transcript expression following Leishmania-infected sand fly bites was suppressed. Expression profiles translated to an earlier and significantly larger recruitment of leukocytes including neutrophils, macrophages, Gr(+) monocytes, NK cells and CD4(+) T cells to the bite site of exposed compared to naive mice post-infected bites. Additionally, up to 48 hours post-infected bites the number of IFN-gamma-producing CD4(+)T cells and NK cells arriving at the bite site was significantly higher in exposed compared to naive mice. Thereafter, NK cells become cytolytic and persist at the bite site up to a week post-bite. Conclusion/Significance The quiet environment induced by a Leishmania-infected sand fly bite in naive mice was significantly altered in animals previously exposed to saliva of uninfected flies. We propose that the enhanced recruitment of Gr(+) monocytes, NK cells and CD4 Th1 cells observed at the bite site of exposed mice creates an inhospitable environment that counters the establishment of L. major infection. C1 [Teixeira, Clarissa; Gomes, Regis; Oliveira, Fabiano; Meneses, Claudio; Gilmore, Dana C.; Valenzuela, Jesus G.; Kamhawi, Shaden] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Teixeira, Clarissa; Gomes, Regis] Fiocruz MS, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil. [Elnaiem, Dia-Eldin A.] Univ Maryland Eastern Shore, Dept Zool, Princess Anne, MD USA. RP Teixeira, C (reprint author), NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM jvalenzuela@niaid.nih.gov; skamhawi@niaid.nih.gov RI Oliveira, Fabiano/B-4251-2009 OI Oliveira, Fabiano/0000-0002-7924-8038 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, 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 49 TC 7 Z9 7 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 APR PY 2014 VL 8 IS 4 DI 10.1371/journal.pntd.0002781 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AG3TK UT WOS:000335342400020 PM 24762408 ER PT J AU Wood, KE Lau, A Mantzioris, E Gibson, RA Ramsden, CE Muhlhausler, BS AF Wood, K. E. Lau, A. Mantzioris, E. Gibson, R. A. Ramsden, C. E. Muhlhausler, B. S. TI A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Omega-6 PUFA; Linoleic acid (LA); Omega-3 PUFA; ALA; Diet ID FISH-OIL; METABOLITES; PATHWAYS; DOCOSATRIENES; BIOSYNTHESIS; LEUKOTOXIN; PRODUCTS; DISEASE; TRPV1 AB This study aimed to determine the effect of reducing the dietary linoleic acid (LA) intake from similar to 5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks. Nutrient intakes were estimated from diet diaries and blood samples were collected for assessment of fatty acid composition in plasma and erythrocyte phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA intervention (P < 0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were significantly reduced after the low LA diet phase (P < 0.001). The n-3 LCPUFA content of plasma phospholipids was significantly increased after the low LA diet compared to baseline (6.22% vs. 5.53%, P < 0.001). These data demonstrate that reducing LA intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Wood, K. E.; Lau, A.] Flinders Univ S Australia, Sch Med, Dept Nutr & Dietet, Adelaide, SA 5042, Australia. [Mantzioris, E.] Univ S Australia, Sch Pharm & Med Sci, Adelaide, SA 5001, Australia. [Wood, K. E.; Gibson, R. A.; Muhlhausler, B. S.] Univ Adelaide, FOODplus Res Ctr, Sch Agr Food & Wine, Glen Osmond, SA 5064, Australia. [Ramsden, C. E.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. RP Muhlhausler, BS (reprint author), Univ Adelaide, FOODplus Res Ctr, Sch Agr Food & Wine, Glen Osmond, SA 5064, Australia. EM beverly.muhlhausler@adelaide.edu.au RI Mantzioris, Evangeline/G-8681-2011; Gibson, Robert/E-7546-2012 OI Mantzioris, Evangeline/0000-0002-1480-9869; Gibson, Robert/0000-0002-8750-525X FU FOODplus Research Centre at the University of Adelaide; Career Development Award from the National Health and Medical Research Council of Australia (NHMRC); NHMRC Senior Research Fellowship; Ministry of Health (MOH) Health Science Scholarship from Singapore; Australia Postgraduate Award FX this work was funded by the FOODplus Research Centre at the University of Adelaide. BSM is supported by a Career Development Award from the National Health and Medical Research Council of Australia (NHMRC). RG is supported by an NHMRC Senior Research Fellowship. AL was supported by a Ministry of Health (MOH) Health Science Scholarship from Singapore. KW is supported by an Australia Postgraduate Award. NR 33 TC 14 Z9 14 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 EI 1532-2823 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD APR PY 2014 VL 90 IS 4 BP 133 EP 138 DI 10.1016/j.plefa.2013.12.010 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA AG4ZV UT WOS:000335429800006 PM 24456663 ER PT J AU Crompton, JG Clever, D Vizcardo, R Rao, M Restifo, NP AF Crompton, Joseph G. Clever, David Vizcardo, Raul Rao, Mahendra Restifo, Nicholas P. TI Reprogramming antitumor immunity SO TRENDS IN IMMUNOLOGY LA English DT Review DE regenerative medicine; cancer immunotherapy; T cell reprogramming ID PLURIPOTENT STEM-CELLS; CD8(+) T-CELLS; TUMOR-INFILTRATING LYMPHOCYTES; IN-VIVO; SOMATIC-CELLS; HEMATOPOIETIC PROGENITORS; ADOPTIVE IMMUNOTHERAPY; MYOCARDIAL-INFARCTION; HUMAN FIBROBLASTS; MELANOMA PATIENTS AB Regenerative medicine holds great promise in replacing tissues and organs lost to degenerative disease and injury. Application of the principles of cellular reprogramming for the treatment of cancer, however, is not well established. Here, we present an overview of cellular reprogramming techniques used in regenerative medicine, and within this context, envision how the scope of regenerative medicine may be expanded to treat metastatic cancer by revitalizing an exhausted and senescent immune system. C1 [Crompton, Joseph G.; Clever, David; Vizcardo, Raul; Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA. [Crompton, Joseph G.; Clever, David] Univ Cambridge, Dept Med, Sch Clin Med, Cambridge CB2 2QH, England. [Crompton, Joseph G.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90095 USA. [Rao, Mahendra; Restifo, Nicholas P.] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM restifo@nih.gov OI Restifo, Nicholas P./0000-0003-4229-4580 FU Wellcome Trust Translational Medicine and Therapeutics Programme FX We apologize to those investigators whose work was not cited due to space constraints. We wish to thank Ethan Tyler and Alan Hoofring of the National Institutes of Health Medical Arts Design Section for their beautiful rendering of the figures for this manuscript. This study was funded by a generous gift from Mr. Li Jinyuan, Chairman of the Tiens Group, NIH-Center for Regenerative Medicine and by the Intramural Research Program of the NCI, Center for Cancer Research, NIH, Bethesda, MD, 20892. JG Crompton also acknowledges funding support from the Wellcome Trust Translational Medicine and Therapeutics Programme. The authors have no conflicting financial interests. NR 91 TC 8 Z9 8 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 EI 1471-4981 J9 TRENDS IMMUNOL JI Trends Immunol. PD APR PY 2014 VL 35 IS 4 BP 178 EP 185 DI 10.1016/j.it.2014.02.003 PG 8 WC Immunology SC Immunology GA AG5AB UT WOS:000335430400007 PM 24661777 ER PT J AU Spanagel, R Noori, HR Heilig, M AF Spanagel, Rainer Noori, Hamid R. Heilig, Markus TI Stress and alcohol interactions: animal studies and clinical significance SO TRENDS IN NEUROSCIENCES LA English DT Review DE alcohol; glucocorticoids; EPA axis; stress; organ cation transporter (OCT) ID CORTICOTROPIN-RELEASING-FACTOR; ORGANIC CATION TRANSPORTER-3; OPIOID RECEPTOR ANTAGONIST; AMINOBUTYRIC-ACID RELEASE; ETHANOL-SEEKING; NEUROPEPTIDE-Y; CRHR1 GENE; MONOAMINERGIC NEUROTRANSMISSION; GLUCOCORTICOID-RECEPTOR; DOPAMINOCEPTIVE NEURONS AB Alcohol is frequently consumed for stress relief, but the individual determinants and the temporal course of stress-induced alcohol use are not well understood. Preclinical studies may help shed light on these factors. We synthesize here the findings from numerous rodent studies of stress and alcohol interactions. Stress-induced alcohol consumption is age-dependent, has a high genetic load, and results from an interaction of the stress and reward systems. Specifically, glucocorticoids, acting within the nucleus accumbens (NAc), are important mediators of this stress-induced alcohol intake. In addition, increased activation of the corticotropin-releasing hormone (CRH) system within the extended amygdala appears to mediate stress-induced relapse. Finally, these preclinical studies have helped to identify several attractive targets for novel treatments of alcohol abuse and addiction. C1 [Spanagel, Rainer; Noori, Hamid R.] Heidelberg Univ, Med Fac Mannheim, CIMH, Inst Psychopharmacol, D-69115 Heidelberg, Germany. [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. RP Spanagel, R (reprint author), Heidelberg Univ, Med Fac Mannheim, CIMH, Inst Psychopharmacol, Bergheimer Str 58, D-69115 Heidelberg, Germany. OI Heilig, Markus/0000-0003-2706-2482 FU Bundesministerium fur Bildung und Forschung (NGFN Plus) [FKZ: 01GS08152]; e:Med program [FKZ: 01ZX1311A [41]]; Deutsche Forschungsgemeinschaft [DFG: SFB 636 (B1)]; Reinhart-Koselleck Award [SP 383/5-1]; Ministerium fur Wissenschaft; Forschung and Kunst (MWK) in Baden-Wurttemberg; intramural program of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) FX We thank Sandra Helinski for screening the literature for our metaanalyses (see [18]). Our work is supported by the Bundesministerium fur Bildung und Forschung (NGFN Plus; FKZ: 01GS08152 and the e:Med program; FKZ: 01ZX1311A [41]), the Deutsche Forschungsgemeinschaft [DFG: SFB 636 (B1)], Reinhart-Koselleck Award SP 383/5-1, the Ministerium fur Wissenschaft, Forschung and Kunst (MWK) in Baden-Wurttemberg, and the intramural program of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). NR 93 TC 27 Z9 29 U1 6 U2 26 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD APR PY 2014 VL 37 IS 4 BP 219 EP 227 DI 10.1016/j.tins.2014.02.006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AG5AD UT WOS:000335430600006 PM 24636458 ER PT J AU Chung, JY Insel, TR AF Chung, Joyce Y. Insel, Thomas R. TI Mind the Gap: Neuroscience Literacy and the Next Generation of Psychiatrists SO ACADEMIC PSYCHIATRY LA English DT Article DE Psychiatric residency training; Milestones; Next; Accreditation System; Neuroscience education; Curriculum development ID RESIDENTS AB The National Institute of Mental Health seeks to address the gap between modern neuroscience and psychiatric training. The authors describe a two-pronged approach: first, to identify and support trainees in clinical neuroscience and second, to promote neuroscience literacy in psychiatric residency programs. C1 [Chung, Joyce Y.; Insel, Thomas R.] NIMH, Bethesda, MD 20892 USA. RP Chung, JY (reprint author), NIMH, Bethesda, MD 20892 USA. EM chungj@mail.nih.gov NR 9 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1042-9670 EI 1545-7230 J9 ACAD PSYCHIATR JI Acad. Psych. PD APR PY 2014 VL 38 IS 2 BP 121 EP 123 DI 10.1007/s40596-014-0054-6 PG 3 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA AF0OQ UT WOS:000334414300003 PM 24619911 ER PT J AU Etkin, A Cuthbert, B AF Etkin, Amit Cuthbert, Bruce TI Beyond the DSM: Development of a Transdiagnostic Psychiatric Neuroscience Course SO ACADEMIC PSYCHIATRY LA English DT Article DE Research domain criteria project (RDoC); Neuroscience course; Psychiatry residents ID SCHIZOPHRENIA; CLASSIFICATION; DISORDERS; ANXIETY; MEMORY; RISK AB Objective Clinical and neurobiological data suggest that psychiatric disorders, as traditionally defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM), are (1) more comorbid than expected by chance, (2) often share neurobiological signatures, and (3) reflect alterations across multiple brain systems that mediate particular mental processes. As such, emerging conceptualizations such at the National Institute of Mental Health's Research Domain Criteria Project (RDoC) have suggested that a different way to understand psychopathology may be with respect to the degree of dysfunction in each of these brain systems, seen dimensionally, which both cross traditional diagnostic boundaries and extend to a healthy range of functioning. At present, however, this scientific perspective has not been incorporated into neuroscience education in psychiatry, nor has its relationship to clinical care been made clear. Methods We describe the rationale and implementation of a reformulated neuroscience course given to psychiatric residents at Stanford University centered on the conceptual framework of RDoC. Data are presented on resident feedback before and after revision of the course. Results A clear motivation and rationale exists for teaching neuroscience in a transdiagnostic framework. This course was taken up well by the residents, with overall feedback significantly more positive than that prior to the course revision. Conclusion This "proof of concept" neuroscience course illustrates a potential route for bridging between rapid advances in psychiatric neuroscience and the clinical education for trainees not otherwise versed in neuroscience but who are needed for scientific advances to translate to the clinic. The promise of this approach may be in part related to the similarity between this framework and problem-based approaches common in routine clinical care. In such approaches, clinicians focus on the expressed complaints of their individual patient and identify specific symptoms as the target of treatment-symptoms which are presumably the expression of dysfunction in specific brain systems. C1 [Etkin, Amit] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Cuthbert, Bruce] NIMH, Bethesda, MD 20892 USA. RP Etkin, A (reprint author), Stanford Univ, Sch Med, Stanford, CA 94305 USA. EM amitetkin@stanford.edu NR 16 TC 13 Z9 13 U1 3 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1042-9670 EI 1545-7230 J9 ACAD PSYCHIATR JI Acad. Psych. PD APR PY 2014 VL 38 IS 2 BP 145 EP 150 DI 10.1007/s40596-013-0032-4 PG 6 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA AF0OQ UT WOS:000334414300008 PM 24493358 ER PT J AU Courter, JR Madani, N Sodroski, J Schon, A Freire, E Kwong, PD Hendrickson, WA Chaiken, IM LaLonde, JM Smith, AB AF Courter, Joel R. Madani, Navid Sodroski, Joseph Schoen, Arne Freire, Ernesto Kwong, Peter D. Hendrickson, Wayne A. Chaiken, Irwin M. LaLonde, Judith M. Smith, Amos B., III TI Structure-Based Design, Synthesis and Validation of CD4-Mimetic Small Molecule Inhibitors of HIV-1 Entry: Conversion of a Viral Entry Agonist to an Antagonist SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN TRIMER; CD4 RECEPTOR-BINDING; CONFORMATIONAL-CHANGES; GP120; ANTIBODY AB CONSPECTUS: This Account provides an overview of a multidisciplinary consortium focused on structure-based strategies to devise small molecule antagonists of HIV-1 entry into human T-cells, which if successful would hold considerable promise for the development of prophylactic modalities to prevent HIV transmission and thereby alter the course of the AIDS pandemic. Entry of the human immunodeficiency virus (HIV) into target T-cells entails an interaction between CD4 on the host T-cell and gp120, a component of the trimeric envelope glycoprotein spike on the virion surface. The resultant interaction initiates a series of conformational changes within the envelope spike that permits binding to a chemokine receptor, formation of the gp41 fusion complex, and cell entry. A hydrophobic cavity at the CD4-gp120 interface, defined by X-ray crystallography, provided an initial site for small molecule antagonist design. This site however has evolved to facilitate viral entry. As such, the binding of prospective small molecule inhibitors within this gp120 cavity can inadvertently trigger an allosteric entry signal. Structural characterization of the CD4-gp120 interface, which provided the foundation for small molecule structure-based inhibitor design, will be presented first. An integrated approach combining biochemical, virological, structural, computational, and synthetic studies, along with a detailed analysis of ligand binding energetics, revealed that modestly active small molecule inhibitors of HIV entry can also promote viral entry into cells lacking the CD4 receptor protein; these competitive inhibitors were termed small molecule CD4 mimetics. Related congeners were subsequently identified with both improved binding affinity and more potent viral entry inhibition. Further assessment of the affinity-enhanced small molecule CD4 mimetics demonstrated that premature initiation of conformational change within the viral envelope spike, prior to cell encounter, can lead to irreversible deactivation of viral entry machinery. Related congeners, which bind the same gp120 site, possess different propensities to elicit the allosteric response that underlies the undesired enhancement of CD4-independent viral entry. Subsequently, key hotspots in the CD4-gp120 interface were categorized using mutagenesis and isothermal titration calorimetry according to the capacity to increase binding affinity without triggering the allosteric signal. This analysis, combined with cocrystal structures of small molecule viral entry agonists with gp120, led to the development of fully functional antagonists of HIV-1 entry. Additional structure-based design exploiting two hotspots followed by synthesis has now yielded low micromolar inhibitors of viral entry. C1 [Courter, Joel R.; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Madani, Navid; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Ragon Inst MGH MIT & Harvard, Dept Microbiol & Immunol,Med Sch,Dept Immunol & I, Boston, MA 02115 USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hendrickson, Wayne A.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Hendrickson, Wayne A.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA. [Chaiken, Irwin M.] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA. [LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. RP Smith, AB (reprint author), Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. FU NIH [P01 GM 56550] FX The authors thank all previous co-workers who have helped advance this project. The research presented in this Account has been primarily supported for over 15 years through an NIH Program Project (P01 GM 56550). NR 42 TC 25 Z9 25 U1 2 U2 36 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 EI 1520-4898 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD APR PY 2014 VL 47 IS 4 BP 1228 EP 1237 DI 10.1021/ar4002735 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA AF4CE UT WOS:000334658200025 PM 24502450 ER PT J AU Emmert, D Campos, CR Ward, D Lu, PH Namanja, HA Bohn, K Miller, DS Sharom, FJ Chmielewski, J Hrycyna, CA AF Emmert, Dana Campos, Christopher R. Ward, David Lu, Peihua Namanja, Hilda A. Bohn, Kelsey Miller, David S. Sharom, Frances J. Chmielewski, Jean Hrycyna, Christine A. TI Reversible Dimers of the Atypical Antipsychotic Quetiapine Inhibit P-Glycoprotein-Mediated Efflux in Vitro with Increased Binding Affinity and in Situ at the Blood-Brain Barrier SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE P-glycoprotein; blood-brain barrier; quetiapine; inhibitor; ABC transporter; antipsychotic agent ID DRUG-DRUG INTERACTIONS; HUMAN MULTIDRUG TRANSPORTER; ENDOTHELIAL-CELL LINE; 2ND-GENERATION ANTIPSYCHOTICS; BIVALENT MODULATORS; FLAVONOID DIMERS; DEFICIENT MICE; CANCER-CELLS; RESISTANCE; PHARMACOKINETICS AB The multidrug resistance transporter P-glycoprotein (P-gp) is highly expressed in the capillary endothelial cells of the blood-brain barrier (BBB) where it functions to limit the brain penetration of many drugs, including antipsychotic agents used to treat schizophrenia. Therefore, in an effort to inhibit the transporter, we designed dimers of the antipsychotic drug and P-gp substrate quetiapine (QT), linked by variable length tethers. In P-gp overexpressing cells and in human brain capillary endothelial hCMEC/D3 cells, the dimer with the shortest tether length(QT(2)C(2)) (1) was the most potent inhibitor showing >80-fold better inhibition of P-gp-mediated transport than monomeric QT. The dimers, which are linked via ester moieties, are designed to revert to the therapeutic monomer once inside the target cells. We demonstrated that the addition of two sterically blocking methyl groups to the linker (QT(2)C(2)Me(2), 8) increased the half-life of the molecule in plasma 10-fold as compared to the dimer lacking methyl groups (QT(2)C(2), 1), while retaining inhibitory potency for P-gp transport and sensitivity to cellular esterases. Experiments with purified P-gp demonstrated that QT(2)C2 (1) and QT(2)C(2)Me(2) (8) interacted with both the H- and R-binding sites of the tra(n)sporter with binding affinities 20- to 30-fold higher than that of monomeric QT. Using isolated rat brain capillaries, QT(2)C(2)Me(2) (8) was a more potent inhibitor of P-gp transport than QT. Lastly, we showed that QT(2)C(2)Me(2) (8) increased the accumulation of the P-gp substrate verapamil in rat brain in situ three times more than QT. Together, these results indicate that the QT dimer QT(2)C(2)Me(2) (8) strongly inhibited P-gp transport activity in human brain capillary endothelial cells, in rat brain capillaries, and at the BBB in an animal model. C1 [Emmert, Dana; Namanja, Hilda A.; Bohn, Kelsey; Chmielewski, Jean; Hrycyna, Christine A.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Campos, Christopher R.; Miller, David S.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Ward, David; Lu, Peihua; Sharom, Frances J.] Univ Guelph, Dept Mol & Cellular Biol, Guelph, ON N1G 2W1, Canada. RP Chmielewski, J (reprint author), Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN 47907 USA. EM hrycyna@purdue.edu; chml@purdue.edu OI Bohn, Kelsey/0000-0001-5856-1095 FU NIH/NEI [1R21EY018481-01]; Canadian Cancer Society [770248] FX This work was supported by a grant from NIH/NEI 1R21EY018481-01 (C.A.H. and J.C.) and a research grant (#770248) from the Canadian Cancer Society (F.J.S.). NR 82 TC 1 Z9 1 U1 3 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD APR PY 2014 VL 5 IS 4 BP 305 EP 317 DI 10.1021/cn4002329 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA AF4BZ UT WOS:000334657700008 PM 24483607 ER PT J AU Watanabe, R Sato, K Hanaoka, H Harada, T Nakajima, T Kim, I Paik, CH Wu, AM Choyke, PL Kobayashi, H AF Watanabe, Rira Sato, Kazuhide Hanaoka, Hirofumi Harada, Toshiko Nakajima, Takahito Kim, Insook Paik, Chang H. Wu, Anna M. Choyke, Peter L. Kobayashi, Hisataka TI Minibody-Indocyanine Green Based Activatable Optical Imaging Probes: The Role of Short Polyethylene Glycol Linkers SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Molecular imaging; minibody; indocyanine green; prostate cancer; near-infrared fluorescence ID ANTIGEN; CANCER; ANTIBODIES; TUMORS; MICE AB Minibodies show rapider blood clearance than IgGs due to smaller size that improves target-to-background ratio (TBR) in in vivo imaging. Additionally, the ability to activate an optical probe after binding to the target greatly improves the TBR. An optical imaging probe based on a minibody against prostate-specific membrane antigen (PSMA-MB) and conjugated with an activatable fluorophore, indocyanine green (ICG), was designed to fluoresce only after binding to cell-surface PSMA. To further reduce background signal, short polyethylene glycol (PEG) linkers were employed to improve the covalent bonding ratio of ICG. New PSMA-MBs conjugated with bifunctional ICG derivatives specifically visualized PSMA-positive tumor xenografts in mice bearing both PSMA-positive and -negative tumors within 6 h postinjection. The addition of short PEG linkers significantly improved TBRs; however, it did not significantly alter the biodistribution. Thus, minibody-ICG conjugates could be a good alternative to IgG-ICG in the optical cancer imaging for further clinical applications. C1 [Watanabe, Rira; Sato, Kazuhide; Hanaoka, Hirofumi; Harada, Toshiko; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kim, Insook] Leidos Biomed Res Inc, Appl Dev Res Directorate, Frederick Natl Lab, Frederick, MD 21702 USA. [Paik, Chang H.] NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Wu, Anna M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU Intramural Research Program of the NCI/NIH; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This research was supported by the Intramural Research Program of the NCI/NIH. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. NR 23 TC 10 Z9 11 U1 2 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD APR PY 2014 VL 5 IS 4 BP 411 EP 415 DI 10.1021/ml400533y PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AF2VU UT WOS:000334571400026 PM 24900850 ER PT J AU Nelson, KM Thiede, H Jenkins, RA Carey, JW Hutcheson, R Golden, MR AF Nelson, Kimberly M. Thiede, Hanne Jenkins, Richard A. Carey, James W. Hutcheson, Rebecca Golden, Matthew R. TI PERSONAL AND CONTEXTUAL FACTORS RELATED TO DELAYED HIV DIAGNOSIS AMONG MEN WHO HAVE SEX WITH MEN SO AIDS EDUCATION AND PREVENTION LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; CARE; INTERCOURSE; PREVENTION; MORTALITY; INFECTION; DISEASE; COST; RISK AB Delayed HIV diagnosis among men who have sex with men (MSM) in the United States continues to be a significant personal and public health issue. Using qualitative and quantitative data from 75 recently tested, HIV-sero-positive MSM (38 delayed and 37 nondelayed testers), the authors sought to further elucidate potential personal and contextual factors that may contribute to delayed HIV diagnosis among MSM. Findings indicate that MSM who experience multiple life stressors, whether personal or contextual, have an increased likelihood of delaying HIV diagnosis. Furthermore, MSM who experience multiple life stressors without the scaffolding of social support, stable mental health, and self-efficacy to engage in protective health behaviors may be particularly vulnerable to delaying diagnosis. Interventions targeting these factors as well as structural interventions targeting physiological and safety concerns are needed to help MSM handle their life stressors more effectively and seek HIV testing in a timelier manner. C1 [Nelson, Kimberly M.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Thiede, Hanne; Golden, Matthew R.] Publ Hlth Seattle & King Cty, Seattle, WA USA. [Jenkins, Richard A.] Natl Inst Drug Abuse, Bethesda, MD USA. [Carey, James W.] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. [Golden, Matthew R.] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. [Golden, Matthew R.] Univ Washington, Sch Med, Seattle, WA USA. RP Nelson, KM (reprint author), Univ Washington, Dept Psychol, Box 351525, Seattle, WA 98195 USA. EM knelson6@uw.edu FU NIMH NIH HHS [F31 MH088851, F31MH088851]; PHS HHS [U64/CCU019523] NR 30 TC 3 Z9 3 U1 1 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 EI 1943-2755 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD APR PY 2014 VL 26 IS 2 BP 122 EP 133 PG 12 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA AF1MK UT WOS:000334477800003 PM 24694326 ER PT J AU Knepper, MA AF Knepper, Mark A. TI Proteomic pearl diving versus systems biology in cell physiology. Focus on "Proteomic mapping of proteins released during necrosis and apoptosis from cultured neonatal cardiac myocytes" SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Editorial Material ID MUSCLE C1 NHLBI, Epithelial Syst Biol Lab, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Epithelial Syst Biol Lab, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU NHLBI NIH HHS [Z01 HL001285, ZO1-HL001285] NR 9 TC 2 Z9 2 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2014 VL 306 IS 7 BP C634 EP C635 DI 10.1152/ajpcell.00010.2014 PG 2 WC Cell Biology; Physiology SC Cell Biology; Physiology GA AF4KS UT WOS:000334681500002 PM 24429064 ER PT J AU Scuteri, A Cunha, PG Rosei, EA Badariene, J Bekaert, S Cockcroft, JR Cotter, J Cucca, F De Buyzere, ML De Meyer, T Ferrucci, L Franco, O Gale, N Gillebert, TC Hofman, A Langlois, M Laucevicius, A Laurent, S Raso, FUSM Morrell, CH Muiesan, ML Munnery, MM Navickas, R Oliveira, P Orru', M Pilia, MG Rietzschel, ER Ryliskyte, L Salvetti, M Schlessinger, D Sousa, N Stefanadis, C Strait, J Van Daele, C Villa, I Vlachopoulos, C Witteman, J Xaplanteris, P Nilsson, P Lakatta, EG AF Scuteri, Angelo Cunha, Pedro G. Rosei, E. Agabiti Badariene, Jolita Bekaert, Sofie Cockcroft, John R. Cotter, Jorge Cucca, Francesco De Buyzere, Marc L. De Meyer, Tim Ferrucci, Luigi Franco, Osca Gale, Nichols Gillebert, Thierry C. Hofman, A. Langlois, Michel Laucevicius, Aleksandras Laurent, Stephane Raso, Francesco U. S. Mattace Morrell, Cristopher H. Muiesan, Maria Lorenza Munnery, Margaret M. Navickas, Rokas Oliveira, Pedro Orru', Marco Pilia, Maria Grazia Rietzschel, Ernst R. Ryliskyte, Ligita Salvetti, Massimo Schlessinger, David Sousa, Nuno Stefanadis, Christodoulos Strait, James Van Daele, Caroline Villa, Isabel Vlachopoulos, Charalambos Witteman, Jacqueline Xaplanteris, Panagiotis Nilsson, Peter Lakatta, Edward G. CA MARE Consortium TI Arterial stiffness and influences of the metabolic syndrome: A cross-countries study SO ATHEROSCLEROSIS LA English DT Article DE Arterial stiffness; Cross-cultural comparison; Metabolic syndrome; Pulse wave velocity ID PULSE-WAVE VELOCITY; CARDIOVASCULAR EVENTS; ISCHEMIC-STROKE; INDEPENDENT PREDICTOR; CLINICAL-APPLICATIONS; COGNITIVE FUNCTION; AORTIC STIFFNESS; RISK-FACTOR; HYPERTENSION; AGE AB Specific clusters of metabolic syndrome (MetS) components impact differentially on arterial stiffness, indexed as pulse wave velocity (PWV). Of note, in several population-based studies participating in the MARE (Metabolic syndrome and Arteries REsearch) Consortium the occurrence of specific clusters of MetS differed markedly across Europe and the US. The aim of the present study was to investigate whether specific clusters of MetS are consistently associated with stiffer arteries in different populations. We studied 20,570 subjects from 9 cohorts representing 8 different European countries and the US participating in the MARE Consortium. MetS was defined in accordance with NCEP ATPIII criteria as the simultaneous alteration in >= 3 of the 5 components: abdominal obesity (W), high triglycerides (T), low HDL cholesterol (H), elevated blood pressure (B), and elevated fasting glucose (G). PWV measured in each cohort was "normalized" to account for different acquisition methods. MetS had an overall prevalence of 24.2% (4985 subjects). MetS accelerated the age-associated increase in PWV levels at any age, and similarly in men and women. MetS clusters TBW, GBW, and GTBW are consistently associated with significantly stiffer arteries to an extent similar or greater than observed in subjects with alteration in all the five MetS components - even after controlling for age, sex, smoking, cholesterol levels, and diabetes mellitus - in all the MARE cohorts. In conclusion, different component clusters of MetS showed varying associations with arterial stiffness (PWV). (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Scuteri, Angelo] IRCCS, San Raffaele Pisana HSR, Rome, Italy. [Cunha, Pedro G.; Cotter, Jorge; Villa, Isabel] Univ Minho, Ctr Hosp, Ctr Res & Treatment Arterial Hypertens & Cardiova, Dept Internal Med, Guimaraes Braga, Portugal. [Cunha, Pedro G.; Cotter, Jorge; Sousa, Nuno] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Guimaraes Braga, Portugal. [Cunha, Pedro G.; Cotter, Jorge; Sousa, Nuno] PT Govt Associate Lab, ICVS 3Bs, Guimaraes, Portugal. [Rosei, E. Agabiti; Muiesan, Maria Lorenza; Salvetti, Massimo] Univ Brescia, Dipartimento Sci Clin & Sperimentali, Brescia, Italy. [Badariene, Jolita; Laucevicius, Aleksandras; Navickas, Rokas] Vilnius Univ, Fac Med, Clin Cardiovasc Dis, Vilnius, Lithuania. [Badariene, Jolita; Laucevicius, Aleksandras; Navickas, Rokas; Ryliskyte, Ligita] Vilnius Univ, Hosp Santariskiu Klinikos, Ctr Cardiol & Angiol, Vilnius, Lithuania. [Bekaert, Sofie] Ghent Univ Hosp, Bimetra, Clin Res Ctr Ghent, Ghent, Belgium. [Cucca, Francesco; Orru', Marco; Pilia, Maria Grazia] Cardiff Univ, Wales Heart Res Inst, Cardiff, Wales. [De Meyer, Tim] Univ Ghent, Fac Biosci Engn, Dept Math Modelling Stat & Bioinformat, B-9000 Ghent, Belgium. [Ferrucci, Luigi] IRP NIA, NIH, Baltimore, MD USA. [Franco, Osca; Hofman, A.; Raso, Francesco U. S. Mattace; Witteman, Jacqueline] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Langlois, Michel] Univ Ghent, AZ Sint Jan Bruges Hosp, Asklepios Core Lab, B-9000 Ghent, Belgium. [Langlois, Michel] Univ Ghent, Dept Cardiovasc Dis, B-9000 Ghent, Belgium. [Laurent, Stephane] Pompidou Hosp, INSERM U970, Dept Pharmacol, Paris, France. [Laurent, Stephane] Univ Paris 05, Paris, France. [Morrell, Cristopher H.; Strait, James; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Morrell, Cristopher H.] Loyola Coll, Baltimore, MD 21210 USA. [Oliveira, Pedro; Ryliskyte, Ligita] Univ Porto, Inst Ciencias Biomed Abel Salazar, Dept Estudo Populacoes, P-4100 Oporto, Portugal. [Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Stefanadis, Christodoulos; Vlachopoulos, Charalambos; Xaplanteris, Panagiotis] Athens Med Sch, Dept Cardiol 1, Athens, Greece. [Nilsson, Peter] Lund Univ, Univ Hosp, Dept Clin Sci, Malmo, Sweden. [De Buyzere, Marc L.; Gillebert, Thierry C.; Rietzschel, Ernst R.; Van Daele, Caroline] Ghent Univ Hosp, Dept Cardiovasc Dis, Ghent, Belgium. [De Buyzere, Marc L.; Gillebert, Thierry C.; Rietzschel, Ernst R.; Van Daele, Caroline] Univ Ghent, B-9000 Ghent, Belgium. RP Scuteri, A (reprint author), IRCCS, San Raffaele Pisana HSR, Rome, Italy. EM angeloelefante@interfree.it RI Salvetti, Massimo/E-9929-2010; Cunha, Pedro/K-6743-2014; Sousa, Nuno/C-2782-2009; Laurent, Stephane/J-8624-2015; Mattace- Raso, Francesco/L-2541-2015; Oliveira, Pedro/B-2224-2010; OI Cunha, Pedro/0000-0002-8518-4130; Oliveira, Pedro/0000-0002-2470-0795; Gillebert, Thierry/0000-0002-3832-919X; Sousa, Nuno/0000-0002-8755-5126 FU MARE consortium FX We thank all participants in the cohorts for contributing data to the MARE consortium as well as the funding agencies supporting these cohorts. NR 35 TC 35 Z9 37 U1 2 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2014 VL 233 IS 2 BP 654 EP 660 DI 10.1016/j.atherosclerosis.2014.01.041 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AE9OM UT WOS:000334337200051 PM 24561493 ER PT J AU Bajer, MM Kunze, MM Blees, JS Bokesch, HR Chen, HY Brauss, TF Dong, ZG Gustafson, KR Biondi, RM Henrich, CJ McMahon, JB Colburn, NH Schmid, T Brune, B AF Bajer, Magdalena M. Kunze, Michael M. Blees, Johanna S. Bokesch, Heidi R. Chen, Hanyong Brauss, Thilo F. Dong, Zigang Gustafson, Kirk R. Biondi, Ricardo M. Henrich, Curtis J. McMahon, James B. Colburn, Nancy H. Schmid, Tobias Bruene, Bernhard TI Characterization of pomiferin triacetate as a novel mTOR and translation inhibitor SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Mammalian target of rapamycin; Natural product; Translation; Pomiferin triacetate ID TUMOR-SUPPRESSOR PDCD4; RENAL-CELL CARCINOMA; ANTICANCER AGENTS; MACLURA-POMIFERA; RAPAMYCIN; CANCER; GROWTH; DEGRADATION; MECHANISM; PATHWAY AB Deregulation of the phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR)70 kDa ribosomal protein S6 kinase 1 (p70(S6K)) pathway is commonly observed in many tumors. This pathway controls proliferation, survival, and translation, and its overactivation is associated with poor prognosis for tumor-associated survival. Current efforts focus on the development of novel inhibitors of this pathway. In a cell-based high-throughput screening assay of 15,272 pure natural compounds, we identified pomiferin triacetate as a potent stabilizer of the tumor suppressor programmed cell death 4 (Pdcd4). Mechanistically, pomiferin triacetate appeared as a general inhibitor of the PI3K-Akt-mTOR-p70(S6K) cascade. Interference with this pathway occurred downstream of Akt but upstream of p70(S6K). Specifically, mTOR kinase emerged as the molecular target of pomiferin triacetate, with similar activities against mTOR complexes I and 2. In an in vitro mTOR kinase assay pomiferin triacetate dose-dependently inhibited mTOR with an IC50 of 6.2 mu M. Molecular docking studies supported the interaction of the inhibitor with the catalytic site of mTOR. Importantly, pomiferin triacetate appeared to be highly selective for mTOR compared to a panel of 17 lipid and 50 protein kinases tested. As a consequence of the mTOR inhibition, pomiferin triacetate efficiently attenuated translation. In summary, pomiferin triacetate emerged as a novel and highly specific mTOR inhibitor with strong translation inhibitory effects. Thus, it might be an interesting lead structure for the development of mTOR- and translation-targeted anti-tumor therapies. (C) 2014 Elsevier Inc. All rights reserved. C1 [Bajer, Magdalena M.; Kunze, Michael M.; Blees, Johanna S.; Brauss, Thilo F.; Schmid, Tobias; Bruene, Bernhard] Goethe Univ Frankfurt, Fac Med, Inst Biochem 1, D-60590 Frankfurt, Germany. [Bokesch, Heidi R.; Gustafson, Kirk R.; Henrich, Curtis J.; McMahon, James B.] NCI, Ctr Canc Res, Mol Targets Lab, Frederick, MD 21702 USA. [Bokesch, Heidi R.; Henrich, Curtis J.] Leidos Biomed Res,Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA. [Colburn, Nancy H.] NCI, Ctr Canc Res, Lab Canc Prevent, Frederick, MD 21702 USA. [Chen, Hanyong; Dong, Zigang] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. [Biondi, Ricardo M.] Univ Clin, Dept Internal Med 1, Res Grp PhosphoSites, D-60590 Frankfurt, Germany. RP Schmid, T (reprint author), Goethe Univ Frankfurt, Fac Med, Inst Biochem 1, D-60590 Frankfurt, Germany. EM tschmid@biochem.uni-frankfurt.de OI Biondi, Ricardo/0000-0002-8873-7167 FU Deutsche Forschungsgemeinschaft (DFG) [GRK1172, SCHM2663]; Hessian Ministry of Higher Education, Research and Arts; Frederick National Laboratory for Cancer Research; National Cancer Institute; National Institutes of Health (NIH) [HHSN261200800001E]; Intramural Research Program of NIH; Center for Cancer Research FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG) (GRK1172, SCHM2663) and the LOEWE Schwerpunkt OSF (III L 4-518/55.004 (2009)) funded by the Hessian Ministry of Higher Education, Research and Arts. This project was funded in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. This research was also supported in part by the Intramural Research Program of NIH, National Cancer Institute, 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 51 TC 5 Z9 5 U1 1 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 APR 1 PY 2014 VL 88 IS 3 BP 313 EP 321 DI 10.1016/j.bcp.2014.01.034 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF1MX UT WOS:000334479100005 PM 24513322 ER PT J AU Cai, J Song, BW Cai, YX Ma, Y Lam, AL Magiera, J Sekar, S Wyse, BD Ambo, A Sasaki, Y Lazarus, LH Smith, MT Li, TY AF Cai, Jun Song, Bowen Cai, Yunxin Ma, Yu Lam, Ai-Leen Magiera, Julia Sekar, Sunder Wyse, Bruce D. Ambo, Akihiro Sasaki, Yusuke Lazarus, Lawrence H. Smith, Maree T. Li, Tingyou TI Endomorphin analogues with mixed mu-opioid (MOP) receptor agonism/delta-opioid (DOP) receptor antagonism and lacking beta-arrestin2 recruitment activity SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Endomorphin-2; Opioid; Dmt; Analgesics ID IN-VITRO CHARACTERIZATION; AGONIST/DELTA-ANTAGONIST; PHARMACOLOGICAL CHARACTERIZATION; VIVO ANTINOCICEPTION; POTENT; LIGANDS; PEPTIDES; EFFICACY; TETRAPEPTIDE; DERIVATIVES AB Analogues of endomorphin (Dmt-Pro-Xaa-Xaa-NH2) modified at position 4 or at positions 4 and 3, and tripeptides (Dmt-Pro-Xaa-NH2) modified at position 3, with various phenylalanine analogues (Xaa = Trp, 1-Nal, 2-Nal, Tmp, Dmp, Dmt) were synthesized and their effects on in vitro opioid activity were investigated. Most of the peptides exhibited high mu-opioid (MOP) receptor binding affinity (K-iMOP = 0.13-0.81 nM), modest MOP-selectivity (Ki delta-opioid (DOP)/K-iMOP = 3.5-316), and potent functional MOP agonism (GPI, IC50 = 0.274-249 nM) without DOP and kappa-opioid (KOP) receptor agonism. Among them, compounds 7 (Dmt-Pro-Tmp-Tmp-NH2) and 9 (Dmt-Pro-1-Nal-NH2) were opioids with potent mixed MOP receptor agonism/DOP receptor antagonism and devoid of beta-arrestin2 recruitment activity. They may offer a unique template for the discovery of potent analgesics that produce less respiratory depression, less gastrointestinal dysfunction and that have a lower propensity to induce tolerance and dependence compared with morphine. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Cai, Jun; Song, Bowen; Cai, Yunxin; Ma, Yu; Li, Tingyou] Nanjing Med Univ, Sch Pharm, Nanjing 211166, Jiangsu, Peoples R China. [Lam, Ai-Leen; Magiera, Julia; Sekar, Sunder; Wyse, Bruce D.; Smith, Maree T.] Univ Queensland, Ctr Integrated Preclin Drug Dev, Brisbane, Qld 4072, Australia. [Ambo, Akihiro; Sasaki, Yusuke] Tohoku Pharmaceut Univ, Aoba Ku, Sendai, Miyagi 9818558, Japan. [Lazarus, Lawrence H.] NIEHS, Lab Pharmacol & Chem, Med Chem Grp, Res Triangle Pk, NC 27709 USA. [Li, Tingyou] Nanjing Med Univ, Collaborat Innovat Ctr Cardiovasc Dis Translat Me, Nanjing 211166, Jiangsu, Peoples R China. RP Smith, MT (reprint author), Univ Queensland, Ctr Integrated Preclin Drug Dev, Brisbane, Qld 4072, Australia. EM maree.smith@uq.edu.au; l_tingyou@njmu.edu.cn RI Smith, Maree/I-4005-2015 OI Smith, Maree/0000-0003-2281-3734 FU Collaborative Innovation Center for Cardiovascular Disease Translational Medicine; Intramural Research Program of the NJMU [KY109RC01110801]; University of Queensland; Queensland Government Smart State Research Facilities Fund FX These studies were supported in part by Collaborative Innovation Center for Cardiovascular Disease Translational Medicine and in part by the Intramural Research Program of the NJMU to T. L (KY109RC01110801). Research undertaken at The University of Queensland was supported by research funds from The University of Queensland and utilized infrastructure funded by the Queensland Government Smart State Research Facilities Fund. We thank A Loening and S Gambhir of Stanford University (CA, USA) for the kind gift of pcDNA3.1-Rluc8. NR 33 TC 3 Z9 3 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD APR 1 PY 2014 VL 22 IS 7 BP 2208 EP 2219 DI 10.1016/j.bmc.2014.02.015 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA AE9OS UT WOS:000334337800021 PM 24613457 ER PT J AU Moore, HM AF Moore, Helen M. TI Moving Toward Biospecimen Harmonization with Evidence-Based Practices SO BIOPRESERVATION AND BIOBANKING LA English DT Editorial Material C1 [Moore, Helen M.] NCI, Biorepositories & Biospecimen Res Branch, Canc Diag Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Moore, HM (reprint author), NCI, Biorepositories & Biospecimen Res Branch, 9609 Med Ctr Dr,Rm 3W422,MSC 9728, Bethesda, MD 20892 USA. EM moorehe@mail.nih.gov NR 3 TC 3 Z9 3 U1 0 U2 1 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 APR 1 PY 2014 VL 12 IS 2 BP 79 EP 80 DI 10.1089/bio.2014.1221 PG 2 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA AF4OQ UT WOS:000334693500001 PM 24749873 ER PT J AU Engel, KB Vaught, J Moore, HM AF Engel, Kelly B. Vaught, Jim Moore, Helen M. TI National Cancer Institute Biospecimen Evidence-Based Practices: A Novel Approach to Pre-analytical Standardization SO BIOPRESERVATION AND BIOBANKING LA English DT Article ID COLLECTION TUBES; QUALITY; TISSUE AB Variable biospecimen collection, processing, and storage practices may introduce variability in biospecimen quality and analytical results. This risk can be minimized within a facility through the use of standardized procedures; however, analysis of biospecimens from different facilities may be confounded by differences in procedures and inferred biospecimen quality. Thus, a global approach to standardization of biospecimen handling procedures and their validation is needed. Here we present the first in a series of procedural guidelines that were developed and annotated with published findings in the field of human biospecimen science. The series of documents will be known as NCI Biospecimen Evidence-Based Practices, or BEBPs. Pertinent literature was identified via the National Cancer Institute (NCI) Biospecimen Research Database (brd.nci.nih.gov) and findings were organized by specific biospecimen pre-analytical factors and analytes of interest (DNA, RNA, protein, morphology). Meta-analysis results were presented as annotated summaries, which highlight concordant and discordant findings and the threshold and magnitude of effects when applicable. The detailed and adaptable format of the document is intended to support the development and execution of evidence-based standard operating procedures (SOPs) for human biospecimen collection, processing, and storage operations. C1 [Engel, Kelly B.] Preferred Staffing Grp, Arlington, VA USA. [Vaught, Jim; Moore, Helen M.] NCI, Biorepositories & Biospecimen Res Branch, Canc Diag Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Moore, HM (reprint author), NCI, Biorepositories & Biospecimen Res Branch, 9609 Med Ctr Dr,Rm 3W422,MSC 9728, Bethesda, MD 20892 USA. EM moorehe@mail.nih.gov NR 16 TC 11 Z9 11 U1 0 U2 3 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 APR 1 PY 2014 VL 12 IS 2 BP 148 EP 150 DI 10.1089/bio.2013.0091 PG 3 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA AF4OQ UT WOS:000334693500010 PM 24749882 ER PT J AU Yang, YB Schmitz, R Mitala, J Whiting, A Xiao, WM Ceribelli, M Wright, GW Zhao, H Yang, YD Xu, WH Rosenwald, A Ott, G Gascoyne, RD Connors, JM Rimsza, LM Campo, E Jaffe, ES Delabie, J Smeland, EB Braziel, RM Tubbs, RR Cook, JR Weisenburger, DD Chan, WC Wiestner, A Kruhlak, MJ Iwai, K Bernal, F Staudt, LM AF Yang, Yibin Schmitz, Roland Mitala, Joseph Whiting, Amanda Xiao, Wenming Ceribelli, Michele Wright, George W. Zhao, Hong Yang, Yandan Xu, Weihong Rosenwald, Andreas Ott, German Gascoyne, Randy D. Connors, Joseph M. Rimsza, Lisa M. Campo, Elias Jaffe, Elaine S. Delabie, Jan Smeland, Erlend B. Braziel, Rita M. Tubbs, Raymond R. Cook, James R. Weisenburger, Dennis D. Chan, Wing C. Wiestner, Adrian Kruhlak, Michael J. Iwai, Kazuhiro Bernal, Federico Staudt, Louis M. TI Essential Role of the Linear Ubiquitin Chain Assembly Complex in Lymphoma Revealed by Rare Germline Polymorphisms SO CANCER DISCOVERY LA English DT Article ID B-CELL LYMPHOMA; NF-KAPPA-B; ZINC-FINGER 7; PROTEASE ACTIVITY; ACTIVATION; GENE; MALT1; RECEPTOR; SHARPIN; KINASE AB Constitutive activation of NF-kappa B is a hallmark of the activated B cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), owing to upstream signals from the B-cell receptor (BCR) and MYD88 pathways. The linear polyubiquitin chain assembly complex (LUBAC) attaches linear polyubiquitin chains to I kappa B kinase-gamma, a necessary event in some pathways that engage NF-kappa B. Two germline polymorphisms affecting the LUBAC subunit RNF31 are rare among healthy individuals (similar to 1%) but enriched in ABC DLBCL (7.8%). These polymorphisms alter RNF31 alpha-helices that mediate binding to the LUBAC subunit RBCK1, thereby increasing RNF31-RBCK1 association, LUBAC enzymatic activity, and NF-kappa B engagement. In the BCR pathway, LUBAC associates with the CARD11-MALT1-BCL10 adapter complex and is required for ABC DLBCL viability. A stapled RNF31 alpha-helical peptide based on the ABC DLBCL-associated Q622L polymorphism inhibited RNF31-RBCK1 binding, decreased NF-kappa B activation, and killed ABC DLBCL cells, credentialing this protein-protein interface as a therapeutic target. SIGNIFICANCE: We provide genetic, biochemical, and functional evidence that the LUBAC ubiquitin ligase is a therapeutic target in ABC DLBCL, the DLBCL subtype that is most refractory to current therapy. More generally, our findings highlight the role of rare germline-encoded protein variants in cancer pathogenesis. (C) 2014 AACR. C1 [Yang, Yibin; Schmitz, Roland; Mitala, Joseph; Whiting, Amanda; Xiao, Wenming; Ceribelli, Michele; Zhao, Hong; Yang, Yandan; Xu, Weihong; Bernal, Federico; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA. [Jaffe, Elaine S.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Kruhlak, Michael J.] NCI, Expt Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Wright, George W.] NCI, Biometr Res Branch, DCTD, Bethesda, MD 20892 USA. [Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ USA. [Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Tubbs, Raymond R.; Cook, James R.] Cleveland Clin Pathol & Lab Med Inst, Cleveland, OH USA. [Weisenburger, Dennis D.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA. [Chan, Wing C.] Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE USA. [Chan, Wing C.] Univ Nebraska, Med Ctr, Dept Microbiol, Omaha, NE 68105 USA. [Rosenwald, Andreas] Univ Wurzburg, Dept Pathol, Wurzburg, Germany. [Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Gascoyne, Randy D.; Connors, Joseph M.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Campo, Elias] Univ Barcelona, Hosp Clin, Barcelona, Spain. [Delabie, Jan] Univ Oslo, Univ Hosp, Rikshosp, Pathol Clin, Oslo, Norway. [Smeland, Erlend B.] Univ Oslo, Univ Hosp, Rikshosp, Inst Canc Res, Oslo, Norway. [Smeland, Erlend B.] Univ Oslo, Norwegian Radium Hosp, Fac Div, Ctr Canc Biomed, Oslo, Norway. [Iwai, Kazuhiro] Kyoto Univ, Grad Sch Med, Dept Mol & Cellular Physiol, Kyoto, Japan. RP Staudt, LM (reprint author), NCI, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 4N115, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov RI Jaffe, Elaine/G-8984-2014; Campo, elias/O-7192-2016; OI Jaffe, Elaine/0000-0003-4632-0301; Campo, elias/0000-0001-9850-9793; Delabie, Jan/0000-0001-5023-0689 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; NCI SPECS grant [UO1-CA 114778]; Dr. Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe) FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by an NCI SPECS grant (UO1-CA 114778) to L. M. Staudt. R. Schmitz was supported by the Dr. Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe). NR 50 TC 42 Z9 42 U1 1 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD APR PY 2014 VL 4 IS 4 BP 480 EP 493 DI 10.1158/2159-8290.CD-13-0915 PG 14 WC Oncology SC Oncology GA AE9RT UT WOS:000334347300027 PM 24491438 ER PT J AU Leese, MP Jourdan, FL Major, MR Dohle, W Thomas, MP Hamel, E Ferrandis, E Mahon, MF Newman, SP Purohit, A Potter, BVL AF Leese, Mathew P. Jourdan, Fabrice L. Major, Meriel R. Dohle, Wolfgang Thomas, Mark P. Hamel, Ernest Ferrandis, Eric Mahon, Mary F. Newman, Simon P. Purohit, Atul Potter, Barry V. L. TI Synthesis, Anti-tubulin and Antiproliferative SAR of Steroidomimetic Dihydroisoquinolinones SO CHEMMEDCHEM LA English DT Article DE colchicine; dihydroisoquinolinones; electrostatic repulsion; microtubules; tubulin ID BREAST-CANCER CELLS; ANTICANCER AGENTS; IN-VITRO; MICROTUBULE DISRUPTORS; TUBULIN; INHIBITION; ANALOGS; VIVO; COLCHICINE; MECHANISM AB A SAR translation strategy adopted for the discovery of tetrahydroisoquinolinone (THIQ)-based steroidomimetic microtubule disruptors has been extended to dihydroisoquinolinone (DHIQ)-based compounds. A steroid A,B-ring-mimicking DHIQ core was connected to methoxyaryl D-ring mimics through methylene, carbonyl, and sulfonyl linkers, and the resulting compounds were evaluated against two cancer cell lines. The carbonyl-linked DHIQs in particular exhibit significant in vitro antiproliferative activities (e.g., 6-hydroxy-7-methoxy-2-(3,4,5-trimethoxybenzoyl)-3,4-dihydroisoquinolin-1(2H)-one (16g): GI(50) 51nM in DU-145 cells). The broad anticancer activity of DHIQ 16g was confirmed in the NCI 60-cell line assay giving a mean activity of 33nM. Furthermore, 6-hydroxy-2-(3,5-dimethoxybenzoyl)-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (16f) and 16g and their sulfamate derivatives 17f and 17g (2-(3,5-dimethoxybenzoyl)-7-methoxy-6-sulfamoyloxy-3,4-dihydroisoquinolin-1(2H)-one and 7-methoxy-2-(3,4,5-trimethoxybenzoyl)-6-sulfamoyloxy-3,4-dihydroisoquinolin-1(2H)-one, respectively) show excellent activity against the polymerization of tubulin, close to that of the clinical combretastatin A-4, and bind competitively at the colchicine binding site of tubulin. Compounds 16f and 17f were also shown to demonstrate in vitro anti-angiogenic activity. Additionally, X-ray and computational analyses of 17f reveal that electrostatic repulsion between the two adjacent carbonyl groups, through conformational biasing, dictates the adoption of a steroid-like conformation that may partially explain the excellent in vitro activities. C1 [Leese, Mathew P.; Jourdan, Fabrice L.; Major, Meriel R.; Dohle, Wolfgang; Thomas, Mark P.; Potter, Barry V. L.] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. [Hamel, Ernest] NCI, Screening Technol Branches, Frederick, MD 21702 USA. [Ferrandis, Eric] Inst Rech Henri Beaufour, F-91966 Les Ulis, France. [Mahon, Mary F.] Univ Bath, Dept Chem, Bath BA2 7AY, Avon, England. [Newman, Simon P.; Purohit, Atul] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sect Invest Med, Oncol Drug Discovery Grp, London W12 0NN, England. RP Leese, MP (reprint author), Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. EM B.V.L.Potter@bath.ac.uk FU Sterix Ltd.; Wellcome Trust [082837, 101010] FX We thank Ms. Alison Smith for technical support and the NCI DTP for providing in vitro screening resources. This work was supported by Sterix Ltd., a member of the IPSEN Group, and in part by the Wellcome Trust (Program Grant 082837 to B. V. L. P.). B. V. L. P. is a Wellcome Trust Senior Investigator (Grant 101010). NR 24 TC 4 Z9 4 U1 1 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1860-7179 EI 1860-7187 J9 CHEMMEDCHEM JI ChemMedChem PD APR PY 2014 VL 9 IS 4 BP 798 EP 812 DI 10.1002/cmdc.201400017 PG 15 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AE1SE UT WOS:000333749200016 PM 24596315 ER PT J AU Milton, JN Gordeuk, VR Taylor, JG Gladwin, MT Steinberg, MH Sebastiani, P AF Milton, Jacqueline N. Gordeuk, Victor R. Taylor, James G. Gladwin, Mark T. Steinberg, Martin H. Sebastiani, Paola TI Prediction of Fetal Hemoglobin in Sickle Cell Anemia Using an Ensemble of Genetic Risk Prediction Models SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE genetic association studies; risk factors; hemoglobins; genetics; anemia, sickle cell ID GENOME-WIDE ASSOCIATION; OLFACTORY RECEPTOR GENE; DISEASE; BCL11A; SCORE; ATHEROSCLEROSIS; HEMATOLOGY; MODIFIERS; CLUSTER; PROFILE AB Background- Fetal hemoglobin (HbF) is the major modifier of the clinical course of sickle cell anemia. Its levels are highly heritable, and its interpersonal variability is modulated in part by 3 quantitative trait loci that affect HbF gene expression. Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) in these quantitative trait loci that are highly associated with HbF but explain only 10% to 12% of the variance of HbF. Combining SNPs into a genetic risk score can help to explain a larger amount of the variability of HbF level, but the challenge of this approach is to select the optimal number of SNPs to be included in the genetic risk score. Methods and Results- We developed a collection of 14 models with genetic risk score composed of different numbers of SNPs and used the ensemble of these models to predict HbF in patients with sickle cell anemia. The models were trained in 841 patients with sickle cell anemia and were tested in 3 independent cohorts. The ensemble of 14 models explained 23.4% of the variability in HbF in the discovery cohort, whereas the correlation between predicted and observed HbF in the 3 independent cohorts ranged between 0.28 and 0.44. The models included SNPs in BCL11A, the HBS1L-MYB intergenic region, and the site of the HBB gene cluster, quantitative trait loci previously associated with HbF. Conclusions- An ensemble of 14 genetic risk models can predict HbF levels with accuracy between 0.28 and 0.44, and the approach may also prove useful in other applications. C1 [Milton, Jacqueline N.; Sebastiani, Paola] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA. [Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Taylor, James G.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, Bethesda, MD 20892 USA. [Gladwin, Mark T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA. [Steinberg, Martin H.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Milton, JN (reprint author), Boston Univ, Dept Biostat, 801 Massachusetts Ave, Boston, MA 02118 USA. EM jnmilton@bu.edu OI Taylor, James/0000-0002-4421-1809 FU National Institutes of Health [R21HL114237, R01 HL87681, RC2 L101212, 5T32 HL007501, 2R25 HL003679-8, R01 HL079912, 2M01 RR10284-10, R01HL098032, R01HL096973, P01HL103455, 1 ZIA HL005116, 1 ZIA HL006016]; Institute for Transfusion Medicine and the Hemophilia Center of Western Pennsylvania [U54 HL70583]; C-Data Project of the Comprehensive Sickle Cell Centers [U54HL70583] FX This work was supported by National Institutes of Health grants R21HL114237 (P. S.), R01 HL87681 (M. H. S.), RC2 L101212 (M. H. S.), 5T32 HL007501 (J.N.M.), 2R25 HL003679-8 (V. R. G.), R01 HL079912 (V. R. G.), 2M01 RR10284-10 (V. R. G.), R01HL098032 (M. T. G.), R01HL096973 (M. T. G.), and P01HL103455 (M. T. G.); the Institute for Transfusion Medicine and the Hemophilia Center of Western Pennsylvania (M. T. G.), U54 HL70583; C-Data Project of the Comprehensive Sickle Cell Centers, U54HL70583; and National Institutes of Health intramural funding 1 ZIA HL005116 and 1 ZIA HL006016. NR 50 TC 9 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD APR PY 2014 VL 7 IS 2 BP 110 EP 115 DI 10.1161/CIRCGENETICS.113.000387 PG 6 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AF1YQ UT WOS:000334510200004 PM 24585758 ER PT J AU Kocarnik, JM Pendergrass, SA Carty, CL Pankow, JS Schumacher, FR Cheng, I Durda, P Ambite, JL Deelman, E Cook, NR Liu, SM Wactawski-Wende, J Hutter, C Brown-Gentry, K Wilson, S Best, LG Pankratz, N Hong, CP Cole, SA Voruganti, VS Buzkova, P Jorgensen, NW Jenny, NS Wilkens, LR Haiman, CA Kolonel, LN LaCroix, A North, K Jackson, R Le Marchand, L Hindorff, LA Crawford, DC Gross, M Peters, U AF Kocarnik, Jonathan M. Pendergrass, Sarah A. Carty, Cara L. Pankow, James S. Schumacher, Fredrick R. Cheng, Iona Durda, Peter Ambite, Jose Luis Deelman, Ewa Cook, Nancy R. Liu, Simin Wactawski-Wende, Jean Hutter, Carolyn Brown-Gentry, Kristin Wilson, Sarah Best, Lyle G. Pankratz, Nathan Hong, Ching-Ping Cole, Shelley A. Voruganti, V. Saroja Buzkova, Petra Jorgensen, Neal W. Jenny, Nancy S. Wilkens, Lynne R. Haiman, Christopher A. Kolonel, Laurence N. LaCroix, Andrea North, Kari Jackson, Rebecca Le Marchand, Loic Hindorff, Lucia A. Crawford, Dana C. Gross, Myron Peters, Ulrike TI Multiancestral Analysis of Inflammation-Related Genetic Variants and C-Reactive Protein in the Population Architecture Using Genomics and Epidemiology Study SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE ethnic groups; C-reactive protein; inflammation; polymorphism, single nucleotide; molecular epidemiology; genetic pleiotropy; continental population groups ID CORONARY-ARTERY-DISEASE; WIDE ASSOCIATION; HEART-DISEASE; CRP LEVELS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK; METABOLIC-SYNDROME; PHYSICAL-ACTIVITY; BLOOD-PRESSURE; POLYMORPHISMS AB Background- C-reactive protein (CRP) is a biomarker of inflammation. Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with CRP concentrations and inflammation-related traits such as cardiovascular disease, type 2 diabetes mellitus, and obesity. We aimed to replicate previous CRP-SNP associations, assess whether these associations generalize to additional race/ethnicity groups, and evaluate inflammation-related SNPs for a potentially pleiotropic association with CRP. Methods and Results- We selected and analyzed 16 CRP-associated and 250 inflammation-related GWAS SNPs among 40 473 African American, American Indian, Asian/Pacific Islander, European American, and Hispanic participants from 7 studies collaborating in the Population Architecture using Genomics and Epidemiology (PAGE) study. Fixed-effect meta-analyses combined study-specific race/ethnicity-stratified linear regression estimates to evaluate the association between each SNP and high-sensitivity CRP. Overall, 18 SNPs in 8 loci were significantly associated with CRP (Bonferroni-corrected P < 3.1x10(-3) for replication, P < 2.0x10(-4) for pleiotropy): Seven of these were specific to European Americans, while 9 additionally generalized to African Americans (1), Hispanics (5), or both (3); 1 SNP was seen only in African Americans and Hispanics. Two SNPs in the CELSR2/PSRC1/SORT1 locus showed a potentially novel association with CRP: rs599839 (P=2.0x10(-6)) and rs646776 (P=3.1x10(-5)). Conclusions- We replicated 16 SNP-CRP associations, 10 of which generalized to African Americans and/or Hispanics. We also identified potentially novel pleiotropic associations with CRP for two SNPs previously associated with coronary artery disease and/or low-density lipoprotein-cholesterol. These findings demonstrate the benefit of evaluating genotype-phenotype associations in multiple race/ethnicity groups and looking for pleiotropic relationships among SNPs previously associated with related phenotypes. C1 [Kocarnik, Jonathan M.; Carty, Cara L.; LaCroix, Andrea; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Pendergrass, Sarah A.] Penn State Univ, University Pk, PA 16802 USA. [Pankow, James S.; Hong, Ching-Ping] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Pankratz, Nathan] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Gross, Myron] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Schumacher, Fredrick R.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Cheng, Iona] Canc Prevent Inst Calif, Fremont, CA USA. [Durda, Peter; Jenny, Nancy S.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Ambite, Jose Luis; Deelman, Ewa] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA. [Cook, Nancy R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Liu, Simin] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Hutter, Carolyn] NCI, Epidemiol & Genom Res Program, DCCPS, Bethesda, MD 20892 USA. [Brown-Gentry, Kristin; Wilson, Sarah; Crawford, Dana C.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA. [Best, Lyle G.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA. [Cole, Shelley A.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Voruganti, V. Saroja] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Voruganti, V. Saroja] Univ N Carolina, UNC Nutr Res Inst, Chapel Hill, NC USA. [Buzkova, Petra; Jorgensen, Neal W.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Wilkens, Lynne R.; Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [North, Kari] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Jackson, Rebecca] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Hindorff, Lucia A.] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA. RP Peters, U (reprint author), 1100 Fairview Ave N,M4-B402,POB 19024, Seattle, WA 98109 USA. EM upeters@fhcrc.org RI Liu, Simin/I-3689-2014; OI Liu, Simin/0000-0003-2098-3844; Pankow, James/0000-0001-7076-483X FU National Human Genome Research Institute (NHGRI); Genetic Epidemiology of Causal Variants Across the Life Course [CALiCo] [U01HG004803]; Epidemiological Architecture for Genes Linked to Environment [EAGLE] [U01HG004798]; Multiethnic Cohort study [MEC] [U01HG004802]; Women's Health Initiative [WHI] [U01HG004790]; Coordinating Center [U01HG004801]; NHGRI PAGE program [U01HG004803, U01HG004802, U01HG004790, U01HG004798-01]; Centers for Disease Control and Prevention (CDC); National Cancer Institute [R37CA54281, R01CA63464, P01CA33619, U01CA136792, U01CA98758]; National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118]; NHLBI [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, HHSN268201200036C, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129]; NIH, NHLBI [N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205]; National Institute on Aging (NIA) [AG-023629, AG-15928, AG-20098, AG-027058]; NCI [R25CA94880]; NHLBI Broad Agency Announcement (BAA) [HHSN268200960011C]; NHLBI. [N01 HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, HL080295, U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, U01 HL65521] FX The Population Architecture Using Genomics and Epidemiology (PAGE) program is funded by the National Human Genome Research Institute (NHGRI), supported by U01HG004803 (Genetic Epidemiology of Causal Variants Across the Life Course [CALiCo]), U01HG004798 (Epidemiological Architecture for Genes Linked to Environment [EAGLE]), U01HG004802 (Multiethnic Cohort study [MEC]), U01HG004790 (Women's Health Initiative [WHI]), and U01HG004801 (Coordinating Center), and their respective NHGRI American Recovery and Reinvestment Act (ARRA) supplements. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. The complete list of PAGE members can be found at http://www.pagestudy.org.; The data and materials included in this report result from collaboration between the following studies: EAGLE is funded through the NHGRI PAGE program (U01HG004798-01 and its NHGRI ARRA supplement). The study participants derive from the National Health and Nutrition Examination Surveys (NHANES), and these studies are supported by the Centers for Disease Control and Prevention (CDC). The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the CDC.; The MEC characterization of epidemiological architecture is funded through the NHGRI PAGE program (U01HG004802 and its NHGRI ARRA supplement). The MEC study is funded through the National Cancer Institute (R37CA54281, R01CA63464, P01CA33619, U01CA136792, and U01CA98758).; Funding support for the WHI study is provided through the NHGRI PAGE program (U01HG004790 and its NHGRI ARRA supplement). The WHI program is funded by the National Heart, Lung, and Blood Institute (NHLBI); the National Institutes of Health (NIH); and the US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118 to 32119, 32122, 42107-26, 42129-32, and 44221. We thank the WHI investigators and staff for their dedication and the study participants for making the program possible. A full listing of WHI investigators can be found at http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf.; Funding support for the CALiCo program was provided through the NHGRI PAGE program (U01HG004803 and its NHGRI ARRA supplement). The following studies contributed to this article and are funded by the following agencies: The Atherosclerosis Risk in Communities Study is performed as a collaborative study supported by NHLBI contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. The Coronary Artery Risk Development in Young Adults study is supported by the following NIH, NHLBI contracts: N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, and N01-HC-45205. The Cardiovascular Health Study is supported by contracts HHSN268201200036C, N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01-HC-55222, N01-HC-75150, and N01-HC-45133 and grant HL080295 from the NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging (NIA). The Strong Heart Study is supported by NHLBI grants U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, and U01 HL65521. The opinions expressed in this article are those of the author(s) and do not necessarily reflect the views of the Indian Health Service.; Assistance with phenotype harmonization, SNP selection and annotation, data cleaning, data management, integration and dissemination, and general study coordination was provided by the PAGE Coordinating Center (U01HG004801-01 and its NHGRI ARRA supplement). The National Institute of Mental Health also contributes to the support for the Coordinating Center. Funding for work by J.M. Kocarnik was supported by grant R25CA94880 from NCI. Funding for performing C-reactive protein assays in a portion of WHI subjects was provided by NHLBI Broad Agency Announcement (BAA) award HHSN268200960011C. NR 49 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD APR PY 2014 VL 7 IS 2 BP 178 EP 188 DI 10.1161/CIRCGENETICS.113.000173 PG 11 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AF1YQ UT WOS:000334510200012 PM 24622110 ER PT J AU Raff, H Sharma, ST Nieman, LK AF Raff, Hershel Sharma, Susmeeta T. Nieman, Lynnette K. TI Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing's Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia SO COMPREHENSIVE PHYSIOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-HORMONE; NIGHT SALIVARY CORTISOL; DEXAMETHASONE-SUPPRESSION TEST; INFERIOR PETROSAL SINUS; POSITRON-EMISSION-TOMOGRAPHY; ACUTE REGULATORY PROTEIN; ECTOPIC ACTH SYNDROME; ADRENOCORTICOTROPIN-SECRETING TUMORS; BETA-HYDROXYSTEROID DEHYDROGENASE; CLINICAL-PRACTICE GUIDELINE AB The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing's syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing's syndrome). Endogenous Cushing's syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing's syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. C1 [Raff, Hershel] Med Coll Wisconsin, Endocrine Res Lab, Aurora St Lukes Med Ctr, Aurora Res Inst, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Sharma, Susmeeta T.; Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Raff, H (reprint author), Med Coll Wisconsin, Endocrine Res Lab, Aurora St Lukes Med Ctr, Aurora Res Inst, Milwaukee, WI 53226 USA. EM hraff@mcw.edu FU Intramural NIH HHS [Z01 HD008831-01, Z01 HD000638-14] NR 283 TC 13 Z9 14 U1 4 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2040-4603 J9 COMPR PHYSIOL JI Compr. Physiol. PD APR PY 2014 VL 4 IS 2 BP 739 EP 769 DI 10.1002/cphy.c130035 PG 31 WC Physiology SC Physiology GA AE9SP UT WOS:000334350100007 PM 24715566 ER PT J AU Goldstein, DS AF Goldstein, David S. TI Dysautonomia in Parkinson Disease SO COMPREHENSIVE PHYSIOLOGY LA English DT Article ID MULTIPLE SYSTEM ATROPHY; PURE AUTONOMIC FAILURE; CARDIAC SYMPATHETIC DENERVATION; NEUROGENIC ORTHOSTATIC HYPOTENSION; GLIAL CYTOPLASMIC INCLUSIONS; CENTRAL DOPAMINE DEFICIENCY; SILDENAFIL CITRATE VIAGRA; BLOOD-PRESSURE RESPONSES; HEAD-UP TILT; ALPHA-SYNUCLEIN AB Dysautonomias are conditions in which altered function of one or more components of the autonomic nervous system (ANS) adversely affects health. This review updates knowledge about dysautonomia in Parkinson disease (PD). Most PD patients have symptoms or signs of dysautonomia; occasionally, the abnormalities dominate the clinical picture. Components of the ANS include the sympathetic noradrenergic system (SNS), the parasympathetic nervous system (PNS), the sympathetic cholinergic system (SCS), the sympathetic adrenomedullary system (SAS), and the enteric nervous system (ENS). Dysfunction of each component system produces characteristic manifestations. In PD, it is cardiovascular dysautonomia that is best understood scientifically, mainly because of the variety of clinical laboratory tools available to assess functions of catecholamine systems. Most of this review focuses on this aspect of autonomic involvement in PD. PD features cardiac sympathetic denervation, which can precede the movement disorder. Loss of cardiac SNS innervation occurs independently of the loss of striatal dopaminergic innervation underlying the motor signs of PD and is associated with other nonmotor manifestations, including anosmia, REM behavior disorder, orthostatic hypotension (OH), and dementia. Autonomic dysfunction in PD is important not only in clinical management and in providing potential biomarkers but also for understanding disease mechanisms (e.g., autotoxicity exerted by catecholamine metabolites). Since Lewy bodies and Lewy neurites containing alpha-synuclein constitute neuropathologic hallmarks of the disease, and catecholamine depletion in the striatum and heart are characteristic neurochemical features, a key goal of future research is to understand better the link between alpha-synucleinopathy and loss of catecholamine neurons in PD. C1 NINDS, Clin Neurocardiol Sect, Clin Neurosci Program, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, Clin Neurosci Program, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Intramural NIH HHS [ZIA NS003033-07] NR 227 TC 19 Z9 19 U1 1 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2040-4603 J9 COMPR PHYSIOL JI Compr. Physiol. PD APR PY 2014 VL 4 IS 2 BP 805 EP 826 DI 10.1002/cphy.c130026 PG 22 WC Physiology SC Physiology GA AE9SP UT WOS:000334350100010 PM 24715569 ER PT J AU Darbari, DS Nouraie, M Taylor, JG Brugnara, C Castro, O Ballas, SK AF Darbari, Deepika S. Nouraie, Mehdi Taylor, James G. Brugnara, Carlo Castro, Oswaldo Ballas, Samir K. TI Alpha-thalassaemia and response to hydroxyurea in sickle cell anaemia SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE vaso-occlusive pain crisis; hydroxyurea; sickle cell anaemia; alpha-thalassaemia ID BABY HUG; DISEASE; HYDROXYCARBAMIDE; HEMOGLOBIN; FREQUENCY; CHILDREN; THERAPY; BLACKS; TRAIT; GENE AB Background Hydroxyurea (HU) reduces vaso-occlusive crises (VOC) and other complications of sickle cell anaemia (SCA). Alpha-thalassaemia is a known modifier of SCA. Studies on the efficacy of HU in SCA patients with alpha-thalassaemia have yielded varying results. Objective To determine the effect of alpha-thalassaemia in response to HU therapy in the Multicenter Study of Hydroxyurea (MSH) cohort. Methods We compared the laboratory parameters and VOC incidence in the MSH cohort stratified by the presence or the absence of alpha-thalassaemia. Results Hydroxyurea showed significant (P=0.001 for all baseline vs. follow-up comparisons) treatment effect on red cell indices irrespective of alpha-globin gene deletion. The magnitude of the HU-related changes was similar for mean corpuscular volume (MCV) (no alpha-thalassaemia 13fl and alpha-thalassaemia 13fl) and mean corpuscular haemoglobin (MCH) (no alpha-thalassaemia 4pg and alpha-thalassaemia 4pg) in both groups. Foetal haemoglobin (HbF) and F-cells also increased significantly with HU treatment in both groups. Total haemoglobin increased after HU treatment in both groups, but the increase was smaller and not statistically significant in patients with alpha-thalassaemia. In contrast, HU-related reduction in VOCs was more pronounced in patients with alpha-thalassaemia (VOC incidence rate ratio HU/placebo: 0.63 for alpha-thalassaemia and 0.54 for no alpha-thalassaemia (P for interaction 0.003). Conclusion Hydroxyurea decreases VOCs in SCA patients with and without alpha-thalassaemia, and the degree of VOC reduction was more pronounced in the patients with alpha-thalassaemia. Despite the lower baseline values, changes in standard laboratory parameters such as MCV and HbF percent remain useful in monitoring HU therapy in the presence of alpha-thalassaemia. C1 [Darbari, Deepika S.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Haematol, Washington, DC 20010 USA. [Darbari, Deepika S.] George Washington Univ, Med Ctr, Dept Paediat, Washington, DC 20037 USA. [Nouraie, Mehdi; Castro, Oswaldo] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Taylor, James G.] NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Brugnara, Carlo] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ballas, Samir K.] Thomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19107 USA. RP Darbari, DS (reprint author), Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Haematol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM ddarbari@cnmc.org OI Taylor, James/0000-0002-4421-1809 FU NHLBI [1 ZIAHL006012-04]; NIH [P50 HL118006-01] FX This study was supported by the intramural research programmes of NHLBI 1 ZIAHL006012-04 (DSD, JGT) and NIH Grant P50 HL118006-01 (MN). NR 18 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-4441 EI 1600-0609 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD APR PY 2014 VL 92 IS 4 BP 341 EP 345 DI 10.1111/ejh.12245 PG 5 WC Hematology SC Hematology GA AE9MO UT WOS:000334332100011 PM 24330217 ER PT J AU Liu, J Cao, S Peppers, G Kim, SH Graham, BS AF Liu, Jie Cao, Shirley Peppers, Gretchen Kim, Sung-Han Graham, Barney S. TI Clonotype-specific avidity influences the dynamics and hierarchy of virus-specific regulatory and effector CD4+T-cell responses SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Precursor frequency; Respiratory syncytial virus; T-cell hierarchy; T-cell receptor (TCR) avidity; Treg cell ID CD4(+) T-CELLS; FOXP3 EXPRESSION; SELF-TOLERANCE; FLOW-CYTOMETRY; CUTTING EDGE; IN-VIVO; INFECTION; ANTIGEN; IMMUNITY; TCR AB A key component of immunity against viruses, CD4(+) T cells expand and differentiate into functional subsets upon primary infection, where effector (Teff) cells facilitate infection control and regulatory (Treg) cells mitigate immunopathology. After secondary infection, Teff cells mount a robust response from the memory pool. Here, we show that Treg-cell responses are diminished upon secondary infection, and Treg-cell response dynamics are associated more with T-cell receptors (TCRs) repertoire and avidity than with epitope specificity. In the murine model, the IA(b)M(209) epitope of respiratory syncytial virus is recognized by both CD4(+) Treg and Teff cells, while the IA(b)M2(26) epitope is recognized almost exclusively by CD4(+) Teff cells expressing high avidity TCR V8.1/8.2 and dominating the CD4(+) T-cell response during primary and secondary infections. IA(b)M(209)-Teff cells express relatively low avidity TCRs during early primary infection, but high avidity TCR V7-expressing IA(b)M(209)-Teff cells emerge during the late phase, and become dominant after secondary infection. The emerging high avidity IA(b)M(209)-Teff cells outcompete IA(b)M(209)-Treg cells that share the same epitope, but have low avidity and are restricted to TCR V2 and V6 subpopulations. These data indicate that MHC-peptide-TCR interactions can produce different kinetic and functional profiles in CD4(+) T-cell populations even when responding to the same epitope. C1 [Liu, Jie; Cao, Shirley; Peppers, Gretchen; Kim, Sung-Han; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU National Institute of Allergy and Infectious Diseases FX We thank Drs. Antonio J. Pagan and Marc K. Jenkins, University of Minnesota Medical School, Center for Immunology and Dept. of Microbiology, for determining the number of antigen-specific CD4+ T-cell precursors, and the NIAID-sponsored Tetramer Core facility at Emory University (Atlanta, GA) for assisting in the construction of the class II tetramers. This study was supported by the intramural program of the National Institute of Allergy and Infectious Diseases. NR 56 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 2014 VL 44 IS 4 BP 1058 EP 1068 DI 10.1002/eji.201343766 PG 11 WC Immunology SC Immunology GA AE7JR UT WOS:000334174400017 PM 24510524 ER PT J AU Shirley, MC Sirocco, KY AF Shirley, Mariela C. Sirocco, Karen Y. TI Introduction to Special Section: ADHD, Impulsivity, and Alcohol Abuse SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SUBSTANCE USE DISORDERS; DRINKING C1 [Shirley, Mariela C.] NIH, Off Res Womens Hlth, Off Director, Bethesda, MD 20892 USA. [Sirocco, Karen Y.] NIDA, NIH, Bethesda, MD 20892 USA. RP Shirley, MC (reprint author), NIH, Off Res Womens Hlth, Off Director, Div Program Coordinat Planning & Strateg Initiat, 6707 Democracy Blvd Suite 400, Bethesda, MD 20892 USA. EM shirleym@od.nih.gov; siroccok@mail.nih.gov NR 21 TC 2 Z9 2 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 EI 1936-2293 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD APR PY 2014 VL 22 IS 2 BP 97 EP 99 DI 10.1037/a0036124 PG 3 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA AF2CT UT WOS:000334520900001 PM 24708145 ER PT J AU Glasker, S Smith, J Raffeld, M Li, J Oldfield, EH Vortmeyer, AO AF Glaesker, Sven Smith, Jonathan Raffeld, Mark Li, Jie Oldfield, Edward H. Vortmeyer, Alexander O. TI VHL-deficient vasculogenesis in hemangioblastoma SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE von Hippel-Lindau disease; Hemangioblastoma; Vasculogenesis; Angiogenesis ID HIPPEL-LINDAU-DISEASE; CEREBELLAR HEMANGIOBLASTOMA; GENE; TUMORIGENESIS; HISTOGENESIS; DELETION; BRAIN AB Hemangioblasts are capable of differentiation into vascular structures and blood. Patients with von Hippel-Lindau (VHL) disease develop hemangioblastomas which are composed of VHL-deficient tumor cells with protracted hemangioblastic differentiation potential. In a subset of these tumors, hemangioblastic differentiation is characterized by different stages of red blood cell formation. It has remained controversial, however, whether VHL-deficient hemangioblastic cells are similarly capable of differentiating into vascular cells and functioning vascular structures in vivo. By histologic, immunohistologic and microdissection-based genetic analysis of 60 VHL disease-associated hemangioblastomas, we re-examined the controversial question whether VHL-deficient neoplastic hemangioblastic cells are capable of vascular differentiation (vasculogenesis). In most tumors (n = 47), there was no evidence of either vasculogenesis or hematopoiesis; tumor cells were either scattered between reactive angiogenetic vascular structures or arranged in solid clusters. A subset of tumors (n = 13), however, revealed vaculogenetic structures that were composed of cuboidal or flat cells and frequently contained red blood cell precursors or mature red blood cells. Microdissection-based deletion analysis of epithelial cells confirmed them to be VHL-deficient tumor cells. Immunohistochemistry for CD31 was consistently negative in these structures, and no evidence could be obtained for connectivity with reactive vasculature. We demonstrate that hemangioblastic differentiation capacity of VHL-deficient hemangioblastic cells includes not only erythropoiesis, but also differentiation into primitive vasculogenetic structures. Tumor cells, however, do not appear to have the potential of terminal differentiation into mature and functional vascular structures. (C) 2014 Elsevier Inc All rights reserved. C1 [Glaesker, Sven] Univ Freiburg, Med Ctr, Dept Neurosurg, Freiburg, Germany. [Oldfield, Edward H.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Smith, Jonathan] Mayo Clin, Dept Neurol, Rochester, MN USA. [Raffeld, Mark] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Li, Jie; Vortmeyer, Alexander O.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. RP Vortmeyer, AO (reprint author), Yale Univ, Sch Med, Dept Pathol, Neuropathol Program, 416A Lauder Hall,310 Cedar St,POB 208023, New Haven, CT 06520 USA. EM alexander.vortmeyer@yale.edu NR 13 TC 3 Z9 3 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 EI 1096-0945 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD APR PY 2014 VL 96 IS 2 BP 162 EP 167 DI 10.1016/j.yexmp.2013.12.011 PG 6 WC Pathology SC Pathology GA AF4AZ UT WOS:000334655100005 PM 24394472 ER PT J AU Surh, I Rao, DB Cesta, MF Hebert, CD Mann, JF Cunny, H Kissling, GE Malarkey, D Chhabra, RS AF Surh, Inok Rao, Deepa B. Cesta, Mark F. Hebert, Charles D. Mann, Jill F. Cunny, Helen Kissling, Grace E. Malarkey, David Chhabra, Rajendra S. TI Species and gender differences in the carcinogenic activity of trimethylolpropane triacrylate in rats and mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Trimethylolpropane triacrylate; Skin; Liver; Uterine; Carcinogenicity ID ALLERGIC CONTACT-DERMATITIS; ULTRAVIOLET CURING INKS; MULTIFUNCTIONAL ACRYLATES; ACRYLIC-MONOMERS; TRANSGENIC MOUSE; GUINEA-PIGS; TG.AC MICE; GENOTOXICITY; MANUFACTURE; TMPTA AB Trimethylolpropane triacrylate (TMPTA) is a multifunctional monomer with industrial applications. To determine the carcinogenic potential, male and female F344/N rats and B6C3F1/N mice were administered TMPTA (0, 0.3, 1.0, or 3.0 mg/kg) in acetone dermally for 2 years. There were no differences in the body weights and survival in the treated animals compared to controls. Nonneoplastic skin lesions at the site of application included epidermal hyperplasia and hyperkeratosis in both rats and mice. There were no incidences of tumors at the site of application in rats and mice. Rare malignant liver neoplasms were observed in female mice that included hepatoblastoma in the 0.3 and 3.0 mg/kg groups, and hepatocholangiocarcinoma in the 1.0 and 3.0 mg/kg groups. The incidences of uterine stromal polyp and stromal polyp or stromal sarcoma (combined) in female mice occurred with positive trends and the incidences were significantly increased in the 3.0 mg/kg group. A marginal increase in the incidences of malignant mesothelioma in male rats may have been related to TMPTA treatment. In conclusion, our studies show that TMPTA is a dermal irritant in both rats and mice of either sex. Increased incidences of tumor formation were observed in female mice and male rats. Published by Elsevier Ltd. C1 [Surh, Inok; Rao, Deepa B.; Cesta, Mark F.; Cunny, Helen; Kissling, Grace E.; Malarkey, David; Chhabra, Rajendra S.] NIEHS, Res Triangle Pk, NC 27709 USA. [Rao, Deepa B.] Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. [Hebert, Charles D.; Mann, Jill F.] So Res Inst, Birmingham, AL 35255 USA. RP Surh, I (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM surhi@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 41 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD APR PY 2014 VL 66 BP 254 EP 261 DI 10.1016/j.fct.2014.01.048 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA AE6WX UT WOS:000334139800031 PM 24503412 ER PT J AU Huang, D Ovcharenko, I AF Huang, Di Ovcharenko, Ivan TI Genome-Wide Analysis of Functional and Evolutionary Features of Tele-Enhancers SO G3-GENES GENOMES GENETICS LA English DT Article DE tissue specificity; nucleotide divergence; transcription factor binding motif; single-nucleotide polymorphism; enhancer ID LONG-RANGE INTERACTION; REGULATORY BLOCKS; MULTISPECIES CONSERVATION; CHROMATIN INTERACTIONS; MAMMALIAN GENOMES; GENE-EXPRESSION; HEART ENHANCERS; MOUSE; TRANSCRIPTION; LANDSCAPE AB We investigated sequence features of enhancers separated from their target gene by at least one intermediate gene/exon (named tele-enhancers in this study) and enhancers residing inside their target gene locus. In this study, we used whole genome enhancer maps and gene expression profiles to establish a large panel of tele-enhancers. By contrasting tele-enhancers to proximal enhancers targeting heart genes, we observed that heart tele-enhancers use unique regulatory mechanisms based on the cardiac transcription factors SRF, TEAD, and NKX-2.5, whereas proximal heart enhancers rely on GATA4 instead. A functional analysis showed that tele-enhancers preferentially regulate house-keeping genes and genes with a metabolic role during heart development. In addition, tele-enhancers are significantly more conserved than their proximal counterparts. Similar trends have been observed for non-heart tissues and cell types, suggesting that our findings represent general characteristics of tele-enhancers. C1 [Huang, Di; Ovcharenko, Ivan] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Ovcharenko, I (reprint author), NIH, Natl Lib Med, 8600 Rockville Pike,Bldg 38A,Room 6S602, Bethesda, MD 20892 USA. EM ovcharen@nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX We are grateful to Mohamed Aniba and Cindy Clark for critical reading of the manuscript. This study was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 69 TC 1 Z9 1 U1 2 U2 8 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD APR PY 2014 VL 4 IS 4 BP 579 EP 593 DI 10.1534/g3.114.010447 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA AF4OW UT WOS:000334694100003 PM 24496725 ER PT J AU Walters, RW Shumilin, IA Yoon, JH Minor, W Parker, R AF Walters, Robert W. Shumilin, Igor A. Yoon, Je-Hyun Minor, Wladek Parker, Roy TI Edc3 Function in Yeast and Mammals Is Modulated by Interaction with NAD-Related Compounds SO G3-GENES GENOMES GENETICS LA English DT Article DE mRNA decay; Edc3; P bodies; decapping ID MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; STRESS GRANULES; P-BODIES; IDENTIFICATION; DEGRADATION; PROTEINS; INSIGHTS AB The control of mRNA translation and degradation is mediated in part by a set of proteins that can inhibit translation and promote decapping, as well as function in the assembly of cytoplasmic mRNP granules referred to as processing bodies (P-bodies). The conserved enhancer of mRNA decapping 3 (Edc3) protein functions to promote both decapping and P-body assembly. Crystal structures of the YjeF_N domain in hEdc3 identified a putative binding site for a small molecule. Structure modeling of the human Edc3 Yjef_N along with other Yjef_N-containing proteins suggests that this molecule is related to NAD(H). We now show human Edc3 directly binds NADH. We also show that human and yeast Edc3 chemically modify NAD in vitro. Mutations that are predicted to disrupt the binding and/or hydrolysis of an NAD-related molecule by yeast and human Edc3 affect the control of mRNA degradation and/or P-body composition in vivo. This suggests that the interaction of Edc3 with an NAD-related molecule affects its function in the regulation of mRNA translation and degradation and provides a possible mechanism to couple the energetics of the cell to posttranscriptional control. Moreover, this provides a unique example of and lends strength to the postulated connection of metabolites, enzymes, and RNA. C1 [Walters, Robert W.; Parker, Roy] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80303 USA. [Parker, Roy] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80303 USA. [Shumilin, Igor A.; Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA USA. [Yoon, Je-Hyun] NIH, Lab Cellular & Mol Biol, Baltimore, MD USA. [Walters, Robert W.] Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. RP Parker, R (reprint author), Univ Colorado, 3415 Colorado Ave,JSCBB B414, Boulder, CO 80303 USA. EM Roy.Parker@colorado.edu RI Minor, Wladek/F-3096-2014; OI Minor, Wladek/0000-0001-7075-7090 FU NIH [GM45443]; Cancer Biology Training Grant at the University of Arizona FX The authors thank members of the Parker Laboratory for helpful insights and discussions and Dr. Jens Lykke-Andersen (University of California at San Diego) and Dr. Mark Larance (University of Dundee, Dundee, UK) for reagents. This study was funded by NIH grant GM45443. R.W.W. was a recipient of a Cancer Biology Training Grant while at the University of Arizona. R.P. is a Howard Hughes Medical Institute Investigator. All of the authors designed the experiments. I.A.S. performed the ITC and modeling analysis. R.W.W. performed all of the other experiments. R.W.W., I.A.S., W.M., and R.P. analyzed the results and wrote the paper. NR 31 TC 3 Z9 3 U1 0 U2 0 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD APR PY 2014 VL 4 IS 4 BP 613 EP 622 DI 10.1534/g3.114.010470 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AF4OW UT WOS:000334694100006 PM 24504254 ER PT J AU Jackson, BM Abete-Luzi, P Krause, MW Eisenmann, DM AF Jackson, Belinda M. Abete-Luzi, Patricia Krause, Michael W. Eisenmann, David M. TI Use of an Activated Beta-Catenin to Identify Wnt Pathway Target Genes in Caenorhabditis elegans, Including a Subset of Collagen Genes Expressed in Late Larval Development SO G3-GENES GENOMES GENETICS LA English DT Article DE Wnt; gene expression; C. elegans; collagen; cell signaling ID C-ELEGANS; SIGNALING COMPONENTS; INTEGRATIVE ANALYSIS; ASYMMETRIC DIVISION; NEGATIVE REGULATOR; VULVAL DEVELOPMENT; HOMOLOG BAR-1; UP-REGULATION; GATA FACTORS; HOX PROTEIN AB The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin-dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1 col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle. C1 [Jackson, Belinda M.; Abete-Luzi, Patricia; Eisenmann, David M.] Univ Maryland Baltimore Cty, Dept Biol Sci, Baltimore, MD 21250 USA. [Krause, Michael W.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Eisenmann, DM (reprint author), Univ Maryland Baltimore Cty, Dept Biol Sci, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM eisenman@umbc.edu OI Krause, Michael/0000-0001-6127-3940 FU NIH Office of Research Infrastructure Programs [P40 OD010440]; National BioResource Project of Japan; National Science Foundation [IBN-0131485]; NIH [GM65424, R25-GM55036]; Ruth Kirschstein NRSA [F31 GM077099]; Intramural Research Program of the NIDDK of the NIH FX We thank A. Fire (Stanford University School of Medicine), H. Korswagen (Hubrecht Institute), and I. Hamza and S. Severance (University of Maryland College Park) for sharing reagents, strains, and unpublished information. We thank W. Chen (Microarray Core Facility, National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK], National Institutes of Health [NIH]) for help with the statistical microarray analysis and C. Bethel (University of Maryland Baltimore County) for assistance with qPCR methodology. We thank members of the Eisenmann lab for advice and support. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440), and from the National BioResource Project of Japan. This work was supported by National Science Foundation grant IBN-0131485 and NIH grant GM65424 to DME. B.M.J. was supported by NIH grant R25-GM55036 and Ruth Kirschstein NRSA F31 GM077099. This work was supported, in part, by the Intramural Research Program of the NIDDK of the NIH. NR 69 TC 5 Z9 5 U1 1 U2 4 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD APR PY 2014 VL 4 IS 4 BP 733 EP 747 DI 10.1534/g3.113.009522 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA AF4OW UT WOS:000334694100016 PM 24569038 ER PT J AU Pattaradilokrat, S Li, J Wu, J Qi, Y Eastman, RT Zilversmit, M Nair, SC Huaman, MC Quinones, M Jiang, H Li, N Zhu, J Zhao, K Kaneko, O Long, CA Su, XZ AF Pattaradilokrat, S. Li, J. Wu, J. Qi, Y. Eastman, R. T. Zilversmit, M. Nair, S. C. Huaman, M. C. Quinones, M. Jiang, H. Li, N. Zhu, J. Zhao, K. Kaneko, O. Long, C. A. Su, X-z TI Plasmodium genetic loci linked to host cytokine and chemokine responses SO GENES AND IMMUNITY LA English DT Article DE genetic mapping; cytokine; chemokine; inflammation; pathogenesis; virulence ID FALCIPARUM-INFECTED ERYTHROCYTES; INNATE IMMUNITY; MALARIA PARASITE; DUFFY ANTIGEN; TGF-BETA; YOELII; EXPRESSION; INVASION; SUSCEPTIBILITY; ACTIVATION AB Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate the effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (CCs) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites. Quantitative trait loci (QTL) analysis linked levels of many CCs, particularly IL-1 beta, IP-10, IFN-gamma, MCP-1 and MIG, and early parasite growth rate to loci on multiple parasite chromosomes, including chromosomes 7, 9, 10, 12 and 13. Comparison of the genome sequences spanning the mapped loci revealed various candidate genes. The loci on chromosomes 7 and 13 had significant (P<0.005) additive effects on IL-1 beta, IL-5 and IP-10 responses, and the chromosome 9 and 12 loci had significant (P=0.017) interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality. These results provide important information for a better understanding of malaria pathogenesis and can be used to examine the role of these factors in human malaria infection. C1 [Pattaradilokrat, S.; Li, J.; Wu, J.; Qi, Y.; Eastman, R. T.; Zilversmit, M.; Nair, S. C.; Huaman, M. C.; Jiang, H.; Long, C. A.; Su, X-z] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20850 USA. [Pattaradilokrat, S.] Chulalongkorn Univ, Fac Sci, Dept Biol, Bangkok, Thailand. [Li, J.; Qi, Y.] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen, Fujian, Peoples R China. [Huaman, M. C.] Adv Biosci Labs, Rockville, MD USA. [Quinones, M.] NIAID, Bioinformat & Computat Biosci Branch, NIH, Rockville, MD 20850 USA. [Jiang, H.] US FDA, Silver Spring, MD USA. [Li, N.] MedImmune, Gaithersburg, MD USA. [Zhu, J.] NIH, Genet & Dev Biol Ctr, Bethesda, MD 20892 USA. [Zhao, K.] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Kaneko, O.] Nagasaki Univ, Inst Trop Med, Dept Protozool, Nagasaki 852, Japan. [Kaneko, O.] Nagasaki Univ, Global Ctr Excellence Program, Nagasaki 852, Japan. RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3E-24B,12735 Twinbrook Pkwy, Rockville, MD 20850 USA. EM xsu@niaid.nih.gov RI Wu, Jian/K-2038-2015; OI Wu, Jian/0000-0001-8011-9551; Su, Xinzhuan/0000-0003-3246-3248 FU Intramural Research Program of the Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Project 111; State Bureau of Foreign Experts; Ministry of Education of China [B06016]; National Natural Science Foundation of China [81271858, 81201324, 81220108019] FX We thank Drs Alan Sher and David Sacks for valuable advice and comments and Brenda Rae Marshall, DPSS, NIAID, for editing. This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health and partially by 'Project 111' sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (B06016) and by the National Natural Science Foundation of China (#81271858, #81201324 and #81220108019). NR 58 TC 7 Z9 7 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 EI 1476-5470 J9 GENES IMMUN JI Genes Immun. PD APR-MAY PY 2014 VL 15 IS 3 BP 145 EP 152 DI 10.1038/gene.2013.74 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA AF8QT UT WOS:000334981400002 PM 24452266 ER PT J AU Pilot, M Greco, C Vonholdt, BM Jedrzejewska, B Randi, E Jedrzejewski, W Sidorovich, VE Ostrander, EA Wayne, RK AF Pilot, M. Greco, C. vonholdt, B. M. Jedrzejewska, B. Randi, E. Jedrzejewski, W. Sidorovich, V. E. Ostrander, E. A. Wayne, R. K. TI Genome-wide signatures of population bottlenecks and diversifying selection in European wolves SO HEREDITY LA English DT Article DE bottleneck; effective population size; genetic differentiation; grey wolf; linkage disequilibrium; selection ID WOLF CANIS-LUPUS; LINKAGE DISEQUILIBRIUM; GREY WOLF; DOG DOMESTICATION; GROWTH-FACTOR; GENOTYPE DATA; SIZE; HISTORY; DNA; MITOCHONDRIAL AB Genomic resources developed for domesticated species provide powerful tools for studying the evolutionary history of their wild relatives. Here we use 61K single-nucleotide polymorphisms (SNPs) evenly spaced throughout the canine nuclear genome to analyse evolutionary relationships among the three largest European populations of grey wolves in comparison with other populations worldwide, and investigate genome-wide effects of demographic bottlenecks and signatures of selection. European wolves have a discontinuous range, with large and connected populations in Eastern Europe and relatively smaller, isolated populations in Italy and the Iberian Peninsula. Our results suggest a continuous decline in wolf numbers in Europe since the Late Pleistocene, and long-term isolation and bottlenecks in the Italian and Iberian populations following their divergence from the Eastern European population. The Italian and Iberian populations have low genetic variability and high linkage disequilibrium, but relatively few autozygous segments across the genome. This last characteristic clearly distinguishes them from populations that underwent recent drastic demographic declines or founder events, and implies long-term bottlenecks in these two populations. Although genetic drift due to spatial isolation and bottlenecks seems to be a major evolutionary force diversifying the European populations, we detected 35 loci that are putatively under diversifying selection. Two of these loci flank the canine platelet-derived growth factor gene, which affects bone growth and may influence differences in body size between wolf populations. This study demonstrates the power of population genomics for identifying genetic signals of demographic bottlenecks and detecting signatures of directional selection in bottlenecked populations, despite their low background variability. C1 [Pilot, M.] Lincoln Univ, Sch Life Sci, Lincoln, England. [Pilot, M.] Polish Acad Sci, Museum & Inst Zool, PL-00679 Warsaw, Poland. [Greco, C.; Randi, E.] Ist Super Protez & Ric Ambientale, Rome, Italy. [Greco, C.; Randi, E.] Ist Super Protez & Ric Ambientale, Ozzano Dell Emilia, BO, Italy. [vonholdt, B. M.; Wayne, R. K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. [Jedrzejewska, B.; Jedrzejewski, W.] Polish Acad Sci, Mammal Res Inst, Bialowieza, Poland. [Randi, E.] Aalborg Univ, Dept 18, Sect Environm Engn, Aalborg, Denmark. [Sidorovich, V. E.] Natl Acad Sci Belarus, Inst Zool, Minsk, Byelarus. [Ostrander, E. A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Wayne, RK (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. EM rwayne@ucla.edu OI Ostrander, Elaine/0000-0001-6075-9738 FU Foundation for Polish Science; Polish Committee for Scientific Research; US National Science Foundation; Intramural Program of the National Human Genome Research Institute; Italian Ministry of Environment; Italian Institute for Environmental Protection and Research FX We thank M Shkvyrya, I Dikiy, E Tsingarska, S Nowak and M Apollonio for providing samples from European wolves used in this project, A Moura for help with preparing the figures, and M Gautier for sharing the R script to plot the outputs from the Kim Tree program. We are grateful to Giorgio Bertorelle, Michael Bruford and four anonymous reviewers for their constructive comments on the manuscript. This project was supported by grants from the Foundation for Polish Science (MP), the Polish Committee for Scientific Research (MP and WJ), the US National Science Foundation (RKW), the Intramural Program of the National Human Genome Research Institute (EAO), the Italian Ministry of Environment and the Italian Institute for Environmental Protection and Research (ER and CG). NR 80 TC 11 Z9 11 U1 14 U2 128 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0018-067X EI 1365-2540 J9 HEREDITY JI Heredity PD APR PY 2014 VL 112 IS 4 BP 428 EP 442 DI 10.1038/hdy.2013.122 PG 15 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA AF3IJ UT WOS:000334605000009 PM 24346500 ER PT J AU Li, CM Zhang, XZ Hoffman, HJ Cotch, MF Themann, CL Wilson, MR AF Li, Chuan-Ming Zhang, Xinzhi Hoffman, Howard J. Cotch, Mary Frances Themann, Christa L. Wilson, M. Roy TI Hearing Impairment Associated With Depression in US Adults, National Health and Nutrition Examination Survey 2005-2010 SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID OLDER-ADULTS; THRESHOLD LEVELS; BLUE MOUNTAINS; MENTAL-HEALTH; UNITED-STATES; POPULATION; SYMPTOMS; ANXIETY; WELL; AGE AB IMPORTANCE Depression among hearing impaired US adults has not been studied previously. OBJECTIVE To estimate the prevalence of and risk factors for depression among adults with hearing loss. DESIGN SETTING AND PARTICIPANTS Adults aged 18 years or older (N =18 318) who participated in the National Health and Nutrition Examination Survey (NHANES) 2005-2010 a nationally representative sample. INTERVENTIONS Multistage probability sampling of US population. MAIN OUTCOMES AND MEASURES Depression assessed by the 9-item Patient Health Questionnaire (PHQ-9) scale and hearing impairment (HI) assessed by self-report and audiometric examination for adults aged 70 years or older. RESULTS The prevalence of moderate to severe depression (PHQ-9 score, >= 10) was 4.9% for individuals reporting excellent hearing 7.1% for those with good hearing and 11.4% for participants who reported a little trouble or greater HI. Using excellent hearing as the reference after adjusting for all covariates multivariate odds ratios (ORs) for depression were 1.4 (95% CI 1.1-1.8) for good hearing 1.7 (1.3-2.2) for a little trouble 2.4 (1.7-3.2) for moderate trouble 1.5 (0.9-2.6) for a lot of trouble and 0.6 (0.1-2.6) for deaf. Moderate HI (defined by better ear pure-tone average of hearing thresholds at 0.5 1,2, and 4 kHz within the range 35to 49-dB hearing level) was significantly associated with depression among older women (OR 3.9 95% CI 1.3-11.3) after adjusting for age sex race/ethnicity lifestyle characteristics and selected health conditions. CONCLUSIONS AND RELEVANCE After accounting for health conditions and other factors including trouble seeing self-reported HI and audiometrically determined HI were significantly associated with depression particularly in women. Health care professionals should be aware of an increased risk for depression among adults with hearing loss. C1 [Li, Chuan-Ming; Hoffman, Howard J.] NIDCD, Epidemiol & Stat Program, NIH, Bethesda, MD 20892 USA. [Zhang, Xinzhi; Wilson, M. Roy] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Themann, Christa L.] NIOSH, Hearing Loss Prevent Team, Ctr Dis Control & Prevent, Cincinnati, OH USA. [Wilson, M. Roy] Wayne State Univ, Detroit, MI USA. RP Li, CM (reprint author), NIDCD, Epidemiol & Stat Program, NIH, 6001 Execut Blvd,Ste 8300, Bethesda, MD 20892 USA. EM chuan-ming.li@nih.gov OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z99 EY999999] NR 30 TC 37 Z9 39 U1 3 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD APR PY 2014 VL 140 IS 4 BP 293 EP 302 DI 10.1001/jamaoto.2014.42 PG 10 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AF4HV UT WOS:000334673500002 PM 24604103 ER PT J AU Bookman, MA Gilks, CB Kohn, EC Kaplan, KO Huntsman, D Aghajanian, C Birrer, MJ Ledermann, JA Oza, AM Swenerton, KD AF Bookman, Michael A. Gilks, C. Blake Kohn, Elise C. Kaplan, Karen O. Huntsman, David Aghajanian, Carol Birrer, Michael J. Ledermann, Jonathan A. Oza, Amit M. Swenerton, Kenneth D. TI Better Therapeutic Trials in Ovarian Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GRADE SEROUS CARCINOMA; OPEN-LABEL; LIPOSOMAL DOXORUBICIN; BREAST-CANCER; BRAF MUTATION; 2-TIER SYSTEM; STAGE-III; CELL-TYPE; PHASE-II; WOMEN AB The Ovarian Task Force of the Gynecologic Cancer Steering Committee convened a clinical trials planning meeting on October 28-29, 2011, with the goals to identify key tumor types, associated molecular pathways, and biomarkers for targeted drug intervention; review strategies to improve early-phase screening, therapeutic evaluation, and comparison of new agents; and optimize design of randomized trials in response to an evolving landscape of scientific, regulatory, and funding priorities. The meeting was attended by international clinical and translational investigators, pharmaceutical industry representatives, government regulators, and patient advocates. Panel discussions focused on disease types, early-phase trials, and randomized trials. A manuscript team summarized the discussions and assisted with formulating key recommendations. A more integrated and efficient approach for screening new agents using smaller selective randomized trials in specific disease-type settings was endorsed, together with collaborative funding models between industry and the evolving national clinical trials network, as well as efforts to enhance public awareness and study enrollment through advocacy. C1 [Bookman, Michael A.] Univ Arizona, Ctr Canc, Tucson, AZ 85724 USA. [Gilks, C. Blake] Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC, Canada. [Kohn, Elise C.] NCI, Mol Signalling Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Kaplan, Karen O.] Prevent Canc Fdn, Alexandria, VA USA. [Huntsman, David] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Swenerton, Kenneth D.] Univ British Columbia, Dept Med Oncol, Vancouver, BC V5Z 1M9, Canada. [Aghajanian, Carol] Mem Sloan Kettering Canc Ctr, Dept Med Oncol, New York, NY 10021 USA. [Birrer, Michael J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Ledermann, Jonathan A.] UCL, Inst Canc, CR UK UCL Canc Trials Ctr, London, England. [Oza, Amit M.] Princess Margaret Hosp, Div Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada. RP Bookman, MA (reprint author), Univ Arizona, Ctr Canc, 1515 N Campbell Ave,Rm 1903, Tucson, AZ 85724 USA. EM mbookman@email.arizona.edu NR 38 TC 19 Z9 19 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2014 VL 106 IS 4 AR dju029 DI 10.1093/jnci/dju029 PG 8 WC Oncology SC Oncology GA AF4OA UT WOS:000334691500014 PM 24627272 ER PT J AU Brenna, JT Burdge, GC Crawford, MA Clayton, P Cunnane, SC Gow, R Hibbeln, JR Sinclair, AJ Stein, J Willatts, P AF Brenna, J. Thomas Burdge, Graham C. Crawford, Michael A. Clayton, Paul Cunnane, Stephen C. Gow, Rachel Hibbeln, Joseph R. Sinclair, Andrew J. Stein, John Willatts, Peter TI RE: Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID FISH C1 [Brenna, J. Thomas] Cornell Univ, Dept Nutr Sci, Ithaca, NY USA. [Burdge, Graham C.] Univ Southampton, Southampton, Hants, England. [Crawford, Michael A.] Univ London Imperial Coll Sci Technol & Med, Dept Canc & Surg, London, England. [Clayton, Paul] Inst Food Brain & Behav, Oxford, England. [Cunnane, Stephen C.] Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. [Gow, Rachel; Hibbeln, Joseph R.] NIAAA, NIH, Bethesda, MD USA. [Sinclair, Andrew J.] Deakin Univ, Dept Med, Waurn Ponds, Vic 3216, Australia. [Stein, John] Univ Oxford, Dept Physiol, Oxford, England. [Willatts, Peter] Univ Dundee, Sch Psychol, Dundee, Scotland. RP Sinclair, AJ (reprint author), Deakin Univ, Dept Med, 75 Pigdons Rd, Waurn Ponds, Vic 3216, Australia. EM andrew.sinclair@deakin.edu.au OI Stein, John/0000-0001-5843-8986; Burdge, Graham/0000-0002-7665-2967 NR 5 TC 2 Z9 2 U1 2 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD APR PY 2014 VL 106 IS 4 AR dju015 DI 10.1093/jnci/dju015 PG 1 WC Oncology SC Oncology GA AF4OA UT WOS:000334691500004 PM 24685922 ER EF