FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Jiang, Y Wu, SH Shu, XO Xiang, YB Ji, BT Milne, GL Cai, QY Zhang, XL Gao, YT Zheng, W Yang, G AF Jiang, Yu Wu, Sheng-Hui Shu, Xiao-Ou Xiang, Yong-Bing Ji, Bu-Tian Milne, Ginger L. Cai, Qiuyin Zhang, Xianglan Gao, Yu-Tang Zheng, Wei Yang, Gong TI Cruciferous Vegetable Intake Is Inversely Correlated with Circulating Levels of Proinflammatory Markers in Women SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Cruciferous vegetables; Inflammation; Oxidative stress; Biomarker. ID S-TRANSFERASE POLYMORPHISMS; COLORECTAL-CANCER RISK; OXIDATIVE STRESS; IN-VIVO; DIETARY ISOTHIOCYANATES; CLINICAL-TRIAL; HEALTH; INFLAMMATION; FRUIT; CONSUMPTION AB Background Higher intakes of cruciferous vegetables or their constituents have been shown to lower inflammation in animal studies. However, evidence for this antiinflammatory effect of cruciferous vegetable consumption in humans is scarce. Objective/Design In this crOss-sectional analysis, we evaluated associations of vegetable intake with a panel of inflammatory and oxidative stress markers among 1,005 middle-aged Chinese women. Dietary intake of foods was assessed by a food frequency questionnaire. Results Multivariable-adjusted circulating concentrations of tumor necrosis factor-a (TNF-alpha), interlukin-1 beta (IL-1 beta), and IL-6 were lower among Women with higher intakes of cruciferous vegetables. The differences in concentrations of inflammatory biomarkers between extreme quintiles of cruciferous vegetable intake were 12.66% for TNF-a (P-trend=0.01), 18.18% for IL-1 beta (P-trend=0.02), and 24.68% for IL-6 (P-trend=0.02). A similar, but less apparent, inverse association was found for intakes of all vegetables combined but not for noncruciferous vegetables. Levels of the urinary oxidative stress markers F-2-isoprostanes and their major metabolite, 2,3-dinor-5,6-dihydro-15-F-2t-IsoP, were not associated with intakes of cruciferous vegetables or all vegetables combined. Conclusions This study suggests that the previously observed health benefits of cruciferous vegetable consumption may be partly associated with the antiinflammatory effects of these vegetables. C1 [Jiang, Yu] Changning Ctr Dis Control & Prevent, Div Chron Dis Control & Prevent, Shanghai, Peoples R China. [Jiang, Yu; Wu, Sheng-Hui; Shu, Xiao-Ou; Cai, Qiuyin; Zhang, Xianglan; Zheng, Wei; Yang, Gong] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37203 USA. [Milne, Ginger L.] Vanderbilt Univ, Sch Med, Dept Med, Div Clin Pharmacol, Nashville, TN 37203 USA. [Xiang, Yong-Bing; Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. [Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Yang, G (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, 2525 West End Ave,Suite 600 IMPH, Nashville, TN 37203 USA. EM Gong.Yang@Vanderbilt.edu RI Milne, Ginger/D-7648-2014 OI Milne, Ginger/0000-0003-3890-151X FU US National Cancer Institute [RO1CAl22364]; inflammation and oxidative stress biomarker assays [R37 CA070867]; baseline data collection and genotyping [NO2-CP-11010-66]; Fogarty International Center [D43 TW008313]; Vanderbilt University Center in Molecular Toxicology [P30 ES000267]; NIH [P30 ES000267] FX This study was supported by Public Health Service grants from the US National Cancer Institute, including grant number RO1CAl22364 (to G.Yang) for the inflammation and oxidative stress biomarker assays, R37 CA070867 (to W.Zheng) for the baseline data collection and genotyping, and a contract, NO2-CP-11010-66 (to X.-0.Shu) for biospecimen collection.Y.Jiang was supported by a training grant from the Fogarty International Center (D43 TW008313 to X.-0.Shu).G.L.Milne acknowledges support from the Vanderbilt University Center in Molecular Toxicology (NIH P30 ES000267). NR 44 TC 12 Z9 12 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 EI 2212-2680 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD MAY PY 2014 VL 114 IS 5 BP 700 EP 708 DI 10.1016/j.jand.2013.12.019 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AG4XR UT WOS:000335424200007 PM 24630682 ER PT J AU White, SF Fowler, KA Sinclair, S Schechter, JC Majestic, CM Pine, DS Blair, RJ AF White, Stuart F. Fowler, Katherine A. Sinclair, Stephen Schechter, Julia C. Majestic, Catherine M. Pine, Daniel S. Blair, R. James TI Disrupted Expected Value Signaling in Youth With Disruptive Behavior Disorders to Environmental Reinforcers SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE disruptive behavior; conduct disorder; decision making; expected value; environmental reinforcers ID CALLOUS-UNEMOTIONAL TRAITS; VENTROMEDIAL PREFRONTAL CORTEX; PSYCHOPATHIC TRAITS; RESPONSE REVERSAL; CONDUCT DISORDER; CHILDREN; REWARD; DISSOCIATION; ADOLESCENTS; DYSFUNCTION AB Objective: Youth with disruptive behavior disorders (DBD), including conduct disorder (CD) and oppositional defiant disorder (ODD), have difficulties in reinforcement-based decision making, the neural basis of which is poorly understood. Studies examining decision making in youth with DBD have revealed reduced reward responses within the ventromedial prefrontal cortex/orbitofrontal cortex (vmPFC/OFC), increased responses to unexpected punishment within the vmPFC and striatum, and reduced use of expected value information in the anterior insula cortex and dorsal anterior cingulate cortex during the avoidance of suboptimal choices. Previous work has used only monetary reinforcement. The current study examined whether dysfunction in youth with DBD during decision making extended to environmental reinforcers. Method: A total of 30 youth (15 healthy youth and 15 youth with DBD) completed a novel reinforcement-learning paradigm using environmental reinforcers (physical threat images, e.g., striking snake image; contamination threat images, e.g., rotting food; appetitive images, e.g., puppies) while undergoing functional magnetic resonance imaging (fMRI). Results: Behaviorally, healthy youth were significantly more likely to avoid physical threat, but not contamination threat, stimuli than youth with DBD. Imaging results revealed that youth with DBD showed significantly reduced use of expected value information in the bilateral caudate, thalamus, and posterior cingulate cortex during the avoidance of suboptimal responses. Conclusions: The current data suggest that youth with DBD show deficits to environmental reinforcers similar to the deficits seen to monetary reinforcers. Importantly, this deficit was unrelated to callous-unemotional (CU) traits, suggesting that caudate impairment may be a common deficit across youth with DBD. C1 [White, Stuart F.; Fowler, Katherine A.; Sinclair, Stephen; Pine, Daniel S.; Blair, R. James] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Schechter, Julia C.; Majestic, Catherine M.] NIMH, Intramural Res Program, Bethesda, MD USA. RP White, SF (reprint author), 9000 Rockville Pike,Bldg 15k,Room 300C, Bethesda, MD 20892 USA. EM whitesf@mail.nih.gov FU Intramural Research Program at NIMH; NIH [1-ZIA-MH00286008, 1-ZIA-MH002781-11]; NIH Combined Neuroscience Institutional Review Board [05-M0105] FX This work was supported by the Intramural Research Program at NIMH, NIH under grant number 1-ZIA-MH00286008 (R J B.) and 1-ZIA-MH002781-11 (D.S.P:). Ethics approval for this study was granted by the NIH Combined Neuroscience Institutional Review Board under protocol number 05-M0105. NR 35 TC 14 Z9 14 U1 4 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2014 VL 53 IS 5 BP 579 EP 588 DI 10.1016/j.jaac.2013.12.023 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AG0HJ UT WOS:000335096200011 PM 24745957 ER PT J AU Gray, GE Moodie, Z Metch, B Gilbert, PB Bekker, LG Churchyard, G Nchabeleng, M Mlisana, K Laher, F Roux, S Mngadi, K Innes, C Mathebula, M Allen, M McElrath, MJ Robertson, M Kublin, J Corey, L AF Gray, Glenda E. Moodie, Zoe Metch, Barbara Gilbert, Peter B. Bekker, Linda-Gail Churchyard, Gavin Nchabeleng, Maphoshane Mlisana, Koleka Laher, Fatima Roux, Surita Mngadi, Kathryn Innes, Craig Mathebula, Matsontso Allen, Mary McElrath, M. Julie Robertson, Michael Kublin, James Corey, Lawrence CA HVTN 503 Phambili Study Team TI Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2h HVTN 503/Phambili study SO LANCET INFECTIOUS DISEASES LA English DT Article ID TEST-OF-CONCEPT; SEXUALLY-TRANSMITTED-DISEASES; IMMUNODEFICIENCY-VIRUS; T-CELLS; IMMUNE-RESPONSES; NONHUMAN-PRIMATES; HEALTHY-ADULTS; RHESUS-MONKEYS; EFFICACY TRIAL; GENITAL-TRACT AB Background The HVTN 503/Phambili study, which assessed the efficacy of the Merck Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine in South Africa, was stopped when futility criteria in the Step study (assessing the same vaccine in the Americas, Caribbean, and Australia) were met. Here we report long-term follow-up data. Methods HVTN 503/Phambili was a double-blind, placebo-controlled, randomised trial that recruited HIV-1 uninfected, sexually active adults aged 18-35 years from five sites in South Africa. Eligible participants were randomly assigned (1:1) by computer-generated random numbers to either vaccine or placebo, stratified by site and sex. Cox proportional hazards models were used to estimate HIV-1 infection in the modified intention-to-treat cohort, all of whom were unmasked early in follow-up. The trial is registered with ClinicalTrials.gov, number NCT00413725 and the South African National Health Research Database, number DOH-27-0207-1539. Findings Between Jan 24,2007, and Sept 19,2007,801 participants (26-7%) of a planned 3000 were randomly assigned (400 to vaccine, 401 to placebo); 216 (27%) received only one injection, 529 (66%) received only two injections, and 56 (7%) received three injections. At a median follow-up of 42 months (IQR 31-42), 63 vaccine recipients (16%) had HIV-1 infection compared with 37 placebo recipients (9%; adjusted HR 1-70,95% CI 1-13-2-55; 1)=0-01). Risk for HIV-1 infection did not differ according to the number of vaccinations received, sex, circumcision, or adenovirus type 5 (Ads) serostatus. Differences in risk behaviour at baseline or during the study, or annualised dropout rate (7-7% [95% CI 6-2-9-5] for vaccine recipients vs 8-8% [7-1-10-7] for placebo recipients; p=0-40) are unlikely explanations for the increased rate of HIV-1 infections seen in vaccine recipients. Interpretation The increased risk of HIV-1 acquisition in vaccine recipients, irrespective of number of doses received, warrants further investigation to understand the biological mechanism. We caution against further use of the Ad5 vector for HIV vaccines. C1 [Gray, Glenda E.; Laher, Fatima] Univ Witwatersrand, Perinatal HIV Res Unit, ZA-1864 Johannesburg, South Africa. [Gray, Glenda E.] South African Med Res Council, Cape Town, South Africa. [Moodie, Zoe; Metch, Barbara; Gilbert, Peter B.; McElrath, M. Julie; Kublin, James; Corey, Lawrence] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Bekker, Linda-Gail; Roux, Surita] Univ Cape Town, Desmond Tutu HIV Fdn, ZA-7925 Cape Town, South Africa. [Churchyard, Gavin] Aurum Inst Hlth Res, Johannesburg, South Africa. [Nchabeleng, Maphoshane; Mathebula, Matsontso] Univ Limpopo, MEDUNSA HIV Clin Res Unit, Mankweng E, South Africa. [Mlisana, Koleka; Mngadi, Kathryn] Univ KwaZulu Natal, Ctr AIDS Programme Res S Afr, Durban, South Africa. [Allen, Mary] NIAID, Vaccine Res Program, Div Aids, NIH, Bethesda, MD 20892 USA. [Robertson, Michael] Merck & Co Inc, Infect Dis & Vaccines Clin Res, N Wales, PA USA. RP Gray, GE (reprint author), Univ Witwatersrand, Perinatal HIV Res Unit, POB 114, ZA-1864 Johannesburg, South Africa. EM gray@pixie.co.za FU National Institute of Allergy and Infectious Diseases, Merck; South African Medical Research Council FX Funding National Institute of Allergy and Infectious Diseases, Merck, and South African Medical Research Council. NR 37 TC 42 Z9 42 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD MAY PY 2014 VL 14 IS 5 BP 388 EP 396 DI 10.1016/S1473-3099(14)70020-9 PG 9 WC Infectious Diseases SC Infectious Diseases GA AG0GF UT WOS:000335093200023 PM 24560541 ER PT J AU del Rosario, MC Ossowski, V Knowler, WC Bogardus, C Baier, LJ Hanson, RL AF del Rosario, Melissa C. Ossowski, Vicky Knowler, William C. Bogardus, Clifton Baier, Leslie J. Hanson, Robert L. TI Potential epigenetic dysregulation of genes associated with MODY and type 2 diabetes in humans exposed to a diabetic intrauterine environment: An analysis of genome-wide DNA methylation SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE In utero; Maternal diabetes; Immunoprecipitation; Microarray ID PIMA-INDIANS; MELLITUS; PATHOPHYSIOLOGY; ANTIBODIES; OBESITY; LISTS; YOUNG; ARRAY; RISK AB Objective. The aim of this study is to investigate the potential role of DNA methylation in mediating the increased risk of developing type 2 diabetes in offspring of mothers who had diabetes during pregnancy. Materials and Methods. Peripheral blood leukocytes were collected from non-diabetic Pima Indians who were either offspring of diabetic mothers (ODM; n = 14) or offspring of nondiabetic mothers (ONDM; n = 14). The two groups were matched for age, sex, age of mother, and fraction of Pima ethnicity. Differentially methylated regions were determined using a MeDIP-chip assay on an Affymetrix Human Tiling 2.0R Array. Data were analyzed using the model based analysis of tiling arrays (MAT) algorithm, and 4883 regions overlapping with putative promoters, were identified as differentially methylated, having met an empirically derived threshold (nominal p < 0.0077). The list of genes with differentially methylated promoters was subjected to KEGG pathway analysis to determine canonical metabolic pathways enriched by these genes. Results. Pathway analysis of genes with differentially methylated promoters identified the top 3 enriched pathways as maturity onset diabetes of the young (MODY), type 2 diabetes, and Notch signaling. Several genes in these pathways are known to affect pancreatic development and insulin secretion. Conclusions. These findings support the hypothesis that epigenetic changes may increase the risk of type 2 diabetes via an effect on beta-cell function in the offspring of mothers with diabetes during pregnancy. Published by Elsevier Inc. C1 [del Rosario, Melissa C.; Ossowski, Vicky; Knowler, William C.; Bogardus, Clifton; Baier, Leslie J.; Hanson, Robert L.] Natl Inst Diabet & Digest & Kidney Dis, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA. RP Hanson, RL (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Diabet Epidemiol & Clin Res Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rhanson@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NIH FX This research is funded by the NIH intramural research program. MCD was supported by the NIH Intramural training program. NR 30 TC 19 Z9 20 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD MAY PY 2014 VL 63 IS 5 BP 654 EP 660 DI 10.1016/j.metabol.2014.01.007 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AG1UC UT WOS:000335200700008 PM 24582139 ER PT J AU Robinson, GW Kang, K Yoo, KH Tang, Y Zhu, BM Yamaji, D Colditz, V Jang, SJ Gronostajski, RM Hennighausen, L AF Robinson, Gertraud W. Kang, Keunsoo Yoo, Kyung Hyun Tang, Yong Zhu, Bing-Mei Yamaji, Daisuke Colditz, Vera Jang, Seung Jian Gronostajski, Richard M. Hennighausen, Lothar TI Coregulation of Genetic Programs by the Transcription Factors NFIB and STAT5 SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID NUCLEAR FACTOR-I; WHEY ACIDIC PROTEIN; MOUSE MAMMARY EPITHELIUM; ESTER LIPASE GENE; TRANSGENIC MICE; WAP GENE; PROGESTERONE-RECEPTOR; CELL-PROLIFERATION; LUNG MATURATION; DNA-SEQUENCES AB Mammary-specific genetic programs are activated during pregnancy by the common transcription factor signal transducer and activator of transcription (STAT) 5. More than one third of these genes carry nuclear factor I/B (NFIB) binding motifs that coincide with STAT5 in vivo binding, suggesting functional synergy between these two transcription factors. The role of NFIB in this governance was investigated in mice from which Nfib had been inactivated in mammary stem cells or in differentiating alveolar epithelium. Although NFIB was not required for alveolar expansion, the combined absence of NFIB and STAT5 prevented the formation of functional alveoli. NFIB controlled the expression of mammary-specific and STAT5-regulated genes and chromatin immunoprecipitation- sequencing established STAT5 and NFIB binding at composite regulatory elements containing histone H3 lysine dimethylation enhancer marks and progesterone receptor binding. By integrating previously published chromatin immunoprecipitation-sequencing data sets, the presence of NFIB-STAT5 modules in other cell types was investigated. Notably, genomic sites bound by NFIB in hair follicle stem cells were also occupied by STAT5 in mammary epithelium and coincided with enhancer marks. Many of these genes were under NFIB control in both hair follicle stem cells and mammary alveolar epithelium. We propose that NFIB-STAT5 modules, possibly in conjunction with other transcription factors, control cell-specific genetic programs. C1 [Robinson, Gertraud W.; Kang, Keunsoo; Yoo, Kyung Hyun; Tang, Yong; Yamaji, Daisuke; Colditz, Vera; Jang, Seung Jian; Hennighausen, Lothar] Natl Inst Diabet & Digest & Kidney Dis, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. [Kang, Keunsoo] Dankook Univ, Dept Microbiol, Cheonan 330714, South Korea. [Tang, Yong] Chengdu Univ Tradit Chinese Med, Chengdu 610072, Peoples R China. [Zhu, Bing-Mei] Nanjing Univ Tradit Chinese Med, Lab Acupuncture & Med, Nanjing 210046, Jiangsu, Peoples R China. [Gronostajski, Richard M.] SUNY Buffalo, Dept Biochem, Dev Genom Grp, New York State Ctr Excellence Bioinformat & Life, Buffalo, NY 14203 USA. RP Hennighausen, L (reprint author), Natl Inst Diabet & Digest & Kidney Dis, NIH, Bldg 8,Room 101, Bethesda, MD 20892 USA. EM lotharh@mail.nih.gov FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health from the National Natural Science Funding of China [81273838]; Natural Science Fund for Colleges and Universities, Department of Education, Jiangsu, China [11KJA360003]; National Heart, Lung, and Blood Institute; National Institutes of Health [HL080624]; New York State Stem Cell Science [C026429] FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Funding for B.M. Z. came from the National Natural Science Funding of China (81273838) and the Natural Science Fund for Colleges and Universities, Department of Education, Jiangsu, China (11KJA360003). R. M. G. was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health (Award HL080624) and New York State Stem Cell Science (Award C026429). NR 55 TC 4 Z9 5 U1 0 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 2014 VL 28 IS 5 BP 758 EP 767 DI 10.1210/me.2012-1387 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AG5IK UT WOS:000335452500014 PM 24678731 ER PT J AU Xue, R Zakharov, MN Xia, Y Bhasin, S Costello, JC Jasuja, R AF Xue, Ran Zakharov, Mikhail N. Xia, Yu Bhasin, Shalender Costello, James C. Jasuja, Ravi TI Research Resource: EPSLiM: Ensemble Predictor for Short Linear Motifs in Nuclear Hormone Receptors SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROSTATE-CANCER CELLS; ANDROGEN RECEPTOR; INTRINSIC DISORDER; COREGULATORS; DOMAIN; BINDING; ACTIVATION; SRC; CLASSIFIER; ANTAGONIST AB Nuclear receptors (NRs) are a superfamily of transcription factors central to regulating many biological processes, including cell growth, death, metabolism, and immune responses. NR-mediated gene expression can be modulated by coactivators and corepressors through direct physical interaction or protein complexes with functional domains in NRs. One class of these domains includes short linear motifs (SLiMs), which facilitate protein-protein interactions, phosphorylation, and ligand binding primarily in the intrinsically disordered regions (IDRs) of proteins. Across all proteins, the number of known SLiMs is limited due to the difficulty in studying IDRs experimentally. Computational tools provide a systematic and data-driven approach for predicting functional motifs that can be used to prioritize experimental efforts. Accordingly, several tools have been developed based on sequence conservation or biophysical features; however, discrepancies in predictions make it difficult to determine the true candidate SLiMs. In this work, we present the ensemble predictor for short linear motifs (EPSLiM), a novel strategy to prioritize the residues that are most likely to be SLiMs in IDRs. EPSLiM applies a generalized linear model to integrate predictions from individual methodologies. We show that EPSLiM outperforms individual predictors, and we apply our method to NRs. The androgen receptor is an example with an N-terminal domain of 559 disordered amino acids that contains several validated SLiMs important for transcriptional activation. We use the androgen receptor to illustrate the predictive performance of EPSLiM and make the results of all human and mouse NRs publically available through the web service http://epslim.bwh.harvard.edu. C1 [Xue, Ran; Bhasin, Shalender; Costello, James C.; Jasuja, Ravi] Harvard Univ, Brigham & Womens Hosp, Sch Med,Res Program Mens Hlth Aging & Metab, Boston Claude D Pepper Older Amer Independence Ct, Boston, MA 02115 USA. [Zakharov, Mikhail N.] NIH, Natl Lib Med, Natl Ctr Bioinformat Technol, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Xia, Yu] McGill Univ, Fac Engn, Dept Bioengn, Montreal, PQ H3A 0C3, Canada. RP Jasuja, R (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Program Mens Hlth Aging & Metab,Boston Claude D P, Boston, MA 02115 USA. EM james.costello@ucdenver.edu; rjasuja@partners.org OI Xia, Yu/0000-0002-5596-5518 FU Evans Foundation; Brigham and Women's Hospital startup funds; National Institute on Aging [5 R01 AG037193-11]; National Science Foundation [CCF-1219007] FX This work was supported by the Evans Foundation (merit award to R.J.), Brigham and Women's Hospital startup funds (S. B. and R.J.), the National Institute on Aging (Grant 5 R01 AG037193-11), and the National Science Foundation (Grant CCF-1219007). NR 49 TC 1 Z9 1 U1 0 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 2014 VL 28 IS 5 BP 768 EP 777 DI 10.1210/me.2014-1006 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AG5IK UT WOS:000335452500015 PM 24678734 ER PT J AU Sallach, J Di Pasquale, G Larchert, F Niehoff, N Rubsam, M Huber, A Chiorini, J Almarza, D Eming, SA Ulus, H Nishimura, S Hacker, UT Hallek, M Niessen, CM Buning, H AF Sallach, Jessica Di Pasquale, Giovanni Larcher, Fernando Niehoff, Nadine Ruebsam, Matthias Huber, Anke Chiorini, Jay Almarza, David Eming, Sabine A. Ulus, Hikmet Nishimura, Stephen Hacker, Ulrich T. Hallek, Michael Niessen, Carien M. Buening, Hildegard TI Tropism-modified AAV Vectors Overcome Barriers to Successful Cutaneous Therapy SO MOLECULAR THERAPY LA English DT Article ID ADENOASSOCIATED VIRUS TYPE-2; HEPARAN-SULFATE PROTEOGLYCAN; GROWTH-FACTOR RECEPTOR; MOUTH-DISEASE VIRUS; GENE-THERAPY; INTEGRIN ALPHA-V-BETA-8; HUMAN KERATINOCYTES; VIRAL-VECTORS; EPIDERMAL MORPHOGENESIS; TRANSDUCTION EFFICIENCY AB Autologous human keratinocytes (HK) forming sheet grafts are approved as skin substitutes. Genetic engineering of HK represents a promising technique to improve engraftment and survival of transplants. Although efficacious in keratinocyte-directed gene transfer, retro-/lenti-viral vectors may raise safety concerns when applied in regenerative medicine. We therefore optimized adeno-associated viral (AAV) vectors of the serotype 2, characterized by an excellent safety profile, but lacking natural tropism for HK, through capsid engineering. Peptides, selected by AAV peptide display, engaged novel receptors that increased cell entry efficiency by up to 2,500-fold. The novel targeting vectors transduced HK with high efficiency and a remarkable specificity even in mixed cultures of HK and feeder cells. Moreover, differentiated keratinocytes in organotypic airlifted three-dimensional cultures were transduced following topical vector application. By exploiting comparative gene analysis we further succeeded in identifying alpha v beta 8 integrin as a target receptor thus solving a major challenge of directed evolution approaches and describing a promising candidate receptor for cutaneous gene therapy. C1 [Sallach, Jessica; Niehoff, Nadine; Ruebsam, Matthias; Huber, Anke; Eming, Sabine A.; Hallek, Michael; Niessen, Carien M.; Buening, Hildegard] Univ Cologne, CMMC, D-50931 Cologne, Germany. [Sallach, Jessica; Huber, Anke; Hallek, Michael; Buening, Hildegard] Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany. [Di Pasquale, Giovanni; Chiorini, Jay] Natl Inst Dent & Crania facial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. [Larcher, Fernando; Almarza, David] Univ Carlos III Madrid UC3M, Ctr Invest Energet Medioambiental Tecnol CIEMAT, Ctr Biomed Res Rare Dis CIBERER U714, Madrid, Spain. [Niehoff, Nadine; Ruebsam, Matthias; Eming, Sabine A.; Niessen, Carien M.] Univ Carlos III Madrid UC3M, Dept Bioengn, Madrid, Spain. [Niehoff, Nadine; Ruebsam, Matthias; Eming, Sabine A.; Niessen, Carien M.] Univ Hosp Cologne, Dept Dermatol, Cologne, Germany. [Eming, Sabine A.; Niessen, Carien M.] Cologne Excellence Ctr Cellular Stress Responses, Cologne, Germany. [Ulus, Hikmet] Childrens Med Surg, Cologne, Germany. [Nishimura, Stephen] UCSF, Dept Pathol & Lab Med, San Francisco, CA USA. [Hacker, Ulrich T.] UCCL, Leipzig, Germany. RP Buning, H (reprint author), Univ Cologne, CMMC, Robert Koch Str 21, D-50931 Cologne, Germany. EM hildegard.buening@uk-koeln.de RI Larcher, Fernando/J-1527-2016 OI Larcher, Fernando/0000-0002-6771-3561 FU Research Priority Program 1230 [SPP1230]; Deutsche Forschungsgemeinschaft (DFG) [BU1310/12]; Center for Molecular Medicine Cologne (CMMC) [B1]; Instituto de Salud Carlos III [PI11/01225]; Comunidad de Madrid [S2010/BMD-2359]; CMMC [C1.1]; National Institutes of Health [HL113032, NS044155]; European Union [LSHBCT-2005-512102] FX This work was supported by grants from the Research Priority Program 1230 (SPP1230) "Mechanisms of gene vector entry and persistence" of the Deutsche Forschungsgemeinschaft (DFG) to H.B. (BU1310/12) and from the Center for Molecular Medicine Cologne (CMMC) to H.B. (B1). F.L. was supported by grants from Instituto de Salud Carlos III (PI11/01225) and Comunidad de Madrid (S2010/BMD-2359), S.A.E. by the CMMC (C1.1), S.N. by the National Institutes of Health (HL113032, NS044155) and M.H. by the European Union (LSHBCT-2005-512102). We thank Jude Samulski (University of North Carolina at Chapel Hill, NC) for providing plasmid pXX6, Vyomesh Patel (Oral & Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD) for sharing reagents, and Hanna Janicki (University of Cologne, Germany), and Stephanie Cambier (UCSF, San Francisco, CA) for technical assistance. The authors declare no conflict of interest. NR 50 TC 13 Z9 13 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 IS 5 BP 929 EP 939 DI 10.1038/mt.2014.14 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AG4WQ UT WOS:000335421500007 PM 24468915 ER PT J AU Doria-Rose, NA Schramm, CA Gorman, J Moore, PL Bhiman, JN DeKosky, BJ Ernandes, MJ Georgiev, IS Kim, HJ Pancera, M Staupe, RP Altae-Tran, HR Bailer, RT Crooks, ET Cupo, A Druz, A Garrett, NJ Hoi, KH Kong, R Louder, MK Longo, NS McKee, K Nonyane, M O'Dell, S Roark, RS Rudicell, RS Schmidt, SD Sheward, DJ Soto, C Wibmer, CK Yang, YP Zhang, ZH Mullikin, JC Binley, JM Sanders, RW Wilson, IA Moore, JP Ward, AB Georgiou, G Williamson, C Karim, SSA Morris, L Kwong, PD Shapiro, L Mascola, JR AF Doria-Rose, Nicole A. Schramm, Chaim A. Gorman, Jason Moore, Penny L. Bhiman, Jinal N. DeKosky, Brandon J. Ernandes, Michael J. Georgiev, Ivelin S. Kim, Helen J. Pancera, Marie Staupe, Ryan P. Altae-Tran, Han R. Bailer, Robert T. Crooks, Ema T. Cupo, Albert Druz, Aliaksandr Garrett, Nigel J. Hoi, Kam H. Kong, Rui Louder, Mark K. Longo, Nancy S. McKee, Krisha Nonyane, Molati O'Dell, Sijy Roark, Ryan S. Rudicell, Rebecca S. Schmidt, Stephen D. Sheward, Daniel J. Soto, Cinque Wibmer, Constantinos Kurt Yang, Yongping Zhang, Zhenhai Mullikin, James C. Binley, James M. Sanders, Rogier W. Wilson, Ian A. Moore, John P. Ward, Andrew B. Georgiou, George Williamson, Carolyn Karim, Salim S. Abdool Morris, Lynn Kwong, Peter D. Shapiro, Lawrence Mascola, John R. CA NISC Comparative Sequencing TI Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; MAXIMUM-LIKELIHOOD; HIV-1-NEUTRALIZING ANTIBODIES; VACCINE EFFICACY; STRUCTURAL BASIS; ENVELOPE TRIMER; B-CELLS; INFECTION; BROAD AB Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development. C1 [Doria-Rose, Nicole A.; Gorman, Jason; Ernandes, Michael J.; Georgiev, Ivelin S.; Pancera, Marie; Staupe, Ryan P.; Altae-Tran, Han R.; Bailer, Robert T.; Druz, Aliaksandr; Kong, Rui; Louder, Mark K.; Longo, Nancy S.; McKee, Krisha; O'Dell, Sijy; Roark, Ryan S.; Rudicell, Rebecca S.; Schmidt, Stephen D.; Soto, Cinque; Yang, Yongping; Kwong, Peter D.; Shapiro, Lawrence; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Schramm, Chaim A.; Zhang, Zhenhai; Shapiro, Lawrence] Columbia Univ, Dept Biochem, New York, NY 10032 USA. [Moore, Penny L.; Bhiman, Jinal N.; Nonyane, Molati; Wibmer, Constantinos Kurt; Morris, Lynn] NHLS, Natl Inst Communicable Dis, Ctr HIV & STIs, ZA-2131 Johannesburg, South Africa. [Moore, Penny L.; Bhiman, Jinal N.; Wibmer, Constantinos Kurt; Morris, Lynn] Univ Witwatersrand, Fac Hlth Sci, ZA-2050 Johannesburg, South Africa. [Moore, Penny L.; Garrett, Nigel J.; Williamson, Carolyn; Karim, Salim S. Abdool; Morris, Lynn] Univ KwaZulu Natal, CAPRISA, ZA-4013 Congella, South Africa. [DeKosky, Brandon J.; Georgiou, George] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. [Kim, Helen J.; Wilson, Ian A.; Ward, Andrew B.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Kim, Helen J.; Wilson, Ian A.; Ward, Andrew B.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Kim, Helen J.; Wilson, Ian A.; Ward, Andrew B.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Crooks, Ema T.; Binley, James M.] Torrey Pines Inst, San Diego, CA 92037 USA. [Cupo, Albert; Moore, John P.] Cornell Univ, Weill Med Coll, New York, NY 10065 USA. [Hoi, Kam H.; Georgiou, George] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Sheward, Daniel J.] Univ Cape Town, Inst Infect Dis & Mol Med, Div Med Virol, ZA-7701 Cape Town, South Africa. [Sheward, Daniel J.] NHLS, ZA-7701 Cape Town, South Africa. [Mullikin, James C.] NIH, NISC Comparat Sequencing Program, Bethesda, MD 20892 USA. [Mullikin, James C.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Sanders, Rogier W.] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands. [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Georgiou, George] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA. [Karim, Salim S. Abdool] Columbia Univ, Dept Epidemiol, New York, NY 10032 USA. RP Morris, L (reprint author), NHLS, Natl Inst Communicable Dis, Ctr HIV & STIs, ZA-2131 Johannesburg, South Africa. EM lynnm@nicd.ac.za; pdkwong@nih.gov; lss8@columbia.edu; jrmascola@nih.gov RI Schmidt, Stephen/B-5398-2012; Ward, Andrew/F-9203-2014; OI Ward, Andrew/0000-0001-7153-3769; Moore, Penny/0000-0001-8719-4028; , Carolyn/0000-0003-0125-1226; Bhiman, Jinal/0000-0001-6354-4003; Abdool Karim, Salim/0000-0002-4986-2133; Wibmer, Constantinos Kurt/0000-0003-2329-2280 FU Vaccine Research Center; NIAID; Fogarty International Center; NHGRI; NIGMS of the National Institutes of Health, USA; International AIDS Vaccine Initiative; National Science Foundation; Scripps CHAV-ID; South African Department of Science and Technology; Wellcome Trust; Hertz Foundation; Donald D. Harrington Foundation; Poliomyelitis Research Foundation; National Research Foundation of South Africa; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38] FX We thank the participants in the CAPRISA 002 study for their commitment. For technical assistance and advice, we thank: K. Mlisana, S. Sibeko, N. Naicker, the CAPRISA 002 clinical team, N. Samsunder, S. Heeralall, B. Lambson, M. Madzivhandila, T. Khoza, C. Mitchell Scheepers, E. Turk, C.-L. Lin, M. Roederer, J. Stuckey, B. Hartman, G. Loots, J. H. Lee, G. Ippolito, B. Briney, S. Hunicke-Smith and J. Wheeler, and members of the WCMC HIVRAD Core and the NIH Vaccine Research Center HIMS, HIMC, SBS and SBIS sections. We thank J. Baalwa, D. Ellenberger, F. Gao, B. Hahn, K. Hong, J. Kim, F. McCutchan, D. Montefiori, J. Overbaugh, E. Sanders-Buell, G. Shaw, R. Swanstrom, M. Thomson, S. Tovanabutra and L. Zhang for contributing the HIV-1Envelope plasmids used in our neutralizationpanel. Funding was provided by the intramural research programs of the Vaccine Research Center and NIAID, the Fogarty International Center, NHGRI, and NIGMS of the National Institutes of Health, USA; the International AIDS Vaccine Initiative; the National Science Foundation; Scripps CHAV-ID; the South African Department of Science and Technology; and fellowships from the Wellcome Trust, Hertz Foundation, Donald D. Harrington Foundation, Poliomyelitis Research Foundation and the National Research Foundation of South Africa. Use of sector 22 (Southeast Region Collaborative Access team) at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract number W-31-109-Eng-38. NR 83 TC 213 Z9 217 U1 4 U2 51 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 MAY 1 PY 2014 VL 509 IS 7498 BP 55 EP + DI 10.1038/nature13036 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG1TM UT WOS:000335199100038 PM 24590074 ER PT J AU Zhang, KH Zhang, J Gao, ZG Zhang, DD Zhu, L Han, GW Moss, SM Paoletta, S Kiselev, E Lu, WZ Fenalti, G Zhang, WR Muller, CE Yang, HY Jiang, HL Cherezov, V Katritch, V Jacobson, KA Stevens, RC Wu, BL Zhao, Q AF Zhang, Kaihua Zhang, Jin Gao, Zhan-Guo Zhang, Dandan Zhu, Lan Han, Gye Won Moss, Steven M. Paoletta, Silvia Kiselev, Evgeny Lu, Weizhen Fenalti, Gustavo Zhang, Wenru Mueller, Christa E. Yang, Huaiyu Jiang, Hualiang Cherezov, Vadim Katritch, Vsevolod Jacobson, Kenneth A. Stevens, Raymond C. Wu, Beili Zhao, Qiang TI Structure of the human P2Y(12) receptor in complex with an antithrombotic drug SO NATURE LA English DT Article ID PROTEIN-COUPLED RECEPTOR; ACTIVE METABOLITE; NUCLEOTIDE RECEPTORS; CRYSTAL-STRUCTURE; AMINO-ACIDS; ANTAGONISTS; IDENTIFICATION; CLOPIDOGREL; INHIBITION; ACTIVATION AB P2Y receptors (P2YRs), a family of purinergic G-protein-coupled receptors (GPCRs), are activated by extracellular nucleotides. There are a total of eight distinct functional P2YRs expressed in human, which are subdivided into P2Y1-like receptors and P2Y(12)-like receptors(1). Their ligands are generally charged molecules with relatively low bioavailability and stability in vivo(2), which limits our understanding of this receptor family. P2Y(12)R regulates platelet activation and thrombus formation(3,4), and several antithrombotic drugs targeting P2Y(12)R-including the prodrugs clopidogrel (Plavix) and prasugrel (Effient) that are metabolized and bind covalently, and the nucleoside analogue ticagrelor (Brilinta) that acts directly on the receptor-have been approved for the prevention of stroke and myocardial infarction. However, limitations of these drugs (for example, a very long half-life of clopidogrel action and a characteristic adverse effect profile of ticagrelor) 5,6 suggest that there is an unfulfilled medical need for developing a new generation of P2Y(12)R inhibitors(7,8). Here we report the 2.6 angstrom resolution crystal structure of human P2Y(12)R in complex with a non-nucleotide reversible antagonist, AZD1283. The structure reveals a distinct straight conformation of helix V, which sets P2Y(12)R apart from all other known class A GPCR structures. With AZD1283 bound, the highly conserved disulphide bridge in GPCRs between helix III and extracellular loop 2 is not observed and appears to be dynamic. Along with the details of the AZD1283-binding site, analysis of the extracellular interface reveals an adjacent ligand-binding region and suggests that both pockets could be required for dinucleotide binding. The structure provides essential insights for the development of improved P2Y(12)R ligands and allosteric modulators as drug candidates. C1 [Zhang, Kaihua; Zhang, Jin; Zhang, Dandan; Zhu, Lan; Lu, Weizhen; Zhang, Wenru; Wu, Beili; Zhao, Qiang] Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China. [Gao, Zhan-Guo; Moss, Steven M.; Paoletta, Silvia; Kiselev, Evgeny; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Han, Gye Won; Fenalti, Gustavo; Cherezov, Vadim; Katritch, Vsevolod; Stevens, Raymond C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Mueller, Christa E.] PharmaCtr Bonn, Inst Pharmaceut, D-53121 Bonn, Germany. [Yang, Huaiyu; Jiang, Hualiang] Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China. [Stevens, Raymond C.] ShanghaiTech Univ, iHuman Inst, Shanghai 201203, Peoples R China. RP Zhao, Q (reprint author), Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China. EM zhaoq@simm.ac.cn RI Jacobson, Kenneth/A-1530-2009; Cherezov, Vadim/L-9812-2013; Katritch, Vsevolod/Q-8357-2016; Muller, Christa/C-7748-2014; Stevens, Raymond/K-7272-2015; OI Jacobson, Kenneth/0000-0001-8104-1493; Cherezov, Vadim/0000-0002-5265-3914; Muller, Christa/0000-0002-0013-6624; Stevens, Raymond/0000-0002-4522-8725; Zhang, Kaihua/0000-0003-3734-3624 FU National Basic Research Program of China [2012CB910400, 2012CB518000]; National Institutes of Health (NIH) [R01 AI100604, U54 GM094618]; National Science Foundation of China [31370729, 31170683]; National Institute of General Medical Sciences Postdoctoral Research Associate program; NIH National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program FX This work was supported by National Basic Research Program of China grants 2012CB910400 and 2012CB518000 (B. W., Q.Z.), National Institutes of Health (NIH) grants R01 AI100604 (B. W., Q.Z.) and U54 GM094618 (V. C., V. K., R. C. S.; Target GPCR-87), National Science Foundation of China grants 31370729 and 31170683 (B. W., Q.Z.), the National Institute of General Medical Sciences Postdoctoral Research Associate program (E. K.) and the NIH National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program (K.A.J.). The authors thank AstraZeneca for their gift of AZD1283, and thank S. Nylander, F. Giordanetto and H. van Giezen for careful review and scientific feedback on the manuscript, A. Walker for assistance with manuscript preparation, and C. Wang and D. Wacker for help on collection of X-ray diffraction data. NR 36 TC 102 Z9 108 U1 9 U2 77 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 MAY 1 PY 2014 VL 509 IS 7498 BP 115 EP 118 DI 10.1038/nature13083 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG1TM UT WOS:000335199100050 PM 24670650 ER PT J AU Zhang, J Zhang, KH Gao, ZG Paoletta, S Zhang, DD Han, GW Li, TT Ma, LM Zhang, WR Muller, CE Yang, HY Jiang, HL Cherezov, V Katritch, V Jacobson, KA Stevens, RC Wu, BL Zhao, Q AF Zhang, Jin Zhang, Kaihua Gao, Zhan-Guo Paoletta, Silvia Zhang, Dandan Han, Gye Won Li, Tingting Ma, Limin Zhang, Wenru Mueller, Christa E. Yang, Huaiyu Jiang, Hualiang Cherezov, Vadim Katritch, Vsevolod Jacobson, Kenneth A. Stevens, Raymond C. Wu, Beili Zhao, Qiang TI Agonist-bound structure of the human P2Y(12) receptor SO NATURE LA English DT Article ID PROTEIN-COUPLED RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTOR; RESOLUTION CRYSTAL-STRUCTURE; A(2A) ADENOSINE RECEPTOR; MEMBRANE-PROTEINS; IDENTIFICATION; ANTAGONISTS; ACTIVATION; RHODOPSIN; COMPLEX AB The P2Y(12) receptor (P2Y(12)R), one of eight members of the P2YR family expressed in humans, is one of the most prominent clinical drug targets for inhibition of platelet aggregation. Although mutagenesis and modelling studies of the P2Y(12)R provided useful insights into ligand binding(1-4), the agonist and antagonist recognition and function at the P2Y(12)R remain poorly understood at the molecular level. Here we report the structures of the human P2Y(12)R in complex with the full agonist 2-methylthio-adenosine-5'-diphosphate (2MeSADP, a close analogue of endogenous agonist ADP) at 2.5 angstrom resolution, and the corresponding ATP derivative 2-methylthio-adenosine-5'-triphosphate (2MeSATP) at 3.1 angstrom resolution. These structures, together with the structure of the P2Y(12)R with antagonist ethyl 6-(4-((benzylsulfonyl) carbamoyl)piperidin-1-yl)-5-cyano-2-methylnicotinate (AZD1283)(5), reveal striking conformational changes between nucleotide and non-nucleotide ligand complexes in the extracellular regions. Further analysis of these changes provides insight into a distinct ligand binding landscape inthed-group of class AG-protein-coupled receptors (GPCRs). Agonist and non-nucleotide antagonist adopt different orientations in the P2Y(12)R, with only partially overlapped binding pockets. The agonist-bound P2Y(12)R structure answers long-standing questions surrounding P2Y(12)R-agonist recognition, and reveals interactions with several residues that had not been reported to be involved in agonist binding. As a first example, to our knowledge, of a GPCR in which agonist access to the binding pocket requires large-scale rearrangements in the highly malleable extracellular region, the structural and docking studies will therefore provide invaluable insight into the pharmacology and mechanisms of action of agonists and different classes of antagonists for the P2Y(12)R and potentially for other closely related P2YRs. C1 [Zhang, Jin; Zhang, Kaihua; Zhang, Dandan; Li, Tingting; Ma, Limin; Zhang, Wenru; Wu, Beili; Zhao, Qiang] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China. [Gao, Zhan-Guo; Paoletta, Silvia; Jacobson, Kenneth A.] Natl Inst Diabet & Digest & Kidney Dis, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Han, Gye Won; Cherezov, Vadim; Katritch, Vsevolod; Stevens, Raymond C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Mueller, Christa E.] Univ Bonn, PharmaCtr Bonn, D-53121 Bonn, Germany. [Yang, Huaiyu; Jiang, Hualiang] Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China. [Stevens, Raymond C.] ShanghaiTech Univ, IHuman Inst, Shanghai 201203, Peoples R China. RP Wu, BL (reprint author), Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China. EM beiliwu@simm.ac.cn; zhaoq@simm.ac.cn RI Jacobson, Kenneth/A-1530-2009; Cherezov, Vadim/L-9812-2013; Katritch, Vsevolod/Q-8357-2016; Muller, Christa/C-7748-2014; Stevens, Raymond/K-7272-2015; OI Jacobson, Kenneth/0000-0001-8104-1493; Cherezov, Vadim/0000-0002-5265-3914; Muller, Christa/0000-0002-0013-6624; Stevens, Raymond/0000-0002-4522-8725; Zhang, Kaihua/0000-0003-3734-3624 FU National Basic Research Program of China [2012CB910400, 2012CB518000, 2014CB910400]; National Institutes of Health [R01AI100604, U54 GM094618]; National Science Foundation of China [31370729]; National Science and Technology Major Project [2013ZX09507001, 2012ZX09301001]; National Institutes of Health NIDDK Intramural Research Program; National Natural Science Foundation of China [91313000] FX This work was supported by the National Basic Research Program of China grants 2012CB910400, 2012CB518000 and 2014CB910400 (B. W., Q.Z.), the National Institutes of Health grants R01AI100604 (B. W., Q.Z.) and U54 GM094618 (V. C., V. K., R. C. S.; Target GPCR-87), the National Science Foundation of China grants 31370729 and National Science and Technology Major Project 2013ZX09507001 and 2012ZX09301001 (B. W., Q.Z.), National Institutes of Health NIDDK Intramural Research Program (K.A.J.) and the National Natural Science Foundation of China 91313000 (H.J.). The authors thank S. Nylander, E. Kiselev and S. Moss for scientific feedback on the manuscript, A. Walker for assistance with manuscript preparation and K. Kadyshevskaya for help with figure preparation. The synchrotron radiation experiments were performed at the BL41XU of SPring-8 with the approval of the Japan Synchrotron Radiation Research Institute (JASRI) (proposal no. 2013B1049). We thank the beamline staff members of the BL41XU for help with X-ray data collection. NR 34 TC 81 Z9 85 U1 5 U2 52 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD MAY 1 PY 2014 VL 509 IS 7498 BP 119 EP 122 DI 10.1038/nature13288 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG1TM UT WOS:000335199100051 PM 24784220 ER PT J AU Kimmel, SE French, B Geller, NL AF Kimmel, Stephen E. French, Benjamin Geller, Nancy L. CA COAG Investigators TI Genotype-Guided Dosing of Vitamin K Antagonists REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID ANTICOAGULATION; TRIAL C1 [Kimmel, Stephen E.; French, Benjamin] Univ Penn, Philadelphia, PA 19104 USA. [Geller, Nancy L.] NHLBI, Bethesda, MD 20892 USA. RP Kimmel, SE (reprint author), Univ Penn, Philadelphia, PA 19104 USA. EM stevek@mail.med.upenn.edu NR 2 TC 6 Z9 6 U1 0 U2 0 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 MAY 1 PY 2014 VL 370 IS 18 BP 1763 EP 1764 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AG4QM UT WOS:000335405200023 PM 24785213 ER PT J AU Davis, FM Azimi, I Faville, RA Peters, AA Jalink, K Putney, JW Goodhill, GJ Thompson, EW Roberts-Thomson, SJ Monteith, GR AF Davis, F. M. Azimi, I. Faville, R. A. Peters, A. A. Jalink, K. Putney, J. W., Jr. Goodhill, G. J. Thompson, E. W. Roberts-Thomson, S. J. Monteith, G. R. TI Induction of epithelial-mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent SO ONCOGENE LA English DT Article DE epithelial-mesenchymal transition; calcium; vimentin; STAT3; signal transduction; breast cancer ID GENE-EXPRESSION; UP-REGULATION; MIGRATION; TRPM7; PROGRESSION; METASTASIS; CHANNELS; ACTIVATION; CONTRIBUTES; PHENOTYPE AB Signals from the tumor microenvironment trigger cancer cells to adopt an invasive phenotype through epithelial-mesenchymal transition (EMT). Relatively little is known regarding key signal transduction pathways that serve as cytosolic bridges between cell surface receptors and nuclear transcription factors to induce EMT. A better understanding of these early EMT events may identify potential targets for the control of metastasis. One rapid intracellular signaling pathway that has not yet been explored during EMT induction is calcium. Here we show that stimuli used to induce EMT produce a transient increase in cytosolic calcium levels in human breast cancer cells. Attenuation of the calcium signal by intracellular calcium chelation significantly reduced epidermal growth factor (EGF)-and hypoxia-induced EMT. Intracellular calcium chelation also inhibited EGF-induced activation of signal transducer and activator of transcription 3 (STAT3), while preserving other signal transduction pathways such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. To identify calcium-permeable channels that may regulate EMT induction in breast cancer cells, we performed a targeted siRNA-based screen. We found that transient receptor potential-melastatin- like 7 (TRPM7) channel expression regulated EGF-induced STAT3 phosphorylation and expression of the EMT marker vimentin. Although intracellular calcium chelation almost completely blocked the induction of many EMT markers, including vimentin, Twist and N-cadherin, the effect of TRPM7 silencing was specific for vimentin protein expression and STAT3 phosphorylation. These results indicate that TRPM7 is a partial regulator of EMT in breast cancer cells, and that other calcium-permeable ion channels are also involved in calcium-dependent EMT induction. In summary, this work establishes an important role for the intracellular calcium signal in the induction of EMT in human breast cancer cells. Manipulation of calcium-signaling pathways controlling EMT induction in cancer cells may therefore be an important therapeutic strategy for preventing metastases. C1 [Davis, F. M.; Azimi, I.; Peters, A. A.; Roberts-Thomson, S. J.; Monteith, G. R.] Univ Queensland, Sch Pharm, Brisbane, Qld 4072, Australia. [Faville, R. A.; Goodhill, G. J.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Jalink, K.] Netherlands Canc Inst, Div Cell Biol, Amsterdam, Netherlands. [Putney, J. W., Jr.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. [Goodhill, G. J.] Univ Queensland, Sch Math & Phys, Brisbane, Qld 4072, Australia. [Thompson, E. W.] St Vincents Inst, Fitzroy, Vic, Australia. [Thompson, E. W.] Univ Melbourne, St Vincents Hosp, Dept Surg, Fitzroy, Vic 3065, Australia. RP Monteith, GR (reprint author), Univ Queensland, Sch Pharm, Brisbane, Qld 4072, Australia. EM gregm@uq.edu.au RI Peters, Amelia/E-4254-2010; Roberts-Thomson, Sarah/B-4282-2011; Thompson, Erik/A-1425-2009; Azimi, Iman/E-2043-2011; Davis, Felicity/P-1387-2016; Monteith, Gregory/B-1626-2008 OI Roberts-Thomson, Sarah/0000-0001-8202-5786; Thompson, Erik/0000-0002-9723-4924; Azimi, Iman/0000-0001-9477-9999; Davis, Felicity/0000-0001-9112-118X; Monteith, Gregory/0000-0002-4345-530X FU National Health and Medical Research Council (NHMRC) [569645, 1022263]; Intramural Research Program of the US National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS); NHMRC Biomedical Postgraduate Scholarship [511262]; UQ Postdoctoral Fellowship; National Breast Cancer Foundation FX The research was partially supported by the National Health and Medical Research Council (NHMRC; project grants 569645 and 1022263) and the Intramural Research Program of the US National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS). FD was funded by an NHMRC Biomedical Postgraduate Scholarship (511262), RF was funded by a UQ Postdoctoral Fellowship and EWT was funded in part by the National Breast Cancer Foundation. NR 53 TC 54 Z9 56 U1 4 U2 38 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 MAY 1 PY 2014 VL 33 IS 18 BP 2307 EP 2316 DI 10.1038/onc.2013.187 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AG5ID UT WOS:000335451800004 PM 23686305 ER PT J AU Martin, D Nguyen, Q Molinolo, A Gutkind, JS AF Martin, D. Nguyen, Q. Molinolo, A. Gutkind, J. S. TI Accumulation of dephosphorylated 4EBP after mTOR inhibition with rapamycin is sufficient to disrupt paracrine transformation by the KSHV vGPCR oncogene SO ONCOGENE LA English DT Article DE Kaposi's sarcoma; mTOR; PI3K; 4EBP; rapamycin; cancer ID PROTEIN-COUPLED RECEPTOR; KAPOSIS-SARCOMA; MAMMALIAN TARGET; HERPESVIRUS; CELL; PATHOGENESIS; INFECTION; GROWTH; EXPRESSION; NEOPLASIA AB Dysregulation of the PI3K/Akt/mTOR pathway is one of the most frequent events in human cancer. However, the clinical benefits of PI3K/Akt/mTOR inhibitors have not yet achieved their predicted potential in many of the most prevalent human cancers. Of interest, treatment of Kaposi's sarcoma (KS) patients with rapamycin provided the first evidence of the antineoplastic activity of mTOR inhibitors in humans, becoming the standard of care for KS arising in renal transplant patients. Thus, the study of KS may provide a unique opportunity to dissect the contribution of specific mTOR downstream targets to cancer development. The KS associated herpesvirus (KSHV) is the etiological agent for KS, and the KSHV-encoded oncogene viral-G protein-coupled receptor (vGPCR) promotes the potent activation of the PI3K-Akt-mTOR pathway by both direct and paracrine mechanisms. We focused on a direct target of mTOR, EIF4EBP1/2/3 (4EBP), which inhibits the translation of eukaryotic initiation factor 4E (eiF4E)-bound mRNAs. 4EBP phosphorylation by mTOR relieves its inhibitory activity, hence resulting in increased eiF4E-dependent mRNA translation. We developed a paracrine transformation model, recapitulating the cellular composition of KS lesions, in which vGPCR-expressing cells promote the rapid proliferation of endothelial cells, thus expressing KSHV-latent genes by the release of growth factors. Using this model, we show here that the accumulation of dephosphorylated 4EBP in response to rapamycin or by the expression of an mTOR-insensitive mutant of 4EBP1 is sufficient to disrupt the eiF4E function downstream of mTOR to a similar extent than the mTOR catalytic inhibitor Torin2 and to halt KS development. We also provide evidence that eiF4E contributes to paracrine neoplastic, signaling through the release of pro-angiogenic factors that are acting on endothelial cells, expressing KSHV-latent genes. These findings may provide a preclinical platform and the rationale for the development of novel mTOR, inhibiting agents that may selectively disrupt the mTOR-4EBP interaction for the treatment of KS and other tumor lesions, exhibiting hyperactive mTOR pathway function. C1 [Martin, D.; Nguyen, Q.; Molinolo, A.; Gutkind, J. S.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bldg 30 Room 320,30 Convent Dr MSC 4340, Bethesda, MD 20892 USA. EM sg39v@nih.gov FU National Institutes of Health Intramural AIDS-Targeted Antiviral Program; National Institute of Dental and Craniofacial Research FX This research was supported by the National Institutes of Health Intramural AIDS-Targeted Antiviral Program and the National Institute of Dental and Craniofacial Research. We apologize to colleagues whose primary research papers may not have been cited due to space constraints. NR 28 TC 4 Z9 4 U1 1 U2 5 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 MAY 1 PY 2014 VL 33 IS 18 BP 2405 EP 2412 DI 10.1038/onc.2013.193 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AG5ID UT WOS:000335451800013 PM 23708663 ER PT J AU Pattanayak, P Bluemke, DA AF Pattanayak, Puskar Bluemke, David A. TI Cardiac MR Imaging to Probe Tissue Composition of the Heart by Using T1 Mapping SO RADIOLOGY LA English DT Editorial Material ID CARDIOVASCULAR MAGNETIC-RESONANCE; DIFFUSE MYOCARDIAL FIBROSIS; SYSTEMIC-SCLEROSIS; CARDIOMYOPATHY; BIOPSY C1 [Pattanayak, Puskar; Bluemke, David A.] Natl Inst Biomed Imaging & Engn, Dept Radiol & Imaging Sci, NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Bluemke, DA (reprint author), Natl Inst Biomed Imaging & Engn, Dept Radiol & Imaging Sci, NIH, Ctr Clin, 10 Ctr Dr,Room 1C355, Bethesda, MD 20892 USA. EM bluemked@nih.gov OI Bluemke, David/0000-0002-8323-8086 NR 15 TC 1 Z9 1 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2014 VL 271 IS 2 BP 320 EP 322 DI 10.1148/radiol.14140287 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG1CQ UT WOS:000335153000002 PM 24761952 ER PT J AU Zavodni, AEH Wasserman, BA McClelland, RL Gomes, AS Folsom, AR Polak, JF Lima, JAC Bluemke, DA AF Zavodni, Anna E. H. Wasserman, Bruce A. McClelland, Robyn L. Gomes, Antoinette S. Folsom, Aaron R. Polak, Joseph F. Lima, Joao A. C. Bluemke, David A. TI Carotid Artery Plaque Morphology and Composition in Relation to Incident Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis (MESA) SO RADIOLOGY LA English DT Article ID INTIMA-MEDIA THICKNESS; RISK-ASSESSMENT STRATEGIES; LIPID-LOWERING THERAPY; LEFT-VENTRICULAR MASS; HIGH-RESOLUTION; IN-VIVO; INTRAPLAQUE HEMORRHAGE; VULNERABLE PATIENT; PREDICTIVE ABILITY; ROC CURVE AB Purpose: To determine if carotid plaque morphology and composition with magnetic resonance (MR) imaging can be used to identify asymptomatic subjects at risk for cardiovascular events. Materials and Methods: Institutional review boards at each site approved the study, and all sites were Health Insurance Portability and Accountability Act (HIPAA) compliant. A total of 946 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated with MR imaging and ultrasonography (US). MR imaging was used to define carotid plaque composition and remodeling index (wall area divided by the sum of wall area and lumen area), while US was used to assess carotid wall thickness. Incident cardiovascular events, including myocardial infarction, resuscitated cardiac arrest, angina, stroke, and death, were ascertained for an average of 5.5 years. Multivariable Cox proportional hazards models, C statistics, and net reclassification improvement (NRI) for event prediction were determined. Results: Cardiovascular events occurred in 59 (6%) of participants. Carotid IMT as well as MR imaging remodeling index, lipid core, and calcium in the internal carotid artery were significant predictors of events in univariate analysis (P < .001 for all). For traditional risk factors, the C statistic for event prediction was 0.696. For MR imaging remodeling index and lipid core, the C statistic was 0.734 and the NRI was 7.4% and 15.8% for participants with and those without cardiovascular events, respectively (P = .02). The NRI for US IMT in addition to traditional risk factors was not significant. Conclusion: The identification of vulnerable plaque characteristics with MR imaging aids in cardiovascular disease prediction and improves the reclassification of baseline cardiovascular risk. (C) RSNA, 2014 C1 [Zavodni, Anna E. H.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Imaging, Toronto, ON, Canada. [Wasserman, Bruce A.; Lima, Joao A. C.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Lima, Joao A. C.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [McClelland, Robyn L.] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Gomes, Antoinette S.] Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90024 USA. [Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Polak, Joseph F.] Tufts Med Ctr, Dept Radiol, Boston, MA USA. [Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Bluemke, DA (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10-1C355, Bethesda, MD 20892 USA. EM david.bluemke@nih.gov OI Bluemke, David/0000-0002-8323-8086 FU NHLBI NIH HHS [N01 HC095163, N01HC95159, N01HC95168, R01 HL069905] NR 35 TC 15 Z9 16 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2014 VL 271 IS 2 BP 381 EP 389 DI 10.1148/radiol.14131020 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG1CQ UT WOS:000335153000009 PM 24592924 ER PT J AU Todarello, G Feng, NP Kolachana, BS Li, C Vakkalanka, R Bertolino, A Weinberger, DR Straub, RE AF Todarello, Giovanna Feng, Ningping Kolachana, Bhaskar S. Li, Chao Vakkalanka, Radhakrishna Bertolino, Alessandro Weinberger, Daniel R. Straub, Richard E. TI Incomplete penetrance of NRXN1 deletions in families with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Copy number variation; CNV; Deletion; NRXN1; Neurexin; Schizophrenia ID HIDDEN-MARKOV MODEL; SNP GENOTYPING DATA; CHROMOSOMAL-ABNORMALITIES; CNVS; ASSOCIATION; DISORDERS; SPECTRUM AB Neurexin 1 (NRXN1) is a presynaptic neuronal adhesion molecule that interacts with postsynaptic neuroligins in both glutamatergic and GABAergic synapses and is important in synaptic formation and function. NRXN1 deletions increase the risk of schizophrenia, so our aims were to explore this in our family sample, to distinguish de novo from inherited mutations, to examine transmission to affected and unaffected siblings and to estimate penetrance. We performed copy number analyses in NRXN1 using data from Illumina BeadArrays from 635 subjects with schizophrenia (276 in genotyped families), 487 of their unaffected parents and 309 unaffected siblings as well as 635 normal controls, all from the CBDB/NIMH Genetic Study of Schizophrenia. Deletions called by software were confirmed by quantitative PCR and comparative genome hybridization. There were deletions in 15 individuals in 11 families, including de novo exonic deletions in one case and one unaffected sibling. We observed no deletions in controls, 7 deletions in cases (1.10%), and an unexpectedly high deletion frequency in parents (n = 5, 1.02%) and siblings (n = 3, 0.97%). Three families showed inheritance from an unaffected parent, and in two families an unaffected parent did not transmit to the affected offspring. Thus we have added to the evidence that NRXN1 deletions are more frequent in patients with schizophrenia than in healthy individuals. However, the presence of de novo deletions in unaffected relatives and transmission from and to unaffected family members demonstrated that while the deletions may well have been necessary for some carriers to develop schizophrenia, they were not always sufficient. (C) 2014 Elsevier B. V. All rights reserved. C1 [Todarello, Giovanna] Univ Bari, Psychiat Neurosci Grp, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy. [Feng, Ningping; Kolachana, Bhaskar S.; Vakkalanka, Radhakrishna; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Li, Chao; Weinberger, Daniel R.; Straub, Richard E.] Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Bertolino, Alessandro] Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy. [Bertolino, Alessandro] Hoffman La Roche Ltd, Pharma Res & Early Dev, Neurosci DTA, Basel, Switzerland. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21230 USA. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21230 USA. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD 21230 USA. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Inst Med Genet, Baltimore, MD 21230 USA. RP Straub, RE (reprint author), Johns Hopkins Univ, Lieber Inst Brain Dev, Med Campus,855 North Wolfe St,Suite 300, Baltimore, MD 21205 USA. EM richard.straub@libd.org FU National Institute of Mental Health, NIH FX This study was supported by direct funding of Intramural Research Program of the National Institute of Mental Health, NIH to the Weinberger lab and the Lieber Institute for Brain Development. NR 27 TC 14 Z9 15 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2014 VL 155 IS 1-3 BP 1 EP 7 DI 10.1016/j.schres.2014.02.023 PG 7 WC Psychiatry SC Psychiatry GA AG5EN UT WOS:000335442200001 PM 24680031 ER PT J AU Liu, YM Shim, E Nguyen, P Gibbons, AT Mitchell, JB Poirier, MC AF Liu, Yongmin Shim, Eunwoo Phuonggiang Nguyen Gibbons, Alexander T. Mitchell, James B. Poirier, Miriam C. TI Tempol Protects Cardiomyocytes from Nucleoside Reverse Transcriptase Inhibitor-Induced Mitochondrial Toxicity SO TOXICOLOGICAL SCIENCES LA English DT Article DE mitochondria; antiretroviral therapy; electron microscopy; oxidative phosphorylation; superoxide; Seahorse extracellular flux analyzer ID ANTIRETROVIRAL NUCLEOSIDE; PERINATAL EXPOSURE; DYSFUNCTION; ANALOGS; HEART; DNA AB Nucleoside reverse transcriptase inhibitors (NRTIs), essential components of combinational therapies used for treatment of human immunodeficiency virus-1, damage heart mitochondria. Here, we have shown mitochondrial compromise in H9c2 rat cardiomyocytes exposed for 16 passages (P) to the NRTIs zidovudine (AZT, 50 mu M) and didanosine (ddI, 50 mu M), and we have demonstrated protection from mitochondrial compromise in cells treated with 200 mu M 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (Tempol) or 200 mu M 1-hydroxy-4-[2-triphenylphosphonio)-acetamido]-2,2,6,6-tetramethylpiperidine (Tempol-H), along with AZT/ddI, for 16P. Exposure to AZT/ddI caused a moderate growth inhibition at P3, P5, P7, and P13, which was not altered by addition of Tempol or Tempol-H. Mitochondrial oxidative phosphorylation capacity was determined as uncoupled oxygen consumption rate (OCR) by Seahorse XF24 Analyzer. At P5, P7, and P13, AZT/ddI-exposed cells showed an OCR reduction of 8.8-57.2% in AZT/ddI-exposed cells, compared with unexposed cells. Addition of Tempol or Tempol-H, along with AZT/ddI, resulted in OCR levels increased by about 300% above the values seen with AZT/ddI alone. The Seahorse data were further supported by electron microscopy (EM) studies in which P16 cells exposed to AZT/ddI/Tempol had less mitochondrial pathology than P16 cells exposed to AZT/ddI. Western blots of P5 cells showed that Tempol and Tempol-H upregulated expression of mitochondrial uncoupling protein-2 (UCP-2). However, Complex I activity that was reduced by AZT/ddI, was not restored in the presence of AZT/ddI/Tempol. Superoxide levels were increased in the presence of AZT/ddI and significantly decreased in cells exposed to AZT/3TC/Tempol at P3, P7, and P10. In conclusion, Tempol protects against NRTI-induced mitochondrial compromise, and UCP-2 plays a role through mild uncoupling. C1 [Liu, Yongmin; Shim, Eunwoo; Phuonggiang Nguyen; Gibbons, Alexander T.; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, Lab Canc Biol & Genet, CCR,NIH, Bethesda, MD 20892 USA. [Mitchell, James B.] NCI, Tumor Biol Sect, Radiat Biol Branch, CCR,NIH, Bethesda, MD 20892 USA. RP Liu, YM (reprint author), NCI, Carcinogen DNA Interact Sect, NIH, Bldg 37,Rm 4032,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. EM yongminl@mail.nih.gov OI Nguyen, Phuonggiang/0000-0003-1638-1584 FU National Institutes of Health, Center for Cancer Research, National Cancer Institute FX Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute. NR 26 TC 4 Z9 4 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2014 VL 139 IS 1 BP 133 EP 141 DI 10.1093/toxsci/kfu034 PG 9 WC Toxicology SC Toxicology GA AG0ZN UT WOS:000335144600012 PM 24591154 ER PT J AU Chen, SA Zhou, DJ Hsin, LY Kanaya, N Wong, C Yip, R Sakamuru, S Xia, MH Yuan, YC Witt, K Teng, C AF Chen, Shiuan Zhou, Dujin Hsin, Li-Yu Kanaya, Noriko Wong, Cynthie Yip, Richard Sakamuru, Srilatha Xia, Menghang Yuan, Yate-Ching Witt, Kristine Teng, Christina TI AroER Tri-Screen Is a Biologically Relevant Assay for Endocrine Disrupting Chemicals Modulating the Activity of Aromatase and/or the Estrogen Receptor SO TOXICOLOGICAL SCIENCES LA English DT Article DE Aromatase-expressing cell line; EDCs; estrogen receptor; high-throughput screening; MCF-7 cells; qHTS; Tox21 ID BREAST-CANCER CELLS; BISPHENOL-A; MCF-7 CELLS; RNA-SEQ; EXPRESSION; ESTRADIOL; INHIBITORS; ALPHA; MECHANISMS; TAMOXIFEN AB Endocrine disrupting chemicals (EDCs) interfere with the biosynthesis, metabolism, and functions of steroid hormones, including estrogens and androgens. Aromatase enzyme converts androgen to estrogen. Thus, EDCs against aromatase significantly impact estrogen- and/or androgen-dependent functions, including the development of breast cancer. The current study aimed to develop a biologically relevant cell-based high-throughput screening assay to identify EDCs that act as aromatase inhibitors (AIs), estrogen receptor (ER) agonists, and/or ER antagonists. The AroER tri-screen assay was developed by stable transfection of ER-positive, aromatase-expressing MCF-7 breast cancer cells with an estrogen responsive element (ERE) driven luciferase reporter plasmid. The AroER tri-screen can identify: estrogenic EDCs, which increase luciferase signal without 17 beta-estradiol (E2); anti-estrogenic EDCs, which inhibit the E2-induced luciferase signal; and AI-like EDCs, which suppress a testosterone-induced luciferase signal. The assay was first optimized in a 96-well plate format and then miniaturized into a 1536-well plate format. The AroER tri-screen was demonstrated to be suitable for high-throughput screening in the 1536-well plate format, with a 6.9-fold signal-to-background ratio, a 5.4% coefficient of variation, and a screening window coefficient (Z-factor) of 0.78. The assay suggested that bisphenol A (BPA) functions mainly as an ER agonist. Results from screening the 446 drugs in the National Institutes of Health Clinical Collection revealed 106 compounds that modulated ER and/or aromatase activities. Among these, two AIs (bifonazole and oxiconazole) and one ER agonist (paroxetine) were confirmed through alternative aromatase and ER activity assays. These findings indicate that AroER tri-screen is a useful high-throughput screening system for identifying ER ligands and aromatase-inhibiting chemicals. C1 [Chen, Shiuan; Zhou, Dujin; Hsin, Li-Yu; Kanaya, Noriko; Wong, Cynthie; Yip, Richard; Yuan, Yate-Ching] City Hope Natl Med Ctr, Beckman Res Inst, Dept Canc Biol, Duarte, CA 91010 USA. [Sakamuru, Srilatha; Xia, Menghang] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Witt, Kristine; Teng, Christina] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Chen, SA (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Canc Biol, Duarte, CA 91010 USA. EM schen@coh.org FU CBCRP [17UB-8701]; NTP-NCATS [ES-7020-01]; National Cancer Institute of the National Institutes of Health [P30CA33572]; National Cancer Institute of the NIH [P30CA33572] FX CBCRP (17UB-8701 to S. C.); NTP-NCATS Interagency Agreement (ES-7020-01); National Cancer Institute of the National Institutes of Health (P30CA33572). Research reported in this publication included work performed in the Bioinformatics core, High Throughput Screening core, and Integrative Genomics core supported by the National Cancer Institute of the NIH under award number P30CA33572. NR 41 TC 4 Z9 4 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2014 VL 139 IS 1 BP 198 EP 209 DI 10.1093/toxsci/kfu023 PG 12 WC Toxicology SC Toxicology GA AG0ZN UT WOS:000335144600016 PM 24496634 ER PT J AU Iantorno, M Weiss, RG AF Iantorno, Micaela Weiss, Robert G. TI Using advanced noninvasive imaging techniques to probe the links between regional coronary artery endothelial dysfunction and atherosclerosis SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID MAGNETIC-RESONANCE; CARDIOVASCULAR RISK; PHENOTYPIC HETEROGENEITY; MENTAL STRESS; NITRIC-OXIDE; BLOOD-FLOW; DISEASE; HEART; INFLAMMATION; PLAQUE AB Cardiovascular disease remains the number one cause of death in the US annually. The development in recent years of imaging strategies that can identify coronary endothelial dysfunction noninvasively provides new information about the early presence and local spatial heterogeneity of endothelial function in patients with, and those at risk for, coronary artery disease. In this article, we will briefly review the mechanisms relating endothelial function and atherosclerosis, contemporary imaging strategies now able to quantify coronary endothelial function noninvasively, and recent insights on human coronary endothelial function. (C) 2014 Elsevier Inc. All rights reserved. C1 [Iantorno, Micaela] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Iantorno, Micaela; Weiss, Robert G.] Johns Hopkins Univ Hosp, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. RP Weiss, RG (reprint author), Johns Hopkins Univ Hosp, Blalock 544,600 N Wolfe St, Baltimore, MD 21287 USA. EM rweiss@jhmi.edu FU NHLBI NIH HHS [R01 HL084186] NR 56 TC 2 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD MAY PY 2014 VL 24 IS 4 BP 149 EP 156 DI 10.1016/j.tcm.2013.10.001 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG4XJ UT WOS:000335423400003 PM 24296299 ER PT J AU Zhang, YZ Zhao, DH Yang, HP Liu, AJ Chang, XZ Hong, DJ Bonnemann, C Yuan, Y Wu, XR Xiong, H AF Zhang, Yan-Zhi Zhao, Dan-Hua Yang, Hai-Po Liu, Ai-Jie Chang, Xing-Zhi Hong, Dao-Jun Bonnemann, Carsten Yuan, Yun Wu, Xi-Ru Xiong, Hui TI Novel collagen VI mutations identified in Chinese patients with Ullrich congenital muscular dystrophy SO WORLD JOURNAL OF PEDIATRICS LA English DT Article DE collagen VI; in-frame; missense; triple helical domain; Ullrich congenital muscular dystrophy ID MUSCLE; DEFICIENCY; DOMINANT; DISEASES AB Background: We determined the clinical and molecular genetic characteristics of 8 Chinese patients with Ullrich congenital muscular dystrophy (UCMD). Methods: Clinical data of probands were collected and muscle biopsies of patients were analyzed. Exons of COL6A1, COL6A2 and COL6A3 were analyzed by direct sequencing. Mutations in COL6A1, COL6A2 and COL6A3 were identified in 8 patients. Results: Among these mutations, 5 were novel [three in the triple helical domain (THD) and 2 in the second C-terminal (C2) domain]. We also identified five known missense or in-frame deletion mutations in THD and C domains. Immunohistochemical studies on muscle biopsies from patients showed reduced level of collagen VI at the muscle basement membrane and mis-localization of the protein in interstitial and perivascular regions. Conclusions: The novel mutations we identified underscore the importance of THD and C2 domains in the assembly and function of collagen VI, thereby providing useful information for the genetic counseling of UCMD patients. C1 [Zhang, Yan-Zhi; Yang, Hai-Po; Liu, Ai-Jie; Chang, Xing-Zhi; Wu, Xi-Ru; Xiong, Hui] Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China. [Zhao, Dan-Hua; Hong, Dao-Jun; Yuan, Yun] Peking Univ, Hosp 1, Dept Neurol, Beijing 100034, Peoples R China. [Bonnemann, Carsten] NINDS, Neuromuscular & Neurdgenet Disorders Childhood Se, NIH, Bethesda, MD 20892 USA. RP Xiong, H (reprint author), Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China. EM xh_bjbj@163.com FU Beijing Natural Science Foundation of China [7112133]; National Basic Research Program of China (973 Program) [2012CB944602]; National Natural Science Foundation of China [81271400] FX This work was supported by grants from the Beijing Natural Science Foundation of China (7112133), the National Basic Research Program of China (973 Program, 2012CB944602), and the National Natural Science Foundation of China (81271400). NR 21 TC 2 Z9 5 U1 0 U2 4 PU ZHEJIANG UNIV SCH MEDICINE PI HANGZHOU PA CHILDRENS HOSPITAL, 57 ZHUGAN XIANG, HANGZHOU, 310003, PEOPLES R CHINA SN 1708-8569 EI 1867-0687 J9 WORLD J PEDIATR JI World Journal of Pediatrics PD MAY PY 2014 VL 10 IS 2 BP 126 EP 132 DI 10.1007/s12519-014-0481-1 PG 7 WC Pediatrics SC Pediatrics GA AG4CT UT WOS:000335367600005 PM 24801232 ER PT J AU Bossert, JM Stern, AL AF Bossert, Jennifer M. Stern, Anna L. TI Role of ventral subiculum in context-induced reinstatement of heroin seeking in rats SO ADDICTION BIOLOGY LA English DT Article DE muscimol + baclofen; Conditioned cues; hippocampus; relapse; reinstatement; drug environment; heroin self-administration ID MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS SHELL; COCAINE-SEEKING; INDUCED RELAPSE; DRUG-SEEKING; PROJECTIONS; ORGANIZATION; HIPPOCAMPAL; BEHAVIOR; INACTIVATION AB In rats, reexposure to heroin-paired contexts after extinction of lever responding in a different context reinstates heroin seeking. Previous reports indicate that ventral hippocampus/Ca1 region plays a critical role in cocaine-, cue- and context-induced reinstatement of cocaine seeking. Here, we examined whether ventral subiculum, the output region of ventral hippocampus, is involved in context-induced reinstatement of heroin seeking. We found that reversible inactivation of ventral subiculum, but not posterior Ca1, with the gamma-aminobutyric acid agonists muscimol + baclofen decreased context-induced reinstatement of heroin seeking. Our findings, together with previous studies on cocaine seeking, indicate a critical role of ventral subiculum in context-induced relapse across drug classes. C1 [Bossert, Jennifer M.; Stern, Anna L.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Bossert, JM (reprint author), NIDA, IRP, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM jbossert@intra.nida.nih.gov FU National Institute on Drug Abuse (NIH, DHHS) FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIH, DHHS) funds to the Neurobiology of Relapse Section (PI: Yavin Shaham). We thank Hila Eichenbaum for her help in conducting the experiments and Yavin Shaham for his help in the writing of the manuscript. NR 27 TC 11 Z9 11 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD MAY PY 2014 VL 19 IS 3 BP 338 EP 342 DI 10.1111/adb.12015 PG 5 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA AF3FS UT WOS:000334597500003 PM 23231571 ER PT J AU Ishiguro, H Hall, FS Horiuchi, Y Sakurai, T Hishimoto, A Grumet, M Uhl, GR Onaivi, ES Arinami, T AF Ishiguro, Hiroki Hall, Frank S. Horiuchi, Yasue Sakurai, Takeshi Hishimoto, Akitoyo Grumet, Martin Uhl, George R. Onaivi, Emmanuel S. Arinami, Tadao TI NrCAM-regulating neural systems and addiction-related behaviors SO ADDICTION BIOLOGY LA English DT Article DE glutamate; cell adhesion molecule; Behavior ID MARBLE-BURYING BEHAVIOR; OBSESSIVE-COMPULSIVE DISORDER; NOVELTY-SEEKING BEHAVIOR; KNOCKOUT MICE; NR-CAM; PERSONALITY PROFILE; NEURITE OUTGROWTH; PLACE PREFERENCE; COCAINE REWARD; TEMPERAMENT AB We have previously shown that a haplotype associated with decreased NrCAM expression in brain is protective against addiction vulnerability for polysubstance abuse in humans and that Nrcam knockout mice do not develop conditioned place preferences for morphine, cocaine or amphetamine. In order to gain insight into NrCAM involvement in addiction vulnerability, which may involve specific neural circuits underlying behavioral characteristics relevant to addiction, we evaluated several behavioral phenotypes in Nrcam knockout mice. Consistent with a potential general reduction in motivational function, Nrcam knockout mice demonstrated less curiosity for novel objects and for an unfamiliar conspecific, showed also less anxiety in the zero maze. Nrcam heterozygote knockout mice reduced alcohol preference and buried fewer marbles in home cage. These observations provide further support for a role of NrCAM in substance abuse including alcoholism vulnerability, possibly through its effects on behavioral traits that may affect addiction vulnerability, including novelty seeking, obsessive compulsion and responses to aversive or anxiety-provoking stimuli. Additionally, in order to prove glutamate homeostasis hypothesis of addiction, we analyzed glutamatergic molecules regulated by NRCAM expression. Glutaminase appears to be involved in NrCAM-related molecular pathway in two different tissues from human and mouse. An inhibitor of the enzyme, prolyl-leucyl-glycinamide, treatment produced, at least, some of the phenotypes of mice shown in alcohol preference and in anxiety-like behavior. Thus, NrCAM could affect addiction-related behaviors via at least partially modulation of some glutamatergic pathways and neural function in brain. C1 [Ishiguro, Hiroki] Univ Yamanashi, Grad Sch Med Sci, Dept Neuropsychiat & Clin Eth, Chuo Ku, Yamanashi 4093898, Japan. [Ishiguro, Hiroki; Horiuchi, Yasue; Arinami, Tadao] Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Med Genet, Tsukuba, Ibaraki, Japan. [Hall, Frank S.; Uhl, George R.] NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD USA. [Sakurai, Takeshi] Mt Sinai Sch Med, Dept Psychiat, Seaver Autism Ctr, New York, NY USA. [Sakurai, Takeshi] Mt Sinai Sch Med, Dept Pharmacol, Seaver Autism Ctr, New York, NY USA. [Sakurai, Takeshi] Mt Sinai Sch Med, Black Family Stem Cell Inst, New York, NY USA. [Hishimoto, Akitoyo] Kobe Univ, Dept Neuropsychiat, Grad Sch Med Sci, Kobe, Hyogo 657, Japan. [Grumet, Martin] Rutgers State Univ, WM Keck Ctr Collaborat Neurosci, Piscataway, NJ USA. [Onaivi, Emmanuel S.] William Paterson Univ, Dept Pharmacol, Wayne, NJ USA. RP Ishiguro, H (reprint author), Univ Yamanashi, Grad Sch Med Sci, Dept Neuropsychiat & Clin Eth, Chuo Ku, 1110 Shimokato, Yamanashi 4093898, Japan. EM hishiguro@yamanashi.ac.jp RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 FU KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology (Japan) [20375489, 20659177]; Ministry of Health, Labour and Welfare [18A-1]; Japan Brain Foundation; National Institute on Drug Abuse, NIH/DHHS (USA); Seaver Foundation FX The present study was supported by KAKENHI (20375489 and 20659177) from the Ministry of Education, Culture, Sports, Science and Technology (Japan), Research Grant (18A-1) for Nervous and Mental Disorders from Ministry of Health, Labour and Welfare, and Grant support from the Japan Brain Foundation. The present study was also supported in part by intramural funding from the National Institute on Drug Abuse, NIH/DHHS (USA). Dr. Sakurai is a Seaver fellow and partly supported by the Seaver Foundation. NR 57 TC 6 Z9 6 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD MAY PY 2014 VL 19 IS 3 BP 343 EP 353 DI 10.1111/j.1369-1600.2012.00469.x PG 11 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA AF3FS UT WOS:000334597500004 PM 22780223 ER PT J AU Litten, RZ Ryan, M Falk, D Fertig, J AF Litten, Raye Z. Ryan, Megan Falk, Daniel Fertig, Joanne TI AlcoholMedications Development: Advantages and Caveats of Government/Academia Collaborating with the Pharmaceutical Industry SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Medications Development; Pharmacotherapy; Collaboration; Conflict of Interest; Research Bias ID ALCOHOL DEPENDENCE; CONTROLLED-TRIAL; RISK AB The process of developing pharmacological treatments for alcohol use disorder is notoriously complex and challenging. The path to market is long, costly, and inefficient. One way of expediting and reducing the drug development process is through collaborationsbuilding partnerships among government, academia, pharmaceutical and biotechnology companies, healthcare organizations and advocacy groups, and the patients (end consumers) themselves. By forging collaborations, particularly with pharmaceutical companies, the alcohol treatment field stands to reap benefits in generating new medications for use in mainstream treatment settings. At the same time, there are certain caveats that should be considered, particularly by academic researchers, before entering into such partnerships. This commentary examines the advantages and caveats of government and academia collaborations with pharmaceutical companies. C1 [Litten, Raye Z.; Ryan, Megan; Falk, Daniel; Fertig, Joanne] NIAAA, Div Treatment & Recovery Res, Clin Invest Grp NCIG, Bethesda, MD 20892 USA. RP Litten, RZ (reprint author), NIAAA, Div Treatment & Recovery Res, 5635 Fishers Lane, Bethesda, MD 20892 USA. EM rlitten@mail.nih.gov NR 22 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2014 VL 38 IS 5 BP 1196 EP 1199 DI 10.1111/acer.12357 PG 4 WC Substance Abuse SC Substance Abuse GA AF4BU UT WOS:000334657200002 PM 24689461 ER PT J AU Mitchell, MC Teigen, EL Ramchandani, VA AF Mitchell, Mack C., Jr. Teigen, Erin L. Ramchandani, Vijay A. TI Absorption and Peak Blood Alcohol Concentration After Drinking Beer, Wine, or Spirits SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Absorption; Pharmacokinetics; Beverage Type Differences; Blood Alcohol Concentrations; Gastric Emptying Rate ID ETHANOL; FOOD; PHARMACOKINETICS; METABOLISM AB BackgroundBoth the amount and the rate of absorption of ethanol (EtOH) from alcoholic beverages are key determinants of the peak blood alcohol concentration (BAC) and exposure of organs other than gut and liver. Previous studies suggest EtOH is absorbed more rapidly in the fasting than in the postprandial state. The concentration of EtOH and the type of beverage may determine gastric emptying/absorption of EtOH. MethodsThe pharmacokinetics of EtOH were measured in 15 healthy men after consumption of 0.5g of EtOH/kg body weight. During this 3-session crossover study, subjects consumed in separate sessions, beer (5.1% v/v), white wine (12.5% v/v), or vodka/tonic (20% v/v) over 20minutes following an overnight fast. BAC was measured by gas chromatography at multiple points after consumption. ResultsPeak BAC (C-max) was significantly higher (p<0.001) after vodka/tonic (77.417.0mg/dl) than after wine (61.7 +/- 10.8mg/dl) or beer (50.3 +/- 9.8mg/dl) and was significantly higher (p<0.001) after wine than beer. The time to C-max occurred significantly earlier (p<0.01) after vodka/tonic (36 +/- 10minutes) compared to wine (54 +/- 14 minutes) or beer (62 +/- 23 minutes). Six subjects exceeded a C-max of 80mg/dl after vodka/tonic, but none exceeded this limit after beer or wine. The area under the concentration-time curve (AUC) was significantly greater after drinking vodka/tonic (p<0.001) than after wine or beer. Comparison of AUCs indicated the relative bioavailability of EtOH was lower after drinking beer. ConclusionsFindings indicate that BAC is higher after drinking vodka/tonic than beer or wine after fasting. A binge pattern is significantly more likely to result in BAC above 80mg/dl after drinking vodka/tonic than beer or wine. Men drinking on an empty stomach should know BAC will vary depending on beverage type and the rate and amount of EtOH. C1 [Mitchell, Mack C., Jr.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Teigen, Erin L.] ABMRF Fdn Alcohol Res, Baltimore, MD USA. [Ramchandani, Vijay A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, Bethesda, MD USA. RP Mitchell, MC (reprint author), Univ Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Mack.Mitchell@utsouthwestern.edu FU ABMRF/The Foundation for Alcohol Research, Baltimore, Maryland FX This paper was supported by ABMRF/The Foundation for Alcohol Research, Baltimore, Maryland. NR 15 TC 8 Z9 9 U1 5 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2014 VL 38 IS 5 BP 1200 EP 1204 DI 10.1111/acer.12355 PG 5 WC Substance Abuse SC Substance Abuse GA AF4BU UT WOS:000334657200003 PM 24655007 ER PT J AU Yokoyama, A Yokoyama, T Brooks, PJ Mizukami, T Matsui, T Kimura, M Matsushita, S Higuchi, S Maruyama, K AF Yokoyama, Akira Yokoyama, Tetsuji Brooks, Philip J. Mizukami, Takeshi Matsui, Toshifumi Kimura, Mitsuru Matsushita, Sachio Higuchi, Susumu Maruyama, Katsuya TI Macrocytosis, Macrocytic Anemia, and Genetic Polymorphisms of Alcohol Dehydrogenase-1B and Aldehyde Dehydrogenase-2in Japanese AlcoholicMen SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Acetaldehyde; Alcohol Dehydrogenase; Aldehyde Dehydrogenase; Anemia; Mean Corpuscular Volume ID MEAN CORPUSCULAR VOLUME; SQUAMOUS-CELL CARCINOMA; ACETALDEHYDE CONCENTRATIONS; ALDH2 GENOTYPES; BONE-MARROW; HUMAN-LIVER; MEN; ETHANOL; RISK; BLOOD AB BackgroundOxidation of ethanol by alcohol dehydrogenase (ADH) generates acetaldehyde (AcH), which is converted to acetate by aldehyde dehydrogenase-2 (ALDH2). Roughly 40% of East Asians are ALDH2-deficient due to an inactive enzyme encoded by the ALDH2*2 allele. ALDH2-deficient individuals have a dramatically elevated risk of esophageal cancer from alcohol consumption. MethodsWe investigated the relationship between ALDH2*2, ADH1B*2 (encoding a highly active ADH) and erythrocyte abnormalities, in a population of Japanese alcoholic men (N=1,238). ResultsMacrocytosis (mean corpuscular volume [MCV] 100fl) and macrocytic anemia (MCV 100fl and hemoglobin <13.5g/dl) were found in 62.4 and 24.1% of the subjects, respectively. Age-adjusted daily alcohol consumption did not differ according to ADH1B and ALDH2 genotypes. However, macrocytosis and macrocytic anemia were strongly associated with the ALDH2*1/*2 genotype multivariate odds ratios (ORs; 95% confidence interval [CI]=2.85 [1.95 to 4.18] and 3.68 [2.64 to 5.15], respectively, versus ALDH2*1/*1). In comparison with the ADH1B*1/*1 and ALDH2*1/*1 genotype combination, the ADH1B*1/*1 and ALDH2*1/*2 genotype combination and the ADH1B*2 allele and ALDH2*1/*2 genotype combination increased stepwise the ORs (95% CI) for macrocytosis (1.65 [0.92 to 2.94] and 4.07 [2.33 to 7.11], respectively, p for difference in OR=0.015) and macrocytic anemia (2.80 [1.52 to 5.15] and 5.32 [3.29 to 8.62], respectively, p for difference in OR=0.045). Genotype effects were more prominent on the risks of the more advanced erythrocyte abnormalities. Older age, cigarette smoking, and low body mass index independently increased the risks of the erythrocyte abnormalities. Consumption of beer, which contains folate, decreased the risks, whereas consumption of alcoholic beverages lacking folate did not. ConclusionsThese results suggest that the erythrocyte abnormalities in alcoholics are attributable to high AcH exposure as well as to nutritional deficiencies and may be prevented by folate. C1 [Yokoyama, Akira; Mizukami, Takeshi; Matsui, Toshifumi; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya] Natl Hosp Org Kurihama Med & Addict Ctr, Yokosuka, Kanagawa 2390841, Japan. [Yokoyama, Tetsuji] Natl Inst Publ Hlth, Dept Hlth Promot, Saitama, Japan. [Brooks, Philip J.] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD USA. [Brooks, Philip J.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. [Matsui, Toshifumi] Kyorin Univ Hosp, Dept Geriatr Med, Tokyo, Japan. RP Yokoyama, A (reprint author), Natl Hosp Org Kurihama Med & Addict Ctr, Clin Res Unit, 5-3-1 Nobi, Yokosuka, Kanagawa 2390841, Japan. EM a_yokoyama@kurihama1.hosp.go.jp NR 44 TC 8 Z9 8 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2014 VL 38 IS 5 BP 1237 EP 1246 DI 10.1111/acer.12372 PG 10 WC Substance Abuse SC Substance Abuse GA AF4BU UT WOS:000334657200007 PM 24588059 ER PT J AU Vatsalya, V Momenan, R Hommer, DW Ramchandani, VA AF Vatsalya, Vatsalya Momenan, Reza Hommer, Daniel W. Ramchandani, Vijay A. TI Cardiac Reactivity During the Ascending Phase of Acute Intravenous Alcohol Exposure and Association with Subjective Perceptions of Intoxication in Social Drinkers SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Clamp; Intravenous Infusion; Heart Rate; Heart Rate Variability; Subjective Perceptions ID HEART-RATE-VARIABILITY; NERVOUS-SYSTEM; INGESTION; DISEASE; ETHANOL; RELIABILITY; SENSITIVITY; CHALLENGES; VALIDITY; ADULTS AB BackgroundThe aim of this study was to characterize cardiac reactivity measures, heart rate (HR), and heart rate variability (HRV), following acute intravenous (IV) alcohol administration and their association with subjective responses in social drinkers. MethodsTwenty-four subjects (11 females) received IV alcohol infusions to attain and clamp the breath alcohol concentration (BrAC) at 50mg% or placebo in separate sessions. Serial 5-minute cardiac recordings at baseline and during the infusion were analyzed to obtain frequency and time domain cardiac measures. Self-reported subjective perceptions were also obtained at the same time points. ResultsHR showed significant decreases from baseline, while the HRV measure pNN50 showed steady increases during the ascending phase of alcohol infusion. HR was inversely correlated with pNN50 across time and treatment. There was a significant association of HR with subjective feelings of high, intoxication, feeling drug effects, and liking drug effects across time during the ascending phase. ConclusionsAcute IV alcohol resulted in decreases in HR and increases in HRV consistent with autonomic parasympathetic activation. The association of these changes with subjective responses suggests that cardiac reactivity may serve as a physiological marker of subjective alcohol effects. This study broadens the understanding of acute cardiovascular effects of alcohol and clinically significant cardiac conditions such as arrhythmia and cardiomyopathy associated with chronic alcohol drinking. C1 [Vatsalya, Vatsalya; Ramchandani, Vijay A.] NIAAA, Sect Human Psychopharmacol, LCTS, Bethesda, MD 20892 USA. [Momenan, Reza; Hommer, Daniel W.] NIAAA, Sect Brain Electrophysiol & Imaging, LCTS, Bethesda, MD 20892 USA. RP Ramchandani, VA (reprint author), NIAAA, Sect Human Psychopharmacol, LCTS, 10 Ctr Dr,Room 2-2352, Bethesda, MD 20892 USA. EM vijayr@mail.nih.gov FU NIAAA Division of Intramural Clinical and Biological Research [1Z01 AA000466] FX This study was supported by the NIAAA Division of Intramural Clinical and Biological Research (1Z01 AA000466). The authors gratefully acknowledge the NIH Clinical Center Alcohol Clinic and Day Hospital staff for clinical support, research staff (Elizabeth Edenberg, Mike Hoefer, Nina Saxena, Shilpa Kumar, Seth Eappen, Julnar Issa) for data collection support, and the study volunteers for their participation in the study. NR 60 TC 1 Z9 1 U1 2 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 MAY PY 2014 VL 38 IS 5 BP 1247 EP 1254 DI 10.1111/acer.12377 PG 8 WC Substance Abuse SC Substance Abuse GA AF4BU UT WOS:000334657200008 PM 24655119 ER PT J AU Yong, WD Spence, JP Eskay, R Fitz, SD Damadzic, R Lai, DB Foroud, T Carr, LG Shekhar, A Chester, JA Heilig, M Liang, TB AF Yong, Weidong Spence, John Paul Eskay, Robert Fitz, Stephanie D. Damadzic, Ruslan Lai, Dongbing Foroud, Tatiana Carr, Lucinda G. Shekhar, Anantha Chester, Julia A. Heilig, Markus Liang, Tiebing TI dAlcohol-Preferring Rats Show Decreased CorticotropinReleasing Hormone-2 Receptor Expression and Differences in HPA Activation Compared to Alcohol-Nonpreferring SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcoholism; Corticotropin-Releasing Hormone Type 2 Receptor; Selective Breeding; Stress; Amygdala ID ANXIETY-LIKE BEHAVIOR; QUANTITATIVE TRAIT LOCUS; SOCIAL-INTERACTION TEST; MESSENGER-RNAS; CRF RECEPTORS; GENETIC PREDISPOSITION; DRINKING BEHAVIOR; RESTRAINT STRESS; ACOUSTIC STARTLE; CENTRAL NUCLEUS AB BackgroundCorticotropin-releasing hormone (CRH) and urocortins (UCNs) bind to corticotropin-releasing hormone type 2 receptor (CRF2 receptor), a Gs protein-coupled receptor that plays an important role in modulation of anxiety and stress responses. The Crhr2 gene maps to a quantitative trait locus (QTL) for alcohol preference on chromosome 4 previously identified in inbred alcohol-preferring (iP) and-nonpreferring (iNP) F2 rats. MethodsReal-time polymerase chain reaction was utilized to screen for differences in Crhr2 mRNA expression in the central nervous system (CNS) of male iP and iNP rats. DNA sequence analysis was then performed to screen for polymorphism in Crhr2 in order to identify genetic variation, and luciferase reporter assays were then applied to test their functional significance. Next, binding assays were used to determine whether this polymorphism affected CRF2 receptor binding affinity as well as CRF2 receptor density in the CNS. Finally, social interaction and corticosterone levels were measured in the P and NP rats before and after 30-minute restraint stress. ResultsCrhr2 mRNA expression studies found lower levels of Crhr2 mRNA in iP rats compared to iNP rats. In addition, DNA sequencing identified polymorphisms in the promoter region, coding region, and 3-untranslated region between the iP and iNP rats. A 7bp insertion in the Crhr2 promoter of iP rats altered expression in vitro as measured by reporter assays, and we found that CRF2 receptor density was lower in the amygdala of iP as compared to iNP rats. Male P rats displayed decreased social interaction and significantly higher corticosterone levels directly following 30-minute restraint when compared to male NP rats. ConclusionsThis study identified Crhr2 as a candidate gene of interest underlying the chromosome 4 QTL for alcohol consumption that was previously identified in the P and NP model. Crhr2 promoter polymorphism is associated with reduced mRNA expression in certain brain regions, particularly the amygdala, and lowered the density of CRF2 receptor in the amygdala of iP compared to iNP rats. Together, these differences between the animals may contribute to the drinking disparity as well as the anxiety differences of the P and NP rats. C1 [Yong, Weidong] Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing 100730, Peoples R China. [Yong, Weidong] Peking Union Med Coll, Beijing 100021, Peoples R China. [Yong, Weidong] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. [Spence, John Paul; Fitz, Stephanie D.; Shekhar, Anantha] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Eskay, Robert; Damadzic, Ruslan; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Lai, Dongbing; Foroud, Tatiana] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Carr, Lucinda G.; Liang, Tiebing] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Chester, Julia A.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. RP Liang, TB (reprint author), Indiana Univ Sch Med, Dept Med, Clin Bldg,Room 500A,541 Clin Dr, Indianapolis, IN 46202 USA. EM tliang@iu.edu FU State High-Tech Program [863-2012AA022403]; National Institute on Alcohol Abuse and Alcoholism (NIAAA) grants [R01AA10707, P60 AA007611, AA07611, R01 MH065702]; Indiana Clinical & Translational Institute through a CTSA award from NIH, NCATS [TR000162] FX This research was supported by the State High-Tech Program (863-2012AA022403), the National Institute on Alcohol Abuse and Alcoholism (NIAAA) grants R01AA10707, P60 AA007611, AA07611, and R01 MH065702. JPS was supported by a predoctoral award from the Indiana Clinical & Translational Institute through a CTSA award from NIH, NCATS (TR000162). The authors declare that there are no conflict of interests of any kind regarding this work. NR 55 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2014 VL 38 IS 5 BP 1275 EP 1283 DI 10.1111/acer.12379 PG 9 WC Substance Abuse SC Substance Abuse GA AF4BU UT WOS:000334657200011 PM 24611993 ER PT J AU Umhau, JC Schwandt, M Solomon, MG Yuan, PX Nugent, A Zarate, CA Drevets, WC Hall, SD George, DT Heilig, M AF Umhau, John C. Schwandt, Melanie Solomon, Matthew G. Yuan, Peixiong Nugent, Allison Zarate, Carlos A. Drevets, Wayne C. Hall, Samuel D. George, David T. Heilig, Markus TI Cerebrospinal FluidMonocyte Chemoattractant Protein-1 in Alcoholics: Support for a NeuroinflammatoryModel of Chronic Alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Monocyte Chemoattractant Protein-1; Alcoholism; Inflammation; Cerebrospinal Fluid; Cytokine ID MICROGLIAL ACTIVATION; BRAIN; MCP-1; INFLAMMATION; DISEASE; ETHANOL; NEURODEGENERATION; IMPAIRMENT; RATS; RECRUITMENT AB BackgroundLiver inflammation in alcoholism has been hypothesized to influence the development of a neuroinflammatory process in the brain characterized by neurodegeneration and altered cognitive function. Monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) elevations have been noted in the alcoholic brain at autopsy and may have a role in this process. MethodsWe studied cerebrospinal fluid (CSF) levels of MCP-1 as well as interleukin-1 and tumor necrosis factor- in 13 healthy volunteers and 28 alcoholics during weeks 1 and 4 following detoxification. Serum liver enzymes were obtained as markers of alcohol-related liver inflammation. ResultsCompared to healthy volunteers, MCP-1 levels were significantly higher in alcoholics both on day 4 and day 25 (p<0.0001). Using multiple regression analysis, we found that MCP-1 concentrations were positively associated with the liver enzymes gamma glutamyltransferase (GGT; p=0.03) and aspartate aminotransferase/glutamic oxaloacetic transaminase (AST/GOT; p=0.004). ConclusionsThese preliminary findings are consistent with the hypothesis that neuroinflammation as indexed by CSF MCP-1 is associated with alcohol-induced liver inflammation, as defined by peripheral concentrations of GGT and AST/GOT. C1 [Umhau, John C.; Schwandt, Melanie; Solomon, Matthew G.; Hall, Samuel D.; George, David T.; Heilig, Markus] NIAAA, NIH, Bethesda, MD USA. [Yuan, Peixiong; Nugent, Allison; Zarate, Carlos A.] NIMH, NIH, Bethesda, MD 20892 USA. [Drevets, Wayne C.] Johnson & Johnson Consumer Prod Inc, Janssen Pharmaceut, Titusville, NJ USA. RP Umhau, JC (reprint author), Whiteriver Indian Hosp, Whiteriver Serv Unit, US Publ Hlth Serv, 200 W Hosp Dr, Whiteriver, AZ 85941 USA. EM umhau@jhu.edu RI Schwandt, Melanie/L-9866-2016; OI Heilig, Markus/0000-0003-2706-2482; Nugent, Allison/0000-0003-2569-2480 FU Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism; National Institute of Mental Health, both of the National Institutes of Health FX The Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, and the National Institute of Mental Health, both of the National Institutes of Health, supported this study. Monte Phillips provided invaluable technical assistance. NR 47 TC 7 Z9 7 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2014 VL 38 IS 5 BP 1301 EP 1306 DI 10.1111/acer.12367 PG 6 WC Substance Abuse SC Substance Abuse GA AF4BU UT WOS:000334657200014 PM 24689518 ER PT J AU Smith, KL John, CS Sypek, EI Ongur, D Cohen, BM Barry, SM Bechtholt, AJ AF Smith, Karen L. John, Catherine S. Sypek, Elizabeth I. Oenguer, Dost Cohen, Bruce M. Barry, Sarah M. Bechtholt, Anita J. TI Exploring the Role of Central Astrocytic Glutamate Uptake in Ethanol Reward inMice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Ethanol; Astrocyte; Glutamate; Drinking in the Dark; Place Preference ID CONDITIONED PLACE PREFERENCE; MALE C57BL/6J MICE; KV2.1 POTASSIUM CHANNELS; ALCOHOL-PREFERRING RATS; NMDA RECEPTOR; METABOTROPIC GLUTAMATE; STRAIN DIFFERENCES; PREFRONTAL CORTEX; PRELIMBIC CORTEX; PACKING DENSITY AB BackgroundAlcoholism is associated with specific brain abnormalities revealed through postmortem studies, including a reduction in glial cell number and dysregulated glutamatergic neurotransmission. Whether these abnormalities contribute to the etiology of alcoholism, are consequences of alcohol use, or both is still unknown. MethodsWe investigated the role of astrocytic glutamate uptake in ethanol (EtOH) binge drinking in mice, using the drinking in the dark (DID) paradigm by blocking the astrocytic glutamate transporter (GLT-1) with intracerebroventricular (ICV) administration of dihydrokainic acid (DHK). To determine whether astrocytic glutamate uptake regulates the conditioned rewarding effects of EtOH, we examined the effects of ICV DHK on the acquisition and expression of EtOH-induced conditioned place preference. ResultsBlocking central astrocytic glutamate uptake selectively attenuated EtOH binge drinking behavior in mice. DHK did not alter the acquisition or expression of preference for EtOH-associated cues, indicating that reduced astrocytic glutamate trafficking may decrease binge-like drinking without altering the conditioned rewarding effects of EtOH. ConclusionsSeveral alternative conclusions are plausible, however, interpreting these data in the context of the human literature, these findings suggest that the reduction of glia in the alcoholic brain may not be a predisposing factor to developing alcoholism and could be a consequence of EtOH toxicity that decreases excessive EtOH intake. C1 [Smith, Karen L.; John, Catherine S.; Sypek, Elizabeth I.; Oenguer, Dost; Cohen, Bruce M.; Barry, Sarah M.; Bechtholt, Anita J.] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA USA. [Smith, Karen L.] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Lab Addict Disorders, Boston, MA 02118 USA. [Bechtholt, Anita J.] NIAAA, NIH, Bethesda, MD 20892 USA. RP Bechtholt, AJ (reprint author), NIAAA, NIH, 5635 Fishers Lane,Room 2056, Bethesda, MD 20892 USA. EM anita.bechtholt@gmail.com OI sypek, elizabeth/0000-0001-6904-2426 FU NIAAA [R03AA019577]; Shervert Frazier Research Institute; Englehard Foundation FX Funding for this work was provided by NIAAA (R03AA019577), AJB; the Shervert Frazier Research Institute, BMC & DO the Englehard Foundation, BMC. The authors would like to thank Dr. Uwe Rudolph for logistical support. Dr. Bechtholt contributed to this article as an employee of McLean Hospital-Harvard Medical School. The views expressed are her own and do not necessarily represent the views of the National Institutes of Health or the United States Government. NR 53 TC 5 Z9 5 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2014 VL 38 IS 5 BP 1307 EP 1314 DI 10.1111/acer.12361 PG 8 WC Substance Abuse SC Substance Abuse GA AF4BU UT WOS:000334657200015 PM 24655029 ER PT J AU Murphy, RA Reinders, I Register, TC Ayonayon, HN Newman, AB Sattedield, S Goodpaster, BH Simonsick, EM Kritchevsky, SB Harris, TB AF Murphy, Rachel A. Reinders, Ilse Register, Thomas C. Ayonayon, Hilsa N. Newman, Anne B. Sattedield, Suzanne Goodpaster, Bret H. Simonsick, Eleanor M. Kritchevsky, Stephen B. Harris, Tamara B. TI Associations of BMI and adipose tissue area and density with incident mobility limitation and poor performance in older adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID MUSCLE FAT INFILTRATION; BODY-MASS INDEX; PHYSICAL FUNCTION; SKELETAL-MUSCLE; RISK-FACTORS; CARDIOVASCULAR HEALTH; LIFE EXPECTANCY; DISABILITY; OBESITY; STRENGTH AB Background: Obesity is a risk factor for disability, but risk of. specific adipose depots is not completely understood. Objective: We investigated associations between mobility limitation, performance, and the following adipose measures: body mass index (BMI) and areas and densities of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) in older adults. Design: This was a prospective population-based study of men (n = 1459) and women (n = 1552) initially aged 70-79 y and free from mobility limitation. BMI was determined from measured height and weight. Adipose tissue area and density in Hounsfield units were measured in the thigh and abdomen by using computed tomography. Mobility limitation was defined as 2 consecutive reports of difficulty walking one-quarter mile or climbing 10 steps during semiannual assessments over 13 y. Poor performance was defined as a gait speed <1 m/s after 9 y of follow-up (n = 1542). Results: In models adjusted for disability risk factors, BMI, and areas of VAT, abdominal SAT, and IMAT were positively associated with mobility limitation in men and women. In women, thigh SAT area was positively associated with mobility limitation risk, whereas VAT density was inversely associated. Associations were similar for poor performance. BMI and thigh IMAT area (independent of BMI were particularly strong indicators of incident mobility limitation and poor performance. For example, in women, the HR (95% Cl) and OR (95% Cl) associated with an SD increment in BMI for mobility limitation and poor performance were 1.31 (1.21, 1.42) and 1.41 (1.13, 1.76), respectively. In men, the HR (95% Cl) and OR (95% Cl) associated with an SD increment in thigh IMAT for mobility limitation and poor performance were 1.37 (1.27, 1.47) and 1.54 (1.18, 2.02), respectively. Conclusions: Even into old age, higher BMI is associated with mobility limitation and poor performance. The amount of adipose tissue in abdominal and thigh depots may also convey risk beyond BMI. C1 [Murphy, Rachel A.; Reinders, Ilse; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20814 USA. [Register, Thomas C.] Wake Forest Sch Med, Stiehl Ctr Aging, Sect Comparat Med Pathol, Winston Salem, NC USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Stiehl Ctr Aging, Sect Gerontol & Geriatr, Winston Salem, NC USA. [Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Sattedield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Medicine, Memphis, TN 38163 USA. [Goodpaster, Bret H.] Univ Pittsburgh, Dept Med, Ctr Aging & Populat Hlth, Pittsburgh, PA USA. [Simonsick, Eleanor M.] NIA, Translat Gerontol Branch, Intramural Res Program, Bethesda, MD 20814 USA. RP Murphy, RA (reprint author), NIA, Lab Populat Sci, 7201 Wisconsin Ave,3C-309, Bethesda, MD 20814 USA. EM rachel.murphy@nih.gov RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research [R01-NR-012459]; Intramural Research Program of the NIH, NIA; Banning Postdoctoral Fellowship FX Supported by the National Institute on Aging (NIA) (contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106 and grant R01-AG028050) and the National Institute of Nursing Research (grant R01-NR-012459); in part by the Intramural Research Program of the NIH, NIA; and by a Banning Postdoctoral Fellowship (to RAM). NR 37 TC 11 Z9 11 U1 3 U2 13 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 2014 VL 99 IS 5 BP 1059 EP 1065 DI 10.3945/ajcn.113.080796 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AF7LD UT WOS:000334895700014 PM 24522448 ER PT J AU Tasevska, N Park, Y Jiao, L Hollenbeck, A Subar, AF Potischman, N AF Tasevska, Natasha Park, Yikyung Jiao, Li Hollenbeck, Albert Subar, Amy F. Potischman, Nancy TI Sugars and risk of mortality in the NIH-AARP Diet and Health Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID CORONARY-HEART-DISEASE; SWEETENED BEVERAGE CONSUMPTION; FOOD FREQUENCY QUESTIONNAIRES; TYPE-2 DIABETES-MELLITUS; PANCREATIC-CANCER RISK; MILK EXTRINSIC SUGARS; FRUCTOSE CORN SYRUP; MIDDLE-AGED WOMEN; GROWTH-FACTOR-I; GLYCEMIC LOAD AB Background: Although previous studies have linked intake of sugars with incidence of cancer and other chronic diseases, its association with mortality remains unknown. Objective: We investigated the association of total sugars, added sugars, total fructose, added fructose, sucrose, and added sucrose with the risk of all-cause, cardiovascular disease, cancer, and other-cause mortality in the NIH-AARP Diet and Health Study. Design: The participants (n = 353,751), aged 50-71 y, were followed for up to 13 y. Intake of individual sugars over the previous 12 mo was assessed at baseline by using a 124-item NIH Diet History Questionnaire. Results: In fully adjusted models (fifth quartile compared with first quartile), all-cause mortality was positively associated with the intake of total sugars [HR (95% Cl): 1.13 (1.06, 1.20); P-trend < 0.0001], total fructose [1.10 (1.04, 1.17); P-trend < 0.0001], and added fructose [1.07 (1.01, 1.13); P-trend = 0.065) in women and total fructose [1.06 (1.01, 1.10); P-trend = 0.002] in men. In men, a weak inverse association was found between other-cause mortality and dietary added sugars (P-trend = 0.04), sucrose (P-trend = 0.03), and added sucrose (P-trend = 0.006). Investigation of consumption of sugars by source showed that the positive association with mortality risk was confined only to sugars from beverages, whereas the inverse association was confined to sugars from solid foods. Conclusions: In this large prospective study, total fructose intake was weakly positively associated with all-cause mortality in both women and men, whereas added sugar, sucrose, and added sucrose intakes were inversely associated with other-cause mortality in men. In our analyses, intake of added sugars was not associated with an increased risk of mortality. The NIFI-AARP Diet and Health Study was registered at clinicaltrials.gov as NCT00340015. C1 [Tasevska, Natasha; Subar, Amy F.; Potischman, Nancy] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Tasevska, Natasha] Arizona State Univ, Nutr Program, Sch Nutr & Hlth Promot, Phoenix, AZ USA. [Park, Yikyung; Jiao, Li] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Jiao, Li] Baylor Coll Med, Sect Gastroenterol & Hepatol, Dept Med, Houston, TX 77030 USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Tasevska, N (reprint author), Arizona State Univ, Sch Nutr & Hlth Promot, Nutr Program, 500 North 3rd St, Phoenix, AZ 85004 USA. EM natasha.tasevska@asti.edu OI Park, Yikyung/0000-0002-6281-489X FU Intramural Research Program of the National Cancer Institute, NIH, Department of Health and Human Services FX Supported by the Intramural Research Program of the National Cancer Institute, NIH, Department of Health and Human Services. NR 79 TC 13 Z9 13 U1 2 U2 23 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 2014 VL 99 IS 5 BP 1077 EP 1088 DI 10.3945/ajcn.113.069369 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AF7LD UT WOS:000334895700017 PM 24552754 ER PT J AU Kris-Etherton, PM Pratt, CA Saltzman, E Van Horn, L AF Kris-Etherton, Penny M. Pratt, Charlotte A. Saltzman, Edward Van Horn, Linda TI Introduction to Nutrition Education in Training Medical and Other Health Care Professionals SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material C1 [Kris-Etherton, Penny M.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. [Pratt, Charlotte A.] NIH, NHLBI, Bethesda, MD 20892 USA. [Saltzman, Edward] Tufts Univ, Sch Med, Dept Nutr Sci, Boston, MA 02111 USA. [Van Horn, Linda] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. RP Kris-Etherton, PM (reprint author), Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. EM pmk3@psu.edu NR 6 TC 0 Z9 0 U1 2 U2 8 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 2014 VL 99 IS 5 BP 1151S EP 1152S DI 10.3945/ajcn.113.073494 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AF7LD UT WOS:000334895700029 PM 24670942 ER PT J AU Kris-Etherton, PM Akabas, SR Bales, CW Bistrian, B Braun, L Edwards, MS Laur, C Lenders, CM Levy, MD Palmer, CA Pratt, CA Ray, S Rock, CL Saltzman, E Seidner, DL Van Horn, L AF Kris-Etherton, Penny M. Akabas, Sharon R. Bales, Connie W. Bistrian, Bruce Braun, Lynne Edwards, Marilyn S. Laur, Celia Lenders, Carine M. Levy, Matthew D. Palmer, Carole A. Pratt, Charlotte A. Ray, Sumantra Rock, Cheryl L. Saltzman, Edward Seidner, Douglas L. Van Horn, Linda TI The need to advance nutrition education in the training of health care professionals and recommended research to evaluate implementation and effectiveness SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID LIFE-STYLE INTERVENTION; MEDICAL-EDUCATION; NATIONAL CONSENSUS; CLINICAL NUTRITION; RISK-FACTORS; WEIGHT-LOSS; DIET; CURRICULUM; OVERWEIGHT; MANAGEMENT AB Nutrition is a recognized determinant in 3 (ie, diseases of the heart, malignant neoplasms, cerebrovascular diseases) of the top 4 leading causes of death in the United States. However, many health care providers are not adequately trained to address lifestyle recommendations that include nutrition and physical activity behaviors in a manner that could mitigate disease development or progression. This contributes to a compelling need to markedly improve nutrition education for,health care professionals and to establish curricular standards and requisite nutrition and physical activity competencies in the education, training, and continuing education for health care professionals. This article reports the present status of nutrition and physical activity education for health care professionals, evaluates the current pedagogic models, and underscores the urgent need to realign and synergize these models to reflect evidence-based and outcomes-focused education. C1 [Kris-Etherton, Penny M.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. [Akabas, Sharon R.] Columbia Univ, Inst Human Nutr, New York, NY 10032 USA. [Bales, Connie W.] Duke Univ, Med Ctr, Durham, NC USA. [Bistrian, Bruce] Harvard Univ, Sch Med, Boston, MA USA. [Braun, Lynne] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Edwards, Marilyn S.] Univ Texas Houston, Sch Med, Houston, TX USA. [Laur, Celia; Ray, Sumantra] UK Med Res Council, Human Nutr Res Unit, Cambridge, England. [Lenders, Carine M.] Boston Med Ctr, Div Pediat Nutr, Boston, MA USA. [Levy, Matthew D.] Medstar Georgetown Univ Hosp, Dept Pediat, Div Primary Care & Gen Pediat, Washington, DC USA. [Palmer, Carole A.] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. [Pratt, Charlotte A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Rock, Cheryl L.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Saltzman, Edward] Tufts Univ, Sch Med, Dept Nutr Sci, Boston, MA 02111 USA. [Seidner, Douglas L.] Vanderbilt Univ, Vanderbilt Ctr Human Nutr, Med Ctr, Nashville, TN USA. [Van Horn, Linda] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. RP Kris-Etherton, PM (reprint author), Penn State Univ, Dept Nutr Sci, 319 Chandlee Lab, University Pk, PA 16802 USA. EM pmk3@psu.edu FU Medical Research Council [MC_U105960384]; NIDDK NIH HHS [K23 DK082732, P30 DK046200, P30 DK058404] NR 98 TC 20 Z9 20 U1 1 U2 25 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 2014 VL 99 IS 5 BP 1153S EP 1166S DI 10.3945/ajcn.113.073502 PG 14 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AF7LD UT WOS:000334895700030 PM 24717343 ER PT J AU Beauchamp, MK Leveille, SG Patel, KV Kiely, DK Phillips, CL Bandinelli, S Ferrucci, L Guralnik, J Bean, JF AF Beauchamp, Marla K. Leveille, Suzanne G. Patel, Kushang V. Kiely, Dan K. Phillips, Caroline L. Bandinelli, Stefania Ferrucci, Luigi Guralnik, Jack Bean, Jonathan F. TI What Physical Attributes Underlie Self- Reported vs. Observed Ability to Walk 400 m in Later Life? SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Physical Performance; Rehabilitation; Successful Aging; Mobility Limitation ID INCIDENT MOBILITY DISABILITY; LOWER-EXTREMITY FUNCTION; OLDER-ADULTS; 400-METER WALK; SUBSEQUENT DISABILITY; MAINTAINING MOBILITY; MUSCLE POWER; PERFORMANCE; INCHIANTI; MORTALITY AB Objective The aims of this study were to evaluate and contrast the physical attributes that are associated with self-reported vs. observed ability to walk 400 m among older adults. Design Analysis of baseline and 3-yr data from 1026 participants 65 yrs or older in the InCHIANTI (Invecchiare in Chianti) study was conducted. Observed and self-reported ability to walk 400 m at baseline and at 3 yrs were primary outcomes. Predictors included leg speed, leg strength, leg strength symmetry, range of motion, balance, and kyphosis. Results Balance, leg speed, leg strength, kyphosis, leg strength symmetry, and knee range of motion were associated with self-reported ability to walk 400 m at baseline (P < 0.001, c = 0.85). Balance, leg speed, and knee range of motion were associated with observed 400-m walk (P < 0.001, c = 0.85) at baseline. Prospectively, baseline leg speed and leg strength were predictive of both self-reported (P < 0.001, c = 0.79) and observed (P < 0.001, c = 0.72) ability to walk 400 m at 3 yrs. Conclusions The profiles of attributes that are associated with self-reported vs. observed walking ability differ. The factor most consistently associated with current and future walking ability is leg speed. These results draw attention to important foci for rehabilitation. C1 [Beauchamp, Marla K.; Bean, Jonathan F.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Leveille, Suzanne G.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care,Coll Nursing Hlth Sci, Univ Massachusetts Boston,Med Sch, Boston, MA 02215 USA. [Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Kiely, Dan K.] Harvard Univ, Sch Med, Hebrew Senior Life, Inst Aging Res, Boston, MA USA. [Phillips, Caroline L.] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Rehabil Unit, Florence, Italy. [Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA. [Guralnik, Jack] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Div Gerontol, Baltimore, MD 21201 USA. RP Beauchamp, MK (reprint author), Spaulding Cambridge Outpatient Ctr, 1575 Cambridge St, Cambridge, MA 02138 USA. RI Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 FU Canadian Institutes of Health Research; National Institutes of Health (NIH) [1K24HD070966-01]; Intramural Research Program of the NIH, National Institute on Aging FX Supported by a fellowship from the Canadian Institutes of Health Research (to M.K.B.) and by a National Institutes of Health (NIH) K24 award (1K24HD070966-01) (to J.F.B.). This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. NR 40 TC 3 Z9 3 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAY PY 2014 VL 93 IS 5 BP 396 EP 404 DI 10.1097/PHM.0000000000000034 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AF3GV UT WOS:000334600700005 PM 24322434 ER PT J AU Mai, PL Vadaparampil, ST Breen, N McNeel, TS Wideroff, L Graubard, BI AF Mai, Phuong L. Vadaparampil, Susan Thomas Breen, Nancy McNeel, Timothy S. Wideroff, Louise Graubard, Barry I. TI Awareness of Cancer Susceptibility Genetic Testing The 2000, 2005, and 2010 National Health Interview Surveys SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID HEREDITARY BREAST; OVARIAN-CANCER; RISK-ASSESSMENT; FAMILY-HISTORY; PHYSICIANS; WOMEN; INFORMATION; RACE/ETHNICITY; ACCULTURATION; HISPANICS AB Background: Genetic testing for several cancer susceptibility syndromes is clinically available; however, existing data suggest limited population awareness of such tests. Purpose: To examine awareness regarding cancer genetic testing in the U. S. population aged >= 25 years in the 2000, 2005, and 2010 National Health Interview Surveys. Methods: The weighted percentages of respondents aware of cancer genetic tests, and percent changes from 2000-2005 and 2005-2010, overall and by demographic, family history, and healthcare factors were calculated. Interactions were used to evaluate the patterns of change in awareness between 2005 and 2010 among subgroups within each factor. To evaluate associations with awareness in 2005 and 2010, percentages were adjusted for covariates using multiple logistic regression. The analysis was performed in 2012. Results: Awareness decreased from 44.4% to 41.5% (p<0.001) between 2000 and 2005, and increased to 47.0% (p<0.001) in 2010. Awareness increased between 2005 and 2010 in most subgroups, particularly among individuals in the South (p(interaction)=0.03) or with a usual place of care (p(interaction)=0.01). In 2005 and 2010, awareness was positively associated with personal or family cancer history and high perceived cancer risk, and inversely associated with racial/ethnic minorities, age 25-39 or >= 60 years, male gender, lower education and income levels, public or no health insurance, and no provider contact in 12 months. Conclusions: Despite improvement from 2005 to 2010, <= 50% of the U. S. adult population was aware of cancer genetic testing in 2010. Notably, disparities persist for racial/ethnic minorities and individuals with limited health care access or income. Published by Elseiver Inc. on behalf of American Journal of Preventive Medicine C1 [Mai, Phuong L.; Graubard, Barry I.] Natl Inst Drug Abuse, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. [Breen, Nancy] Natl Inst Drug Abuse, Appl Res Program, Hlth Serv & Econ Branch, NIH, Bethesda, MD USA. [Wideroff, Louise] Natl Inst Drug Abuse, NCI, Div Basic Neurosci & Behav Res, NIH, Bethesda, MD USA. [McNeel, Timothy S.] Informat Management Serv Inc, Calverton, MD USA. [Vadaparampil, Susan Thomas] Univ S Florida, Coll Med, Moffitt Canc Ctr, Hlth Outcomes & Behav Program, Tampa, FL USA. [Vadaparampil, Susan Thomas] Univ S Florida, Coll Med, Dept Oncol Sci, Tampa, FL USA. RP Mai, PL (reprint author), 9609 Med Ctr Dr,RM 6-E540 MSC 9772, Bethesda, MD 20892 USA. EM maip@mail.nih.gov FU National Cancer Institute, NIH FX This research was funded by the Intramural Research Program of the National Cancer Institute, NIH. We would like to thank all of the respondents for participating in the surveys. NR 34 TC 14 Z9 14 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2014 VL 46 IS 5 BP 440 EP 448 DI 10.1016/j.amepre.2014.01.002 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AF5QQ UT WOS:000334768400003 PM 24745633 ER PT J AU Rudzinski, ER Anderson, JR Lyden, ER Bridge, JA Barr, FG Gastier-Foster, JM Bachmeyer, K Skapek, SX Hawkins, DS Teot, LA Parham, DM AF Rudzinski, Erin R. Anderson, James R. Lyden, Elizabeth R. Bridge, Julia A. Barr, Frederic G. Gastier-Foster, Julie M. Bachmeyer, Karen Skapek, Stephen X. Hawkins, Douglas S. Teot, Lisa A. Parham, David M. TI Myogenin, AP2 beta, NOS-1, and HMGA2 Are Surrogate Markers of Fusion Status in Rhabdomyosarcoma A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE rhabdomyosarcoma; immunohistochemistry; fusion status ID PARAFFIN-EMBEDDED TISSUES; ALVEOLAR RHABDOMYOSARCOMA; EMBRYONAL RHABDOMYOSARCOMA; INTERGROUP-RHABDOMYOSARCOMA; GENE FUSIONS; EXPRESSION; CLASSIFICATION; IMMUNOHISTOCHEMISTRY; DIAGNOSIS; SURVIVAL AB Pediatric rhabdomyosarcoma (RMS) is traditionally classified on the basis of the histologic appearance into alveolar (ARMS) and embryonal (ERMS) subtypes. The majority of ARMS contain a PAX3-FOXO1 or PAX7-FOXO1 gene fusion, but about 20% do not. Intergroup Rhabdomyosarcoma Study stage-matched and group-matched ARMS typically behaves more aggressively than ERMS, but recent studies have shown that it is, in fact, the fusion status that drives the outcome for RMS. Gene expression microarray data indicate that several genes discriminate between fusion-positive and fusion-negative RMS with high specificity. Using tissue microarrays containing a series of both ARMS and ERMS, we identified a panel of 4 immunohistochemical markers-myogenin, AP2 beta, NOS-1, and HMGA2-which can be used as surrogate markers of fusion status in RMS. These antibodies provide an alternative to molecular methods for identification of fusion-positive RMS, particularly in cases in which there is scant or poor-quality material. In addition, these antibodies may be useful in fusion-negative ARMS as an indicator that a variant gene fusion may be present. C1 [Rudzinski, Erin R.] Seattle Childrens Hosp, Dept Labs, Seattle, WA 98015 USA. [Hawkins, Douglas S.] Fred Hutchinson Canc Res Ctr, Div Hematol Oncol, Seattle, WA 98104 USA. [Hawkins, Douglas S.] Univ Washington, Seattle, WA 98195 USA. [Anderson, James R.; Lyden, Elizabeth R.] Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE USA. [Bridge, Julia A.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [Barr, Frederic G.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA. [Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA. [Skapek, Stephen X.; Hawkins, Douglas S.] Univ Texas SW Med Ctr Dallas, Dept Pediat Hematol Oncol, Dallas, TX 75390 USA. [Teot, Lisa A.] Childrens Hosp Boston, Dept Pathol, Boston, MA USA. [Parham, David M.] Univ Oklahoma Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. RP Rudzinski, ER (reprint author), Seattle Childrens Hosp, Dept Labs, OC-8-720,4800 Sandpoint Way NE, Seattle, WA 98015 USA. EM erin.rudzinski@seattlechildrens.org RI Gastier-Foster, Julie/E-3105-2011 FU St. Baldrick's Foundation [179772]; NIH [RC2-CA148216]; NCI FX Research supported by St. Baldrick's Foundation Childhood Cancer Research Grant, 179772 (E. R. R.); NIH-RC2-CA148216 (S. X. S., J.A.B., F. G. B., J.M.G.-F.). F. G. B. is supported by the Intramural Research Program of the NCI. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 24 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 2014 VL 38 IS 5 BP 654 EP 659 DI 10.1097/PAS.0000000000000195 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA AF7ZG UT WOS:000334933700008 PM 24618610 ER PT J AU Schisterman, EF Mumford, SL Chen, Z Browne, RW Barr, DB Kim, S Louis, GMB AF Schisterman, E. F. Mumford, S. L. Chen, Z. Browne, R. W. Barr, D. Boyd Kim, S. Louis, G. M. Buck TI Lipid concentrations and semen quality: the LIFE study SO ANDROLOGY LA English DT Article DE lipoprotein metabolism; epidemiology; semen quality; fecundity ID CHROMATIN STRUCTURE ASSAY; IN-VITRO FERTILIZATION; HUMAN-FERTILITY; UNITED-STATES; HUMAN-SPERM; GENERAL-POPULATION; HEALTHY-MEN; CHOLESTEROL; DECLINE; OBESITY AB The decline in sperm count rates over the last 50years appears to parallel the rising prevalence of obesity. As lipid levels are strongly associated with obesity, high lipids levels or hyperlipidaemia may thus play an important role in the decline in fertility in addition to other environmental or lifestyle factors. The objective of this population based cohort study was to evaluate the association between men's serum lipid concentrations and semen quality parameters among 501 male partners of couples desiring pregnancy and discontinuing contraception. Each participant provided prospectively up to two semen samples (94% of men provided one or more semen samples, and 77% of men provided a second sample approximately 1month later). Linear mixed effects models were used to estimate the associations between baseline lipid concentrations and semen quality parameters, adjusted for age, body mass index and race. We found that higher levels of serum total cholesterol, free cholesterol and phospholipids were associated with a significantly lower percentage of spermatozoa with intact acrosome and smaller sperm head area and perimeter. Our results suggest that lipid concentrations may affect semen parameters, specifically sperm head morphology, highlighting the importance of cholesterol and lipid homeostasis for male fecundity. C1 [Schisterman, E. F.; Mumford, S. L.; Chen, Z.; Kim, S.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20854 USA. [Browne, R. W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA. [Barr, D. Boyd] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,7B03, Rockville, MD 20854 USA. EM schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [N01-HD-3-3355, N01-HD-3-3356, N01-HD-3-3358] FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (contracts #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). We acknowledge the Reproductive Health Assessment Team, Biomonitoring and Health Assessment Branch, National Institute for Occupational Health and Safety (NIOSH) for the analysis of semen samples under a Memo of Understanding with the NICHD. NR 62 TC 11 Z9 12 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 EI 2047-2927 J9 ANDROLOGY-US JI Andrology PD MAY PY 2014 VL 2 IS 3 BP 408 EP 415 DI 10.1111/j.2047-2927.2014.00198.x PG 8 WC Andrology SC Endocrinology & Metabolism GA AF7GC UT WOS:000334881300016 PM 24596332 ER PT J AU Hu, ZY Lan, KH He, SS Swaroop, M Hu, X Southall, N Zheng, W Liang, TJ AF Hu, Zongyi Lan, Keng-Hsin He, Shanshan Swaroop, Manju Hu, Xin Southall, Noel Zheng, Wei Liang, T. Jake TI Novel Cell-Based Hepatitis C Virus Infection Assay for Quantitative High-Throughput Screening of Anti-Hepatitis C Virus Compounds (vol 58, pg 995, 2014) SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Correction C1 [Hu, Zongyi] Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Adv Translat Sci, Bethesda, MD USA. RP Hu, ZY (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RI Southall, Noel/H-8991-2012 OI Southall, Noel/0000-0003-4500-880X NR 1 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2014 VL 58 IS 5 BP 2995 EP 2995 DI 10.1128/AAC.02529-14 PG 1 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AE9XF UT WOS:000334364300072 ER PT J AU Hosono, Y Abe, T Ishiai, M Islam, MN Arakawa, H Wang, WD Takeda, S Ishii, Y Takata, M Seki, M Enomoto, T AF Hosono, Yoshifumi Abe, Takuya Ishiai, Masamichi Islam, M. Nurul Arakawa, Hiroshi Wang, Weidong Takeda, Shunichi Ishii, Yutaka Takata, Minoru Seki, Masayuki Enomoto, Takemi TI Tumor suppressor RecQL5 controls recombination induced by DNA crosslinking agents SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE RecQL5; BRCA2; Fanconi anemia; ICL repair; Rad51 filament; Tumor suppressor ID IMMUNOGLOBULIN GENE CONVERSION; FANCONI-ANEMIA; HOMOLOGOUS RECOMBINATION; VERTEBRATE CELLS; GENOME STABILIZATION; REPAIR PATHWAY; BREAST-CANCER; HELICASE; REPLICATION; SUSCEPTIBILITY AB RecQ family DNA helicases function in the maintenance of genome stability. Mice deficient in RecQL5, one of five RecQ helicases, show a cancer predisposition phenotype, suggesting that RecQL5 plays a tumor suppressor role. RecQL5 interacts with Rad51, a key factor in homologous recombination (HR), and displaces Rad51 from Rad51single stranded DNA (ssDNA) filaments in vitro. However, the precise roles of RecQL5 in the cell remain elusive. Here, we present evidence suggesting that RecQL5 is involved in DNA interstrand crosslink (ICL) repair. Chicken DT40 RECQL5 gene knockout (KO) cells showed sensitivity to ICL-inducing agents such as cisplatin (CDDP) and mitomycin C (MMC) and a higher number of chromosome aberrations in the presence of MMC than wild-type cells. The phenotypes of RECQL5 KO cells resembled those of Fanconi anemia gene KO cells. Genetic analysis using corresponding gene knockout cells showed that RecQL5 is involved in the FANCD1 (BRCA2)-dependent ICL repair pathway in which Rad51-55DNA filament formation is promoted by BRCA2. The disappearance but not appearance of Rad51-foci was delayed in RECQL5 KO cells after MMC treatment. Deletion of Rad54, which processes the Rad51-ssDNA filament in HR, in RECQL5 KO cells increased sensitivity to CDDP and further delayed the disappearance of Rad51-foci, suggesting that RecQL5 and Rad54 have different effects on the Rad51-s5DNA filament. Furthermore, the frequency and variation of CDDP-induced gene conversion at the immunoglobulin locus were increased in RECQL5 KO cells. These results suggest that RecQL5 plays a role in regulating the incidence and quality of ICL-induced recombination. (C) 2014 Elsevier B.V. All tights reserved. C1 [Hosono, Yoshifumi; Seki, Masayuki] Tohoku Pharmaceut Univ, Grad Sch Pharmaceut Sci, Mol Cell Biol Lab, Aoba Ku, Sendai, Miyagi 9818558, Japan. [Abe, Takuya; Arakawa, Hiroshi] IFOM, FIRC Inst Mol Oncol Fdn, I-20139 Milan, Italy. [Ishiai, Masamichi; Takata, Minoru] Kyoto Univ, Ctr Radiat Biol, Dept Late Effect Studies, Lab DNA Damage Signaling,Sakyo Ku, Kyoto 6068501, Japan. [Islam, M. Nurul; Wang, Weidong] NIA, Genet Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Islam, M. Nurul] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Takeda, Shunichi] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Sakyo Ku, Kyoto 6068501, Japan. [Ishii, Yutaka] Shujitsu Univ, Sch Pharm, Naka Ku, Okayama 7038516, Japan. [Seki, Masayuki] Tohoku Pharmaceut Univ, Dept Biochem, Aoba Ku, Sendai, Miyagi 9818558, Japan. [Enomoto, Takemi] Musashino Univ, Fac Pharm, Pharmaceut Sci Res Inst, Mol Cell Biol Lab, Nishitokyo, Tokyo 2028585, Japan. RP Seki, M (reprint author), Tohoku Pharmaceut Univ, Dept Biochem, Aoba Ku, 4-1 Komatsushima 4-Chome, Sendai, Miyagi 9818558, Japan. EM Leno@musashino-u.ac.jp; t_eno@musashino-u.ac.jp RI ABE, TAKUYA/A-2861-2015 OI ABE, TAKUYA/0000-0001-5298-082X FU Ministry of Education, Culture, Sports, Science and Technology of Japan (NEXT KAKENHI Grant) [22131002]; Japan Society for the Promotion of Science (JSPS KAKENHI Grant) [23370065, 12J07075]; Intramural Research Program of the National Institute on Aging, National Institutes of Health [Z01:AG000657-09] FX This work was supported by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan (NEXT KAKENHI Grant Number 22131002) and also by the Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number 23370065 and 12J07075). This work was supported in part by the Intramural Research Program of the National Institute on Aging (Z01:AG000657-09), National Institutes of Health (W.W.). NR 54 TC 2 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 EI 0006-3002 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAY PY 2014 VL 1843 IS 5 BP 1002 EP 1012 DI 10.1016/j.bbamcr.2014.01.005 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AF1LZ UT WOS:000334476700018 PM 24418621 ER PT J AU Liggett, JL Zhang, XB Eling, TE Baek, SJ AF Liggett, Jason L. Zhang, Xiaobo Eling, Thomas E. Baek, Seung Joon TI Anti-tumor activity of non-steroidal anti-inflammatory drugs: Cyclooxygenase-independent targets SO CANCER LETTERS LA English DT Review DE NSAIDs; COX; Sulindac sulfide; Tolfenamic acid; NAG-1 ID NF-KAPPA-B; COLON-CANCER CELLS; ENDOPLASMIC-RETICULUM STRESS; ACTIVATING TRANSCRIPTION FACTOR-3; EPITHELIAL-MESENCHYMAL TRANSITION; FAMILIAL ADENOMATOUS POLYPOSIS; COX-2 INHIBITOR CELECOXIB; NUCLEAR BETA-CATENIN; TOLFENAMIC ACID; COLORECTAL-CANCER AB Non-steroidal anti-inflammatory drugs (NSAIDs) are used extensively for analgesic and antipyretic treatments. In addition, NSAIDs reduce the risk and mortality to several cancers. Their mechanisms in anti-tumorigenesis are not fully understood, but both cyclooxygenase (COX)-dependent and -independent pathways play a role. We and others have been interested in elucidating molecular targets of NSAID-induced apoptosis. In this review, we summarize updated literature regarding cellular and molecular targets modulated by NSAIDs. Among those NSAIDs, sulindac sulfide and tolfenamic acid are emphasized in this review because these two drugs have been well investigated for their anti-tumorigenic activity in many different types of cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Liggett, Jason L.; Baek, Seung Joon] Univ Tennessee, Coll Vet Med, Dept Biomed & Diagnost Sci, Knoxville, TN 37996 USA. [Zhang, Xiaobo] Northwest A&F Univ, Coll Anim Sci & Technol, Yangling 712100, Shaanxi, Peoples R China. [Eling, Thomas E.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Baek, SJ (reprint author), Univ Tennessee, Coll Vet Med, Dept Biomed & Diagnost Sci, 2407 River Dr, Knoxville, TN 37996 USA. EM sbaek2@utk.edu FU American Cancer Society [CNE-111611]; National Institutes of Health [R01CA108975]; University of Tennessee, Center of Excellence in Livestock Diseases and Human Health FX We apologize to all colleagues whose important work we could not cite due to space restrictions. The authors thank Misty Bailey for her critical review. This work was supported by grants from the American Cancer Society (CNE-111611), National Institutes of Health (R01CA108975), and the University of Tennessee, Center of Excellence in Livestock Diseases and Human Health. NR 103 TC 22 Z9 22 U1 0 U2 25 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 MAY 1 PY 2014 VL 346 IS 2 BP 217 EP 224 DI 10.1016/j.canlet.2014.01.021 PG 8 WC Oncology SC Oncology GA AF6JJ UT WOS:000334820800008 PM 24486220 ER PT J AU Yeo, D Huynh, N Beutler, JA Christophi, C Shulkes, A Baldwin, GS Nikfarjam, M He, H AF Yeo, Dannel Nhi Huynh Beutler, John A. Christophi, Christopher Shulkes, Arthur Baldwin, Graham S. Nikfarjam, Mehrdad He, Hong TI Glaucarubinone and gemcitabine synergistically reduce pancreatic cancer growth via down-regulation of P21-activated kinases SO CANCER LETTERS LA English DT Article DE Glaucarubinone; Gemcitabine; Pancreatic cancer; P21-activated kinases ID PAK4; COMBINATION; INHIBITION; ACTIVATION; RESECTION; MALARIA; DRUGS AB Pancreatic cancer is one of the most lethal of human malignancies. Nearly 100% cases of pancreatic cancer carry mutations in KRas. P-21-activated kinases (PAKs) are activated by and act downstream of KRas. Glaucarubinone, a natural product first isolated from the seeds of the tree Simarouba glauca, was originally developed as an antimalarial drug, and has more recently been recognised as an anticancer agent. The aims of this study were to determine whether glaucarubinone, alone or in combination with the front-line chemotherapeutic agent gemcitabine, would inhibit the growth of pancreatic cancer cells in vitro or in vivo and the mechanism involved. Growth of the human pancreatic cancer cell lines PANC-1 and MiaPaCa-2 was measured by H-3-thymidine incorporation in vitro, and by volume as xenografts in SCID mice. The expression and activities of the two serine/threonine kinases PAK1 and PAK4, which are key regulators of cancer progression, were measured by Western blotting. Here we report that glaucarubinone decreased proliferation and migration of pancreatic cancer cells in vitro, and reduced their growth as xenografts in vivo. Treatment with glaucarubinone and gemcitabine reduced proliferation in vitro and tumor growth in vivo more than treatment with either glaucarubinone or gemcitabine alone. Treatment with glaucarubinone reduced PAK1 and PAK4 activities, which were further decreased by the combination of glaucarubinone and gemcitabine. These results indicate that glaucarubinone reduced pancreatic cancer cell growth at least in part via inhibition of pathways involving PAKI and PAK4. The synergistic inhibition by glaucarubinone and gemcitabine observed both in vitro and in vivo suggests that glaucarubinone may be a useful adjunct to current regimes of chemotherapy. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Yeo, Dannel; Nhi Huynh; Christophi, Christopher; Shulkes, Arthur; Baldwin, Graham S.; Nikfarjam, Mehrdad; He, Hong] Univ Melbourne, Dept Surg, Austin Hlth, Heidelberg, Vic 3084, Australia. [Beutler, John A.] NCI, Mol Targets Lab, Frederick, MD 21702 USA. RP He, H (reprint author), Univ Melbourne, Dept Surg, Austin Hlth, Studley Rd, Heidelberg, Vic 3084, Australia. EM hong.he@unimelb.edu.au OI Baldwin, Graham/0000-0002-0944-8747; Nikfarjam, Mehrdad/0000-0003-4866-276X FU National Health and Medical Research Council (NHMRC) of Australia [508908, 1041831, 1020983]; Austin Hospital Medical Research Foundation; NIH National Cancer Institute Center for Cancer Research; Australian Rotary Health FX We thank the Drug Synthesis & Chemistry Branch, NCI, for supplying the glaucarubinone used in this study, and Hiroshi Maruta for stimulating discussions. This work was supported by National Health and Medical Research Council (NHMRC) of Australia Grants 508908 (HH) [27], 1041831 (GB & AS), and 1020983 (GB), by the Austin Hospital Medical Research Foundation, and by the Intramural Research Program of the NIH National Cancer Institute Center for Cancer Research. Dannel Yeo is supported by the Ph.D scholarship from Australian Rotary Health. NR 28 TC 21 Z9 22 U1 1 U2 14 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 MAY 1 PY 2014 VL 346 IS 2 BP 264 EP 272 DI 10.1016/j.canlet.2014.01.001 PG 9 WC Oncology SC Oncology GA AF6JJ UT WOS:000334820800013 PM 24491405 ER PT J AU Ivetac, A Swift, SE Boyer, PL Diaz, A Naughton, J Young, JAT Hughes, SH McCammon, JA AF Ivetac, Anthony Swift, Sara E. Boyer, Paul L. Diaz, Arturo Naughton, John Young, John A. T. Hughes, Stephen H. McCammon, J. Andrew TI Discovery of Novel Inhibitors of HIV-1 Reverse Transcriptase Through Virtual Screening of Experimental and Theoretical Ensembles SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE HIV; molecular dynamics; NNRTI; reverse transcriptase; virtual screening ID IMMUNODEFICIENCY-VIRUS TYPE-1; RELAXED COMPLEX SCHEME; AIDED DRUG DESIGN; NONNUCLEOSIDE INHIBITORS; RECEPTOR FLEXIBILITY; POTENT; MECHANISM; DOCKING; DERIVATIVES; SIMULATION AB Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are potent anti-HIV chemotherapeutics. Although there are FDA-approved NNRTIs, challenges such as the development of resistance have limited their utility. Here, we describe the identification of novel NNRTIs through a combination of computational and experimental approaches. Based on the known plasticity of the NNRTI binding pocket (NNIBP), we adopted an ensemble-based virtual screening strategy: coupling receptor conformations from 10 X-ray crystal structures with 120 snapshots from a total of 480ns of molecular dynamics (MD) trajectories. A screening library of 2864 National Cancer Institute (NCI) compounds was built and docked against the ensembles in a hierarchical fashion. Sixteen diverse compounds were tested for their ability to block HIV infection in human tissue cultures using a luciferase-based reporter assay. Three promising compounds were further characterized, using a HIV-1 RT-based polymerase assay, to determine the specific mechanism of inhibition. We found that 2 of the three compounds inhibited the polymerase activity of RT (with potency similar to the positive control, the FDA-approved drug nevirapine). Through a computational approach, we were able to discover two compounds which inhibit HIV replication and block the activity of RT, thus offering the potential for optimization into mature inhibitors. C1 [Ivetac, Anthony; Swift, Sara E.; McCammon, J. Andrew] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. [Boyer, Paul L.; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Diaz, Arturo; Naughton, John; Young, John A. T.] Salk Inst Biol Studies, Nomis Ctr Immunobiol & Microbial Pathogenesis, La Jolla, CA 92037 USA. [McCammon, J. Andrew] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [McCammon, J. Andrew] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. RP Ivetac, A (reprint author), Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. EM aivetac@mccammon.ucsd.edu FU National Science Foundation, the National Institutes of Health and Howard Hughes Medical Institute; National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research FX We acknowledge the San Diego Supercomputing Center, the Center for Theoretical Biological Physics, and the National Biomedical Computational Resource for computational resources and the National Science Foundation, the National Institutes of Health and Howard Hughes Medical Institute for financial support. We also acknowledge the Nomis, Auen, and Morris Foundations and the James B. Pendleton Charitable Trust for their support. This study was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 39 TC 9 Z9 10 U1 0 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-0277 EI 1747-0285 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD MAY PY 2014 VL 83 IS 5 BP 521 EP 531 DI 10.1111/cbdd.12277 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AF6XD UT WOS:000334857000002 PM 24405985 ER PT J AU Mueller, GA Maleki, SJ Pedersen, LC AF Mueller, Geoffrey A. Maleki, Soheila J. Pedersen, Lars C. TI The Molecular Basis of Peanut Allergy SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Review DE Peanut allergy; Molecular basis; Peanut allergens; Major allergens; Minor allergens; Protein structures; Cross-reactivity; Molecular modifications ID GLYCATION END-PRODUCTS; ARA H 2; PLANT FOOD ALLERGENS; IGE-BINDING EPITOPES; CRYSTAL-STRUCTURE; ARACHIS-HYPOGAEA; IMMUNOGLOBULIN-E; CARBOHYDRATE DETERMINANTS; FUNCTIONAL-ASPECTS; TRYPSIN-INHIBITOR AB Peanut allergens can trigger a potent and sometimes dangerous immune response in an increasing number of people. The molecular structures of these allergens form the basis for understanding this response. This review describes the currently known peanut allergen structures and discusses how modifications both enzymatic and non-enzymatic affect digestion, innate immune recognition, and IgE interactions. The allergen structures help explain cross-reactivity among allergens from different sources, which is useful in improving patient diagnostics. Surprisingly, it was recently noted that similar short peptide sequences among unrelated peanut allergens could also be a source of cross-reactivity. The molecular features of peanut allergens continue to inform predictions and provide new research directions in the study of allergic disease. C1 [Mueller, Geoffrey A.; Pedersen, Lars C.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Maleki, Soheila J.] ARS, USDA, So Reg Res Ctr, New Orleans, LA USA. RP Mueller, GA (reprint author), NIEHS, Struct Biol Lab, 111 TW Alexander Dr,MD-MR-01, Res Triangle Pk, NC 27709 USA. EM Mueller3@niehs.nih.gov FU National Institute of Environmental Health Sciences, National Institutes of Health [Z01-ES102885-01, ZIA-ES102645] FX The authors wish to thank Drs. Robert London, Michael Fessler, and Jason Williams for critical readings of the manuscript. This research was supported by Research Project Number Z01-ES102885-01 and ZIA-ES102645 in the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. NR 81 TC 4 Z9 5 U1 6 U2 38 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 EI 1534-6315 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD MAY PY 2014 VL 14 IS 5 AR 429 DI 10.1007/s11882-014-0429-5 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA AE7KS UT WOS:000334177300001 PM 24633613 ER PT J AU Taylor, SM Fairhurst, RM AF Taylor, Steve M. Fairhurst, Rick M. TI Malaria parasites and red cell variants: when a house is not a home SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE enzymopathy; hemoglobinopathy; malaria; ovalocytosis; Plasmodium falciparum erythrocyte membrane protein 1 ID PLASMODIUM-FALCIPARUM MALARIA; INFECTED ERYTHROCYTES; SICKLE HEMOGLOBIN; TRAIT; RESISTANCE; PROTECTS; MECHANISM; CHILDREN; VIVAX; TRANSMISSION AB Purpose of reviewMultiple red cell variants are known to confer protection from malaria. Here, we review advances in identifying new variants that modulate malaria risk and in defining molecular mechanisms that mediate malaria protection.Recent findingsNew red cell variants, including an innate variant in the red cell's major Ca2+ pump and the acquired state of iron deficiency, have been associated with protection from clinical falciparum malaria. The polymorphisms hemoglobin C (HbC) and hemoglobin S (HbS) - known to protect carriers from severe falciparum malaria - enhance parasite passage to mosquitoes and may promote malaria transmission. At the molecular level, substantial advances have been made in understanding the impact of HbS and HbC upon the interactions between host microRNAs and Plasmodium falciparum protein translation; remodeling of red cell cytoskeletal components and transport of parasite proteins to the red cell surface; and chronic activation of the human innate immune system, which induces tolerance to blood-stage parasites. Several polymorphisms have now been associated with protection from clinical vivax malaria or reduced Plasmodium vivax density, including Southeast Asian ovalocytosis and two common forms of glucose-6-phosphate dehydrogenase deficiency.SummaryRed cell variants that modulate malaria risk can serve as models to identify clinically relevant mechanisms of pathogenesis, and thus define parasite and host targets for next-generation therapies. C1 [Taylor, Steve M.] Duke Univ, Med Ctr, Duke Global Hlth Inst, Div Infect Dis & Int Hlth, Durham, NC 27706 USA. [Taylor, Steve M.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10A, Rockville, MD 20852 USA. EM rfairhurst@niaid.nih.gov FU NIAID [K08AI100924]; NIAID, NIH FX S.M.T. is supported by an award from the NIAID, K08AI100924. R. M. F. is supported by the Intramural Research Program of the NIAID, NIH. NR 42 TC 9 Z9 10 U1 5 U2 27 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 EI 1531-7048 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAY PY 2014 VL 21 IS 3 BP 193 EP 200 DI 10.1097/MOH.0000000000000039 PG 8 WC Hematology SC Hematology GA AF8HW UT WOS:000334957500006 PM 24675047 ER PT J AU Muller, BG van den Bos, W Pinto, PA de la Rosette, JJ AF Muller, Berrend G. van den Bos, Willemien Pinto, Peter A. de la Rosette, Jean J. TI Imaging modalities in focal therapy: patient selection, treatment guidance, and follow-up SO CURRENT OPINION IN UROLOGY LA English DT Review DE focal therapy; MRI; prostate cancer; ultrasonography ID INTENSITY FOCUSED ULTRASOUND; LOCALIZED PROSTATE-CANCER; TRANSRECTAL ULTRASOUND; MULTIPARAMETRIC MRI; ACTIVE SURVEILLANCE; BIOPSY; ULTRASONOGRAPHY; REGISTRATION; ELASTOGRAPHY; MULTICENTER AB Purpose of reviewFocal therapy for prostate cancer is emerging as a management option between active surveillance and radical treatments. In this article, we present two of the most important imaging modalities in focal therapy, multiparametric MRI (mpMRI) and ultrasonography. We review the recent advances within these two platforms.Recent findingsState-of-the-art imaging in all phases of focal therapy is essential for treatment safety. In patient selection, treatment guidance, and follow-up, different aspects of imaging are important. mpMRI is an imaging technology with high imaging resolution and contrast. This makes it an excellent technology for patient selection and treatment planning and follow-up. Ultrasound has the unique property of real-time image acquisition. This makes it an excellent technology for real-time treatment guidance. There are multiple novelties in these two platforms that have increased the accuracy considerably. Examples in ultrasound are contrast-enhanced ultrasonography, elastography, shear-wave elastography, and histoscanning. In mpMRI, these advantages consist of multiple sequences combined to one image and magnetic resonance thermometry.SummaryStandardization of multiparametric transrectal ultrasound and mpMRI is of paramount importance. For targeted treatment and follow-up, a good negative predictive value of the test is important. There is much to gain from both of these developing fields and imaging accuracy of the two platforms is comparable. Standardization in conduct and interpretation, three-dimensional reconstruction, and fusion of the two platforms can make focal therapy the standard of care for prostate cancer. C1 [Muller, Berrend G.; van den Bos, Willemien; de la Rosette, Jean J.] AMC Univ Hosp, Dept Urol, Amsterdam, Netherlands. [Pinto, Peter A.] NCI, Dept Urol, Bethesda, MD 20892 USA. RP Muller, BG (reprint author), Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM b.g.muller@amc.uva.nl FU National Institutes of Health (NIH); Cure for Cancer Foundation FX Disclosures: P.A.P. receives an unrestricted research grant from the National Institutes of Health (NIH). B. G. M. and W.v.d.B. receive an unrestricted research grant from the 'Cure for Cancer Foundation'. NR 45 TC 12 Z9 13 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0963-0643 EI 1473-6586 J9 CURR OPIN UROL JI Curr. Opin. Urol. PD MAY PY 2014 VL 24 IS 3 BP 218 EP 224 DI 10.1097/MOU.0000000000000041 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AF1XB UT WOS:000334506100003 PM 24637316 ER PT J AU Kelly, NR Shank, LM Bakalar, JL Tanofsky-Kraff, M AF Kelly, Nichole R. Shank, Lisa M. Bakalar, Jennifer L. Tanofsky-Kraff, Marian TI Pediatric Feeding and Eating Disorders: Current State of Diagnosis and Treatment SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Pediatric; Child; Adolescent; Eating disorder; Feeding disorder; Binge eating; Loss of control eating; Anorexia nervosa; Bulimia nervosa; Pica; Rumination; Avoidant/restrictive food intake; Compensatory behavior; Regurgitation; Weight; Overweight; Obesity ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE REMEDIATION THERAPY; FAMILY-BASED TREATMENT; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; ADOLESCENT GIRLS; RUMINATION SYNDROME; INCORPORATING DIMENSIONS; BEHAVIORAL TREATMENT; OVERWEIGHT CHILDREN AB The Diagnostic and Statistical Manual of Mental Disorders now recognizes six primary feeding and eating disorders including pica, rumination disorder, avoidant/restrictive food intake disorder, anorexia nervosa, bulimia nervosa and binge-eating disorder. Guided by research from the past 3 years, the current review outlines diagnostic criteria for each disorder, their clinical correlates and treatment options. Recent modifications to diagnostic criteria will likely help to improve treatment outcomes and prognosis. Nevertheless, several concerns remain regarding the validity of current diagnostic criteria for youth, including the clinical relevance of the size and frequency of binge eating episodes. Additionally, the lack of randomized controlled trials has led to an overreliance on data from quasi-experimental studies, case series and single case studies that impede development of strong clinical recommendations for treating feeding and eating disorders. Recommendations for future research include identifying empirically supported treatments and prevention programs focused on early markers of pediatric feeding and eating concerns. C1 [Kelly, Nichole R.; Shank, Lisa M.; Bakalar, Jennifer L.; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, DoD, Bethesda, MD 20814 USA. [Kelly, Nichole R.; Shank, Lisa M.; Bakalar, Jennifer L.; Tanofsky-Kraff, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20814 USA. RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, DoD, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM nichole.kelly@nih.gov; lisa.shank@usuhs.edu; jennifer.bakalar@usuhs.edu; marian.tanofsky-kraff@usuhs.edu NR 120 TC 5 Z9 7 U1 7 U2 36 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 EI 1535-1645 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD MAY PY 2014 VL 16 IS 5 AR 446 DI 10.1007/s11920-014-0446-z PG 12 WC Psychiatry SC Psychiatry GA AF0XI UT WOS:000334437700004 PM 24643374 ER PT J AU Muranski, P AF Muranski, Pawel TI An easy way to make a good anti-tumor chimeric antigen receptor T cell? SO CYTOTHERAPY LA English DT Editorial Material ID EFFECTOR C1 [Muranski, Pawel] NHLBI, Stem Cell Allogen Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Muranski, P (reprint author), Bldg 10 CRC Rm3E5288,9000 Rockville Pike, Bethesda, MD 20892 USA. EM muranskp@mail.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1465-3249 EI 1477-2566 J9 CYTOTHERAPY JI Cytotherapy PD MAY PY 2014 VL 16 IS 5 BP 577 EP 578 DI 10.1016/j.jcyt.2014.03.003 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA AF5BC UT WOS:000334728000001 PM 24725890 ER PT J AU Estampador, AC Pomeroy, J Renstrom, F Nelson, SM Mogren, I Persson, M Sattar, N Domellof, M Franks, PW AF Estampador, Angela C. Pomeroy, Jeremy Renstrom, Frida Nelson, Scott M. Mogren, Ingrid Persson, Margareta Sattar, Naveed Domellof, Magnus Franks, Paul W. TI Infant Body Composition and Adipokine Concentrations in Relation to Maternal Gestational Weight Gain SO DIABETES CARE LA English DT Article ID INSULIN SENSITIVITY; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; PREGNANCY; OBESITY; GROWTH; WOMEN; INTERLEUKIN-6; ADIPOSITY AB OBJECTIVETo investigate associations of maternal gestational weight gain and body composition and their impact on offspring body composition and adipocytokine, glucose, and insulin concentrations at age 4 months.RESEARCH DESIGN AND METHODSThis was a prospective study including 31 mother-infant pairs (N = 62). Maternal body composition was assessed using doubly labeled water. Infant body composition was assessed at 4 months using air displacement plethysmography, and venous blood was assayed for glucose, insulin, adiponectin, interleukin-6 (IL-6), and leptin concentrations.RESULTSRate of gestational weight gain in midpregnancy was significantly associated with infant fat mass (r = 0.41, P = 0.03); rate of gestational weight in late pregnancy was significantly associated with infant fat-free mass (r = 0.37, P = 0.04). Infant birth weight was also strongly correlated with infant fat-free mass at 4 months (r = 0.63, P = 0.0002). Maternal BMI and maternal fat mass were strongly inversely associated with infant IL-6 concentrations (r = -0.60, P = 0.002 and r = -0.52, P = 0.01, respectively). Infant fat-free mass was inversely related to infant adiponectin concentrations (r = -0.48, P = 0.008) and positively correlated with infant blood glucose adjusted for insulin concentrations (r = 0.42, P = 0.04). No significant associations for leptin were observed.CONCLUSIONSTiming of maternal weight gain differentially impacts body composition of the 4-month-old infant, which in turn appears to affect the infant's glucose and adipokine concentrations. C1 [Estampador, Angela C.; Pomeroy, Jeremy; Renstrom, Frida; Franks, Paul W.] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Pomeroy, Jeremy] NIH, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. [Renstrom, Frida; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Div Med, Genet Epidemiol & Clin Res Grp, Umea, Sweden. [Nelson, Scott M.] Univ Glasgow, Fac Med, Glasgow, Lanark, Scotland. [Mogren, Ingrid; Persson, Margareta] Umea Univ Hosp, Dept Clin Sci, Obstet & Gynecol Unit, S-90185 Umea, Sweden. [Persson, Margareta] Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden. [Sattar, Naveed] Univ Glasgow, Cardiovasc Res Ctr, British Heart Fdn, Glasgow, Lanark, Scotland. [Domellof, Magnus] Umea Univ, Dept Clin Sci, Pediat Unit, Umea, Sweden. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Franks, PW (reprint author), Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. EM paul.franks@med.lu.se RI Domellof, Magnus/E-5307-2011; OI Domellof, Magnus/0000-0002-0726-7029; Estampador, Angela/0000-0003-0097-4529; Nelson, Scott/0000-0002-9099-3047; Franks, Paul/0000-0002-0520-7604; Sattar, Naveed/0000-0002-1604-2593; Mogren, Ingrid/0000-0003-2985-1135 FU Torsten Foundation; Ragnar Soderberg Foundation; Fredrik and Ingrid Thurings Foundation; Vasterbotten regional health authority FX The study was a preparatory project for the LifeGene Study (www.lifegene.se) and was funded by the Torsten and Ragnar Soderberg Foundations, the Fredrik and Ingrid Thurings Foundation, and the Vasterbotten regional health authority (all grants to P.W.F.). NR 40 TC 5 Z9 5 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2014 VL 37 IS 5 BP 1432 EP 1438 DI 10.2337/dc13-2265 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AF6QQ UT WOS:000334840100060 PM 24623025 ER PT J AU Cuellar-Rodriguez, J Connor, D Murray, P Gea-Banacloche, J AF Cuellar-Rodriguez, J. Connor, D. Murray, P. Gea-Banacloche, J. CA Natl Inst Hlth NIH TI Discrepant results from sampling different lumens of multilumen catheters: the case for sampling all lumens SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID PEDIATRIC ONCOLOGY PATIENTS; BLOOD-STREAM INFECTION; CENTRAL VENOUS CATHETERS; CLINICAL UTILITY; CULTURES DRAWN; VOLUME; DIAGNOSIS; SENSITIVITY; GUIDELINES; CANCER AB It is unclear whether blood culture samples should be obtained through one or multiple catheter lumens. We measured how frequently drawing blood cultures from all the lumens from a multilumen catheter resulted in discordant results and how often these caused medical interventions. We performed a retrospective review of the microbiology database of the National Institutes of Health (NIH) Clinical Center. Most patients were immunocompromised. All blood cultures obtained from May 1, 2007 to April 30, 2009 were reviewed. We analyzed all positive blood cultures (i.e., positivity of any of the blood cultures drawn through the catheter lumens) when simultaneous samples from different lumens were obtained, and reviewed the medical charts of those in which blood cultures from different lumens had discordant results (i.e., not all lumens revealed the same organism). We also analyzed how often the discordant results lead to a medical intervention, defined as a change of antimicrobials and/or removal of the catheter. There were 405 episodes of positive blood cultures, in which simultaneous samples of different lumens of a multilumen catheter were obtained. Eighty-five episodes (21 %) were considered to be contaminants and excluded. We analyzed 320 episodes of positive blood cultures in 153 patients; 173 episodes (54.1 %) had discordant results. In 77 % of the 173 episodes, the discordant isolate led to a medical intervention. In immunocompromised patients, sampling all the lumens of a multilumen catheter results in more positive blood cultures, and many of these result in medical interventions. When evaluating bloodstream infection in patients with multilumen catheters, sampling all lumens should be strongly considered. C1 [Cuellar-Rodriguez, J.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Connor, D.] Univ Pittsburgh, Sch Med, Dept Med & Biomed Informat, Pittsburgh, PA 15261 USA. [Murray, P.] BD Diagnost, Sparks, MD 21152 USA. [Gea-Banacloche, J.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Gea-Banacloche, J (reprint author), NCI, Expt Transplantat & Immunol Branch, 10 Ctr Dr,Bldg 10,Room CRC 3-3130, Bethesda, MD 20892 USA. EM banacloj@mail.nih.gov NR 21 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0934-9723 EI 1435-4373 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD MAY PY 2014 VL 33 IS 5 BP 831 EP 835 DI 10.1007/s10096-013-2021-7 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA AF8AV UT WOS:000334938300019 PM 24297770 ER PT J AU van Duyvenvoorde, HA Lui, JC Kant, SG Oostdijk, W Gijsbers, ACJ Hoffer, MJV Karperien, M Walenkamp, MJE Noordam, C Voorhoeve, PG Mericq, V Pereira, AM Claahsen-van de Grinten, HL van Gool, SA Breuning, MH Losekoot, M Baron, J Ruivenkamp, CAL Wit, JM AF van Duyvenvoorde, Hermine A. Lui, Julian C. Kant, Sarina G. Oostdijk, Wilma Gijsbers, Antoinet C. J. Hoffer, Mariette J. V. Karperien, Marcel Walenkamp, Marie J. E. Noordam, Cees Voorhoeve, Paul G. Mericq, Veronica Pereira, Alberto M. Claahsen-van de Grinten, Hedi L. van Gool, Sandy A. Breuning, Martijn H. Losekoot, Monique Baron, Jeffrey Ruivenkamp, Claudia A. L. Wit, Jan M. TI Copy number variants in patients with short stature SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE short stature; small for gestational age; idiopathic short stature; growth; copy number variations (CNV); single-nucleotide polymorphism (SNP) array ID IDIOPATHIC SHORT STATURE; GENOME-WIDE ASSOCIATION; FOR-GESTATIONAL-AGE; FACTOR-I RECEPTOR; HETEROZYGOUS EXPRESSION; GROWTH-RETARDATION; SHORT CHILDREN; HUMAN HEIGHT; GENE; MUTATION AB Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n = 40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes. published online 25 September 2013 C1 [van Duyvenvoorde, Hermine A.; Oostdijk, Wilma; van Gool, Sandy A.; Wit, Jan M.] Leiden Univ, Med Ctr, Dept Pediat, NL-2300 RC Leiden, Netherlands. [van Duyvenvoorde, Hermine A.; Pereira, Alberto M.] Leiden Univ, Med Ctr, Dept Endocrinol & Metab Dis, NL-2300 RC Leiden, Netherlands. [van Duyvenvoorde, Hermine A.; Kant, Sarina G.; Gijsbers, Antoinet C. J.; Hoffer, Mariette J. V.; Breuning, Martijn H.; Losekoot, Monique; Ruivenkamp, Claudia A. L.] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2300 RC Leiden, Netherlands. [Lui, Julian C.; Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Dev, Bethesda, MD USA. [Karperien, Marcel] Univ Twente, MIRA Inst Biomed Technol & Tech Med, Dept Dev BioEngn, NL-7500 AE Enschede, Netherlands. [Walenkamp, Marie J. E.] Vrije Univ Amsterdam Med Ctr, Dept Pediat, Amsterdam, Netherlands. [Noordam, Cees; Claahsen-van de Grinten, Hedi L.] Radboud Univ Nijmegen, Med Ctr, Dept Pediat, NL-6525 ED Nijmegen, Netherlands. [Voorhoeve, Paul G.] Canisius Wilhelmina Hosp, Dept Pediat, Nijmegen, Netherlands. [Mericq, Veronica] Univ Chile, Inst Maternal & Child Dis, Santiago, Chile. RP van Duyvenvoorde, HA (reprint author), Leiden Univ, Med Ctr, Dept Clin Genet, S6-P,POB 9600, NL-2300 RC Leiden, Netherlands. EM H.A.van_Duyvenvoorde@lumc.nl RI Noordam, C./H-8077-2014; Lui, Chun Kin Julian/E-2253-2012; Kant, Sarina/F-8596-2010; OI Mericq, Veronica/0000-0003-2287-0181 FU Novo Nordisk FX Dr Oostdijk received grant support from Novo Nordisk. Dr Walenkamp has served on an advisory board for Ipsen and has received speaker honorariums from Ferring, Ipsen and Pfizer. Professor Dr Wit has served on advisory boards for Tercica, Ipsen, Pfizer, Prolor, Teva and Biopartners, and has received speaker honorariums from Pfizer, Lilly, Ipsen and Ferring. The remaining authors declare no conflict of interest. NR 44 TC 18 Z9 19 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2014 VL 22 IS 5 BP 602 EP 609 DI 10.1038/ejhg.2013.203 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AF3GS UT WOS:000334600400008 PM 24065112 ER PT J AU Bohlega, S Al-Ajlan, H Al-Saif, A AF Bohlega, Saeed Al-Ajlan, Huda Al-Saif, Amr TI Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE FBLN1; fibulins; homozygosity mapping; exome sequencing; neurodegenerative disease ID EPIDERMAL-GROWTH-FACTOR; MACULAR DEGENERATION; CUTIS LAXA; GENE; REGIONS AB Fibulin-1 is an extracellular matrix protein that has an important role in the structure of elastic fibers and basement membranes of various tissues. Using homozygosity mapping and exome sequencing, we discovered a missense mutation, p.(Cys397Phe), in fibulin-1 in three patients from a consanguineous family presented with a novel syndrome of syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. The mutation discovered segregated with the phenotype and was not found in 374 population-matched alleles. The affected cysteine is highly conserved across vertebrates and its mutation is predicted to abolish a disulfide bond that defines the tertiary structure of fibulin-1. Our findings emphasize the crucial role fibulin-1 has in development of the central nervous system and various connective tissues. published online 2 October 2013 C1 [Bohlega, Saeed] King Faisal Specialist Hosp & Res Ctr, Dept Neurosci, Riyadh 11211, Saudi Arabia. [Al-Ajlan, Huda; Al-Saif, Amr] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [Al-Saif, Amr] NIH, Neurogenet Lab, Bethesda, MD 20892 USA. RP Al-Saif, A (reprint author), NIH, Neurogenet Lab, 35 Convent Dr Rm 1a1015, Bethesda, MD 20892 USA. EM amr.al-saif@nih.gov NR 16 TC 0 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2014 VL 22 IS 5 BP 640 EP 643 DI 10.1038/ejhg.2013.210 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AF3GS UT WOS:000334600400013 PM 24084572 ER PT J AU Rousseau, J Gioia, R Layrolle, P Lieubeau, B Heymann, D Rossi, A Marini, JC Trichet, V Forlino, A AF Rousseau, Julie Gioia, Roberta Layrolle, Pierre Lieubeau, Blandine Heymann, Dominique Rossi, Antonio Marini, Joan C. Trichet, Valerie Forlino, Antonella TI Allele-specific Col1a1 silencing reduces mutant collagen in fibroblasts from Brtl mouse, a model for classical osteogenesis imperfecta SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE allele-specific Col1a1 silencing; siRNA; shRNA; osteogenesis imperfecta; lentiviral vector ID IN-UTERO TRANSPLANTATION; MURINE MODEL; PRECLINICAL MODELS; LENTIVIRAL VECTOR; MAMMALIAN-CELLS; RNAI; EXPRESSION; BONE; THERAPY; LETHAL AB Gene silencing approaches have the potential to become a powerful curative tool for a variety of monogenic diseases caused by gain-of-function mutations. Classical osteogenesis imperfecta (OI), a dominantly inherited bone dysplasia, is characterized in its more severe forms by synthesis of structurally abnormal type I collagen, which exerts a negative effect on extracellular matrix. Specific suppression of the mutant (Mut) allele would convert severe OI forms to the mild type caused by a quantitative defect in normal collagen. Here, we describe the in vitro and ex vivo investigation of a small interfering RNA (siRNA) approach to allele-specific gene silencing using Mut Col1a1 from the Brtl mouse, a well-characterized model for classical human OI. A human embryonic kidney cell line, which expresses the firefly luciferase gene, combined with either wild-type or Mut Brtl Col1a1 exon 23 sequences, was used for the first screening. The siRNAs selected based on their specificity and the corresponding short hairpin RNAs (shRNAs) subcloned in a lentiviral vector were evaluated ex vivo in Brtl fibroblasts for their effect on collagen transcripts and protein. A preferential reduction of the Mut allele of up to 52% was associated with about 40% decrease of the Mut protein, with no alteration of cell proliferation. Interestingly, a downregulation of HSP47, a specific collagen chaperone known to be upregulated in some OI cases, was detected. Our data support further testing of shRNAs and their delivery by lentivirus as a strategy to specifically suppress the Mut allele in mesenchymal stem cells of OI patients for autologous transplantation. published online 11 September 2013 C1 [Rousseau, Julie; Layrolle, Pierre; Heymann, Dominique; Trichet, Valerie] INSERM, UMR 957, Nantes, France. [Rousseau, Julie; Layrolle, Pierre; Heymann, Dominique; Trichet, Valerie] Univ Nantes, Nantes Atlantique Univ, Fac Med, Lab Physiopathol Resorpt Osseuse & Therapie Tumeu, Nantes, France. [Gioia, Roberta; Rossi, Antonio; Forlino, Antonella] Univ Pavia, Dept Mol Med, Biochem Unit, I-27100 Pavia, Italy. [Lieubeau, Blandine] INRA USC707, Nantes, France. [Lieubeau, Blandine] Oniris Univ Nantes, EA IECM 4644, LUNAM Univ, Nantes, France. [Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. RP Forlino, A (reprint author), Univ Pavia, Dept Mol Med, Biochem Unit, Via Taramelli 3b, I-27100 Pavia, Italy. EM aforlino@unipv.it RI Forlino, Antonella/H-5385-2015; Rossi, Antonio/E-9935-2012; Layrolle, Pierre/K-9257-2015; Trichet, Valerie/L-1553-2015 OI Forlino, Antonella/0000-0002-6385-1182; Layrolle, Pierre/0000-0001-9800-5210; FU Region des Pays de la Loire [JG/ND/RECH N 660]; Agence Nationale de la Recherche [N R07196NS]; AFM TELETHON [N.16017]; [PRIN20094C2H2M]; [Cariplo 2011-0270]; Fondazione Telethon FX This study was supported by the Region des Pays de la Loire (JG/ND/RECH N 660, to JR), the Agence Nationale de la Recherche 2007 Project N R07196NS, PRIN20094C2H2M to AR, Cariplo 2011-0270 to AF and AFM TELETHON N.16017 to AF and VT. NR 46 TC 3 Z9 3 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2014 VL 22 IS 5 BP 667 EP 674 DI 10.1038/ejhg.2013.198 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AF3GS UT WOS:000334600400017 PM 24022296 ER PT J AU Zhang, H Shi, JX Liang, FM Wheeler, W Stolzenberg-Solomon, R Yu, K AF Zhang, Han Shi, Jianxin Liang, Faming Wheeler, William Stolzenberg-Solomon, Rachael Yu, Kai TI A fast multilocus test with adaptive SNP selection for large-scale genetic-association studies SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE genome-wide association study; cis-regulating meQTLs mapping; multilocus test; variable selection; multiple comparisons; pathway analysis ID GENOME-WIDE ASSOCIATION; DISTANCE-BASED REGRESSION; PANCREATIC-CANCER; P VALUES; SUSCEPTIBILITY; METHYLATION; ADJUSTMENT; VARIANTS; PATTERNS; DISEASES AB As increasing evidence suggests that multiple correlated genetic variants could jointly influence the outcome, a multilocus test that aggregates association evidence across multiple genetic markers in a considered gene or a genomic region may be more powerful than a single-marker test for detecting susceptibility loci. We propose a multilocus test, AdaJoint, which adopts a variable selection procedure to identify a subset of genetic markers that jointly show the strongest association signal, and defines the test statistic based on the selected genetic markers. The P-value from the AdaJoint test is evaluated by a computationally efficient algorithm that effectively adjusts for multiple-comparison, and is hundreds of times faster than the standard permutation method. Simulation studies demonstrate that AdaJoint has the most robust performance among several commonly used multilocus tests. We perform multilocus analysis of over 26 000 genes/regions on two genome-wide association studies of pancreatic cancer. Compared with its competitors, AdaJoint identifies a much stronger association between the gene CLPTM1L and pancreatic cancer risk (6.0 x 10(-8)), with the signal optimally captured by two correlated single-nucleotide polymorphisms (SNPs). Finally, we show AdaJoint as a powerful tool for mapping cis-regulating methylation quantitative trait loci on normal breast tissues, and find many CpG sites whose methylation levels are jointly regulated by multiple SNPs nearby. published online 11 September 2013 C1 [Zhang, Han; Shi, Jianxin; Stolzenberg-Solomon, Rachael; Yu, Kai] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20850 USA. [Liang, Faming] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Wheeler, William] Informat Management Serv Inc, Silver Spring, MD USA. RP Yu, K (reprint author), NCI, Div Canc Epidemiol & Genet, Biostat Branch, 9609 Med Ctr Dr,Room 7E630, Rockville, MD 20850 USA. EM yuka@mail.nih.gov RI Zhang, Han/K-2118-2016 OI Zhang, Han/0000-0001-7977-9616 FU Intramural Program of the National Institutes of Health; National Cancer Institute; National Science Foundation [DMS-0607755, CMMI-0926803]; King Abdullah University of Science and Technology [KUS-C1-016-04] FX We thank three anonymous referees for their helpful comments. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD. (http://biowulf.nih.gov). The work of H Zhang, J Shi, R Stolzenberg-Solomon and K Yu were supported by the Intramural Program of the National Institutes of Health and the National Cancer Institute. The work of F Liang was supported in part by the National Science Foundation (DMS-0607755, CMMI-0926803); and the award (KUS-C1-016-04) made by the King Abdullah University of Science and Technology. NR 36 TC 5 Z9 5 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2014 VL 22 IS 5 BP 696 EP 702 DI 10.1038/ejhg.2013.201 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AF3GS UT WOS:000334600400021 PM 24022295 ER PT J AU Gopalan, N Andrade, BB Swaminathan, S AF Gopalan, Narendran Andrade, Bruno Bezerril Swaminathan, Soumya TI Tuberculosis-immune reconstitution inflammatory syndrome in HIV: from pathogenesis to prediction SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY LA English DT Review DE HAART; HIV; paradoxical reaction; TB; IRIS; ART; biomarkers for IRIS ID CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; RISK-FACTORS; RESTORATION DISEASE; MYCOBACTERIAL INFECTIONS; HIV-1-INFECTED PATIENTS; SYNDROME IRIS; SOUTH-AFRICA; ACTIVATION AB Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is an exaggerated, dysregulated immune response against dead or viable antigens of Mycobacterium tuberculosis that frequently occurs after initiation of antiretroviral therapy despite an effective suppression of HIV viremia. Scientific advances in IRIS pathogenesis have led researchers and clinicians to postulate risk factors that could possibly predict this syndrome, in an attempt to reduce the incidence and the severity of IRIS, with appropriate anti-inflammatory therapy. This review is a summary of the available literature on pathogenic mechanisms involved from the macro to the micro level, the clinical spectrum, available predictors and the scope of these biomarkers to function as specific therapeutic targets, that could effectively modulate or ameliorate this syndrome in future. C1 [Gopalan, Narendran; Swaminathan, Soumya] Natl Inst Res TB, Madras 600031, Tamil Nadu, India. [Andrade, Bruno Bezerril] NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Swaminathan, S (reprint author), Natl Inst Res TB, 1 Mayor Sathyamoorthy Rd, Madras 600031, Tamil Nadu, India. EM doctorsoumya@yahoo.com RI Andrade, Bruno/J-9111-2012 OI Andrade, Bruno/0000-0001-6833-3811 NR 79 TC 4 Z9 5 U1 0 U2 5 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1744-666X EI 1744-8409 J9 EXPERT REV CLIN IMMU JI Expert Rev. Clin. Immunol. PD MAY PY 2014 VL 10 IS 5 BP 631 EP 645 DI 10.1586/1744666X.2014.892828 PG 15 WC Immunology SC Immunology GA AF2AG UT WOS:000334514400007 PM 24580108 ER PT J AU Liangpunsakul, S Kleiner, DE AF Liangpunsakul, Suthat Kleiner, David E. TI The Alcoholic Hepatitis Histologic Score: Structured Prognostic Biopsy Evaluation Comes to Alcoholic Hepatitis SO GASTROENTEROLOGY LA English DT Editorial Material ID LIVER-BIOPSY; MORTALITY; DIAGNOSIS C1 [Liangpunsakul, Suthat] Indiana Univ, Med Ctr, Dept Med, Div Gastroenterol & Hepatol, Indianapolis, IN USA. [Liangpunsakul, Suthat] Richard L Roudebush Vet Adm Med Ctr, Indianapolis, IN USA. [Kleiner, David E.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Liangpunsakul, S (reprint author), Indiana Univ Sch Med, Div Gastroenterol & Hepatol, 550 N Univ Blvd,4100, Indianapolis, IN 46202 USA. EM sliangpu@iupui.edu NR 16 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2014 VL 146 IS 5 BP 1156 EP 1158 DI 10.1053/j.gastro.2014.03.016 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AF1XQ UT WOS:000334507600010 PM 24680970 ER PT J AU Manna, SK Tanaka, N Krausz, KW Haznadar, M Xue, X Matsubara, T Bowman, ED Fearon, ER Harris, CC Shah, YM Gonzalez, FJ AF Manna, Soumen K. Tanaka, Naoki Krausz, Kristopher W. Haznadar, Majda Xue, Xiang Matsubara, Tsutomu Bowman, Elise D. Fearon, Eric R. Harris, Curtis C. Shah, Yatrik M. Gonzalez, Frank J. TI Biomarkers of Coordinate Metabolic Reprogramming in Colorectal Tumors in Mice and Humans SO GASTROENTEROLOGY LA English DT Article DE Azoxymethane; Apc(Min/+); ColorectalCancer; Metabolomics; Cancer Biomarker; Metabolic Reprogramming ID FATTY-ACID OXIDATION; MOUSE MODEL; ARGININE METHYLATION; CANCER; CARCINOMA; CELLS; PROLIFERATION; PROGRESSION; INHIBITION; REGULATOR AB BACKGROUND & AIMS: There are no robust noninvasive methods for colorectal cancer screening and diagnosis. Metabolomic and gene expression analyses of urine and tissue samples from mice and humans were used to identify markers of colorectal carcinogenesis. METHODS: Mass spectrometry-based metabolomic analysis of urine and tissues from wild-type C57BL/6J and Apc(Min/+) mice, as well as from mice with azoxymethane-induced tumors, was employed in tandem with gene expression analysis. Metabolic profiling was also performed on colon tumor and adjacent nontumor tissues from 39 patients. The effects of beta-catenin activity on metabolic profiles were assessed in mice with colon-specific disruption of Apc. RESULTS: Thirteen markers were found in urine associated with development of colorectal tumors in Apc(Min/+) mice. Metabolites related to polyamine metabolism, nucleic acid metabolism, and methylation, identified tumor-bearing mice with 100% accuracy, and also accurately identified mice with polyps. Changes in gene expression in tumor samples from mice revealed that derangement of metabolites were a reflection of coordinate metabolic reprogramming in tumor tissue. Similar changes in urinary metabolites were observed in mice with azoxymethane-induced tumors and in mice with colon-specific activation of b-catenin. The metabolic alterations indicated by markers in urine, therefore, appear to occur during early stages of tumorigenesis, when cancer cells are proliferating. In tissues from patients, tumors had stage-dependent increases in 17 metabolites associated with the same metabolic pathways identified in mice. Ten metabolites that were increased in tumor tissues, compared with nontumor tissues (proline, threonine, glutamic acid, arginine, N1-acetylspermidine, xanthine, uracil, betaine, symmetric dimethylarginine, and asymmetric-dimethylarginine), were also increased in urine from tumor-bearing mice. CONCLUSIONS: Gene expression and metabolomic profiles of urine and tissue samples from mice with colorectal tumors and of colorectal tumor samples from patients revealed pathways associated with derangement of specific metabolic pathways that are indicative of early-stage tumor development. These urine and tissue markers might be used in early detection of colorectal cancer. C1 [Manna, Soumen K.; Tanaka, Naoki; Krausz, Kristopher W.; Matsubara, Tsutomu; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. [Haznadar, Majda; Bowman, Elise D.; Harris, Curtis C.] NCI, Lab Human Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA. [Xue, Xiang; Shah, Yatrik M.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Fearon, Eric R.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Fearon, Eric R.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Fearon, Eric R.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Gonzalez, FJ (reprint author), Ctr Canc Res, Lab Metab, 31 Ctr Dr, Bethesda, MD 20892 USA. EM gonzalef@mail.nih.gov RI Xue, Xiang/P-9071-2014 OI Xue, Xiang/0000-0003-4704-1814 FU National Cancer Institute Intramural Research Program; Office of Dietary Supplement Research; National Institutes of Health [CA148828, DK095201] FX This work is funded by the National Cancer Institute Intramural Research Program (FJG), Office of Dietary Supplement Research (SKM), and National Institutes of Health (CA148828 and DK095201) (YMS). NR 34 TC 18 Z9 19 U1 2 U2 40 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2014 VL 146 IS 5 BP 1313 EP 1324 DI 10.1053/j.gastro.2014.01.017 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AF1XQ UT WOS:000334507600032 PM 24440673 ER PT J AU Kang, W Sung, PS Park, SH Yoon, S Chang, DY Kim, S Han, KH Kim, JK Rehermann, B Chwae, YJ Shin, EC AF Kang, Wonseok Sung, Pil Soo Park, Su-Hyung Yoon, Sarah Chang, Dong-Yeop Kim, Seungtaek Han, Kwang Hyub Kim, Ja Kyung Rehermann, Barbara Chwae, Yong-Joon Shin, Eui-Cheol TI Hepatitis C Virus Attenuates Interferon-Induced Major Histocompatibility Complex Class I Expression and Decreases CD8(+) T Cell Effector Functions SO GASTROENTEROLOGY LA English DT Article DE JFH-1; Antigen Presentation; Immune Evasion; Adaptive Immune Response ID NATURAL-KILLER-CELLS; PROTEIN-KINASE; IMMUNE-RESPONSES; ENVELOPE PROTEIN; CORE PROTEIN; INFECTION; DETERMINANTS; PERSISTENCE; INHIBITION; CLEARANCE AB BACKGROUND & AIMS: Major histocompatibility complex (MHC) class I-restricted CD8(+) T cells are required for clearance of hepatitis C virus (HCV) infection. MHC class I expression is up-regulated by type I and II interferons (IFNs). However, little is known about the effects of HCV infection on IFN-induced expression of MHC class I. METHODS: We used the HCV cell culture system (HCVcc) with the genotype 2a Japanese fulminant hepatitis-1 strain to investigate IFN-induced expression of MHC class I and its regulatory mechanisms. HCVcc-infected Huh-7.5 cells were analyzed by flow cytometry, metabolic labeling, immunoprecipitation, and immunoblotting analyses. Protein kinase R (PKR) was knocked down with lentiviruses that express small hairpin RNAs. The functional effects of MHC class I regulation by HCV were demonstrated in co-culture studies, using HCV-specific CD8(+) T cells. RESULTS: Although the baseline level of MHC class I was not affected by HCV infection, IFN-induced expression of MHC class I was notably attenuated in HCV-infected cells. This was associated with replicating HCV RNA, not with viral protein. HCV infection reduced IFN-induced synthesis of MHC class I protein and induced phosphorylation of PKR and eIF2 alpha. IFN-induced MHC class I expression was restored by small hairpin RNA-mediated knockdown of PKR in HCV-infected cells. Co-culture of HCV-specific CD8(+) T cells and HCV-infected cells that expressed HLA-A2 demonstrated that HCV infection reduced the effector functions of HCV-specific CD8(+) T cells; these functions were restored by small hairpin RNA-mediated knockdown of PKR. CONCLUSIONS: IFN-induced expression of MHC class I is attenuated in HCV-infected cells by activation of PKR, which reduces the effector functions of HCV-specific CD8(+) T cells. This appears to be an important mechanism by which HCV circumvents antiviral adaptive immune responses. C1 [Kang, Wonseok; Sung, Pil Soo; Chang, Dong-Yeop; Shin, Eui-Cheol] Korea Adv Inst Sci & Technol, Lab Immunol & Infect Dis, Grad Sch Med Sci & Engn, Taejon 305701, South Korea. [Kang, Wonseok; Kim, Seungtaek; Han, Kwang Hyub; Kim, Ja Kyung] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea. [Park, Su-Hyung; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Yoon, Sarah; Chwae, Yong-Joon] Ajou Univ, Sch Med, Dept Microbiol, Suwon 441749, South Korea. RP Shin, EC (reprint author), Korea Adv Inst Sci & Technol, Lab Immunol & Infect Dis, Grad Sch Med Sci & Engn, 291 Daehak Ro, Taejon 305701, South Korea. EM ecshin@kaist.ac.kr RI Park, Su-Hyung/N-3514-2014; Shin, Eui-Cheol/C-1690-2011 FU National Research Foundation of Korea; Ministry of Science, ICT & Future Planning of Korea [20100030075, 2012-M3C1A1-048860]; Korea Advanced Institute of Science and Technology Future Systems Healthcare Project from the Ministry of Science, ICT & Future Planning of Korea; Yonsei Liver Blood Bank (YLBB); Sanofi-Aventis Korea; Intramural Research Program of the National Institutes of Health, The National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported by the National Research Foundation of Korea, funded by the Ministry of Science, ICT & Future Planning of Korea (20100030075 and 2012-M3C1A1-048860). This work was partly supported by the Korea Advanced Institute of Science and Technology Future Systems Healthcare Project from the Ministry of Science, ICT & Future Planning of Korea. This study was also supported by the Yonsei Liver Blood Bank (YLBB), in part by a grant from Sanofi-Aventis Korea. This research was supported in part by the Intramural Research Program of the National Institutes of Health, The National Institute of Diabetes and Digestive and Kidney Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 13 Z9 15 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2014 VL 146 IS 5 BP 1351 EP + DI 10.1053/j.gastro.2014.01.054 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AF1XQ UT WOS:000334507600035 PM 24486950 ER PT J AU Cheng, I Kocarnik, JM Dumitrescu, L Lindor, NM Chang-Claude, J Avery, CL Caberto, CP Love, SA Slattery, ML Chan, AT Baron, JA Hindorff, LA Park, SL Schumacher, FR Hoffmeister, M Kraft, P Butler, AM Duggan, DJ Hou, LF Carlson, CS Monroe, KR Lin, Y Carty, CL Mann, S Ma, J Giovannucci, EL Fuchs, CS Newcomb, PA Jenkins, MA Hopper, JL Haile, RW Conti, DV Campbell, PT Potter, JD Caan, BJ Schoen, RE Hayes, RB Chanock, SJ Berndt, SI Kuery, S Bezieau, S Ambite, JL Kumaraguruparan, G Richardson, DM Goodloe, RJ Dilks, HH Baker, P Zanke, BW Lemire, M Gallinger, S Hsu, L Jiao, S Harrison, TA Seminara, D Haiman, CA Kooperberg, C Wilkens, LR Hutter, CM White, E Crawford, DC Heiss, G Hudson, TJ Brenner, H Bush, WS Casey, G Le Marchand, L Peters, U AF Cheng, Iona Kocarnik, Jonathan M. Dumitrescu, Logan Lindor, Noralane M. Chang-Claude, Jenny Avery, Christy L. Caberto, Christian P. Love, Shelly-Ann Slattery, Martha L. Chan, Andrew T. Baron, John A. Hindorff, Lucia A. Park, Sungshim Lani Schumacher, Fredrick R. Hoffmeister, Michael Kraft, Peter Butler, Anne M. Duggan, David J. Hou, Lifang Carlson, Chris S. Monroe, Kristine R. Lin, Yi Carty, Cara L. Mann, Sue Ma, Jing Giovannucci, Edward L. Fuchs, Charles S. Newcomb, Polly A. Jenkins, Mark A. Hopper, John L. Haile, Robert W. Conti, David V. Campbell, Peter T. Potter, John D. Caan, Bette J. Schoen, Robert E. Hayes, Richard B. Chanock, Stephen J. Berndt, Sonja I. Kuery, Sebastien Bezieau, Stephane Ambite, Jose Luis Kumaraguruparan, Gowri Richardson, Danielle M. Goodloe, Robert J. Dilks, Holli H. Baker, Paxton Zanke, Brent W. Lemire, Mathieu Gallinger, Steven Hsu, Li Jiao, Shuo Harrison, Tabitha A. Seminara, Daniela Haiman, Christopher A. Kooperberg, Charles Wilkens, Lynne R. Hutter, Carolyn M. White, Emily Crawford, Dana C. Heiss, Gerardo Hudson, Thomas J. Brenner, Hermann Bush, William S. Casey, Graham Le Marchand, Loic Peters, Ulrike TI Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia SO GUT LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; PROSTATE-CANCER; CHROMOSOME 8Q24; MULTIPLE LOCI; COLON-CANCER; BREAST-CANCER; IDENTIFIES 5; DESIGN; METAANALYSIS AB Objective Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92x10(-4) was used to determine statistical significance of the associations. Results Two correlated SNPs-rs10090154 and rs4242382-in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p = 1.74x10(-5)), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24. C1 [Cheng, Iona] Canc Prevent Inst Calif, Fremont, CA 94538 USA. [Kocarnik, Jonathan M.; Carlson, Chris S.; Lin, Yi; Carty, Cara L.; Mann, Sue; Newcomb, Polly A.; Potter, John D.; Hsu, Li; Jiao, Shuo; Harrison, Tabitha A.; Kooperberg, Charles; Hutter, Carolyn M.; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Dumitrescu, Logan; Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol, Nashville, TN 37235 USA. [Dumitrescu, Logan; Crawford, Dana C.] Vanderbilt Univ, Dept Biophys, Nashville, TN 37235 USA. [Dumitrescu, Logan; Goodloe, Robert J.; Dilks, Holli H.; Baker, Paxton; Crawford, Dana C.; Bush, William S.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA. [Lindor, Noralane M.; Richardson, Danielle M.] Mayo Clin Arizona, Dept Hlth Sci Res, Scottsdale, AZ 85260 USA. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Avery, Christy L.; Love, Shelly-Ann; Butler, Anne M.; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Caberto, Christian P.; Park, Sungshim Lani; Wilkens, Lynne R.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Chan, Andrew T.; Ma, Jing; Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp & Harvard, Dept Med, Channing Div Network Med, Boston, MA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Hindorff, Lucia A.] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA. [Schumacher, Fredrick R.; Monroe, Kristine R.; Conti, David V.; Haiman, Christopher A.; Casey, Graham] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hoffmeister, Michael; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Duggan, David J.] Translat Genom Res Inst, Div Genet Basis Human Dis, Phoenix, AZ USA. [Hou, Lifang] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jenkins, Mark A.; Hopper, John L.] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Haile, Robert W.] Stanford Canc Inst, Palo Alto, CA USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Caan, Bette J.] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA 15260 USA. [Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, Dept Environm Med, New York, NY USA. [Chanock, Stephen J.; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kuery, Sebastien; Bezieau, Stephane] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. [Ambite, Jose Luis; Kumaraguruparan, Gowri] Univ So Calif, Informat Sci Inst, Marinadel Rey, CA USA. [Dilks, Holli H.] Vanderbilt Univ, Vanderbilt Technol Adv Genom, Nashville, TN 37235 USA. [Zanke, Brent W.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Lemire, Mathieu; Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Gallinger, Steven] Mt Sinai Hosp, Dept Surg, Toronto, ON M5G 1X5, Canada. [Hsu, Li] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Hutter, Carolyn M.; White, Emily; Peters, Ulrike] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Brenner, Hermann] Germany German Canc Consortium DKTK, Heidelberg, Germany. [Bush, William S.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37235 USA. RP Cheng, I (reprint author), Canc Prevent Inst Calif, 2201 Walnut Ave,Suite 300, Fremont, CA 94538 USA. EM iona.cheng@cpic.org; jkocarni@fhcrc.org RI KURY, Sebastien/G-5971-2015; Hoffmeister, Michael/B-5745-2012; Bezieau, stephane/G-5621-2015; Jenkins, Mark/P-7803-2015; Brenner, Hermann/B-4627-2017; OI KURY, Sebastien/0000-0001-5497-0465; Hoffmeister, Michael/0000-0002-8307-3197; Bezieau, stephane/0000-0003-0095-1319; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Bush, William/0000-0002-9729-6519; Potter, John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X FU National Human Genome Research Institute (NHGRI); CALiCo [U01HG004803]; EAGLE [U01HG004798]; MEC [U01HG004802]; WHI [U01HG004790]; Coordinating Center [U01HG004801]; NHGRI ARRA supplements; NHGRI PAGE program [U01HG004803, U01HG004802, U01HG004790, U01HG004798-01]; NHGRI ARRA supplement; Vanderbilt CTSA from NCATS/NIH [UL1 TR000445]; NHGRI PAGE program (NHGRI ARRA supplement); National Cancer Institute [R37CA54281, R01 CA63464, P01CA33619, U01CA136792, U01CA98758]; National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Atherosclerosis Risk in Communities (ARIC); National Heart, Lung, and Blood Institute contracts [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C]; National Institutes of Health; NIH Roadmap for Medical Research; National Institutes of Mental Health; [R01HL087641]; [R01HL59367]; [R01HL086694]; [UL1RR025005] FX PAGE: (a) The Population Architecture Using Genomics and Epidemiology (PAGE) program is funded by the National Human Genome Research Institute (NHGRI), supported by U01HG004803 (CALiCo), U01HG004798 (EAGLE), U01HG004802 (MEC), U01HG004790 (WHI) and U01HG004801 (Coordinating Center), and their respective NHGRI ARRA supplements. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The complete list of PAGE members can be found at http://www.pagestudy.org. (b) The data and materials included in this report result from collaboration between the following studies: The 'Epidemiologic Architecture for Genes Linked to Environment (EAGLE)' is funded through the NHGRI PAGE program (U01HG004798-01 and its NHGRI ARRA supplement). The dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center's BioVU which is supported by institutional funding and by the Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH. The Vanderbilt University Center for Human Genetics Research, Computational Genomics Core provided computational and/or analytical support for this work. The Multiethnic Cohort study (MEC) characterisation 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, R01 CA63464, P01CA33619, U01CA136792 and U01CA98758). Funding support for the 'Epidemiology of putative genetic variants: The Women's Health Initiative' 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, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C. The authors 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 Genetic Epidemiology of Causal Variants Across the Life Course (CALiCo) program was provided through the NHGRI PAGE program (U01HG004803 and its NHGRI ARRA supplement). The following study contributed to this manuscript and is funded by the following agencies: The Atherosclerosis Risk in Communities (ARIC) Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. Assistance with phenotype harmonisation, 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 Institutes of Mental Health also contributes to the support for the Coordinating Center.; The PAGE consortium thanks the staff and participants of all PAGE studies for their important contributions. NR 70 TC 14 Z9 14 U1 2 U2 13 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD MAY PY 2014 VL 63 IS 5 BP 800 EP 807 DI 10.1136/gutjnl-2013-305189 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AF0GX UT WOS:000334393400016 PM 23935004 ER PT J AU Giangrande, P Seitz, R Behr-Gross, ME Berger, K Hilger, A Klein, H Schramm, W Mannucci, PM AF Giangrande, P. Seitz, R. Behr-Gross, M. E. Berger, K. Hilger, A. Klein, H. Schramm, W. Mannucci, P. M. TI Kreuth III: European consensus proposals for treatment of haemophilia with coagulation factor concentrates SO HAEMOPHILIA LA English DT Article DE treatment; factor VIII; prophylaxis; guidelines; haemophilia ID CARE AB This report summarizes recommendations relating to haemophilia therapy arising from discussions among experts from 36 European countries during the Kreuth III meeting in April 2013. To optimize the organization of haemophilia care nationally, it is recommended that a formal body be established in each country to include the relevant clinicians, national haemophilia patient organization, health ministry, paying authority and (if appropriate) regulatory authorities. The minimum factor VIII consumption level in a country should be 3I.U. per capita. Decisions on whether to adopt a new product should not be based solely on cost. Prophylaxis for children with severe haemophilia is already recognized as the optimum therapy. Ongoing prophylaxis for individual adults should also be provided when required based on clinical decision making by the clinician in consultation with the patient. Children with inhibitors who have failed, or who are not suitable for, immune tolerance therapy should be offered prophylaxis with bypassing agents. Single factor concentrates should be used as therapy wherever possible in patients with rare bleeding disorders. Orphan drug designation for a factor concentrate should not be used to hinder the development, licencing and marketing of other products for the same condition which have demonstrably different protein modification or enhancement. C1 [Giangrande, P.] Oxford Haemophilia & Thrombosis Ctr, Oxford, England. [Giangrande, P.] European Haemophilia Consortium, Brussels, Belgium. [Seitz, R.; Hilger, A.] Paul Ehrlich Inst, Langen, Germany. [Behr-Gross, M. E.] European Directorate Qual Med & HealthCare EDQM, Strasbourg, France. [Berger, K.] Univ Hosp Munich, Munich, Germany. [Klein, H.] NIH, Bethesda, MD 20892 USA. [Schramm, W.] Rudolf Marx Stiftung, Munich, Germany. [Mannucci, P. M.] Fdn IRCCS Ca Granda Osped Maggiore, Milan, Italy. RP Giangrande, P (reprint author), Churchill Hosp, Oxford Haemophilia & Thrombosis Ctr, Oxford OX3 7LE, England. EM paul.giangrande@ndm.ox.ac.uk FU Paul Ehrlich Institut (PEI), Langen, Germany; Ludwig-Maximillian-University (LMU) Munchen, Germany; European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe, Strasbourg, France; Rudolf-Marx-Stiftung FX The Kreuth III initiative was co-sponsored by the Paul Ehrlich Institut (PEI), Langen, Germany, the Ludwig-Maximillian-University (LMU) Munchen, Germany and the European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe, Strasbourg, France. Financial support was granted by the Rudolf-Marx-Stiftung. NR 9 TC 10 Z9 10 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-8216 EI 1365-2516 J9 HAEMOPHILIA JI Haemophilia PD MAY PY 2014 VL 20 IS 3 BP 322 EP 325 DI 10.1111/hae.12440 PG 4 WC Hematology SC Hematology GA AE9RQ UT WOS:000334346900016 PM 24731129 ER PT J AU Earp, MA Kelemen, LE Magliocco, AM Swenerton, KD Chenevix-Trench, G Lu, Y Hein, A Ekici, AB Beckmann, MW Fasching, PA Lambrechts, D Despierre, E Vergote, I Lambrechts, S Doherty, JA Rossing, MA Chang-Claude, J Rudolph, A Friel, G Moysich, KB Odunsi, K Sucheston-Campbell, L Lurie, G Goodman, MT Carney, ME Thompson, PJ Runnebaum, IB Durst, M Hillemanns, P Dork, T Antonenkova, N Bogdanova, N Leminen, A Nevanlinna, H Pelttari, LM Butzow, R Bunker, CH Modugno, F Edwards, RP Ness, RB du Bois, A Heitz, F Schwaab, I Harter, P Karlan, BY Walsh, C Lester, J Jensen, A Kjaer, SK Hogdall, CK Hogdall, E Lundvall, L Sellers, TA Fridley, BL Goode, EL Cunningham, JM Vierkant, RA Giles, GG Baglietto, L Severi, G Southey, MC Liang, D Wu, XF Lu, K Hildebrandt, MAT Levine, DA Bisogna, M Schildkraut, JM Iversen, ES Weber, RP Berchuck, A Cramer, DW Terry, KL Poole, EM Tworoger, SS Bandera, EV Chandran, U Orlow, I Olson, SH Wik, E Salvesen, HB Bjorge, L Halle, MK van Altena, AM Aben, KKH Kiemeney, LA Massuger, LFAG Pejovic, T Bean, YT Cybulski, C Gronwald, J Lubinski, J Wentzensen, N Brinton, LA Lissowska, J Garcia-Closas, M Dicks, E Dennis, J Easton, DF Song, HL Tyrer, JP Pharoah, PDP Eccles, D Campbell, IG Whittemore, AS McGuire, V Sieh, W Rothstein, JH Flanagan, JM Paul, J Brown, R Phelan, CM Risch, HA McLaughlin, JR Narod, SA Ziogas, A Anton-Culver, H Gentry-Maharaj, A Menon, U Gayther, SA Ramus, SJ Wu, AH Pearce, CL Pike, MC Dansonka-Mieszkowska, A Rzepecka, IK Szafron, LM Kupryjanczyk, J Cook, LS Le, ND Brooks-Wilson, A AF Earp, Madalene A. Kelemen, Linda E. Magliocco, Anthony M. Swenerton, Kenneth D. Chenevix-Trench, Georgia Lu, Yi Hein, Alexander Ekici, Arif B. Beckmann, Matthias W. Fasching, Peter A. Lambrechts, Diether Despierre, Evelyn Vergote, Ignace Lambrechts, Sandrina Doherty, Jennifer A. Rossing, Mary Anne Chang-Claude, Jenny Rudolph, Anja Friel, Grace Moysich, Kirsten B. Odunsi, Kunle Sucheston-Campbell, Lara Lurie, Galina Goodman, Marc T. Carney, Michael E. Thompson, Pamela J. Runnebaum, Ingo B. Duerst, Matthias Hillemanns, Peter Doerk, Thilo Antonenkova, Natalia Bogdanova, Natalia Leminen, Arto Nevanlinna, Heli Pelttari, Liisa M. Butzow, Ralf Bunker, Clareann H. Modugno, Francesmary Edwards, Robert P. Ness, Roberta B. du Bois, Andreas Heitz, Florian Schwaab, Ira Harter, Philipp Karlan, Beth Y. Walsh, Christine Lester, Jenny Jensen, Allan Kjaer, Susanne K. Hogdall, Claus K. Hogdall, Estrid Lundvall, Lene Sellers, Thomas A. Fridley, Brooke L. Goode, Ellen L. Cunningham, Julie M. Vierkant, Robert A. Giles, Graham G. Baglietto, Laura Severi, Gianluca Southey, Melissa C. Liang, Dong Wu, Xifeng Lu, Karen Hildebrandt, Michelle A. T. Levine, Douglas A. Bisogna, Maria Schildkraut, Joellen M. Iversen, Edwin S. Weber, Rachel Palmieri Berchuck, Andrew Cramer, Daniel W. Terry, Kathryn L. Poole, Elizabeth M. Tworoger, Shelley S. Bandera, Elisa V. Chandran, Urmila Orlow, Irene Olson, Sara H. Wik, Elisabeth Salvesen, Helga B. Bjorge, Line Halle, Mari K. van Altena, Anne M. Aben, Katja K. H. Kiemeney, Lambertus A. Massuger, Leon F. A. G. Pejovic, Tanja Bean, Yukie T. Cybulski, Cezary Gronwald, Jacek Lubinski, Jan Wentzensen, Nicolas Brinton, Louise A. Lissowska, Jolanta Garcia-Closas, Montserrat Dicks, Ed Dennis, Joe Easton, Douglas F. Song, Honglin Tyrer, Jonathan P. Pharoah, Paul D. P. Eccles, Diana Campbell, Ian G. Whittemore, Alice S. McGuire, Valerie Sieh, Weiva Rothstein, Joseph H. Flanagan, James M. Paul, James Brown, Robert Phelan, Catherine M. Risch, Harvey A. McLaughlin, John R. Narod, Steven A. Ziogas, Argyrios Anton-Culver, Hoda Gentry-Maharaj, Aleksandra Menon, Usha Gayther, Simon A. Ramus, Susan J. Wu, Anna H. Pearce, Celeste L. Pike, Malcolm C. Dansonka-Mieszkowska, Agnieszka Rzepecka, Iwona K. Szafron, Lukasz M. Kupryjanczyk, Jolanta Cook, Linda S. Le, Nhu D. Brooks-Wilson, Angela CA Australian Canc Study Australian Ovarian Canc Study Grp Ovarian Canc Assoc Consortium TI Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA SO HUMAN GENETICS LA English DT Article ID CLEAR-CELL CARCINOMA; GRADE SEROUS CARCINOMA; MICROSATELLITE INSTABILITY; MOLECULAR CHARACTERIZATION; SUSCEPTIBILITY LOCUS; MUTATIONS; VARIANTS; GENE; IDENTIFICATION; ENDOMETRIOSIS AB Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes. C1 [Earp, Madalene A.; Brooks-Wilson, Angela] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada. [Kelemen, Linda E.; Cook, Linda S.] Alberta Hlth Serv Canc Care, Dept Populat Hlth Res, Calgary, AB, Canada. [Kelemen, Linda E.] Univ Calgary, Dept Med Genet, Calgary, AB, Canada. [Kelemen, Linda E.] Univ Calgary, Dept Oncol, Calgary, AB, Canada. [Magliocco, Anthony M.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Anat Pathol, Tampa, FL 33682 USA. [Swenerton, Kenneth D.] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Chenevix-Trench, Georgia; Lu, Yi; Australian Canc Study] QIMR Berghofer Med Res Inst, Herston, Qld, Australia. [Campbell, Ian G.; Australian Ovarian Canc Study Grp] Peter MacCallum Canc Ctr, Div Res, Melbourne, Vic, Australia. [Hein, Alexander; Beckmann, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Ctr Comprehens Canc, Dept Gynecol & Obstet, Univ Hosp Erlangen, D-91054 Erlangen, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Lambrechts, Diether] VIB, Vesalius Res Ctr, Louvain, Belgium. [Lambrechts, Diether] Univ Louvain, Dept Oncol, Lab Translat Genet, Louvain, Belgium. [Despierre, Evelyn; Vergote, Ignace; Lambrechts, Sandrina] Leuven Canc Inst, Dept Obstet & Gynaecol, Div Gynecol Oncol, Louvain, Belgium. [Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Epidemiol & Biostat Sect, Lebanon, NH USA. [Doherty, Jennifer A.; Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA USA. [Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Friel, Grace; Moysich, Kirsten B.; Odunsi, Kunle; Sucheston-Campbell, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Lurie, Galina; Carney, Michael E.] Univ Hawaii, Canc Epidemiol Program, Ctr Canc, Honolulu, HI 96822 USA. [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Runnebaum, Ingo B.; Duerst, Matthias] Univ Jena, Dept Obstet & Gynaecol, Jena Univ Hosp, Jena, Germany. [Hillemanns, Peter] Hannover Med Sch, Clin Obstet, Hannover, Germany. [Hillemanns, Peter] Hannover Med Sch, Clin Gynaecol, Hannover, Germany. [Doerk, Thilo; Bogdanova, Natalia] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany. [Antonenkova, Natalia] Aleksandrov Byelorussian Inst Oncol & Med Radiol, Minsk, Byelarus. [Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.; Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland. [Bunker, Clareann H.; Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Modugno, Francesmary; Edwards, Robert P.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Modugno, Francesmary; Edwards, Robert P.] Univ Pittsburgh, Womens Canc Res Ctr, Magee Womens Res Inst, Inst Canc, Pittsburgh, PA USA. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [du Bois, Andreas; Heitz, Florian; Harter, Philipp] Huyssens Stiftung Knappschaft GmbH, Kliniken Essen Mitte Evang, Dept Gynecol & Gynecol Oncol, Essen, Germany. [du Bois, Andreas; Heitz, Florian; Harter, Philipp] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany. [Schwaab, Ira] Inst Human Genet & Anthropol, Wiesbaden, Germany. [Karlan, Beth Y.; Walsh, Christine; Lester, Jenny] Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Jensen, Allan; Kjaer, Susanne K.; Hogdall, Estrid] Danish Canc Soc, Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark. 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[Southey, Melissa C.; Campbell, Ian G.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA. [Wu, Xifeng; Hildebrandt, Michelle A. T.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Lu, Karen] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Levine, Douglas A.; Bisogna, Maria] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA. [Schildkraut, Joellen M.; Weber, Rachel Palmieri] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Schildkraut, Joellen M.; Iversen, Edwin S.] Duke Canc Inst, Durham, NC USA. [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA. [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Cramer, Daniel W.; Terry, Kathryn L.; Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Bandera, Elisa V.; Chandran, Urmila] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Orlow, Irene; Olson, Sara H.; Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Wik, Elisabeth] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. [Wik, Elisabeth; Salvesen, Helga B.; Bjorge, Line; Halle, Mari K.] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, Bergen, Norway. [Salvesen, Helga B.; Bjorge, Line; Halle, Mari K.] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway. [van Altena, Anne M.; Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Dept Gynecol, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Aben, Katja K. 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[Garcia-Closas, Montserrat] Breakthrough Breast Canc Res Ctr, London, England. [Dicks, Ed; Song, Honglin; Tyrer, Jonathan P.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge, England. [Dennis, Joe; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Eccles, Diana] Univ Southampton, Fac Med, Southampton Univ Hosp, Southampton SO9 5NH, Hants, England. [Campbell, Ian G.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia. [Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph H.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. [Flanagan, James M.; Brown, Robert] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London, England. [Paul, James] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland. [Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. [McLaughlin, John R.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada. [Ziogas, Argyrios; Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, Dept Epidemiol, Ctr Canc Genet Res & Prevent, Irvine, CA 92717 USA. [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Gynaecol Canc Res Ctr, Elizabeth Garrett Anderson Inst Womens Hlth, London, England. [Gayther, Simon A.; Ramus, Susan J.; Wu, Anna H.; Pearce, Celeste L.; Pike, Malcolm C.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K.; Szafron, Lukasz M.; Kupryjanczyk, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Inst Oncol, Dept Pathol, Warsaw, Poland. [Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA. [Cook, Linda S.] Univ Calgary, Fac Med, Dept Community Hlth Sci, Calgary, AB, Canada. [Le, Nhu D.] BC Canc Agcy, Vancouver, BC V5Z 1L3, Canada. [Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada. RP Earp, MA (reprint author), BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, 675 West 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM mearp@bcgsc.ca; abrooks-wilson@bcgsc.ca RI Whittemore, Alice/F-9925-2014; Brooks-Wilson, Angela/E-9399-2012; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Hein, Alexander/F-6999-2010; van Altena, Anne/B-9824-2016; Dork, Thilo/J-8620-2012; Aben, Katja/G-9686-2016; Bandera, Elisa/M-4169-2014; Massuger, Leon/H-8072-2014; Kiemeney, Lambertus/D-3357-2009; Fridley, Brooke/D-8315-2015; Bowtell, David/H-1007-2016; Gronwald, Jacek/A-4576-2017; Bjorge, Line/C-1307-2017; salvesen, Helga/C-1187-2017; OI Brooks-Wilson, Angela/0000-0003-1009-6408; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Hein, Alexander/0000-0003-2601-3398; Aben, Katja/0000-0002-0214-2147; Bandera, Elisa/0000-0002-8789-2755; Kiemeney, Lambertus/0000-0002-2368-1326; Fridley, Brooke/0000-0001-7739-7956; Bowtell, David/0000-0001-9089-7525; Gronwald, Jacek/0000-0002-3643-2871; Bjorge, Line/0000-0002-0240-2770; salvesen, Helga/0000-0002-4438-8831; Dennis, Joe/0000-0003-4591-1214; Halle, Mari/0000-0002-2660-8271; Nevanlinna, Heli/0000-0002-0916-2976; Tworoger, Shelley/0000-0002-6986-7046; Kjaer, Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798; Lissowska, Jolanta/0000-0003-2695-5799; Orlow, Irene/0000-0001-6234-6961; Giles, Graham/0000-0003-4946-9099 FU Canadian Institutes of Health Research [MOP-86727, MOP-84340]; WorkSafeBC 14; OvCaRe: BC's Ovarian Cancer Research Team; American Cancer Society [CRTG-00-196-01-CCE]; California Cancer Research Program [00-01389 V-20170, N01-CN25403, 2II0200]; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; Cancer Institute of New Jersey; Cancer Research UK [C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689]; Celma Mastry Ovarian Cancer Foundation; Danish Cancer Society [94-222-52]; ELAN Program of the University of Erlangen-Nuremberg; Eve Appeal (Oak Foundation); Fred C. and Katherine B. Andersen Foundation; German Cancer Research Center; German Federal Ministry of Education and Research of Germany, Program of Clinical Biomedical Research [01 GB 9401]; Helsinki University Central Hospital Research Fund; Helse Vest; Imperial Experimental Cancer Research Centre [C1312/A15589]; L & S Milken Foundation; the Lon V. Smith Foundation [LVS-39420]; Mayo Foundation; Mermaid I project; Minnesota Ovarian Cancer Alliance; National Health and Medical Research Council of Australia [199600, 209057, 251533, 396414, 400281, 504715]; Nationaal Kankerplan of Belgium; Norwegian Cancer Society; Norwegian Research Council; OHSU Foundation; Polish Ministry of Science and Higher Education [4 PO5C 028 14, 2 PO5A 068 27]; Pomeranian Medical University; Radboud University Medical Center; Roswell Park Cancer Institute Alliance Foundation; Royal Marsden Hospital; Rudolf-Bartling Foundation; Sigrid Juselius Foundation; state of Baden-Wurttemberg through Medical Faculty of the University of Ulm [P.685]; UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; University College London Hospitals; US 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]; Department of Defense Ovarian Cancer Research Program [W81XWH-07-1-0449]; US National Cancer Institute [K07-CA095666, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA15083, P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107]; US National Institutes of Health/National Center for Research Resources/General Clinical Research Center [MO1-RR000056]; US Public Health Service [PSA-042205]; US National Cancer Institute. [R01-CA063678, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044]; The US National Cancer Institute [R01-CA061132, R01-095023, R01-CA106414, R01CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01CA136924, R01-CA149429, R03-CA113148, R03-CA115195, R37CA070867, R37-CA70867, U01-CA069417, U01-CA071966] FX Funding of constituent studies: This project was funded through grants from the Canadian Institutes of Health Research (MOP-86727, MOP-84340); WorkSafeBC 14, and OvCaRe: BC's Ovarian Cancer Research Team. Funding of the constituent studies was provided by the American Cancer Society (CRTG-00-196-01-CCE); the California Cancer Research Program (00-01389 V-20170, N01-CN25403, 2II0200); Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689); the Celma Mastry Ovarian Cancer Foundation; the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal (Oak Foundation); the Fred C. and Katherine B. Andersen Foundation; the German Cancer Research Center; the German Federal Ministry of Education and Research of Germany, Program of Clinical Biomedical Research (01 GB 9401); the Helsinki University Central Hospital Research Fund; Helse Vest; Imperial Experimental Cancer Research Centre (C1312/A15589); the L & S Milken Foundation; the Lon V. Smith Foundation (LVS-39420); the Mayo Foundation; the Mermaid I project; the Minnesota Ovarian Cancer Alliance; the National Health and Medical Research Council of Australia (199600, 209057, 251533, 396414, 400281, and 504715); Nationaal Kankerplan of Belgium; the Norwegian Cancer Society; the Norwegian Research Council; the OHSU Foundation; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); Pomeranian Medical University; Radboud University Medical Center; the Roswell Park Cancer Institute Alliance Foundation; the Royal Marsden Hospital; the Rudolf-Bartling Foundation; the Sigrid Juselius Foundation; the state of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P.685); the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge and the University College London Hospitals; the US Army Medical Research and Material Command (DAMD17-98-1-8659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-10-1-0280); the Department of Defense Ovarian Cancer Research Program (W81XWH-07-1-0449); the US National Cancer Institute (K07-CA095666, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA15083, 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-CA063678, 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, R01CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01CA136924, R01-CA149429, R03-CA113148, R03-CA115195, R37CA070867, R37-CA70867, U01-CA069417, U01-CA071966 and Intramural research funds); the US National Institutes of Health/National Center for Research Resources/General Clinical Research Center (MO1-RR000056); and the US Public Health Service (PSA-042205). NR 52 TC 6 Z9 6 U1 0 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD MAY PY 2014 VL 133 IS 5 BP 481 EP 497 DI 10.1007/s00439-013-1383-3 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA AF2CJ UT WOS:000334519900002 PM 24190013 ER PT J AU Cook, MB Wang, ZM Yeboah, ED Tettey, Y Biritwum, RB Adjei, AA Tay, E Truelove, A Niwa, S Chung, CC Chokkalingam, AP Chu, LW Yeager, M Hutchinson, A Yu, K Rand, KA Haiman, CA Hoover, RN Hsing, AW Chanock, SJ AF Cook, Michael Blaise Wang, Zhaoming Yeboah, Edward D. Tettey, Yao Biritwum, Richard B. Adjei, Andrew A. Tay, Evelyn Truelove, Ann Niwa, Shelley Chung, Charles C. Chokkalingam, Annand P. Chu, Lisa W. Yeager, Meredith Hutchinson, Amy Yu, Kai Rand, Kristin A. Haiman, Christopher A. Hoover, Robert N. Hsing, Ann W. Chanock, Stephen J. CA African Ancestry Prostate Canc GWA TI A genome-wide association study of prostate cancer in West African men SO HUMAN GENETICS LA English DT Article ID POPULATION-STRUCTURE; JAPANESE POPULATION; SUSCEPTIBILITY; REPLICATION; ADMIXTURE; DISEASE; LOCI; ANNOTATION; AMERICANS; VARIANTS AB Age-adjusted mortality rates for prostate cancer are higher for African-American men compared with those of European ancestry. Recent data suggest that West African men also have elevated risk for prostate cancer relative to European men. Genetic susceptibility to prostate cancer could account for part of this difference. We conducted a genome-wide association study (GWAS) of prostate cancer in West African men in the Ghana Prostate Study. Association testing was performed using multivariable logistic regression adjusted for age and genetic ancestry for 474 prostate cancer cases and 458 population-based controls on the Illumina HumanOmni-5 Quad BeadChip. The most promising association was at 10p14 within an intron of a long non-coding RNA (lncRNA RP11-543F8.2) 360 kb centromeric of GATA3 (p = 1.29E-7). In sub-analyses, SNPs at 5q31.3 were associated with high Gleason score (a parts per thousand yen7) cancers, the strongest of which was a missense SNP in PCDHA1 (rs34575154, p = 3.66E-8), and SNPs at Xq28 (rs985081, p = 8.66E-9) and 6q21 (rs2185710, p = 5.95E-8) were associated with low Gleason score (< 7) cancers. We sought to validate our findings in silico in the African Ancestry Prostate Cancer GWAS Consortium, but only one SNP, at 10p14, replicated at p < 0.05. Of the 90 prostate cancer loci reported from studies of men of European, Asian or African-American ancestry, we were able to test 81 in the Ghana Prostate Study, and 10 of these replicated at p < 0.05. Further genetic studies of prostate cancer in West African men are needed to confirm our promising susceptibility loci. C1 [Cook, Michael Blaise; Wang, Zhaoming; Chung, Charles C.; Yeager, Meredith; Hutchinson, Amy; Yu, Kai; Hoover, Robert N.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Wang, Zhaoming; Yeager, Meredith; Hutchinson, Amy] SAIC Frederick Inc, Canc Genom Res Lab, NCI DCEG, Frederick, MD USA. [Yeboah, Edward D.; Tettey, Yao; Biritwum, Richard B.; Adjei, Andrew A.; Tay, Evelyn] Korle Bu Teaching Hosp, Accra, Ghana. [Yeboah, Edward D.; Tettey, Yao; Biritwum, Richard B.; Adjei, Andrew A.; Tay, Evelyn] Univ Ghana, Sch Med, Accra, Ghana. [Truelove, Ann; Niwa, Shelley] WESTAT Corp, Rockville, MD 20850 USA. [Chokkalingam, Annand P.; Hsing, Ann W.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Chu, Lisa W.] Canc Prevent Inst Calif, Fremont, CA 94538 USA. [Rand, Kristin A.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Hsing, Ann W.] Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA. RP Cook, MB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 9609 Med Ctr Dr,Rm 7-E106,MSC 9774, Bethesda, MD 20892 USA. EM cookmich@mail.nih.gov RI Cook, Michael/A-5641-2009 OI Cook, Michael/0000-0002-0533-7302 FU Intramural Research Program of the National Cancer Institute, National Institutes of Health; Intramural Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services [HHSN261200800001E] FX The authors thank Ms. Vicky Okyne for her expert help in coordinating the study; consultants/resident urologists, pathologists, nurses, and interviewers of Korle-Bu Hospital and University of Ghana Medical School for their assistance with subject enrollment, screening, and clinical examination; the study participants for their contribution toward a better understanding of prostate disease; A. DeMarzo and G. Netto of Johns Hopkins University for pathology review; Ms. Violet Devairakkam, Ms. Norma Kim, and Mr. John Heinrich of Research Triangle Institute (RTI) for their expert study management; Prof. Rosalind A. Eeles and her team for crosschecking published prostate cancer loci specified in Table 3; and members of the African Ancestry Prostate Cancer GWAS Consortium for looking-up our most promising associations from our African GWAS. This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. Intramural Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services including Contract No. HHSN261200800001E. NR 56 TC 13 Z9 13 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD MAY PY 2014 VL 133 IS 5 BP 509 EP 521 DI 10.1007/s00439-013-1387-z PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AF2CJ UT WOS:000334519900004 PM 24185611 ER PT J AU Zou, YQ Zwolanek, D Izu, YY Gandhy, S Schreiber, G Brockmann, K Devoto, M Tian, ZZ Hu, Y Veit, G Meier, M Stetefeld, J Hicks, D Straub, V Voermans, NC Birk, DE Barton, ER Koch, M Bonnemann, CG AF Zou, Yaqun Zwolanek, Daniela Izu, Yayoi Gandhy, Shreya Schreiber, Gudrun Brockmann, Knut Devoto, Marcella Tian, Zuozhen Hu, Ying Veit, Guido Meier, Markus Stetefeld, Joerg Hicks, Debbie Straub, Volker Voermans, Nicol C. Birk, David E. Barton, Elisabeth R. Koch, Manuel Boennemann, Carsten G. TI Recessive and dominant mutations in COL12A1 cause a novel EDS/myopathy overlap syndrome in humans and mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID CONGENITAL MUSCULAR-DYSTROPHY; TISSUE-SPECIFIC EXPRESSION; EHLERS-DANLOS-SYNDROME; COLLAGEN-XII; CONNECTIVE-TISSUE; TENASCIN-X; SOLEUS MUSCLE; DIFFERENTIAL EXPRESSION; EMBRYONIC-DEVELOPMENT; POSTNATAL-DEVELOPMENT AB Collagen VI-related myopathies are disorders of connective tissue presenting with an overlap phenotype combining clinical involvement from the muscle and from the connective tissue. Not all patients displaying related overlap phenotypes between muscle and connective tissue have mutations in collagen VI. Here, we report a homozygous recessive loss of function mutation and a de novo dominant mutation in collagen XII (COL12A1) as underlying a novel overlap syndrome involving muscle and connective tissue. Two siblings homozygous for a loss of function mutation showed widespread joint hyperlaxity combined with weakness precluding independent ambulation, while the patient with the de novo missense mutation was more mildly affected, showing improvement including the acquisition of walking. A mouse model with inactivation of the Col12a1 gene showed decreased grip strength, a delay in fiber-type transition and a deficiency in passive force generation while the muscle seems more resistant to eccentric contraction induced force drop, indicating a role for a matrix-based passive force-transducing elastic element in the generation of the weakness. This new muscle connective tissue overlap syndrome expands on the emerging importance of the muscle extracellular matrix in the pathogenesis of muscle disease. C1 [Zou, Yaqun; Gandhy, Shreya; Hu, Ying; Boennemann, Carsten G.] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, NIH, Bethesda, MD 20892 USA. [Zwolanek, Daniela; Koch, Manuel] Univ Cologne, Ctr Biochem, Ctr Mol Med Cologne, Med Fac,Inst Dent Res & Oral Musculoskeletal Biol, D-50931 Cologne, Germany. [Izu, Yayoi; Veit, Guido; Birk, David E.] Univ S Florida, Dept Mol Pharmacol & Physiol, Tampa, FL USA. [Schreiber, Gudrun] Clin Ctr Pediat Neurol, Kassel, Germany. [Brockmann, Knut] Univ Med Ctr, Interdisciplinary Pediat Ctr Children Dev Disabil, Gottingen, Germany. [Devoto, Marcella] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [Devoto, Marcella] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Devoto, Marcella] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Devoto, Marcella] Univ Roma La Sapienza, Dept Mol Med, Rome, Italy. [Tian, Zuozhen; Barton, Elisabeth R.] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. [Meier, Markus; Stetefeld, Joerg] Univ Manitoba, Dept Chem Microbiol Biochem & Med Genet, Winnipeg, MB R3T 2N2, Canada. [Hicks, Debbie; Straub, Volker] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Voermans, Nicol C.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Neurol, Nijmegen, Netherlands. RP Bonnemann, CG (reprint author), NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, NIH, Porter Neurosci Res Ctr, 35 Convent Dr,Bldg 35,Room 2A-116, Bethesda, MD 20892 USA. EM manuel.koch@uni-koeln.de; carsten.bonnemann@nih.gov RI Veit, Guido/C-9596-2009; Birk, David/I-4072-2012; Voermans, N.C./L-4724-2015; OI Veit, Guido/0000-0002-6758-2696; Birk, David/0000-0002-4865-9088; Stetefeld, Joerg/0000-0003-1478-3248 FU NINDS/NIH intramural research funds; MDA-USA; Deutsche Forschungsgemeinschaft [SFB 829]; Koln Fortune Programme of the Medical Faculty; Paul Wellstone Muscular Dystrophy Cooperative Research Center [U54 AR052646]; Heart and Stroke Foundation Canada; Canada Research Chair Program; NIAMS/NIH [AR044745] FX Work in C.G.B.'s lab is supported by NINDS/NIH intramural research funds. The work was started with support of a grant of the MDA-USA to C.G.B. Supported by the Deutsche Forschungsgemeinschaft SFB 829 grant A2 (M.K.) and by the Koln Fortune Programme of the Medical Faculty (M.K.). Work in in E.R.B.'s lab was supported by a Paul Wellstone Muscular Dystrophy Cooperative Research Center (U54 AR052646). J.S. was supported by the Heart and Stroke Foundation Canada and the Canada Research Chair Program. D.B. was supported by NIAMS/NIH AR044745. NR 63 TC 17 Z9 18 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2014 VL 23 IS 9 BP 2339 EP 2352 DI 10.1093/hmg/ddt627 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AE9VL UT WOS:000334359100009 PM 24334604 ER PT J AU Hicks, D Farsani, GT Laval, S Collins, J Sarkozy, A Martoni, E Shah, A Zou, YQ Koch, M Bonnemann, CG Roberts, M Lochmuller, H Bushby, K Straub, V AF Hicks, Debbie Farsani, Golara Torabi Laval, Steven Collins, James Sarkozy, Anna Martoni, Elena Shah, Ashoke Zou, Yaqun Koch, Manuel Boennemann, Carsten G. Roberts, Mark Lochmueller, Hanns Bushby, Kate Straub, Volker TI Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy SO HUMAN MOLECULAR GENETICS LA English DT Article ID CONGENITAL MUSCULAR-DYSTROPHY; EHLERS-DANLOS-SYNDROME; AUTOSOMAL-DOMINANT MYOPATHY; TENASCIN-X DEFICIENCY; BETHLEM MYOPATHY; GLYCINE MUTATIONS; SUPPORT OVERLAP; VI; CONTRACTURES; SEQUENCE AB Bethlem myopathy (BM) [MIM 158810] is a slowly progressive muscle disease characterized by contractures and proximal weakness, which can be caused by mutations in one of the collagen VI genes (COL6A1, COL6A2 and COL6A3). However, there may be additional causal genes to identify as in 50 of BM cases no mutations in the COL6 genes are identified. In a cohort of 24 patients with a BM-like phenotype, we first sequenced 12 candidate genes based on their function, including genes for known binding partners of collagen VI, and those enzymes involved in its correct post-translational modification, assembly and secretion. Proceeding to whole-exome sequencing (WES), we identified mutations in the COL12A1 gene, a member of the FACIT collagens (fibril-associated collagens with interrupted triple helices) in five individuals from two families. Both families showed dominant inheritance with a clinical phenotype resembling classical BM. Family 1 had a single-base substitution that led to the replacement of one glycine residue in the triple-helical domain, breaking the Gly-X-Y repeating pattern, and Family 2 had a missense mutation, which created a mutant protein with an unpaired cysteine residue. Abnormality at the protein level was confirmed in both families by the intracellular retention of collagen XII in patient dermal fibroblasts. The mutation in Family 2 leads to the up-regulation of genes associated with the unfolded protein response (UPR) pathway and swollen, dysmorphic rough-ER. We conclude that the spectrum of causative genes in extracellular matrix (ECM)-related myopathies be extended to include COL12A1. C1 [Hicks, Debbie; Farsani, Golara Torabi; Laval, Steven; Sarkozy, Anna; Shah, Ashoke; Lochmueller, Hanns; Bushby, Kate; Straub, Volker] Inst Med Genet, MRC, Ctr Neuromuscular Dis Newcastle, Newcastle Upon Tyne, Tyne & Wear, England. [Collins, James] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Martoni, Elena] Univ Ferrara, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy. [Zou, Yaqun; Boennemann, Carsten G.] NINDS, NIH, Bethesda, MD 20892 USA. [Koch, Manuel] Univ Cologne, Ctr Biochem, Inst Dent Res & Oral Musculoskeletal Biol, D-50931 Cologne, Germany. [Roberts, Mark] Hope Hosp, Dept Neurol, Salford M6 8HD, Lancs, England. [Roberts, Mark] Hope Hosp, Dept Neuropathol, Salford M6 8HD, Lancs, England. RP Straub, V (reprint author), Newcastle Univ, Inst Med Genet, Cent Pkwy, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. EM volker.straub@ncl.ac.uk OI Lochmuller, Hanns/0000-0003-2324-8001 FU European Community [2012-305121]; 'Integrated European -omics research project for diagnosis and therapy in rare neuromuscular and neurodegenerative diseases (NEUROMICS); European Union [305444]; Newcastle University Faculty of Medical Sciences Fellowship; National Commissioning Group (NCST) FX This work was supported by the European Community's Seventh Framework Programme (FP7/2007-2013) (grant number: 2012-305121), 'Integrated European -omics research project for diagnosis and therapy in rare neuromuscular and neurodegenerative diseases (NEUROMICS) and European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 305444 (RD-Connect). D.H. is supported by a Newcastle University Faculty of Medical Sciences Fellowship. Diagnostic facilities at the Newcastle Muscle Centre is supported by the National Commissioning Group (NCST) for rare neuromuscular disorders. The Institute of Genetic Medicine in Newcastle is part of the MRC Centre for Neuromuscular Diseases. Newcastle University is a partner organization of the TREAT-NMD Alliance. NR 46 TC 16 Z9 17 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2014 VL 23 IS 9 BP 2353 EP 2363 DI 10.1093/hmg/ddt637 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AE9VL UT WOS:000334359100010 PM 24334769 ER PT J AU Perry, JRB Hsu, YH Chasman, DI Johnson, AD Elks, C Albrecht, E Andrulis, IL Beesley, J Berenson, GS Bergmann, S Bojesen, SE Bolla, MK Brown, J Buring, JE Campbell, H Chang-Claude, J Chenevix-Trench, G Corre, T Couch, FJ Cox, A Czene, K D'adamo, AP Davies, G Deary, IJ Dennis, J Easton, DF Engelhardt, EG Eriksson, JG Esko, T Fasching, PA Figueroa, JD Flyger, H Fraser, A Garcia-Closas, M Gasparini, P Gieger, C Giles, G Guenel, P Hagg, S Hall, P Hayward, C Hopper, J Ingelsson, E Kardia, LR Kasiman, K Knight, JA Lahti, J Lawlor, DA Magnusson, PKE Margolin, S Marsh, JA Metspalu, A Olson, JE Pennell, CE Polasek, O Rahman, I Ridker, PM Robino, A Rudan, I Rudolph, A Salumets, A Schmidt, MK Schoemaker, MJ Smith, EN Smith, JA Southey, M Stockl, D Swerdlow, AJ Thompson, DJ Truong, T Ulivi, S Waldenberger, M Wang, Q Wild, S Wilson, JF Wright, AF Zgaga, L Ong, KK Murabito, JM Karasik, D Murray, A AF Perry, John R. B. Hsu, Yi-Hsiang Chasman, Daniel I. Johnson, Andrew D. Elks, Cathy Albrecht, Eva Andrulis, Irene L. Beesley, Jonathan Berenson, Gerald S. Bergmann, Sven Bojesen, Stig E. Bolla, Manjeet K. Brown, Judith Buring, Julie E. Campbell, Harry Chang-Claude, Jenny Chenevix-Trench, Georgia Corre, Tanguy Couch, Fergus J. Cox, Angela Czene, Kamila D'adamo, Adamo Pio Davies, Gail Deary, Ian J. Dennis, Joe Easton, Douglas F. Engelhardt, Ellen G. Eriksson, Johan G. Esko, Tonu Fasching, Peter A. Figueroa, Jonine D. Flyger, Henrik Fraser, Abigail Garcia-Closas, Montse Gasparini, Paolo Gieger, Christian Giles, Graham Guenel, Pascal Haegg, Sara Hall, Per Hayward, Caroline Hopper, John Ingelsson, Erik Kardia, L. R. Kasiman, Katherine Knight, Julia A. Lahti, Jari Lawlor, Debbie A. Magnusson, Patrik K. E. Margolin, Sara Marsh, Julie A. Metspalu, Andres Olson, Janet E. Pennell, Craig E. Polasek, Ozren Rahman, Iffat Ridker, Paul M. Robino, Antonietta Rudan, Igor Rudolph, Anja Salumets, Andres Schmidt, Marjanka K. Schoemaker, Minouk J. Smith, Erin N. Smith, Jennifer A. Southey, Melissa Stoeckl, Doris Swerdlow, Anthony J. Thompson, Deborah J. Truong, Therese Ulivi, Sheila Waldenberger, Melanie Wang, Qin Wild, Sarah Wilson, James F. Wright, Alan F. Zgaga, Lina Ong, Ken K. Murabito, Joanne M. Karasik, David Murray, Anna CA kConFab Investigators ReproGen Consortium TI DNA mismatch repair gene MSH6 implicated in determining age at natural menopause SO HUMAN MOLECULAR GENETICS LA English DT Article ID SECULAR TRENDS; PREMATURE MENOPAUSE; REPRODUCTIVE LIFE; MENARCHE; WOMEN; CANCER; BRCA1; ASSOCIATION; MUTATIONS; COHORT AB The length of female reproductive lifespan is associated with multiple adverse outcomes, including breast cancer, cardiovascular disease and infertility. The biological processes that govern the timing of the beginning and end of reproductive life are not well understood. Genetic variants are known to contribute to 50 of the variation in both age at menarche and menopause, but to date the known genes explain 15 of the genetic component. We have used genome-wide association in a bivariate meta-analysis of both traits to identify genes involved in determining reproductive lifespan. We observed significant genetic correlation between the two traits using genome-wide complex trait analysis. However, we found no robust statistical evidence for individual variants with an effect on both traits. A novel association with age at menopause was detected for a variant rs1800932 in the mismatch repair gene MSH6 (P 1.9 10(9)), which was also associated with altered expression levels of MSH6 mRNA in multiple tissues. This study contributes to the growing evidence that DNA repair processes play a key role in ovarian ageing and could be an important therapeutic target for infertility. C1 [Perry, John R. B.; Murray, Anna] Univ Exeter, Sch Med, Exeter, Devon, England. [Perry, John R. B.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Perry, John R. B.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Perry, John R. B.; Elks, Cathy; Ong, Ken K.] Addenbrookes Hosp, MRC, Epidemiol Unit, Cambridge, England. [Hsu, Yi-Hsiang; Karasik, David] Hebrew SeniorLife Inst Aging Res, Boston, MA USA. [Hsu, Yi-Hsiang; Chasman, Daniel I.; Buring, Julie E.; Ridker, Paul M.; Karasik, David] Harvard Univ, Sch Med, Boston, MA USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA. [Chasman, Daniel I.; Buring, Julie E.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Johnson, Andrew D.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Johnson, Andrew D.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Bethesda, MD 20892 USA. [Albrecht, Eva; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Stoeckl, Doris; Waldenberger, Melanie] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Waldenberger, Melanie] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Andrulis, Irene L.; Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Beesley, Jonathan; Chenevix-Trench, Georgia] Queensland Inst Med Res, Dept Genet, Brisbane, Qld 4006, Australia. [Berenson, Gerald S.] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA. [Bergmann, Sven; Corre, Tanguy] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Bergmann, Sven; Corre, Tanguy] Swiss Inst Bioinformat, Lausanne, Switzerland. [Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark. [Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark. [Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Copenhagen, Denmark. [Bolla, Manjeet K.; Brown, Judith; Dennis, Joe; Easton, Douglas F.; Thompson, Deborah J.; Wang, Qin] Univ Cambridge, Ctr Canc Genet Epidemiol, Cambridge, England. [Bolla, Manjeet K.; Brown, Judith; Dennis, Joe; Easton, Douglas F.; Thompson, Deborah J.; Wang, Qin] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Ong, Ken K.] Univ Cambridge, Dept Paediat, Cambridge, England. [Campbell, Harry; Rudan, Igor; Wild, Sarah; Wilson, James F.; Zgaga, Lina] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Couch, Fergus J.; Olson, Janet E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Cox, Angela] Univ Sheffield, Dept Oncol, CR UK YCR Sheffield Canc Res Ctr, Sheffield S10 2TN, S Yorkshire, England. [Czene, Kamila; Haegg, Sara; Hall, Per; Kasiman, Katherine; Magnusson, Patrik K. E.; Rahman, Iffat] Karolinska Inst, Stockholm, Sweden. [Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [D'adamo, Adamo Pio; Gasparini, Paolo; Robino, Antonietta] Univ Trieste, Inst Maternal & Child Hlth, IRCCS Burlo Garofolo, Trieste, Italy. [Davies, Gail; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9AG, Midlothian, Scotland. [Davies, Gail; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9AG, Midlothian, Scotland. [Davies, Gail; Wright, Alan F.] Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland. [Engelhardt, Ellen G.; Schmidt, Marjanka K.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands. [Schmidt, Marjanka K.] Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan G.] Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, Johan G.; Lahti, Jari] Folkhalsan Res Ctr, Helsinki, Finland. [Eriksson, Johan G.] Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland. [Esko, Tonu] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Esko, Tonu] Broad Inst, Cambridge, MA USA. [Esko, Tonu; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia. [Fasching, Peter A.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, D-91054 Erlangen, Germany. [Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Fraser, Abigail; Lawlor, Debbie A.] Univ Bristol, Sch Social & Community Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England. [Garcia-Closas, Montse; Schoemaker, Minouk J.; Swerdlow, Anthony J.] Inst Canc Res, Div Breast Canc Res, London, England. [Garcia-Closas, Montse; Schoemaker, Minouk J.; Swerdlow, Anthony J.] Inst Canc Res, Div Genet & Epidemiol, London, England. [Garcia-Closas, Montse; Schoemaker, Minouk J.; Swerdlow, Anthony J.] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London, England. [Giles, Graham; Hopper, John] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Giles, Graham] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Guenel, Pascal; Truong, Therese] INSERM, U1018, Villejuif, France. [Haegg, Sara; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden. [Hayward, Caroline] Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. [kConFab Investigators] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Kardia, L. R.; Smith, Jennifer A.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Lahti, Jari] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Marsh, Julie A.; Pennell, Craig E.] Univ Western Australia, Sch Womens & Infants Hlth, Nedlands, WA 6009, Australia. [Polasek, Ozren] Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia. [Salumets, Andres] Univ Tartu, Dept Obstet & Gynecol, EE-51014 Tartu, Estonia. [Salumets, Andres] Competence Ctr Reprod Med & Biol, EE-50410 Tartu, Estonia. [Smith, Erin N.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. [Smith, Erin N.] Univ Calif San Diego, Rady Childrens Hosp, La Jolla, CA 92093 USA. [Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia. [Stoeckl, Doris] Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Ulivi, Sheila] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Perry, JRB (reprint author), Univ Exeter, Sch Med, Exeter, Devon, England. EM john.perry@mrc-epid.cam.ac.uk; A.Murray@exeter.ac.uk RI Johnson, Andrew/G-6520-2013; Magnusson, Patrik/C-4458-2017; Waldenberger, Melanie/B-5355-2014; Rudan, Igor/I-1467-2012; d'Adamo, Adamo Pio/G-4064-2011; Stockl, Doris/B-5352-2014; Knight, Julia/A-6843-2012; Andrulis, Irene/E-7267-2013; Hayward, Caroline/M-8818-2016; Visser, Jenny /F-8156-2011; Garcia-Closas, Montserrat /F-3871-2015; Salumets, Andres/J-2278-2015; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011 OI MARONGIU, MARA/0000-0002-7321-2384; Murray, Anna/0000-0002-2351-2522; Schoemaker, Minouk/0000-0001-8403-2234; Czene, Kamila/0000-0002-3233-5695; Marsh, Julie/0000-0001-8984-6907; Gieger, Christian/0000-0001-6986-9554; Karasik, David/0000-0002-8826-0530; Cox, Angela/0000-0002-5138-1099; Fraser, Abigail/0000-0002-7741-9470; Lawlor, Debbie A/0000-0002-6793-2262; Eriksson, Johan/0000-0002-2516-2060; Giles, Graham/0000-0003-4946-9099; Smith, Jennifer/0000-0002-3575-5468; Lahti, Jari/0000-0002-4310-5297; Zgaga, Lina/0000-0003-4089-9703; Waldenberger, Melanie/0000-0003-0583-5093; Rudan, Igor/0000-0001-6993-6884; d'Adamo, Adamo Pio/0000-0001-9367-4909; Hayward, Caroline/0000-0002-9405-9550; Garcia-Closas, Montserrat /0000-0003-1033-2650; Salumets, Andres/0000-0002-1251-8160; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862 FU UK Medical Research Council [G0600705, 0701594]; Wellcome Trust FX J.R.B.P is a Sir Henry Wellcome Postdoctoral Research Fellow (092447/Z/10/Z). D.A.L. and A.F. work in a centre that receives infrastructure funding from the UK Medical Research Council (G0600705) and A.F. is funded by a UK Medical Research Council Post-doctoral research fellowship (0701594). Further information on funding for individual studies is provided in supplementary information. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust. NR 38 TC 17 Z9 17 U1 3 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2014 VL 23 IS 9 BP 2490 EP 2497 DI 10.1093/hmg/ddt620 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AE9VL UT WOS:000334359100022 PM 24357391 ER PT J AU Yoneyama, S Guo, YR Lanktree, MB Barnes, MR Elbers, CC Karczewski, KJ Padmanabhan, S Bauer, F Baumert, J Beitelshees, A Berenson, GS Boer, JMA Burke, G Cade, B Chen, W Cooper-Dehoff, RM Gaunt, TR Gieger, C Gong, Y Gorski, M Heard-Costa, N Johnson, T Lamonte, MJ Mcdonough, C Monda, KL Onland-Moret, NC Nelson, CP O'Connell, JR Ordovas, J Peter, I Peters, A Shaffer, J Shen, HQ Smith, E Speilotes, L Thomas, F Thorand, B Verschuren, WMM Anand, SS Dominiczak, A Davidson, KW Hegele, RA Heid, I Hofker, MH Huggins, GS Illig, T Johnson, JA Kirkland, S Konig, W Langaee, TY Mccaffery, J Melander, O Mitchell, BD Munroe, P Murray, SS Papanicolaou, G Redline, S Reilly, M Samani, NJ Schork, NJ Van der Schouw, YT Shimbo, D Shuldiner, AR Tobin, MD Wijmenga, C Yusuf, S Hakonarson, H Lange, LA Demerath, EW Fox, CS North, KE Reiner, AP Keating, B Taylor, KC AF Yoneyama, Sachiko Guo, Yiran Lanktree, Matthew B. Barnes, Michael R. Elbers, Clara C. Karczewski, Konrad J. Padmanabhan, Sandosh Bauer, Florianne Baumert, Jens Beitelshees, Amber Berenson, Gerald S. Boer, Jolanda M. A. Burke, Gregory Cade, Brian Chen, Wei Cooper-Dehoff, Rhonda M. Gaunt, Tom R. Gieger, Christian Gong, Yan Gorski, Mathias Heard-Costa, Nancy Johnson, Toby Lamonte, Michael J. Mcdonough, Caitrin Monda, Keri L. Onland-Moret, N. Charlotte Nelson, Christopher P. O'Connell, Jeffrey R. Ordovas, Jose Peter, Inga Peters, Annette Shaffer, Jonathan Shen, Haiqinq Smith, Erin Speilotes, Liz Thomas, Fridtjof Thorand, Barbara Verschuren, W. M. Monique Anand, Sonia S. Dominiczak, Anna Davidson, Karina W. Hegele, Robert A. Heid, Iris Hofker, Marten H. Huggins, Gordon S. Illig, Thomas Johnson, Julie A. Kirkland, Susan Koenig, Wolfgang Langaee, Taimour Y. Mccaffery, Jeanne Melander, Olle Mitchell, Braxton D. Munroe, Patricia Murray, Sarah S. Papanicolaou, George Redline, Susan Reilly, Muredach Samani, Nilesh J. Schork, Nicholas J. Van der Schouw, Yvonne T. Shimbo, Daichi Shuldiner, Alan R. Tobin, Martin D. Wijmenga, Cisca Yusuf, Salim Hakonarson, Hakon Lange, Leslie A. Demerath, Ellen W. Fox, Caroline S. North, Kari E. Reiner, Alex P. Keating, Brendan Taylor, Kira C. CA Look AHEAD Res Grp GIANT Consortium CARe IBC Consortium TI Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE RISK; WAIST-HIP RATIO; INSULIN-RESISTANCE; METABOLIC SYNDROME; ABDOMINAL OBESITY; DRUGGABLE GENOME; BLOOD-PRESSURE; IDENTIFIES 13 AB Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBIs Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 2080 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes 50 000 cosmopolitan tagged SNPs across 2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P 2.4 10(6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR ( SE, 0.048 0.008, P 7.7 10(9)) as was rs7302703-G in HOXC10 ( 0.044 0.008, P 2.9 10(7)) and rs936108-C in PEMT ( 0.035 0.007, P 1.9 10(6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 ( 0.10 0.02, P 1.9 10(6)) and rs1037575-A in ATBDB4 ( 0.046 0.01, P 2.2 10(6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue. C1 [Yoneyama, Sachiko; Monda, Keri L.; North, Kari E.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Guo, Yiran; Hakonarson, Hakon; Keating, Brendan] Childrens Hosp Philadelphia, Ctr Appl Genom, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Guo, Yiran] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Lanktree, Matthew B.] McMaster Univ, Dept Med, Hamilton, ON L8S 4L8, Canada. [Anand, Sonia S.; Yusuf, Salim] McMaster Univ, Dept Med, Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON L8S 4L8, Canada. [Anand, Sonia S.; Yusuf, Salim] McMaster Univ, Dept Clin Epidemiol, Populat Genom Program, Hamilton, ON L8S 4L8, Canada. [Barnes, Michael R.] Queen Mary Univ London, Natl Inst Hlth Biomed Res Unit, London EC1M 6BQ, England. [Johnson, Toby; Munroe, Patricia] Queen Mary Univ London, London EC1M 6BQ, England. [Johnson, Toby; Munroe, Patricia] Queen Mary Univ London, Genome Ctr, William Harvey Res Inst, Barts, London EC1M 6BQ, England. [Barnes, Michael R.] Queen Mary Univ London, London Sch Med, London EC1M 6BQ, England. [Johnson, Toby; Munroe, Patricia] Queen Mary Univ London, London Sch Med & Dent, London EC1M 6BQ, England. [Elbers, Clara C.; Bauer, Florianne; Onland-Moret, N. Charlotte; Van der Schouw, Yvonne T.] UMC Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands. [Karczewski, Konrad J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Padmanabhan, Sandosh] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland. [Dominiczak, Anna] Univ Glasgow, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland. [Baumert, Jens; Peters, Annette; Thorand, Barbara] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany. [Gieger, Christian; Heid, Iris] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany. [Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany. [Beitelshees, Amber; Mitchell, Braxton D.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [O'Connell, Jeffrey R.; Shen, Haiqinq; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Shuldiner, Alan R.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. [Berenson, Gerald S.; Chen, Wei] Tulane Univ, Dept Epidemiol, New Orleans, LA 70112 USA. [Boer, Jolanda M. A.; Verschuren, W. M. Monique] Natl Inst Publ Hlth & Environm, Ctr Nutr Prevent & Hlth Serv, NL-3720 BA Bilthoven, Netherlands. [Burke, Gregory] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Look AHEAD Res Grp] Wake Forest Univ, Sch Med, Look AHEAD Coordinating Ctr, Winston Salem, NC 27157 USA. [Cade, Brian; Redline, Susan] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA. [Cade, Brian; Redline, Susan] Brigham & Womens Hosp, Dept Med, Div Sleep Med, Boston, MA 02115 USA. [Cooper-Dehoff, Rhonda M.; Gong, Yan; Mcdonough, Caitrin; Johnson, Julie A.; Langaee, Taimour Y.] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA. [Cooper-Dehoff, Rhonda M.; Gong, Yan; Mcdonough, Caitrin; Johnson, Julie A.; Langaee, Taimour Y.] Univ Florida, Ctr Pharmacogen, Gainesville, FL 32610 USA. [Gaunt, Tom R.] MRC Integrat Epidemiol Unit, Sch Social & Community Med, Bristol BS8 2BN, Avon, England. [Gorski, Mathias; Heid, Iris] Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany. [Gorski, Mathias] Univ Med Ctr Regensburg, Dept Internal Med 2, D-93053 Regensburg, Germany. [Heard-Costa, Nancy] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Fox, Caroline S.] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02118 USA. [Lamonte, Michael J.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Buffalo, NY 14214 USA. [Monda, Keri L.] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA. [Nelson, Christopher P.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England. [Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England. [Ordovas, Jose] Tufts Univ, Nutr & Genom Lab, Boston, MA 02111 USA. [Peter, Inga] Mt Sinai, Icahn Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Shaffer, Jonathan; Davidson, Karina W.; Shimbo, Daichi] Columbia Univ, Med Ctr, Ctr Behav Cardiovasc Hlth, Div Gen Med, New York, NY 10032 USA. [Smith, Erin] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. [Smith, Erin] Univ Calif San Diego, Sch Med, Radys Childrens Hosp, La Jolla, CA 92093 USA. [Speilotes, Liz] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Speilotes, Liz] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Speilotes, Liz] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Speilotes, Liz] Broad Inst, Cambridge, MA 02141 USA. [Thomas, Fridtjof] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38163 USA. [Hegele, Robert A.] Univ Western Ontario, Schulich Sch Med & Dent, Robarts Res Inst, London, ON N6A 5C1, Canada. [Hofker, Marten H.] Univ Groningen, Univ Med Ctr Groningen, Dept Mol Genet, NL-9700 AB Groningen, Netherlands. [Huggins, Gordon S.] Tufts Med Ctr, Mol Cardiol Res Inst, Ctr Translat Genom, Boston, MA 02111 USA. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany. [Kirkland, Susan] Dalhousie Univ, Dept Community Hlth & Epidemiol, Halifax, NS, Canada. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med 2, D-89081 Ulm, Germany. [Mccaffery, Jeanne] Miriam Hosp, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA. [Mccaffery, Jeanne] Brown Univ, Warren Alpert Sch Med, Providence, RI 02906 USA. [Melander, Olle] Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, SE-20502 Malmo, Sweden. [Murray, Sarah S.; Schork, Nicholas J.] Scripps Hlth, Scripps Res Inst, La Jolla, CA 92037 USA. [Papanicolaou, George] NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20824 USA. [Reilly, Muredach] Univ Penn, Med Ctr, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Schork, Nicholas J.] Scripps Translat Sci Inst, La Jolla, CA 92037 USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA. [Tobin, Martin D.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England. [Tobin, Martin D.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. [Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [Demerath, Ellen W.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [North, Kari E.] Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. [Reiner, Alex P.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Taylor, Kira C.] Univ Louisville, Sch Publ Hlth & Informat Sci, Dept Epidemiol & Populat Hlth, Louisville, KY 40202 USA. RP Taylor, KC (reprint author), Univ Louisville, Sch Publ Hlth & Informat Sci, Dept Epidemiol & Populat Hlth, Louisville, KY 40202 USA. EM kctayl04@louisville.edu RI van der Schouw, Yvonne/F-8327-2014; Gaunt, Tom/O-3918-2014; Guo, Yiran/H-4120-2011; Onland-Moret, N. Charlotte/G-9185-2011; Hegele, Robert/G-3301-2011; Thorand, Barbara/B-5349-2014; Peters, Annette/A-6117-2011; Wijmenga, Cisca/D-2173-2009; Padmanabhan, Sandosh/S-3963-2016 OI Padmanabhan, Sandosh/0000-0003-3869-5808; Gieger, Christian/0000-0001-6986-9554; Mitchell, Braxton/0000-0003-4920-4744; Lanktree, Matthew/0000-0002-5750-6286; Wijmenga, Cisca/0000-0002-5635-1614; Johnson, Toby/0000-0002-5998-3270; van der Schouw, Yvonne/0000-0002-4605-435X; Gaunt, Tom/0000-0003-0924-3247; Karczewski, Konrad/0000-0003-2878-4671; Guo, Yiran/0000-0002-6549-8589; Thorand, Barbara/0000-0002-8416-6440; FU British Heart Foundation [RG/07/005/23633, SP/08/005/25115, PG/07/131/24254]; Medical Research Council [G0902313, MC_UU_12013/8]; NCATS NIH HHS [UL1 TR000064]; NCRR NIH HHS [UL1 RR025774, UL1-RR-024156, UL1RR025005]; NHGRI NIH HHS [U01 HG007416, U01HG004402]; NHLBI NIH HHS [HL080295, K24 HL084034, N01 HC55222, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-65226, N01-HC-95095, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, R01 HL088119, R01HL086694, R01HL087641, R01HL59367, U01 HL72515]; NIA NIH HHS [AG023629, R01 AG016592]; NICHD NIH HHS [HD-061437, HD-062783]; NIDDK NIH HHS [P30 DK017047, P30 DK072488, U01 DK057131, U01 DK057136]; NIEHS NIH HHS [R01 ES021724]; NIGMS NIH HHS [U01 GM074492, U01 GM074518] NR 68 TC 11 Z9 11 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2014 VL 23 IS 9 BP 2498 EP 2510 DI 10.1093/hmg/ddt626 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AE9VL UT WOS:000334359100023 PM 24345515 ER PT J AU Lynch, CD Sundaram, R Maisog, JM Sweeney, AM Louis, GMB AF Lynch, C. D. Sundaram, R. Maisog, J. M. Sweeney, A. M. Louis, G. M. Buck TI Preconception stress increases the risk of infertility: results from a couple-based prospective cohort studyuthe LIFE study SO HUMAN REPRODUCTION LA English DT Article DE infertility; fecundity; stress; cortisol; alpha-amylase ID SALIVARY ALPHA-AMYLASE; HUMAN-REPRODUCTION; PREGNANCY RATES; CORTISOL; CONCEPTION; ADOPTION; IMPACT; PROBABILITIES; INTERVENTION; DETERMINANTS AB Are womens stress levels prospectively associated with fecundity and infertility? Higher levels of stress as measured by salivary alpha-amylase are associated with a longer time-to-pregnancy (TTP) and an increased risk of infertility. Data suggest that stress and reproduction are interrelated; however, the directionality of that association is unclear. In 20052009, we enrolled 501 couples in a prospective cohort study with preconception enrollment at two research sites (Michigan and Texas, USA). Couples were followed for up to 12 months as they tried to conceive and through pregnancy if it occurred. A total of 401 (80) couples completed the study protocol and 373 (93) had complete data available for this analysis. Enrolled women collected saliva the morning following enrollment and then the morning following their first observed study menses for the measurement of cortisol and alpha-amylase, which are biomarkers of stress. TTP was measured in cycles. Covariate data were captured on both a baseline questionnaire and daily journals. Among the 401 (80) women who completed the protocol, 347 (87) became pregnant and 54 (13) did not. After adjustment for female age, race, income, and use of alcohol, caffeine and cigarettes while trying to conceive, women in the highest tertile of alpha-amylase exhibited a 29 reduction in fecundity (longer TTP) compared with women in the lowest tertile [fecundability odds ratios (FORs) 0.71; 95 confidence interval (CI) (0.51, 1.00); P 0.05]. This reduction in fecundity translated into a 2-fold increased risk of infertility among these women [relative risk (RR) 2.07; 95 CI (1.04, 4.11)]. In contrast, we found no association between salivary cortisol and fecundability. Due to fiscal and logistical concerns, we were unable to collect repeated saliva samples and perceived stress questionnaire data throughout the duration of follow-up. Therefore, we were unable to examine whether stress levels increased as women continued to fail to get pregnant. Our ability to control for potential confounders using time-varying data from the daily journals, however, minimizes residual confounding. This is the first US study to demonstrate a prospective association between salivary stress biomarkers and TTP, and the first in the world to observe an association with infertility. This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts N01-HD-3-3355, N01-HD-3-3356, N01-HD-3358). There are no conflicts of interest to declare. Not applicable. C1 [Lynch, C. D.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Sundaram, R.; Maisog, J. M.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA. [Sweeney, A. M.] Texas A&M Hlth Sci Ctr, Dept Epidemiol & Biostat, College Stn, TX 77843 USA. RP Lynch, CD (reprint author), Ohio State Univ, Coll Med, 395 W 12th Ave,Room 580, Columbus, OH 43210 USA. EM courtney.lynch@osumc.edu FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01-HD-3-3355, N01-HD-3-3356, N01-HD-3358] FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts #N01-HD-3-3355, N01-HD-3-3356, N01-HD-3358). NR 44 TC 24 Z9 24 U1 2 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD MAY PY 2014 VL 29 IS 5 BP 1067 EP 1075 DI 10.1093/humrep/deu032 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AF7UX UT WOS:000334921400018 PM 24664130 ER PT J AU Henneberger, PK Liang, XM London, SJ Umbach, DM Sandler, DP Hoppin, JA AF Henneberger, Paul K. Liang, Xiaoming London, Stephanie J. Umbach, David M. Sandler, Dale P. Hoppin, Jane A. TI Exacerbation of symptoms in agricultural pesticide applicators with asthma SO INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE Asthma; Asthma exacerbation; Work-related; Agriculture; Pesticides ID WORK-RELATED ASTHMA; HEALTH; EXPOSURE; FARMERS; PREDICTORS; STATEMENT; DIAGNOSIS; SELECTION; OUTCOMES; WHEEZE AB Exacerbation is a critical event in asthma management. We investigated whether exacerbation of symptoms is associated with farming exposures among agricultural pesticide applicators with asthma. Participants were pesticide applicators with active asthma (wheezing and breathing problems in past 12 months) who completed enrollment questionnaires for the Agricultural Health Study (AHS). Exacerbation of asthma was defined as having visited a hospital emergency room or doctor for an episode of wheezing or whistling in the past 12 months. Exposures of interest were using 36 specific pesticides in the past 12 months and conducting various agricultural activities. Adjusted odds ratios (ORs) were estimated by logistic regression while controlling for potential confounders. The 926 AHS adult pesticide applicators with active asthma included 202 (22 %) with exacerbation. Inverse associations with exacerbation were observed for two herbicides [glyphosate, odds ratio (OR) = 0.5, 95 % confidence interval (CI) 0.3, 0.8, and paraquat, OR = 0.3, 95 % CI 0.1, 0.9] and several agricultural activities (repairing engines, grinding metal, driving diesel tractors, and performing veterinary procedures). Only asthma cases with allergies (i.e., doctor-diagnosed hay fever or eczema, 46 %) had positive exacerbation-pesticide associations, with OR = 2.1 (95 % CI 1.1, 4.1) for the herbicide pendimethalin and OR = 10.2 (95 % CI 1.9, 55) for the insecticide aldicarb. The inverse associations with two pesticides and specific farm activities are consistent with the possibility that asthma cases prone to exacerbation may avoid exposures that trigger symptoms. Although limited by small sample size and a cross-sectional design, our study suggests that use of specific pesticides may contribute to exacerbation of asthma among individuals with allergies. C1 [Henneberger, Paul K.; Liang, Xiaoming] NIOSH, Div Resp Dis Studies, Morgantown, WV 26505 USA. [London, Stephanie J.; Sandler, Dale P.; Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Umbach, David M.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Henneberger, PK (reprint author), NIOSH, Div Resp Dis Studies, MS 2800,1095 Willowdale Rd, Morgantown, WV 26505 USA. EM pkh0@cdc.gov OI Sandler, Dale/0000-0002-6776-0018; London, Stephanie/0000-0003-4911-5290 FU National Institute for Occupational Safety and Health; Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01-ES049030]; National Institutes of Health, National Cancer Institute [Z01-CP010119] FX The authors thank the Agricultural Health Study participants, the staff of the Iowa and North Carolina field stations (Ellen Heywood, Margaret Hayslip), and the Agricultural Health Study coordinating center (Ben Laimon, Marsha Dunn, Kate Torres, Stanley Legum). This work was supported by the National Institute for Occupational Safety and Health and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01-ES049030) and the National Institutes of Health, National Cancer Institute (Z01-CP010119). NR 29 TC 10 Z9 10 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-0131 EI 1432-1246 J9 INT ARCH OCC ENV HEA JI Int. Arch. Occup. Environ. Health PD MAY PY 2014 VL 87 IS 4 BP 423 EP 432 DI 10.1007/s00420-013-0881-x PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AF7ZF UT WOS:000334933600009 PM 23670403 ER PT J AU Grady, C Wiener, L Abdoler, E Trauernicht, E Zadeh, S Diekema, DS Wilfond, BS Wendler, D AF Grady, Christine Wiener, Lori Abdoler, Emily Trauernicht, Emily Zadeh, Sima Diekema, Douglas S. Wilfond, Benjamin S. Wendler, David TI Assent in Research: The Voices of Adolescents SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Adolescents; Clinical research; Assent ID PEDIATRIC RESEARCH; DECISION-MAKING; CHILDREN; PARTICIPATION AB Purpose: Adolescents join clinical research after investigators obtain their positive agreement or "assent." Although intended to respect adolescents, little is known about the views of adolescents or their parents regarding assent or research enrollment decisions. This study aimed to better understand perspectives of adolescent research participants and their parents about assent and parental permission. Methods: Structured interviews were conducted with 13-through 17-year-old teens, enrolled in clinical research at the National Institutes of Health or Seattle Children's Hospital, and separately with one parent. Results: One hundred and seventy-seven adolescenteparent pairs were interviewed. Teens were well distributed by age and gender, represented a wide variety of research and illnesses ranging in severity from mild to life threatening; 20% were healthy volunteers. Teens and parents were generally satisfied with the assent/permission process. Normally, they made the enrollment decision together and teens wanted parents' input and support. About 25% of teens reported pressure to enroll, not only from parents or relatives but also from doctors/nurses/research teams. Only 2% of teens preferred not to sign a consent form. Conclusions: Despite some differing views about how decisions should be made, the current assent/permission process is perceived as satisfactorily respectful by most teens in research. Many teens want to sign consent forms, and teens' signatures should generally be sought. Flexible guidance allows research teams and Institutional Review Boards to customize the assent process for teens in particular studies in order to facilitate an appropriate balance between giving teens a voice reflective of their emerging independence and enabling supportive collaboration with parents. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine. C1 [Grady, Christine; Wendler, David] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Wiener, Lori; Zadeh, Sima] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Abdoler, Emily] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Trauernicht, Emily] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Diekema, Douglas S.; Wilfond, Benjamin S.] Seattle Childrens Res Inst, Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA. RP Grady, C (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM cgrady@nih.gov FU National Institutes of Health (NIH) Office of Evaluation; NIH Clinical Center Department of Bioethics; Intramural Research Program, National Cancer Institute, Center for Cancer Research; Institute for Translational Health Sciences [UL1TR000423] FX This research was supported by National Institutes of Health (NIH) Office of Evaluation, the NIH Clinical Center Department of Bioethics, the Intramural Research Program, National Cancer Institute, Center for Cancer Research, and the Institute for Translational Health Sciences (UL1TR000423). NR 19 TC 5 Z9 5 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD MAY PY 2014 VL 54 IS 5 BP 515 EP 520 DI 10.1016/j.jadohealth.2014.02.005 PG 6 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA AF1XG UT WOS:000334506600004 PM 24630932 ER PT J AU Barzilay, JI Buzkova, P Zieman, SJ Kizer, JR Djousse, L Ix, JH Tracy, RP Siscovick, DS Cauley, JA Mukamal, KJ AF Barzilay, Joshua I. Buzkova, Petra Zieman, Susan J. Kizer, Jorge R. Djousse, Luc Ix, Joachim H. Tracy, Russell P. Siscovick, David S. Cauley, Jane A. Mukamal, Kenneth J. TI Circulating Levels of Carboxy-Methyl-Lysine ( CML) Are Associated With Hip Fracture Risk: The Cardiovascular Health Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE CARBOXY-METHYL-LYSINE; HIP FRACTURE RISK; BONE QUALITY; CARDIOVASCULAR HEALTH STUDY; BONE MINERAL DENSITY ID GLYCATION END-PRODUCTS; COLLAGEN CROSS-LINKS; POSTMENOPAUSAL WOMEN; VERTEBRAL FRACTURES; PENTOSIDINE; SERUM; OSTEOPOROSIS; BONE AB Advanced glycation end products (AGE) in bone tissue are associated with impaired biomechanical properties and increased fracture risk. Here we examine whether serum levels of the AGE carboxy-methyl-lysine (CML) are associated with risk of hip fracture. We followed 3373 participants from the Cardiovascular Health Study (age 78 years; range, 68-102 years; 39.8% male) for a median of 9.22 years (range, 0.01-12.07 years). Rates of incident hip fracture were calculated by quartiles of baseline CML levels, and hazard ratios were adjusted for covariates associated with hip fracture risk. A subcohort of 1315 participants had bone mineral density (BMD) measurement. There were 348 hip fractures during follow-up, with incidence rates of hip fracture by CML quartiles of 0.94, 1.34, 1.18, and 1.69 per 100 participant-years. The unadjusted hazard ratio of hip fracture increased with each 1 SD increase (189ng/mL) of CML level (hazard ratio, 1.27; 95% confidence interval [CI], 1.16-1.40]; p<0.001). Sequential adjustment for age, gender, race/ethnicity, body mass index (BMI), smoking, alcohol consumption, prevalent coronary heart disease (CHD), energy expenditure, and estimated glomerular filtration rate (based on cystatin C), moderately attenuated the hazard ratio for fracture (1.17; 95% CI, 1.05-1.31; p=0.006). In the cohort with BMD testing, total hip BMD was not significantly associated with CML levels. We conclude that increasing levels of CML are associated with hip fracture risk in older adults, independent of hip BMD. These results implicate AGE in the pathogenesis of hip fractures. (c) 2014 American Society for Bone and Mineral Research. C1 [Barzilay, Joshua I.] Kaiser Permanente Georgia, Div Endocrinol, Atlanta, GA USA. [Barzilay, Joshua I.] Emory Sch Med, Div Endocrinol, Atlanta, GA USA. [Buzkova, Petra] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Zieman, Susan J.] NIA, Geriatr Branch Off, NIH, Bethesda, MD 20892 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Div Epidemiol & Populat Hlth, Bronx, NY USA. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Djousse, Luc] Harvard Univ, Sch Med, Boston, MA USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, San Diego VA Healthcare Syst, San Diego, CA 92103 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. [Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA. [Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Barzilay, JI (reprint author), Kaiser Permanente Georgia, 3650 Steve Reynolds Blvd, Duluth, GA 30096 USA. EM Joshua.barzilay@kp.org RI Cauley, Jane/N-4836-2015; Djousse, Luc/F-5033-2017 OI Cauley, Jane/0000-0003-0752-4408; Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL094555, HL080295]; National Institute on Aging (NIA) [AG023629] FX This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grants HL094555 and HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. NR 24 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 2014 VL 29 IS 5 BP 1061 EP 1066 DI 10.1002/jbmr.2123 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AF4CJ UT WOS:000334658700005 PM 24877243 ER PT J AU Iglesias, AI Mihaescu, R Ioannidis, JPA Khoury, MJ Little, J van Duijn, CM Janssens, ACJW AF Iglesias, Adriana I. Mihaescu, Raluca Ioannidis, John P. A. Khoury, Muin J. Little, Julian van Duijn, Cornelia M. Janssens, A. Cecile J. W. TI Scientific reporting is suboptimal for aspects that characterize genetic risk prediction studies: a review of published articles based on the Genetic RIsk Prediction Studies statement SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Review DE Genetic; Risk prediction; GRIPS; Reporting guideline; Epidemiology; Review ID RANDOMIZED CONTROLLED-TRIALS; SINGLE NUCLEOTIDE POLYMORPHISMS; CORONARY-ARTERY-DISEASE; TYPE-2 DIABETES RISK; BEFORE-AND-AFTER; DIAGNOSTIC-ACCURACY; PROSPECTIVE COHORT; PERSONALIZED MEDICINE; CLINICAL INFORMATION; STROBE STATEMENT AB Objectives: Our main objective was to raise awareness of the areas that need improvements in the reporting of genetic risk prediction articles for future publications, based on the Genetic Risk Prediction Studies (GRIPS) statement. Study Design and Setting: We evaluated studies that developed or validated a prediction model based on multiple DNA variants, using empirical data, and were published in 2010. A data extraction form based on the 25 items of the GRIPS statement was created and piloted. Results: Forty-two studies met our inclusion criteria. Overall, more than half of the evaluated items (34 of 62) were reported in at least 85% of included articles. Seventy-seven percentage of the articles were identified as genetic risk prediction studies through title assessment, but only 31% used the keywords recommended by GRIPS in the title or abstract. Seventy-four percentage mentioned which allele was the risk variant. Overall, only 10% of the articles reported all essential items needed to perform external validation of the risk model. Conclusion: Completeness of reporting in genetic risk prediction studies is adequate for general elements of study design but is suboptimal for several aspects that characterize genetic risk prediction studies such as description of the model construction. Improvements in the transparency of reporting of these aspects would facilitate the identification, replication, and application of genetic risk prediction models. (C) 2014 Elsevier Inc. All rights reserved. C1 [Iglesias, Adriana I.; Mihaescu, Raluca; van Duijn, Cornelia M.] Erasmus Univ, Dept Epidemiol, Med Ctr, NL-3015 GE Rotterdam, Netherlands. [Ioannidis, John P. A.] Stanford Univ, Stanford Prevent Res Ctr, Dept Med, Sch Med, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Stanford Prevent Res Ctr, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Stat, Sch Humanities & Sci, Stanford, CA 94305 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Khoury, Muin J.] NCI, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA. [Little, Julian] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON K1H 8M5, Canada. [Janssens, A. Cecile J. W.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. RP Janssens, ACJW (reprint author), Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. EM cecile.janssens@emory.edu OI Janssens, A Cecile/0000-0002-6153-4976 FU ERACOL program; Centre for Medical Systems Biology [CMSB 1-2]; ENGAGE Consortium [HEALTH-F4-2007-201413]; Netherlands Organization for Scientific Research (NWO) FX A.I.I. was a recipient of the ERACOL program, which gives her the opportunity to perform this research in the Netherlands. J.L. holds a Tier 1 Canada Research Chair in Human Genome Epidemiology. C.M.v.D. was supported by the Centre for Medical Systems Biology (CMSB 1-2) and the ENGAGE Consortium, grant agreement HEALTH-F4-2007-201413. A.C.J.W.J. was supported by a Vidi grant from the Netherlands Organization for Scientific Research (NWO). NR 70 TC 2 Z9 2 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 2014 VL 67 IS 5 BP 487 EP 499 DI 10.1016/j.jclinepi.2013.10.006 PG 13 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AF8OG UT WOS:000334974900002 PM 24411311 ER PT J AU Bevans, M Wehrlen, L Castro, K Prince, P Shelburne, N Soeken, K Zabora, J Wallen, GR AF Bevans, Margaret Wehrlen, Leslie Castro, Kathleen Prince, Patricia Shelburne, Nonniekaye Soeken, Karen Zabora, James Wallen, Gwenyth R. TI A problem-solving education intervention in caregivers and patients during allogeneic hematopoietic stem cell transplantation SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE intervention; behavioral medicine; anxiety; distress; coping; cancer; health behavior; family ID RANDOMIZED CLINICAL-TRIAL; ADULT CANCER-PATIENTS; QUALITY-OF-LIFE; FAMILY CAREGIVERS; SELF-EFFICACY; PSYCHOLOGICAL DISTRESS; BREAST-CANCER; CARE; DEMENTIA; METAANALYSIS AB The aim of this study was to determine the effect of problem-solving education on self-efficacy and distress in informal caregivers of allogeneic hematopoietic stem cell transplantation patients. Patient/caregiver teams attended three 1-hour problem-solving education sessions to help cope with problems during hematopoietic stem cell transplantation. Primary measures included the Cancer Self-Efficacy Scale-transplant and Brief Symptom Inventory-18. Active caregivers reported improvements in self-efficacy (p < 0.05) and distress (p < 0.01) post-problem-solving education; caregiver responders also reported better health outcomes such as fatigue. The effect of problem-solving education on self-efficacy and distress in hematopoietic stem cell transplantation caregivers supports its inclusion in future interventions to meet the multifaceted needs of this population. C1 [Bevans, Margaret; Wehrlen, Leslie; Prince, Patricia; Wallen, Gwenyth R.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Castro, Kathleen; Shelburne, Nonniekaye] NCI, Bethesda, MD 20892 USA. [Soeken, Karen] Univ Maryland, College Pk, MD 20742 USA. [Zabora, James] Inova Hlth Syst, Alexandria, VA USA. RP Bevans, M (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Room 2B13, Bethesda, MD 20892 USA. EM mbevans@cc.nih.gov FU Intramural NIH HHS [ZIA CL001150-05] NR 50 TC 7 Z9 7 U1 2 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 EI 1461-7277 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD MAY PY 2014 VL 19 IS 5 BP 602 EP 617 DI 10.1177/1359105313475902 PG 16 WC Psychology, Clinical SC Psychology GA AF6KS UT WOS:000334824600002 PM 23471761 ER PT J AU Kitano, H Chung, JY Ylaya, K Conway, C Takikita, M Fukuoka, J Doki, Y Hanaoka, J Hewitt, SM AF Kitano, Haruhisa Chung, Joon-Yong Ylaya, Kris Conway, Catherine Takikita, Mikiko Fukuoka, Junya Doki, Yoshinori Hanaoka, Jun Hewitt, Stephen M. TI Profiling of Phospho-AKT, Phospho-mTOR, Phospho-MAPK and EGFR in Non-small Cell Lung Cancer SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE AKT; mTOR; Tissue microarray; Non-small cell lung cancer; Image analysis; MAPK; Survival analysis; Immunohistochemistry; EGFR ID GROWTH-FACTOR RECEPTOR; PREDICTS POOR-PROGNOSIS; ORAL MEK INHIBITOR; SIGNALING PATHWAYS; MAMMALIAN TARGET; BREAST-CANCER; PHASE-II; EXPRESSION; KINASE; PI3K AB Activation of numerous pathways has been documented in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) has emerged as a common therapeutic target. The mitogen-activated protein kinase (MAPK) and AKT signaling pathways are downstream of EGFR and deregulated via genetic and epigenetic mechanisms in many human cancers. We evaluated selected markers in the EGFR pathway with reference to outcome. Tissues from 220 cases of NSCLC patients presented in a tissue microarray were assayed with immunohistochemistry for phosphorylated AKT, phosphorylated MAPK, phosphorylated mTOR, and EGFR and then quantified by automated image analysis. Individually, the biomarkers did not predict. Combined as ratios, p-mTOR/p-AKT, and p-MAPK/EGFR function as prognostic markers of survival (p=0.008 and p=0.029, respectively), however, no significance was found after adjustment (p=0.221, p=0.103). The sum of these ratios demonstrates a stronger correlation with survival (p<0.001) and remained statistically significant after adjustment (p=0.026). The algebraic combination of biomarkers offer the capacity to understand factors that predict outcome better than current approaches of evaluating biomarkers individually or in pairs. Our results show the sum of p-mTOR/p-AKT and p-MAPK/EGFR is a potential predictive marker of survival in NSCLC patients. C1 [Kitano, Haruhisa; Chung, Joon-Yong; Ylaya, Kris; Conway, Catherine; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Kitano, Haruhisa; Fukuoka, Junya] Toyama Univ Hosp, Pathol Lab, Toyama, Japan. [Doki, Yoshinori] Toyama Univ, Dept Surg 1, Toyama 930, Japan. [Kitano, Haruhisa; Hanaoka, Jun] Shiga Univ Med Sci, Dept Surg, Otsu, Shiga 52021, Japan. RP Hewitt, SM (reprint author), NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 FU NIH, National Cancer Institute, Center for Cancer Research FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 66 TC 10 Z9 10 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAY PY 2014 VL 62 IS 5 BP 335 EP 346 DI 10.1369/0022155414523022 PG 12 WC Cell Biology SC Cell Biology GA AG0FK UT WOS:000335090500002 PM 24487999 ER PT J AU Rajagopalan, S Long, EO AF Rajagopalan, Sumati Long, Eric O. TI Comment on "Killer Ig- like Receptor 2DL4 Does Not Mediate NK Cell IFN-gamma Responses to Soluble HLA-G Preparations" SO JOURNAL OF IMMUNOLOGY LA English DT Letter C1 [Rajagopalan, Sumati; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Rajagopalan, S (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM sumi@nih.gov FU Intramural NIH HHS [ZIA AI001119-06] NR 4 TC 3 Z9 4 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 IS 9 BP 4003 EP 4003 DI 10.4049/jimmunol.1400430 PG 1 WC Immunology SC Immunology GA AF4HO UT WOS:000334672800001 PM 24748631 ER PT J AU Ma, N Xing, C Xiao, H He, YD Han, GC Chen, GJ Hou, CM Marrero, B Wang, YJ Zhang, SQ Shen, BF Li, Y Wang, RX AF Ma, Ning Xing, Chen Xiao, He He, Youdi Han, Gencheng Chen, Guojiang Hou, Chunmei Marrero, Bernadette Wang, Yujuan Zhang, Shengquan Shen, Beifen Li, Yan Wang, Renxi TI BAFF Suppresses IL-15 Expression in B Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MEMORY T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PLASMA-CELLS; RHEUMATOID-ARTHRITIS; MICE; DISEASE; INTERLEUKIN-15; BCMA; TRANSCRIPTION AB Clinical trials have shown that BAFF inhibitors do not reduce memory B cell levels but can reduce the number of mature B cells. It remains uncertain whether BAFF affects memory-maintaining cytokines such as IL-15. We found that BAFF suppressed IL-15 expression in B cells from lupus-like or experimental allergic encephalomyelitis mice. When BAFF was blocked with atacicept-IgG, IL-15 expression was upregulated in lupus-like or experimental allergic encephalomyelitis mice. Finally, we showed that BAFF suppressed IL-15 expression in transitional 2 B cells by reducing Foxo1 expression and inducing Foxo1 phosphorylation. This study suggests that BAFF suppresses IL-15 expression in autoimmune diseases, and this opens up the possible opportunity for the clinical application of BAFF-and IL-15-specific therapeutic agents. C1 [Ma, Ning; Xing, Chen; Xiao, He; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Shen, Beifen; Li, Yan; Wang, Renxi] Inst Basic Med Sci, Immunol Lab, Beijing 100850, Peoples R China. [Ma, Ning] Jilin Univ, Hosp 1, Dept Rheumatol, Changchun 130021, Peoples R China. [He, Youdi] Capital Med Univ, Beijing Chaoyang Hosp, Dept Neurol, Beijing 100020, Peoples R China. [Marrero, Bernadette] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Yujuan] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Zhang, Shengquan] Anhui Med Univ, Dept Biochem & Mol Biol, Hefei 230032, Peoples R China. RP Wang, RX (reprint author), Inst Basic Med Sci, Immunol Lab, POB 130,3 Taiping Rd 27, Beijing 100850, Peoples R China. EM liyan62033@gmail.com; wang_renxi@yahoo.com RI wang, yujuan/C-8428-2016 FU National Basic Research Program 973 [2013CB530506]; Beijing Natural Science Foundation [7132139] FX This work was supported by National Basic Research Program 973 Grant 2013CB530506 and Beijing Natural Science Foundation Grant 7132139. NR 40 TC 7 Z9 7 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 IS 9 BP 4192 EP 4201 DI 10.4049/jimmunol.1302132 PG 10 WC Immunology SC Immunology GA AF4HO UT WOS:000334672800025 PM 24670802 ER PT J AU Swiecki, M Wang, YM Riboldi, E Kim, AHJ Dzutsev, A Gilfillan, S Vermi, W Ruedl, C Trinchieri, G Colonna, M AF Swiecki, Melissa Wang, Yaming Riboldi, Elena Kim, Alfred H. J. Dzutsev, Amiran Gilfillan, Susan Vermi, William Ruedl, Christiane Trinchieri, Giorgio Colonna, Marco TI Cell Depletion in Mice That Express Diphtheria Toxin Receptor under the Control of SiglecH Encompasses More Than Plasmacytoid Dendritic Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MARGINAL ZONE MACROPHAGES; C-TYPE LECTIN; IN-VIVO; INTERFERON-ALPHA/BETA; IMMUNE-RESPONSES; VIRAL-INFECTION; CUTTING EDGE; SIGN-R1; SPLEEN; MONOCYTOGENES AB Plasmacytoid dendritic cells (pDC) produce IFN-I in response to viruses and are routinely identified in mice by SiglecH expression. SiglecH is a sialic acid-binding Ig-like lectin that has an immunomodulatory role during viral infections. In this study, we evaluated the impact of SiglecH deficiency on cytokine responses in the presence and absence of pDC. We found that lack of SiglecH enhanced IFN-I responses to viral infection, regardless of whether pDC were depleted. We also examined the expression pattern of SiglecH and observed that it was expressed by specialized macrophages and progenitors of classical dendritic cells and pDC. Accordingly, marginal zone macrophages and pDC precursors were eliminated in newly generated SiglecH-diphtheria toxin receptor (DTR)-transgenic (Tg) mice but not in CLEC4C-DTR-Tg mice after diphtheria toxin (DT) treatment. Using two bacterial models, we found that SiglecH-DTR-Tg mice injected with DT had altered bacterial uptake and were more susceptible to lethal Listeria monocytogenes infection than were DT-treated CLEC4C-DTR-Tg mice. Taken together, our findings suggest that lack of SiglecH may affect cytokine responses by cell types other than pDC during viral infections, perhaps by altering viral distribution or burden, and that cell depletion in SiglecH-DTR-Tg mice encompasses more than pDC. C1 [Swiecki, Melissa; Wang, Yaming; Gilfillan, Susan; Vermi, William; Colonna, Marco] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Riboldi, Elena; Dzutsev, Amiran; Trinchieri, Giorgio] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Riboldi, Elena] Univ Piemonte Orientale A Avagadro, Dept Pharmaceut Sci, I-28100 Novara, Italy. [Kim, Alfred H. J.] Washington Univ, Sch Med, Dept Internal Med, Div Rheumatol, St Louis, MO 63110 USA. [Vermi, William] Univ Brescia, Sch Med, Sect Pathol, Dept Mol & Translat Med, I-25123 Brescia, Italy. [Ruedl, Christiane] Nanyang Technol Univ, Div Mol & Cell Biol, Sch Biol Sci, Singapore 637551, Singapore. RP Colonna, M (reprint author), Washington Univ, BJC Inst Hlth, 425 South Euclid Ave,Campus Box 8118, St Louis, MO 63110 USA. EM mcolonna@pathology.wustl.edu RI Kim, Alfred/F-5699-2013; OI Kim, Alfred/0000-0003-4074-0516; Colonna, Marco/0000-0001-5222-4987 FU NHLBI NIH HHS [2T32HL007317-31, T32 HL007317]; NIDDK NIH HHS [1K01DK095972-01A1, K01 DK095972] NR 40 TC 14 Z9 14 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 IS 9 BP 4409 EP 4416 DI 10.4049/jimmunol.1303135 PG 8 WC Immunology SC Immunology GA AF4HO UT WOS:000334672800046 PM 24683186 ER PT J AU Romero, R Kadar, N Miranda, J Korzeniewski, SJ Schwartz, AG Chaemsaithong, P Rogers, W Soto, E Gotsch, F Yeo, L Hassan, SS Chaiworapongsa, T AF Romero, Roberto Kadar, Nicholas Miranda, Jezid Korzeniewski, Steven J. Schwartz, Alyse G. Chaemsaithong, Piya Rogers, Wade Soto, Eleazar Gotsch, Francesca Yeo, Lami Hassan, Sonia S. Chaiworapongsa, Tinnakorn TI The diagnostic performance of the Mass Restricted (MR) score in the identification of microbial invasion of the amniotic cavity or intra-amniotic inflammation is not superior to amniotic fluid interleukin-6 SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Biomarker; chorioamnionitis; IL-6; MMP-8; pregnancy; preterm birth; preterm labor; proteomics; reproducibility ID PRETERM PREMATURE RUPTURE; TUMOR-NECROSIS-FACTOR; POLYMERASE-CHAIN-REACTION; CERVICAL-VAGINAL FLUID; BIRTH-WEIGHT INFANTS; BLOOD-CELL COUNT; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; COMPREHENSIVE PROTEOMIC ANALYSIS; UMBILICAL-CORD INFLAMMATION; LEUKOCYTE ESTERASE-ACTIVITY AB Objective: Intra-amniotic infection/inflammation are major causes of spontaneous preterm labor and delivery. However, diagnosis of intra-amniotic infection is challenging because most are subclinical and amniotic fluid (AF) cultures take several days before results are available. Several tests have been proposed for the rapid diagnosis of microbial invasion of the amniotic cavity (MIAC) or intra-amniotic inflammation. The aim of this study was to examine the diagnostic performance of the AF Mass Restricted (MR) score in comparison with interleukin-6 (IL-6) and matrix metalloproteinase-8 (MMP-8) for the identification of MIAC or inflammation. Methods: AF samples were collected from patients with singleton gestations and symptoms of preterm labor (n - 100). Intra-amniotic inflammation was defined as 4100 white blood cells/mm(3) (WBCs) in AF; MIAC was defined as a positive AF culture. AF IL-6 and MMP-8 were determined using ELISA. The MR score was obtained using the Surface-Enhanced Laser Desorption Ionization Time of Flight (SELDI-TOF) mass spectrometry. Sensitivity and specificity were calculated and logistic regression models were fit to construct receiver-operating characteristic (ROC) curves for the identification of each outcome. The McNemar's test and paired sample non-parametric statistical techniques were used to test for differences in diagnostic performance metrics. Results: (1) The prevalence of MIAC and intra-amniotic inflammation was 34% (34/100) and 40% (40/100), respectively; (2) there were no significant differences in sensitivity of the three tests under study (MR score, IL-6 or MMP-8) in the identification of either MIAC or intra-amniotic inflammation (using the following cutoffs: MR score >2, IL-6 > 11.4 ng/mL, and MMP-8>23 ng/mL); (3) there was no significant difference in the sensitivity among the three tests for the same outcomes when the false positive rate was fixed at 15%; (4) the specificity for IL-6 was not significantly different from that of the MR score in identifying either MIAC or intra-amniotic inflammation when using previously reported thresholds; and (5) there were no significant differences in the area under the ROC curve when comparing the MR score, IL-6 or MMP-8 in the identification of these outcomes. Conclusions: IL-6 and the MR score have equivalent diagnostic performance in the identification of MIAC or intra-amniotic inflammation. Selection from among these three tests (MR score, IL-6 and MMP-8) for diagnostic purposes should be based on factors such as availability, reproducibility, and cost. The MR score requires a protein chip and a SELDI-TOF instrument which are not widely available or considered "state of the art". In contrast, immunoassays for IL-6 can be performed in the majority of clinical laboratories. C1 [Romero, Roberto; Kadar, Nicholas; Miranda, Jezid; Korzeniewski, Steven J.; Schwartz, Alyse G.; Chaemsaithong, Piya; Soto, Eleazar; Gotsch, Francesca; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA. [Romero, Roberto; Kadar, Nicholas; Miranda, Jezid; Korzeniewski, Steven J.; Schwartz, Alyse G.; Chaemsaithong, Piya; Soto, Eleazar; Gotsch, Francesca; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Miranda, Jezid; Korzeniewski, Steven J.; Schwartz, Alyse G.; Chaemsaithong, Piya; Soto, Eleazar; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Rogers, Wade] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Gotsch, Francesca] Azienda Osped Univ, Integrata Verona, Verona, Italy. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS,Hutzel Womens Hosp, 3990 John R St, Detroit, MI 48201 USA. EM romeror@mail.nih.gov FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); NICHD; NIH [HHSN275201300006C] FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); and, in part, with Federal funds from NICHD, NIH under Contract No. HHSN275201300006C. NR 271 TC 22 Z9 23 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD MAY PY 2014 VL 27 IS 8 BP 757 EP 769 DI 10.3109/14767058.2013.844123 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AF5FG UT WOS:000334738800001 PM 24028673 ER PT J AU Romero, R Yoon, BH Chaemsaithong, P Cortez, J Park, CW Gonzalez, R Behnke, E Hassan, SS Chaiworapongsa, T Yeo, L AF Romero, Roberto Yoon, Bo Hyun Chaemsaithong, Piya Cortez, Josef Park, Chan-Wook Gonzalez, Rogelio Behnke, Ernesto Hassan, Sonia S. Chaiworapongsa, Tinnakorn Yeo, Lami TI Bacteria and endotoxin in meconium-stained amniotic fluid at term: could intra-amniotic infection cause meconium passage? SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Amniotic fluid glucose; white blood cell; fetal bowel function; fetal defecation; fetal diarrhea; interleukin-6; intrauterine inflammation/infection; Limulus amebocyte lysate (LAL) ID PRETERM PREMATURE RUPTURE; TUMOR-NECROSIS-FACTOR; IN-UTERO DEFECATION; POLYMERASE-CHAIN-REACTION; ACID-BASE STATUS; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; SYSTEMIC INFLAMMATORY RESPONSE; HUMAN PRENATAL DEVELOPMENT; DELIVERY ROOM MANAGEMENT; DRUG-DEPENDENT MOTHERS AB Background: Meconium-stained amniotic fluid (MSAF) is a common occurrence among women in spontaneous labor at term, and has been associated with adverse outcomes in both mother and neonate. MSAF is a risk factor for microbial invasion of the amniotic cavity (MIAC) and preterm birth among women with preterm labor and intact membranes. We now report the frequency of MIAC and the presence of bacterial endotoxin in the amniotic fluid of patients with MSAF at term. Materials and methods: We conducted a cross-sectional study including women in presumed preterm labor because of uncertain dates who underwent amniocentesis, and were later determined to be at term (n = 108). Patients were allocated into two groups: (1) MSAF (n = 66) and (2) clear amniotic fluid (n = 42). The presence of bacteria was determined by microbiologic techniques, and endotoxin was detected using the Limulus amebocyte lysate (LAL) gel clot assay. Statistical analyses were performed to test for normality and bivariate comparisons. Results: Bacteria were more frequently present in patients with MSAF compared to those with clear amniotic fluid [19.6% (13/66) versus 4.7% (2/42); p<0.05]. The microorganisms were Gram-negative rods (n = 7), Ureaplasma urealyticum (n = 4), Gram-positive rods (n = 2) and Mycoplasma hominis (n = 1). The LAL gel clot assay was positive in 46.9% (31/66) of patients with MSAF, and in 4.7% (2/42) of those with clear amniotic fluid (p < 0.001). After heat treatment, the frequency of a positive LAL gel clot assay remained higher in the MSAF group [18.1% (12/66) versus 2.3% (1/42), p<0.05]. Median amniotic fluid IL-6 concentration (ng/mL) was higher [1.3 (0.7-1.9) versus 0.6 (0.3-1.2), p=0.04], and median amniotic fluid glucose concentration (mg/dL) was lower [6 (0-8.9) versus 9 (7.4-12.6), p<0.001] in the MSAF group, than in those with clear amniotic fluid. Conclusion: MSAF at term was associated with an increased incidence of MIAC. The index of suspicion for an infection-related process in postpartum women and their neonates should be increased in the presence of MSAF. C1 [Romero, Roberto; Yoon, Bo Hyun; Chaemsaithong, Piya; Cortez, Josef; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn; Yeo, Lami] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto; Yoon, Bo Hyun; Chaemsaithong, Piya; Cortez, Josef; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn; Yeo, Lami] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Yoon, Bo Hyun; Park, Chan-Wook] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. [Chaemsaithong, Piya; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn; Yeo, Lami] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Cortez, Josef] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Gonzalez, Rogelio] Pontificia Univ Catolica Chile, Ctr Perinatal Diag & Res CEDIP, Hosp Dr Sotero del Rio, Puente Alto, Chile. [Behnke, Ernesto] Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, Ctr Perinatal Diag & Res CEDIP, Santiago, Chile. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM romeror@mail.nih.gov FU Walter Scott Foundation for Medical Research; Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); NICHD/NIH [HHSN275201300006C] FX This research was supported, in part, by a grant from the Walter Scott Foundation for Medical Research and by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); and in part, with Federal funds from NICHD/NIH under Contract No. HHSN275201300006C. NR 272 TC 8 Z9 8 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD MAY PY 2014 VL 27 IS 8 BP 775 EP 788 DI 10.3109/14767058.2013.844124 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AF5FG UT WOS:000334738800003 PM 24028637 ER PT J AU Wan, RQ Weigand, LA Bateman, R Griffioen, K Mendelowitz, D Mattson, MP AF Wan, Ruiqian Weigand, Letitia A. Bateman, Ryan Griffioen, Kathleen Mendelowitz, David Mattson, Mark P. TI Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE BDNF; GABA; glutamate; nucleus ambiguus; parasympathetic; vagus nerve ID CARDIAC VAGAL NEURONS; NEUROTROPHIC FACTOR; NUCLEUS AMBIGUUS; SYNAPTIC PLASTICITY; DIETARY RESTRICTION; HETEROZYGOUS MICE; BLOOD-PRESSURE; EXERCISE; RECEPTOR; TRKB AB Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haploinsufficiency exhibit elevated resting heart rate, and infusion of BDNF intracerebroventricularly reduces heart rate in both wild-type and BDNF+/- mice. The atropine-induced elevation of heart rate is diminished in BDNF+/- mice and is restored by BDNF infusion, whereas the atenolol-induced decrease in heart rate is unaffected by BDNF levels, suggesting that BDNF signaling enhances parasympathetic tone which is diminished with BDNF haploinsufficiency. Whole-cell recordings from pre-motor cholinergic cardioinhibitory vagal neurons in the nucleus ambiguus indicate that BDNF haploinsufficiency reduces cardioinhibitory vagal neuron activity by increased inhibitory GABAergic and diminished excitatory glutamatergic neurotransmission to these neurons. Our findings reveal a previously unknown role for BDNF in the control of heart rate by a mechanism involving increased activation of brainstem cholinergic parasympathetic neurons Mice with reduced BDNF levels exhibit elevated heart rate, and infusion of BDNF into the brain normalizes heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Recordings from pre-motor cholinergic cardioinhibitory vagal neurons (CVNs) in the nucleus ambiguus indicate that BDNF increases CVN activity by increasing excitatory glutamatergic and decreasing inhibitory GABAergic neurotransmission to these neurons. Perhaps factors that increase parasympathetic tone (e.g., exercise) reduce resting heart rate, in part, by a BDNF-mediated mechanism. C1 [Wan, Ruiqian; Griffioen, Kathleen; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Weigand, Letitia A.; Bateman, Ryan; Mendelowitz, David] George Washington Univ, Dept Physiol & Pharmacol, Washington, DC 20037 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM dmendel@gwu.edu; mark.mattson@nih.gov FU National Institute on Aging Intramural Research Program; NIH [HL49965, HL59895, HL72006]; Glenn Foundation for Medical Research FX This research was supported by the National Institute on Aging Intramural Research Program, by NIH grants HL49965, HL59895, and HL72006 to D. M., and by a grant to M. P. M. from the Glenn Foundation for Medical Research. The authors declare that they have no conflicts of interest. NR 48 TC 12 Z9 12 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2014 VL 129 IS 4 BP 573 EP 580 DI 10.1111/jnc.12656 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AF4RC UT WOS:000334700600002 PM 24475741 ER PT J AU Traynor, BJ AF Traynor, Bryan J. TI A roadmap for genetic testing in ALS SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Editorial Material ID HEXANUCLEOTIDE REPEAT EXPANSION; AMYOTROPHIC-LATERAL-SCLEROSIS; C9ORF72; FTD C1 NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM traynorb@mail.nih.gov FU Intramural NIH HHS [ZIA AG000933-02]; NIA NIH HHS [Z01-AG000949-02, Z01 AG000949] NR 6 TC 2 Z9 2 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 2014 VL 85 IS 5 BP 476 EP 476 DI 10.1136/jnnp-2013-305726 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA AF3NA UT WOS:000334617800004 PM 23868946 ER PT J AU Tucci, A Liu, YT Preza, E Pitceathly, RDS Chalasani, A Plagnol, V Land, JM Trabzuni, D Ryten, M Jaunmuktane, Z Reilly, MM Brandner, S Hargreaves, I Hardy, J Singleton, AB Abramov, AY Houlden, H AF Tucci, Arianna Liu, Yo-Tsen Preza, Elisabeth Pitceathly, Robert D. S. Chalasani, Annapurna Plagnol, Vincent Land, John M. Trabzuni, Daniah Ryten, Mina Jaunmuktane, Zane Reilly, Mary M. Brandner, Sebastian Hargreaves, Iain Hardy, John Singleton, Andrew B. Abramov, Andrey Y. Houlden, Henry CA UKBEC TI Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID MARIE-TOOTH DISEASE; SENSORY NEUROPATHY; HEREDITARY MOTOR; PERIPHERAL NEUROPATHY; EXPRESSION; BRAIN; C12ORF65; DONATION; OPA1; VI AB Objective Charcot-Marie Tooth disease (CMT) forms a clinically and genetically heterogeneous group of disorders. Although a number of disease genes have been identified for CMT, the gene discovery for some complex form of CMT has lagged behind. The association of neuropathy and optic atrophy (also known as CMT type 6) has been described with autosomaldominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylpyrophosphate synthetase-I mutations cause X-linked CMT6, but until now, mutations in the recessive forms of disease have never been identified. Methods We here describe a family with three affected individuals who inherited in an autosomal recessive fashion a childhood onset neuropathy and optic atrophy. Using homozygosity mapping in the family and exome sequencing in two affected individuals we identified a novel protein-truncating mutation in the C12orf65 gene, which encodes for a protein involved in mitochondrial translation. Using a variety of methods we investigated the possibility of mitochondrial impairment in the patients cell lines. Results We described a large consanguineous family with neuropathy and optic atrophy carrying a loss of function mutation in the C12orf65 gene. We report mitochondrial impairment in the patients cell lines, followed by multiple lines of evidence which include decrease of complex V activity and stability (blue native gel assay), decrease in mitochondrial respiration rate and reduction of mitochondrial membrane potential. Conclusions This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy. C1 [Tucci, Arianna; Liu, Yo-Tsen; Preza, Elisabeth; Pitceathly, Robert D. S.; Trabzuni, Daniah; Ryten, Mina; Reilly, Mary M.; Hardy, John; Abramov, Andrey Y.; Houlden, Henry] UCL Inst Neurol, Dept Mol Neurosci, London, England. [Tucci, Arianna; Liu, Yo-Tsen; Preza, Elisabeth; Pitceathly, Robert D. S.; Trabzuni, Daniah; Ryten, Mina; Reilly, Mary M.; Hardy, John; Abramov, Andrey Y.; Houlden, Henry] UCL Inst Neurol, Reta Lila Weston Res Labs, London, England. [Tucci, Arianna; Liu, Yo-Tsen; Preza, Elisabeth; Pitceathly, Robert D. S.; Chalasani, Annapurna; Land, John M.; Trabzuni, Daniah; Ryten, Mina; Reilly, Mary M.; Hargreaves, Iain; Hardy, John; Abramov, Andrey Y.; Houlden, Henry] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [Liu, Yo-Tsen; Pitceathly, Robert D. S.; Reilly, Mary M.; Houlden, Henry] UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London, England. [Liu, Yo-Tsen] Taipei Vet Gen Hosp, Sect Epilepsy, Dept Neurol, Neurol Inst, Taipei, Taiwan. [Liu, Yo-Tsen] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan. [Chalasani, Annapurna; Land, John M.; Hargreaves, Iain] UCL Inst Neurol, Neurometab Unit, London, England. [Plagnol, Vincent] UGI, London, England. [Trabzuni, Daniah] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [Jaunmuktane, Zane; Brandner, Sebastian] Natl Hosp Neurol & Neurosurg, Div Neuropathol, London WC1N 3BG, England. [Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Houlden, H (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England. EM h.houlden@ion.ucl.ac.uk RI Hardy, John/C-2451-2009; Houlden, Henry/C-1532-2008; Singleton, Andrew/C-3010-2009; Abramov, Andrey/H-9053-2012; Trabzuni, Daniah/C-4034-2012; OI Houlden, Henry/0000-0002-2866-7777; Abramov, Andrey/0000-0002-7646-7235; Trabzuni, Daniah/0000-0003-4826-9570; Plagnol, Vincent/0000-0002-5597-9215 FU Wellcome Trust/MRC Joint Call in Neurodegeneration award [WT089698]; NORD; Dystonia Medical Research Foundation (DMRF); Brain Research Trust (BRT); National Institute for Health Research (NIHR) UCLH/UCL Comprehensive Biomedical Research Centre; MRC through the MRC Sudden Death Brain Bank; National Institute of Neurological Disorders and Stroke (National Brain and Tissue Resource for Parkinson's Disease and Related Disorders) [U24 NS072026]; National Institute on Aging (Arizona Alzheimer's Disease Core Center) [P30 AG19610]; Arizona Department of Health Services [211002]; Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]; Michael J. Fox Foundation for Parkinson's Research; [G0901254]; [G0802462] FX This work was supported in part by the Wellcome Trust/MRC Joint Call in Neurodegeneration award (WT089698) to the UK Parkinson's Disease Consortium (UKPDC) whose members are from the UCL/Institute of Neurology, the University of Sheffield and the MRC Protein Phosphorylation Unit at the University of Dundee. This study was also supported by NORD, The Dystonia Medical Research Foundation (DMRF), The Brain Research Trust (BRT) and the National Institute for Health Research (NIHR) UCLH/UCL Comprehensive Biomedical Research Centre. Expression data were provided by the UK Human Brain Expression Consortium (UKBEC), which comprises John A. Hardy, Mina Ryten, Daniah Trabzuni, Michael Weale, Adaikalavan Ramasamy and Colin Smith. UKBEC members are affiliated with the UCL Institute of Neurology (JAH, MR, and DT), King's College London (MW and AR) and the University of Edinburgh (CS). This work was supported by the MRC through the MRC Sudden Death Brain Bank (CS) and by a Project Grant (G0901254 to JH and MW) and Training Fellowship (G0802462 to MR). The Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson's Disease Consortium) and the Michael J. Fox Foundation for Parkinson's Research. NR 26 TC 9 Z9 9 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 2014 VL 85 IS 5 BP 486 EP 492 DI 10.1136/jnnp-2013-306387 PG 7 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA AF3NA UT WOS:000334617800007 PM 24198383 ER PT J AU Hiranita, T Wilkinson, DS Hong, WMC Zou, MF Kopajtic, TA Soto, PL Lupica, CR Newman, AH Katz, JL AF Hiranita, Takato Wilkinson, Derek S. Hong, Weimin C. Zou, Mu-Fa Kopajtic, Theresa A. Soto, Paul L. Lupica, Carl R. Newman, Amy H. Katz, Jonathan L. TI 2-Isoxazol-3-Phenyltropane Derivatives of Cocaine: Molecular and Atypical System Effects at the Dopamine Transporter SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MONOAMINE UPTAKE INHIBITORS; CANNABINOID CB1 RECEPTOR; BEHAVIORAL PHARMACOLOGY; IN-VIVO; MESOLIMBIC DOPAMINE; BENZTROPINE ANALOGS; LOCOMOTOR-ACTIVITY; NONHUMAN-PRIMATES; STIMULANT ACTIONS; SQUIRREL-MONKEYS AB The present study examined RTI-371 [3 beta-(4-methylphenyl)-2 beta[3-(4-chlorophenyl)-isoxazol-5-yl]tropane], a phenyltropane cocaine analog with effects distinct from cocaine, and assessed potential mechanisms for those effects by comparison with its constitutional isomer, RTI-336 [3b-(4-chlorophenyl)-2b-[3-(4methylphenyl)-isoxazol-5-yl]tropane]. In mice, RTI-371 was less effective than cocaine and RTI-336 in stimulating locomotion, and incompletely substituted (similar to 60% maximum at 5 minutes or 1 hour after injection) in a cocaine (10 mg/kg i.p.)/saline discrimination procedure; RTI-336 completely substituted. In contrast to RTI336, RTI-371 was not self-administered, and its pretreatment (1.0-10 mg/kg i.p.) dose-dependently decreased maximal cocaine self-administration more potently than food-maintained responding. RTI-336 pretreatment dose-dependently left-shifted the cocaine self-administration dose-effect curve. Both RTI-336 and RTI-371 displaced [H-3]WIN35,428 [[H-3](2)-3 beta-(4-fluorophenyl)-tropan-2 beta-carboxylic acid methyl ester tartrate] binding to striatal dopamine transporters (DATs) with Ki values of 10.8 and 7.81 nM, respectively, and had lower affinities at serotonin or norepinephrine transporters, or muscarinic and s receptors. The relative low affinity at these sites suggests the DAT as the primary target of RTI-371 with minimal contributions from these other targets. In biochemical assays probing the outward-facing DAT conformation, both RTI-371 and RTI-336 had effects similar to cocaine, suggesting little contribution of DAT conformation to the unique pharmacology of RTI-371. The locomotor-stimulant effects of RTI-371 (3.0-30 mg/kg i.p.) were comparable in wildtype and knockout cannabinoid CB1 receptor (CB1R) mice, indicating that previously reported CB1 allosteric effects do not decrease cocaine-like effects of RTI-371. DAT occupancy in vivo was most rapid with cocaine and least with RTI-371. The slow apparent association rate may allow compensatory actions that in turn dampen cocaine-like stimulation, and give RTI-371 its unique pharmacologic profile. C1 [Hiranita, Takato; Wilkinson, Derek S.; Kopajtic, Theresa A.; Katz, Jonathan L.] NIDA, Psychobiol Sect, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. [Hong, Weimin C.] NIDA, Cellular Pathobiol Sect, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. [Zou, Mu-Fa; Newman, Amy H.] NIDA, Med Chem Sect, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. [Lupica, Carl R.] NIDA, Electrophysiol Sect, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. [Soto, Paul L.] Texas Tech Univ, Coll Educ, Lubbock, TX 79409 USA. RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM jkatz@intra.nida.nih.gov OI Katz, Jonathan/0000-0002-1068-1159 FU Intramural Research Program of the National Institutes of Health [National Institute on Drug Abuse] FX This work was supported by the Intramural Research Program of the National Institutes of Health [National Institute on Drug Abuse]. NR 47 TC 5 Z9 5 U1 1 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2014 VL 349 IS 2 BP 297 EP 309 DI 10.1124/jpet.113.212738 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF2BT UT WOS:000334518300014 PM 24518035 ER PT J AU Sheehan, FT Brochard, S Behnam, AJ Alter, KE AF Sheehan, Frances T. Brochard, Sylvain Behnam, Abrahm J. Alter, Katharine E. TI Three-dimensional humeral morphologic alterations and atrophy associated with obstetrical brachial plexus palsy SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Reliability; magnetic resonance imaging; shape; retroversion; version; inclination ID BIRTH PALSY; HEAD RETROVERSION; GLENOHUMERAL JOINT; SHOULDER FUNCTION; EXTERNAL ROTATION; BICIPITAL GROOVE; BASEBALL PLAYERS; GLENOID VERSION; FOLLOW-UP; RELIABILITY AB Background: Obstetrical brachial plexus palsy (OBPP) is a common birth injury, resulting in severe functional losses. Yet, little is known about how OBPP affects the 3-dimensional (3D) humeral morphology. Thus, the purpose of this study was to measure the 3D humeral architecture in children with unilateral OBPP. Methods: Thirteen individuals (4 female and 9 male patients; mean age, 11.8 +/- 3.3 years; mean Mallet score, 15.1 +/- 3.0) participated in this institutional review board approved study. A 3D T1-weighted gradient-recalled echo magnetic resonance image set was acquired for both upper limbs (involved and noninvolved). Humeral size, version, and inclination were quantified from 3D humeral models derived from these images. Results: The involved humeral head was significantly less retroverted and in declination (medial humeral head pointed anteriorly and inferiorly) relative to the noninvolved side. Osseous atrophy was present in all 3 dimensions and affected the entire humerus. The inter-rater reliability was excellent (intraclass correlation coefficient, 0.96-1.00). Discussion: This study showed that both humeral atrophy and bone shape deformities associated with OBPP are not limited to the axial plane but are 3D phenomena. Incorporating information related to these multi-planar, 3D humeral deformities into surgical planning could potentially improve functional outcomes after surgery. The documented reduction in retroversion is an osseous adaptation, which may help maintain glenohumeral congruency by partially compensating for the internal rotation of the arm. The humeral head declination is a novel finding and may be an important factor to consider when one is developing OBPP management strategies because it has been shown to lead to significant supraspinatus inefficiencies and increased required elevation forces. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Sheehan, Frances T.; Brochard, Sylvain; Behnam, Abrahm J.; Alter, Katharine E.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bethesda, MD 20892 USA. [Brochard, Sylvain] Univ Hosp Brest, Dept Rehabil Med, Brest, France. [Brochard, Sylvain] INSERM U1101, LaTIM, Brest, France. [Behnam, Abrahm J.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA. [Alter, Katharine E.] Mt Washington Pediat Hosp, Baltimore, MD USA. RP Sheehan, FT (reprint author), NIH, Bldg 10,CRC Room 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM fsheehan@cc.nih.gov RI sheehan, frances/B-6962-2009 FU Radiology Department, at the Clinical Center of the National Institutes of Health FX We thank Diane Damiano, PhD, Christopher Hollingsworth, Lindsay Curatalo, Christopher Stanley, and Lori Ohlrich for her help and support in the work. In addition, we thank the Radiology Department, headed by Dr David Bluemke, at the Clinical Center of the National Institutes of Health, for its support of this work. NR 56 TC 6 Z9 6 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAY PY 2014 VL 23 IS 5 BP 708 EP 719 DI 10.1016/j.jse.2013.08.014 PG 12 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA AF5RZ UT WOS:000334771900019 PM 24291045 ER PT J AU Sadowski, SM Weisbrod, AB Ellis, R Patel, D Alimchandani, M Quezado, M Millo, C Venzon, DJ Nilubol, N Linehan, WM Kebebew, E AF Sadowski, Samira M. Weisbrod, Allison B. Ellis, Ryan Patel, Dhaval Alimchandani, Meghna Quezado, Martha Millo, Corina Venzon, David J. Nilubol, Naris Linehan, W. Marston Kebebew, Electron TI Prospective Evaluation of the Clinical Utility of 18-Fluorodeoxyglucose PET CT Scanning in Patients with Von Hippel-Lindaue-Associated Pancreatic Lesions SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CELL LUNG-CANCER; NEUROENDOCRINE TUMORS; ENDOCRINE TUMORS; DISEASE AB BACKGROUND: The natural history of pancreatic neuroendocrine neoplasms (PNENs) in patients with Von Hippel-Lindau (VHL) disease is poorly defined. Management of patients with PNENs is challenging because there are no reliable preoperative criteria to detect malignant lesions, and the majority of resected tumors are found to be benign. The aim of this study was to determine whether 18-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) uptake predicts growth and detects malignant VHL-associated PNENs. STUDY DESIGN: We performed a prospective study of 197 patients with VHL-associated pancreatic lesions. Clinical and imaging characteristics were analyzed to study the associations between FDG-PET uptake, tumor growth, and the development of metastatic disease. RESULTS: One hundred nine of 197 patients had solid pancreatic lesions and underwent both CT and (18)FDG-PET scanning, which identified 165 and 144 lesions, respectively. Metastatic disease was detected by (18)FDG-PET in 3 patients in whom it was not detected by CT scan and suggested non- neoplastic disease in 3 patients. Maximum standardized uptake values (SUV) on (18)FDG-PET correlated with tumor size on CT (r = 0.47, p < 0.0001), and an increase in SUVmax was associated with tumor growth (r = 0.36, p < 0.0062). No association was seen between (18)FDG-PET uptake and age, VHL genotype, or serum chromogranin A levels. CONCLUSIONS: Scanning with FDG-PET identifies metastatic disease not detected by CT scan and avoids resection of non-PNEN lesions that have no malignant potential in patients with VHL-associated PNENs. It should be considered as a valuable functional imaging modality in the clinical management of patients with VHL-associated PNENs. (C) 2014 by the American College of Surgeons C1 [Sadowski, Samira M.; Weisbrod, Allison B.; Ellis, Ryan; Patel, Dhaval; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA. [Alimchandani, Meghna; Quezado, Martha] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Millo, Corina] NCI, Positron Emiss Tomog Dept, NIH, Bethesda, MD 20892 USA. [Venzon, David J.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Sadowski, SM (reprint author), NCI, Endocrine Oncol Branch, NIH, Clin Res Ctr, Bldg 10 CRC,Room 3W-5840, Bethesda, MD 20892 USA. EM samira.sadowskiveuthey@nih.gov FU intramural research program of the Center for Cancer Research; National Cancer Institute; National Institutes of Health FX This research was supported by the intramural research program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 31 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAY PY 2014 VL 218 IS 5 BP 997 EP 1003 DI 10.1016/j.jamcollsurg.2014.01.004 PG 7 WC Surgery SC Surgery GA AF2ZS UT WOS:000334581600016 PM 24661849 ER PT J AU Kayaalp, M Browne, AC Callaghan, FM Dodd, ZA Divita, G Ozturk, S McDonald, CJ AF Kayaalp, Mehmet Browne, Allen C. Callaghan, Fiona M. Dodd, Zeyno A. Divita, Guy Ozturk, Selcuk McDonald, Clement J. TI The pattern of name tokens in narrative clinical text and a comparison of five systems for redacting them SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID AUTOMATIC DE-IDENTIFICATION; MEDICAL-RECORDS; HEALTH AB Objective To understand the factors that influence success in scrubbing personal names from narrative text. Materials and methods We developed a scrubber, the NLM Name Scrubber (NLM-NS), to redact personal names from narrative clinical reports, hand tagged words in a set of gold standard narrative reports as personal names or not, and measured the scrubbing success of NLM-NS and that of four other scrubbing/name recognition tools (MIST, MITdeid, LingPipe, and ANNIE/GATE) against the gold standard reports. We ran three comparisons which used increasingly larger name lists. Results The test reports contained more than 1 million words, of which 2388 were patient and 20 160 were provider name tokens. NLM-NS failed to scrub only 2 of the 2388 instances of patient name tokens. Its sensitivity was 0.999 on both patient and provider name tokens and missed fewer instances of patient name tokens in all comparisons with other scrubbers. MIST produced the best all token specificity and F-measure for name instances in our most relevant study (study 2), with values of 0.997 and 0.938, respectively. In that same comparison, NLM-NS was second best, with values of 0.986 and 0.748, respectively, and MITdeid was a close third, with values of 0.985 and 0.796 respectively. With the addition of the Clinical Center name list to their native name lists, Ling Pipe, MITdeid, MIST, and ANNIE/GATE all improved substantially. MITdeid and Ling Pipe gained the most-reaching patient name sensitivity of 0.995 (F-measure=0.705) and 0.989 (F-measure=0.386), respectively. Discussion The privacy risk due to two name tokens missed by NLM-NS was statistically negligible, since neither individual could be distinguished among more than 150 000 people listed in the US Social Security Registry. Conclusions The nature and size of name lists have substantial influences on scrubbing success. The use of very large name lists with frequency statistics accounts for much of NLM-NS scrubbing success. C1 [Kayaalp, Mehmet; Browne, Allen C.; Callaghan, Fiona M.; Dodd, Zeyno A.; Divita, Guy; Ozturk, Selcuk; McDonald, Clement J.] NIH, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP McDonald, CJ (reprint author), NIH, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike,Bldg 38A-Room 7N707, Bethesda, MD 20894 USA. EM ClemMcDonald@mail.nih.gov FU National Institutes of Health, National Library of Medicine FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 25 TC 0 Z9 0 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY PY 2014 VL 21 IS 3 BP 423 EP 431 DI 10.1136/amiajnl-2013-001689 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA AF3KR UT WOS:000334611600006 PM 24026308 ER PT J AU Goldspiel, BR Flegel, WA DiPatrizio, G Sissung, T Adams, SD Penzak, SR Biesecker, LG Fleisher, TA Patel, JJ Herion, D Figg, WD Lertora, JJL McKeeby, JW AF Goldspiel, Barry R. Flegel, Willy A. DiPatrizio, Gary Sissung, Tristan Adams, Sharon D. Penzak, Scott R. Biesecker, Leslie G. Fleisher, Thomas A. Patel, Jharana J. Herion, David Figg, William D. Lertora, Juan J. L. McKeeby, Jon W. TI Integrating pharmacogenetic information and clinical decision support into the electronic health record SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID IMPLEMENTATION CONSORTIUM GUIDELINES; THIOPURINE METHYLTRANSFERASE GENOTYPE; HLA-B GENOTYPE; PERSONALIZED MEDICINE; HYPERSENSITIVITY; ABACAVIR; UPDATE AB Pharmacogenetics (PG) examines gene variations for drug disposition, response, or toxicity. At the National Institutes of Health Clinical Center (NIH CC), a multidepartment Pharmacogenetics Testing Implementation Committee (PGTIC) was established to develop clinical decision support (CDS) algorithms for abacavir, carbamazepine, and allopurinol, medications for which human leukocyte antigen (HLA) variants predict severe hypersensitivity reactions. Providing PG CDS in the electronic health record (EHR) during order entry could prevent adverse drug events. Medical Logic Module (MLM) programming was used to implement PG CDS in our EHR. The MLM checks to see if an HLA sequence-based gene test is ordered. A message regarding test status (result present, absent, pending, or test not ordered) is displayed on the order form, and the MLM determines if the prescriber can place the order, place it but require an over-ride reason, or be blocked from placing the order. Since implementation, more than 725 medication orders have been placed for over 230 patients by 154 different prescribers for the three drugs included in our PG program. Prescribers commonly used an over-ride reason when placing the order mainly because patients had been receiving the drug without reaction before implementation of the CDS program. Successful incorporation of PG CDS into the NIH CC EHR required a coordinated, interdisciplinary effort to ensure smooth activation and a positive effect on patient care. Prescribers have adapted to using the CDS and have ordered PG testing as a direct result of the implementation. C1 [Goldspiel, Barry R.; Penzak, Scott R.; Patel, Jharana J.] NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. [Flegel, Willy A.; Adams, Sharon D.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. [DiPatrizio, Gary; Herion, David; McKeeby, Jon W.] NIH, Ctr Clin, Dept Clin Res Informat, Bethesda, MD 20892 USA. [Sissung, Tristan; Figg, William D.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. [Fleisher, Thomas A.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. [Lertora, Juan J. L.] NIH, Ctr Clin, Clin Pharmacol Program, Bethesda, MD 20892 USA. RP Goldspiel, BR (reprint author), NIH, Ctr Clin, Dept Pharm, Bldg 10,Room 1C240,MSC 1196, Bethesda, MD 20892 USA. EM bgoldspiel@nih.gov RI Figg Sr, William/M-2411-2016 NR 25 TC 16 Z9 16 U1 1 U2 17 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY PY 2014 VL 21 IS 3 BP 522 EP 528 DI 10.1136/amiajnl-2013-001873 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA AF3KR UT WOS:000334611600019 PM 24302286 ER PT J AU Hong, CW Amalou, H Xu, S Turkbey, B Yan, PK Kruecker, J Pinto, PA Choyke, PL Wood, BJ AF Hong, Cheng William Amalou, Hayet Xu, Sheng Turkbey, Bans Yan, Pingkun Kruecker, Jochen Pinto, Peter A. Choyke, Peter L. Wood, Bradford J. TI Prostate Biopsy for the Interventional Radiologist SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review ID TRANSRECTAL ULTRASOUND BIOPSY; IMPROVE CANCER-DETECTION; SYSTEMATIC BIOPSY; ANTIGEN LEVELS; FUSION BIOPSY; TARGETED BIOPSY; NEEDLE BIOPSIES; GLEASON SCORE; GUIDED BIOPSY; COLOR AB Prostate biopsies are usually performed by urologists in the office setting using transrectal ultrasound (US) guidance. The current standard of care involves obtaining 10-14 Cores from different anatomic sections. Biopsies are usually not directed into a specific lesion because most prostate cancers are not visible on transrectal US. Color Doppler, US contrast agents, elastography, magnetic resonance (MR) imaging, and MR imaging/US fusion are proposed as imaging methods to guide prostate biopsies. Prostate MR imaging and fusion biopsy create opportunities for diagnostic and interventional radiologists to play an increasingly important role in the screening, evaluation, diagnosis, targeted biopsy, surveillance, and focal therapy of patients with prostate cancer. C1 [Hong, Cheng William; Amalou, Hayet; Xu, Sheng; Yan, Pingkun; Kruecker, Jochen; Wood, Bradford J.] NCI, Ctr Intervent Oncol, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Turkbey, Bans; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Yan, Pingkun; Kruecker, Jochen] Philips Res North Amer, Briarcliff Manor, NY USA. RP Wood, BJ (reprint author), NCI, Ctr Intervent Oncol, Ctr Clin, NIH, 10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. EM bwood@nih.gov FU Center for Interventional Oncology; National Cancer Institute; National Institutes of Health (NIH); Pfizer Inc; The Leona M. and Harry B. Helmsley Charitable Trust; Howard Hughes Medical Institute FX This work was supported by the Center for Interventional Oncology, the National Cancer Institute, and the Intramural Research Program of the National Institutes of Health (NIH). NIH and Philips Research North America have a Cooperative Research and Development Agreement. This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc, The Leona M. and Harry B. Helmsley Charitable Trust, and the Howard Hughes Medical Institute as well as other private donors. For a complete list, please visit the Foundation website at http://www.fnih.org/work/programs-development/medical-research-scholars- program. The content of this publication does not reflect the views, or policies of the Department of Health and Human Services, and mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. NR 60 TC 3 Z9 3 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAY PY 2014 VL 25 IS 5 BP 675 EP 684 DI 10.1016/j.jvir.2013.12.568 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AF7LI UT WOS:000334896200002 PM 24581731 ER PT J AU Amalou, H Negussie, AH Ranjan, A Chow, L Xu, S Kroeger, C Neeman, Z O'Grady, NP Wood, BJ AF Amalou, Hayet Negussie, Ayele H. Ranjan, Ashish Chow, Lucy Xu, Sheng Kroeger, Craig Neeman, Ziv O'Grady, Naomi P. Wood, Bradford J. TI Electrically Conductive Catheter Inhibits Bacterial Colonization SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID CENTRAL VENOUS CATHETERS; BLOOD-STREAM INFECTIONS; CANDIDA-ALBICANS BIOFILMS; CSF SHUNT INFECTIONS; IN-VITRO; ESCHERICHIA-COLI; DOUBLE-BLIND; PREVENTION; RESISTANCE; EFFICACY AB Purpose: To design, prototype, and assess a custom vascular access catheter for its ability to inhibit bacterial colonization in vitro and to optimize electric parameters for efficacy and safe translation. Materials and Methods: A vascular access catheter with conductive elements was designed and custom fabricated with two electrodes at the tip, separated by a nonconductive segment. The catheter was colonized with Staphylococcus aureus and incubated at predetermined current levels (4-8 mu A) and durations (4-24 h). Catheters were compared using bacterial counts and scanning electron microscopy (SEM). Results: Bacteria colony-forming units were reduced significantly (P < .05) by > 90% (91.7%-100%) in all uninterrupted treatment arms that included electric current (4 mu A or 8 mu A) of at least 8 hours' duration. Qualitative analysis using SEM revealed that the treated catheter exposed to electric current had markedly less bacteria compared with the untreated catheter. Conclusions: This catheter with elements inhibits bacterial colonization in vitro when very small electric current (4-8 mu A) is applied across the tip for 8-24 hours. In vivo validation is requisite to future translation to the clinical setting. C1 [Amalou, Hayet; Negussie, Ayele H.; Ranjan, Ashish; Chow, Lucy; Xu, Sheng; Neeman, Ziv; Wood, Bradford J.] Ctr Clin, Ctr Intervent Oncol, Bethesda, MD 20892 USA. [O'Grady, Naomi P.] NCI, Bethesda, MD 20892 USA. [O'Grady, Naomi P.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Kroeger, Craig] VitalDyne Inc, Cokato, MN USA. [Neeman, Ziv] Radiol Associates, Philadelphia, PA USA. RP Wood, BJ (reprint author), Ctr Clin, Ctr Intervent Oncol, Bldg 10,MSC 1182, Bethesda, MD 20892 USA. EM bwood@nih.gov FU Intramural Research Program of the National Institutes of Health (NIH); NIH Center for Interventional Oncology; NIH [Z1A CL040015-04 DRD] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), NIH Center for Interventional Oncology, and NIH Grant No. Z1A CL040015-04 DRD. The NIH and VitalDyne, Inc, may have intellectual property in the field. NR 35 TC 1 Z9 1 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAY PY 2014 VL 25 IS 5 BP 797 EP 802 DI 10.1016/j.jvir.2014.01.032 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AF7LI UT WOS:000334896200019 PM 24745908 ER PT J AU Evans, LH Boi, S Malik, F Wehrly, K Peterson, KE Chesebro, B AF Evans, Leonard H. Boi, Stefano Malik, Frank Wehrly, Kathy Peterson, Karin E. Chesebro, Bruce TI Analysis of two monoclonal antibodies reactive with envelope proteins of murine retroviruses: One pan specific antibody and one specific for Moloney leukemia virus SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Monoclonal antibodies; Retroviruses; Env protein; Moloney MuLV; Amphotropic MuLV ID FOCUS-FORMING VIRUSES; CELL-LINES; GENE-TRANSFER; ERYTHROLEUKEMIA-CELLS; POLYTROPIC MULVS; SU PROTEIN; C-VIRUS; FRIEND; MICE; RECOMBINANT AB Many monoclonal antibodies (MAbs) reactive with various proteins of murine leukemia viruses (MuLVs) have been developed. In this report two additional MAbs with differing and unusual specificities are described. MAb 573 is reactive with the envelope protein of all MuLVs tested including viruses in the ecotropic, xenotropic, polytropic and amphotropic classes. Notably, MAb 573 is one of only two reported MAbs that react with the envelope protein of amphotropic MuLVs. This MAb appears to recognize a conformational epitope within the envelope protein, as it reacts strongly with live virus and live infected cells, but does not react with formalin-fixed or alcohol-fixed infected cells or denatured viral envelope protein in immunoblots. In contrast, Mab 538 reacts only with an epitope unique to the envelope protein of the Moloney (Mo-) strain of MuLV, a prototypic ecotropic MuLV that is the basis for many retroviral tools used in molecular biology. MAb 538 can react with live cells and viruses, or detergent denatured or fixed envelope protein. The derivation of these antibodies as well as their characterization with regard to their isotype, range of reactivity with different MuLVs and utility in different immunological procedures are described in this study. Published by Elsevier B.V. C1 [Evans, Leonard H.; Boi, Stefano; Malik, Frank; Wehrly, Kathy; Peterson, Karin E.; Chesebro, Bruce] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. [Boi, Stefano] Univ Cagliari, Dept Biomed Sci, I-09042 Monserrato, CA, Italy. RP Evans, LH (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. EM levans@niaid.nih.gov RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 FU NIH, NIAID; Department of Biomedical Sciences, University of Cagliari, Monserrato (CA), Italy FX This research was supported by the Intramural Research Program of the NIH, NIAID and the Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato (CA), Italy. The authors wish to think Rebecca Linwood, Sue Priola, and Kim Hasenkrug for helpful discussions and Aaron Carmody for flow cytometic analysis. NR 53 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 EI 1879-0984 J9 J VIROL METHODS JI J. Virol. Methods PD MAY PY 2014 VL 200 BP 47 EP 53 DI 10.1016/j.jviromet.2014.02.006 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA AF8QX UT WOS:000334981800009 PM 24556162 ER PT J AU Cogger, VC Mitchell, SJ Warren, A de Cabo, R Le Couteur, DG AF Cogger, Victoria C. Mitchell, Sarah J. Warren, Alessandra de Cabo, Rafael Le Couteur, David G. TI Age-Related Loss of Responsiveness to 2,5-Dimethoxy-4-Iodoamphetamine in Liver Sinusoidal Endothelial Cells SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Liver endothelium; Fenestrations; 2,5-Dimethoxy-4-iodoamphetamine ID GROWTH-FACTOR; RAT-LIVER; PARTIAL-HEPATECTOMY; SIEVE; PSEUDOCAPILLARIZATION; INCREASES; FENESTRATIONS; PERMEABILITY; REGENERATION; FAILURE AB Age-related pseudocapillarization of the liver sinusoidal endothelium is associated with impaired lipid and drug metabolism and the development of disease. 2,5-Dimethoxy-4-iodoamphetamine is a serotonin receptor 2 agonist that has been shown to have beneficial effects on the liver sinusoidal endothelium in the setting of partial hepatectomy. Here, we have assessed whether 2,5-dimethoxy-4-iodoamphetamine influences ultrastructure of the sinusoidal endothelium in normal 7-and 24-month-old C57Bl6 mice. Following 48 hours of 2,5-dimethoxy-4-iodoamphetamine administration, we found that the liver endothelium in the young, but not in the old, mice had increased porosity compared with controls. This effect appeared to be modulated by increased fenestration size rather than a change in fenestration number. 2,5-Dimethoxy-4-iodoamphetamine is a useful manipulator of fenestration size in the young liver and could be harnessed in the search for therapeutic interventions for pseudocapillarization. C1 [Cogger, Victoria C.; Warren, Alessandra; Le Couteur, David G.] Concord Hosp, ANZAC Res Inst, Concord, NSW, Australia. [Cogger, Victoria C.; Warren, Alessandra; Le Couteur, David G.] Univ Sydney, Sydney, NSW 2006, Australia. [Cogger, Victoria C.; Warren, Alessandra; Le Couteur, David G.] Univ Sydney, Charles Perkins Ctr, Sydney, NSW 2006, Australia. [Mitchell, Sarah J.; de Cabo, Rafael] NIA, Expt Gerontol Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Mitchell, Sarah J.] Univ Sydney, Kolling Res Inst, Sydney, NSW 2006, Australia. [Mitchell, Sarah J.] Royal N Shore Hosp, Sydney, NSW, Australia. RP Cogger, VC (reprint author), ANZAC Res Inst, Gate 3 Hosp Rd Concord RG Hosp, Concord, NSW 2139, Australia. EM victoria.cogger@sydney.edu.au RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU National Institutes of Aging, National Institutes of Health; Ageing and Alzheimer's Research Fund of the Concord Hospital; National Medical Health and Research Council of Australia [RGMS ID 2010-01671] FX This study was supported in part by the Intramural Research Program of the National Institutes of Aging, National Institutes of Health, and the Ageing and Alzheimer's Research Fund of the Concord Hospital. National Medical Health and Research Council of Australia CJ Martin Early Career Fellowship (RGMS ID 2010-01671 to S.J.M.). NR 27 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2014 VL 69 IS 5 BP 514 EP 518 DI 10.1093/gerona/glt124 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AF5EY UT WOS:000334738000003 PM 23974079 ER PT J AU Elbers, CC Garcia, ME Kimura, M Cummings, SR Nalls, MA Newman, AB Park, V Sanders, JL Tranah, GJ Tishkoff, SA Harris, TB Aviv, A AF Elbers, Clara C. Garcia, Melissa E. Kimura, Masayuki Cummings, Steven R. Nalls, Mike A. Newman, Anne B. Park, Vicki Sanders, Jason L. Tranah, Gregory J. Tishkoff, Sarah A. Harris, Tamara B. Aviv, Abraham TI Comparison Between Southern Blots and qPCR Analysis of Leukocyte Telomere Length in the Health ABC Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Leukocyte telomere length; Quantitative PCR; Southern blots ID POPULATION-BASED COHORT; BODY-COMPOSITION; ASSOCIATION; HUMANS; ADULTS AB Only a few studies, primarily limited to small samples, have examined the relationship between leukocyte telomere length (LTL) data generated by Southern blots, expressed in kilobases, versus quantitative PCR data, expressed in the telomere product/a single gene product (T/S). In the present study, we compared LTL data generated by the two methods in 681 elderly participants (50% African Americans, 50% of European origin, 49.2% women, mean age 73.72.9 years) in the Health Aging and Body Composition Study. The correlation between the data generated by the two methods was modest (R-2 .27). Both methods captured the age effect on LTL and the longer LTL in women than in men. However, only the Southern blot method showed a significantly longer LTL in African Americans than in European decent individuals, which might be attributed to the larger measurement error of the quantitative PCRbased method than the Southern blots. C1 [Elbers, Clara C.; Tishkoff, Sarah A.] Univ Penn, Dept Biol & Genet, Philadelphia, PA 19104 USA. [Garcia, Melissa E.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Kimura, Masayuki; Aviv, Abraham] Rutgers, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ USA. [Nalls, Mike A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Newman, Anne B.; Sanders, Jason L.] Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15260 USA. [Park, Vicki] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. [Park, Vicki] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Sanders, Jason L.] Univ Pittsburgh, Sch Med, Med Scientist Training Program, Pittsburgh, PA 15260 USA. [Tranah, Gregory J.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. RP Elbers, CC (reprint author), Univ Penn, Dept Biol & Genet, Philadelphia, PA 19104 USA. EM celbers@mail.med.upenn.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU Netherlands Organization for Scientific Research (NWO); NIH [R01AG030678, R01HD071180] FX CCE was supported by a Rubicon grant from the Netherlands Organization for Scientific Research (NWO). AA's NIH research support for this work includes R01AG030678 and R01HD071180. NR 20 TC 20 Z9 20 U1 2 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2014 VL 69 IS 5 BP 527 EP 531 DI 10.1093/gerona/glt121 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AF5EY UT WOS:000334738000005 PM 23946336 ER PT J AU Cai, H Daimon, CM Cong, WN Wang, R Chirdon, P de Cabo, R Sevigny, J Maudsley, S Martin, B AF Cai, Huan Daimon, Caitlin M. Cong, Wei-na Wang, Rui Chirdon, Patrick de Cabo, Rafael Sevigny, Jean Maudsley, Stuart Martin, Bronwen TI Longitudinal Analysis of Calorie Restriction on Rat Taste Bud Morphology and Expression of Sweet Taste Modulators SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Taste buds; Sweet taste; Calorie restriction; T1r3; Aging ID DIETARY ENERGY-INTAKE; CIRCUMVALLATE PAPILLAE; WEIGHT-LOSS; FOOD CRAVINGS; CATALYTIC PROPERTIES; OXIDATIVE STRESS; ALPHA-GUSTDUCIN; UMAMI TASTE; LIFE-SPAN; FAT DIET AB Calorie restriction (CR) is a lifestyle intervention employed to reduce body weight and improve metabolic functions primarily via reduction of ingested carbohydrates and fats. Taste perception is highly related to functional metabolic status and body adiposity. We have previously shown that sweet taste perception diminishes with age; however, relatively little is known about the effects of various lengths of CR upon taste cell morphology and function. We investigated the effects of CR on taste bud morphology and expression of sweet tasterelated modulators in 5-, 17-, and 30-month-old rats. In ad libitum (AL) and CR rats, we consistently found the following parameters altered significantly with advancing age: reduction of taste bud size and taste cell numbers per taste bud and reduced expression of sonic hedgehog, type 1 taste receptor 3 (T1r3), -gustducin, and glucagon-like peptide-1 (GLP-1). In the oldest rats, CR affected a significant reduction of tongue T1r3, GLP-1, and -gustducin expression compared with age-matched AL rats. Leptin receptor immunopositive cells were elevated in 17- and 30-month-old CR rats compared with age-matched AL rats. These alterations of sweet tasterelated modulators, specifically during advanced aging, suggest that sweet taste perception may be altered in response to different lengths of CR. C1 [Cai, Huan; Daimon, Caitlin M.; Cong, Wei-na; Wang, Rui; Chirdon, Patrick; Martin, Bronwen] NIA, Metab Unit, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. [de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Sevigny, Jean] CHU Quebec, Ctr Rech, Ctr Rech Rhumatol & Immunol, Quebec City, PQ, Canada. [Sevigny, Jean] Univ Laval, Fac Med, Dept Microbiol Infectiol & Immunol, Quebec City, PQ G1K 7P4, Canada. [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Martin, B (reprint author), NIA, Metab Unit, Clin Invest Lab, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM martinbro@mail.nih.gov RI Cai, Huan/B-6578-2016; de Cabo, Rafael/J-5230-2016; OI Cai, Huan/0000-0001-7731-8891; de Cabo, Rafael/0000-0002-3354-2442; Sevigny, Jean/0000-0003-2922-1600; , rafael/0000-0003-2830-5693 FU National Institute on Aging, National Institutes of Health [AG000916-01] FX This work was supported entirely by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (AG000916-01). NR 77 TC 5 Z9 5 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2014 VL 69 IS 5 BP 532 EP 544 DI 10.1093/gerona/glt129 PG 13 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AF5EY UT WOS:000334738000006 PM 24077597 ER PT J AU Studenski, SA Peters, KW Alley, DE Cawthon, PM McLean, RR Harris, TB Ferrucci, L Guralnik, JM Fragala, MS Kenny, AM Kiel, DP Kritchevsky, SB Shardell, MD Dam, TTL Vassileva, MT AF Studenski, Stephanie A. Peters, Katherine W. Alley, Dawn E. Cawthon, Peggy M. McLean, Robert R. Harris, Tamara B. Ferrucci, Luigi Guralnik, Jack M. Fragala, Maren S. Kenny, Anne M. Kiel, Douglas P. Kritchevsky, Stephen B. Shardell, Michelle D. Dam, Thuy-Tien L. Vassileva, Maria T. TI The FNIH Sarcopenia Project: Rationale, Study Description, Conference Recommendations, and Final Estimates SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Aging; Sarcopenia; Muscle; Outcomes; Weakness ID LOWER-EXTREMITY FUNCTION; BONE-MINERAL DENSITY; LEG MUSCLE MASS; BODY-COMPOSITION; GAIT SPEED; OSTEOPOROTIC FRACTURES; PHYSICAL PERFORMANCE; OLDER-ADULTS; WHITE WOMEN; STRENGTH AB Low muscle mass and weakness are common and potentially disabling in older adults, but in order to become recognized as a clinical condition, criteria for diagnosis should be based on clinically relevant thresholds and independently validated. The Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project used an evidence-based approach to develop these criteria. Initial findings were presented at a conference in May 2012, which generated recommendations that guided additional analyses to determine final recommended criteria. Details of the Project and its findings are presented in four accompanying manuscripts. The Foundation for the National Institutes of Health Sarcopenia Project used data from nine sources of community-dwelling older persons: Age, Gene/Environment Susceptibility-Reykjavik Study, Boston Puerto Rican Health Study, a series of six clinical trials, Framingham Heart Study, Health, Aging, and Body Composition, Invecchiare in Chianti, Osteoporotic Fractures in Men Study, Rancho Bernardo Study, and Study of Osteoporotic Fractures. Feedback from conference attendees was obtained via surveys and breakout groups. The pooled sample included 26,625 participants (57% women, mean age in men 75.2 [6.1 SD] and in women 78.6 [5.9] years). Conference attendees emphasized the importance of evaluating the influence of body mass on cutpoints. Based on the analyses presented in this series, the final recommended cutpoints for weakness are grip strength < 26kg for men and < 16kg for women, and for low lean mass, appendicular lean mass adjusted for body mass index < 0.789 for men and < 0.512 for women. These evidence-based cutpoints, based on a large and diverse population, may help identify participants for clinical trials and should be evaluated among populations with high rates of functional limitations. C1 [Studenski, Stephanie A.] Univ Pittsburgh, Dept Internal Med, Sch Med, Pittsburgh, PA 15260 USA. [Peters, Katherine W.; Cawthon, Peggy M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Alley, Dawn E.; Guralnik, Jack M.; Shardell, Michelle D.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [McLean, Robert R.; Kiel, Douglas P.] Hebrew Senior Life, Inst Aging Res, Boston, MA USA. [McLean, Robert R.; Kiel, Douglas P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Sch Med, Boston, MA 02215 USA. [Harris, Tamara B.; Ferrucci, Luigi] NIA, Intramural Res Program, NIH, Baltimore, MD 21225 USA. [Fragala, Maren S.] Univ Cent Florida, Coll Educ & Human Performance, Orlando, FL 32816 USA. [Kenny, Anne M.] Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27109 USA. [Dam, Thuy-Tien L.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Vassileva, Maria T.] Fdn Natl Inst Hlth, Biomarkers Consortium, Bethesda, MD USA. RP Studenski, SA (reprint author), NIA, Baltimore Longitudinal Study Aging, 3001 S Hanover St,Fifth Floor, Baltimore, MD 21225 USA. EM studenskisa@mail.nih.gov OI Kiel, Douglas/0000-0001-8474-0310 FU National Institute on Aging [1U13AG041583, P30 AG024827]; Food and Drug Administration; Foundation for the National Institutes of Health; Abbott Nutrition; Amgen; Eli Lilly; Merck; Novartis; Dairy Research Institute FX Funding support for the conference and the work of the consortium was provided by the National Institute on Aging (1U13AG041583 and P30 AG024827), the Food and Drug Administration, and through grants from the Foundation for the National Institutes of Health, made possible by funding from Abbott Nutrition, Amgen, Eli Lilly, Merck, Novartis, and The Dairy Research Institute. NR 40 TC 155 Z9 156 U1 4 U2 23 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2014 VL 69 IS 5 BP 547 EP 558 DI 10.1093/gerona/glu010 PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AF5EY UT WOS:000334738000007 PM 24737557 ER PT J AU Alley, DE Shardell, MD Peters, KW McLean, RR Dam, TTL Kenny, AM Fragala, MS Harris, TB Kiel, DP Guralnik, JM Ferrucci, L Kritchevsky, SB Studenski, SA Vassileva, MT Cawthon, PM AF Alley, Dawn E. Shardell, Michelle D. Peters, Katherine W. McLean, Robert R. Dam, Thuy-Tien L. Kenny, Anne M. Fragala, Maren S. Harris, Tamara B. Kiel, Douglas P. Guralnik, Jack M. Ferrucci, Luigi Kritchevsky, Stephen B. Studenski, Stephanie A. Vassileva, Maria T. Cawthon, Peggy M. TI Grip Strength Cutpoints for the Identification of Clinically Relevant Weakness SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Muscle; Sarcopenia; Grip strength; Physical function; Gait speed ID BONE-MINERAL DENSITY; OLDER-ADULTS; MUSCLE STRENGTH; PHYSICAL PERFORMANCE; BODY-COMPOSITION; WOMENS HEALTH; WHITE WOMEN; MOBILITY; INCHIANTI; RISK AB Weakness is common and contributes to disability, but no consensus exists regarding a strength cutpoint to identify persons at high risk. This analysis, conducted as part of the Foundation for the National Institutes of Health Sarcopenia Project, sought to identify cutpoints that distinguish weakness associated with mobility impairment, defined as gait speed less than 0.8 m/s. In pooled cross-sectional data (9,897 men and 10,950 women), Classification and Regression Tree analysis was used to derive cutpoints for grip strength associated with mobility impairment. In men, a grip strength of 2632 kg was classified as intermediate and less than 26 kg as weak; 11% of men were intermediate and 5% were weak. Compared with men with normal strength, odds ratios for mobility impairment were 3.63 (95% CI: 3.014.38) and 7.62 (95% CI 6.139.49), respectively. In women, a grip strength of 1620 kg was classified as intermediate and less than 16 kg as weak; 25% of women were intermediate and 18% were weak. Compared with women with normal strength, odds ratios for mobility impairment were 2.44 (95% CI 2.202.71) and 4.42 (95% CI 3.944.97), respectively. Weakness based on these cutpoints was associated with mobility impairment across subgroups based on age, body mass index, height, and disease status. Notably, in women, grip strength divided by body mass index provided better fit relative to grip strength alone, but fit was not sufficiently improved to merit different measures by gender and use of a more complex measure. Cutpoints for weakness derived from this large, diverse sample of older adults may be useful to identify populations who may benefit from interventions to improve muscle strength and function. C1 [Alley, Dawn E.; Shardell, Michelle D.; Guralnik, Jack M.] Univ Maryland, Dept Epidemiol & Publ Hlth, Sch Med, Baltimore, MD 21201 USA. [Peters, Katherine W.; Cawthon, Peggy M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [McLean, Robert R.; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [McLean, Robert R.; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA. [McLean, Robert R.; Kiel, Douglas P.] Hebrew Senior Life Inst Aging Res, Inst Aging Res, Boston, MA USA. [Dam, Thuy-Tien L.] Columbia Univ, Dept Med, New York, NY USA. [Kenny, Anne M.; Fragala, Maren S.] Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA. [Fragala, Maren S.] Univ Cent Florida, Orlando, FL 32816 USA. [Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. [Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Dept Internal Med, Winston Salem, NC 27109 USA. [Studenski, Stephanie A.] Univ Pittsburgh, Dept Internal Med, Pittsburgh, PA 15260 USA. [Studenski, Stephanie A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Vassileva, Maria T.] Fdn NIH Biomarkers Consortium, Bethesda, MD USA. RP Alley, DE (reprint author), Univ Maryland, Sch Med, 660 W Redwood St 221B, Baltimore, MD 21201 USA. EM dalley@epi.umaryland.edu OI Kiel, Douglas/0000-0001-8474-0310 FU National Institute on Aging [1U13AG041583, P30 AG024827]; Food and Drug Administration; Foundation for the NIH; Abbott Nutrition; Amgen; Eli Lilly; Merck; Novartis; Dairy Research Institute; NIH, National Institute on Aging FX Funding support for the conference and the work of the consortium was provided by the National Institute on Aging (1U13AG041583 and P30 AG024827), the Food and Drug Administration, and through grants from the Foundation for the NIH, made possible by funding from Abbott Nutrition, Amgen, Eli Lilly, Merck, Novartis, and The Dairy Research Institute. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Additional acknowledgements for each contributing cohort and members of the FNIH Sarcopenia Project can be found in an online supplement. NR 34 TC 65 Z9 67 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2014 VL 69 IS 5 BP 559 EP 566 DI 10.1093/gerona/glu011 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AF5EY UT WOS:000334738000008 PM 24737558 ER PT J AU Cawthon, PM Peters, KW Shardell, MD McLean, RR Dam, TTL Kenny, AM Fragala, MS Harris, TB Kiel, DP Guralnik, JM Ferrucci, L Kritchevsky, SB Vassileva, MT Studenski, SA Alley, DE AF Cawthon, Peggy M. Peters, Katherine W. Shardell, Michelle D. McLean, Robert R. Dam, Thuy-Tien L. Kenny, Anne M. Fragala, Maren S. Harris, Tamara B. Kiel, Douglas P. Guralnik, Jack M. Ferrucci, Luigi Kritchevsky, Stephen B. Vassileva, Maria T. Studenski, Stephanie A. Alley, Dawn E. TI Cutpoints for Low Appendicular Lean Mass That Identify Older Adults With Clinically Significant Weakness SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Muscle; Sarcopenia; Cutpoints ID BONE-MINERAL DENSITY; ALTERNATIVE DEFINITIONS; PHYSICAL FUNCTION; MUSCLE STRENGTH; WHITE WOMEN; MEN; SARCOPENIA; HEALTH; RISK; PERFORMANCE AB Low lean mass is potentially clinically important in older persons, but criteria have not been empirically validated. As part of the FNIH (Foundation for the National Institutes of Health) Sarcopenia Project, this analysis sought to identify cutpoints in lean mass by dual-energy x-ray absorptiometry that discriminate the presence or absence of weakness (defined in a previous report in the series as grip strength < 26kg in men and < 16kg in women). In pooled cross-sectional data stratified by sex (7,582 men and 3,688 women), classification and regression tree (CART) analysis was used to derive cutpoints for appendicular lean body mass (ALM) that best discriminated the presence or absence of weakness. Mixed-effects logistic regression was used to quantify the strength of the association between lean mass category and weakness. In primary analyses, CART models identified cutpoints for low lean mass (ALM < 19.75kg in men and < 15.02kg in women). Sensitivity analyses using ALM divided by body mass index (BMI: ALM(BMI)) identified a secondary definition (ALM(BMI) < 0.789 in men and ALM(BMI) < 0.512 in women). As expected, after accounting for study and age, low lean mass (compared with higher lean mass) was associated with weakness by both the primary (men, odds ratio [OR]: 6.9 [95% CI: 5.4, 8.9]; women, OR: 3.6 [95% CI: 2.9, 4.3]) and secondary definitions (men, OR: 4.3 [95% CI: 3.4, 5.5]; women, OR: 2.2 [95% CI: 1.8, 2.8]). ALM cutpoints derived from a large, diverse sample of older adults identified lean mass thresholds below which older adults had a higher likelihood of weakness. C1 [Cawthon, Peggy M.; Peters, Katherine W.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA. [Shardell, Michelle D.; Guralnik, Jack M.; Alley, Dawn E.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, College Pk, MD 20742 USA. [McLean, Robert R.; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [McLean, Robert R.; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA. [Dam, Thuy-Tien L.] Columbia Univ, Dept Med, New York, NY USA. [Kenny, Anne M.; Fragala, Maren S.] Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA. [Fragala, Maren S.] Univ Cent Florida, Orlando, FL 32816 USA. [Harris, Tamara B.; Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA. [Kiel, Douglas P.] Hebrew Senior Life Inst Aging Res, Inst Aging Res, Boston, MA USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Dept Internal Med, Winston Salem, NC 27109 USA. [Vassileva, Maria T.] Fdn NIH Biomarkers Consortium, Bethesda, MD USA. [Studenski, Stephanie A.] Univ Pittsburgh, Dept Internal Med, Pittsburgh, PA 15260 USA. [Studenski, Stephanie A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Cawthon, PM (reprint author), Calif Pacific Med Ctr, Res Inst, 185 Berry St,Suite 5700, San Francisco, CA 94107 USA. EM pcawthon@sfcc-cpmc.net OI Kiel, Douglas/0000-0001-8474-0310 FU National Institute on Aging [1U13AG041583, P30 AG024827]; Food and Drug Administration; Foundation of the NIH; Abbott Nutrition; Amgen; Eli Lilly; Merck; Novartis; Dairy Research Institute FX Support for the conference and the consortium was provided by the National Institute on Aging (1U13AG041583 and P30 AG024827), the Food and Drug Administration, and through a grant from the Foundation of the NIH, supported by funds from Abbott Nutrition, Amgen, Eli Lilly, Merck, Novartis, and The Dairy Research Institute. NR 27 TC 51 Z9 51 U1 0 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2014 VL 69 IS 5 BP 567 EP 575 DI 10.1093/gerona/glu023 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AF5EY UT WOS:000334738000009 PM 24737559 ER PT J AU McLean, RR Shardell, MD Alley, DE Cawthon, PM Fragala, MS Harris, TB Kenny, AM Peters, KW Ferrucci, L Guralnik, JM Kritchevsky, SB Kiel, DP Vassileva, MT Xue, QL Perera, S Studenski, SA Dam, TTL AF McLean, Robert R. Shardell, Michelle D. Alley, Dawn E. Cawthon, Peggy M. Fragala, Maren S. Harris, Tamara B. Kenny, Anne M. Peters, Katherine W. Ferrucci, Luigi Guralnik, Jack M. Kritchevsky, Stephen B. Kiel, Douglas P. Vassileva, Maria T. Xue, Qian-Li Perera, Subashan Studenski, Stephanie A. Dam, Thuy-Tien L. TI Criteria for Clinically Relevant Weakness and Low Lean Mass and Their Longitudinal Association With Incident Mobility Impairment and Mortality: The Foundation for the National Institutes of Health (FNIH) Sarcopenia Project SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Muscle; Sarcopenia; Mobility; Impairment ID LOWER-EXTREMITY FUNCTION; OSTEOPOROTIC FRACTURES; BODY-COMPOSITION; MUSCLE STRENGTH; OLDER PERSONS; WHITE WOMEN; MEN; EPIDEMIOLOGY; RISK; PERFORMANCE AB This analysis sought to determine the associations of the Foundation for the National Institutes of Health Sarcopenia Project criteria for weakness and low lean mass with likelihood for mobility impairment (gait speed 0.8 m/s) and mortality. Providing validity for these criteria is essential for research and clinical evaluation. Among 4,411 men and 1,869 women pooled from 6 cohort studies, 3-year likelihood for incident mobility impairment and mortality over 10 years were determined for individuals with weakness, low lean mass, and for those having both. Weakness was defined as low grip strength (< 26kg men and < 16kg women) and low grip strength-to-body mass index (BMI; kg/m(2)) ratio (< 1.00 men and < 0.56 women). Low lean mass (dual-energy x-ray absorptiometry) was categorized as low appendicular lean mass (ALM; < 19.75kg men and < 15.02kg women) and low ALM-to-BMI ratio (< 0.789 men and < 0.512 women). Low grip strength (men: odds ratio [OR] 2.31, 95% confidence interval [CI] 1.343.99; women: OR 1.99, 95% CI 1.233.21), low grip strength-to-BMI ratio (men: OR 3.28, 95% CI 1.925.59; women: OR 2.54, 95% CI 1.105.83) and low ALM-to-BMI ratio (men: OR 1.58, 95% CI 1.122.25; women: OR 1.81, 95% CI 1.142.87), but not low ALM, were associated with increased likelihood for incident mobility impairment. Weakness increased likelihood of mobility impairment regardless of low lean mass. Mortality risk patterns were inconsistent. These findings support our cut-points for low grip strength and low ALM-to-BMI ratio as candidate criteria for clinically relevant weakness and low lean mass. Further validation in other populations and for alternate relevant outcomes is needed. C1 [McLean, Robert R.; Kiel, Douglas P.] Hebrew SeniorLife Inst Aging Res, Boston, MA 02131 USA. [McLean, Robert R.; Kiel, Douglas P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Sch Med, Boston, MA 02215 USA. [Shardell, Michelle D.; Alley, Dawn E.; Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Cawthon, Peggy M.; Peters, Katherine W.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Fragala, Maren S.; Kenny, Anne M.] Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA. [Fragala, Maren S.] Univ Cent Florida, Orlando, FL 32816 USA. [Harris, Tamara B.; Ferrucci, Luigi] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27109 USA. [Vassileva, Maria T.] Fdn Natl Inst Hlth, Biomarkers Consortium, Bethesda, MD USA. [Xue, Qian-Li] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. [Xue, Qian-Li] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. [Perera, Subashan; Studenski, Stephanie A.] Univ Pittsburgh, Dept Internal Med, Sch Med, Pittsburgh, PA 15260 USA. [Studenski, Stephanie A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Dam, Thuy-Tien L.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. RP McLean, RR (reprint author), Hebrew SeniorLife Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM rmclean@hsl.harvard.edu OI Kiel, Douglas/0000-0001-8474-0310 FU National Institute on Aging [1U13AG041583, P30 AG024827]; Food and Drug Administration; Foundation for the National Institutes of Health; Abbott Nutrition; Amgen; Eli Lilly; Merck; Novartis; Dairy Research Institute FX Funding support for the conference and the work of the consortium was provided by the National Institute on Aging (1U13AG041583 and P30 AG024827), the Food and Drug Administration and through grants from the Foundation for the National Institutes of Health, made possible by funding from Abbott Nutrition, Amgen, Eli Lilly, Merck, Novartis, and The Dairy Research Institute. NR 33 TC 82 Z9 83 U1 4 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2014 VL 69 IS 5 BP 576 EP 583 DI 10.1093/gerona/glu012 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AF5EY UT WOS:000334738000010 PM 24737560 ER PT J AU Dam, TT Peters, KW Fragala, M Cawthon, PM Harris, TB McLean, R Shardell, M Alley, DE Kenny, A Ferrucci, L Guralnik, J Kiel, DP Kritchevsky, S Vassileva, MT Studenski, S AF Dam, Thuy-Tien Peters, Katherine W. Fragala, Maren Cawthon, Peggy M. Harris, Tamara B. McLean, Robert Shardell, Michelle Alley, Dawn E. Kenny, Anne Ferrucci, Luigi Guralnik, Jack Kiel, Douglas P. Kritchevsky, Steve Vassileva, Maria T. Studenski, Stephanie TI An Evidence-Based Comparison of Operational Criteria for the Presence of Sarcopenia SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Muscle; Sarcopenia; Lean mass ID LOWER-EXTREMITY FUNCTION; BONE-MINERAL DENSITY; OLDER MEN; OSTEOPOROTIC FRACTURES; PHYSICAL PERFORMANCE; WHITE WOMEN; GAIT SPEED; MUSCLE; RISK; EPIDEMIOLOGY AB Several consensus groups have previously published operational criteria for sarcopenia, incorporating lean mass with strength and/or physical performance. The purpose of this manuscript is to describe the prevalence, agreement, and discrepancies between the Foundation for the National Institutes of Health (FNIH) criteria with other operational definitions for sarcopenia. The FNIH Sarcopenia Project used data from nine studies including: Age, Gene and Environment Susceptibility-Reykjavik Study; Boston Puerto Rican Health Study; a series of six clinical trials from the University of Connecticut; Framingham Heart Study; Health, Aging, and Body Composition Study; Invecchiare in Chianti; Osteoporotic Fractures in Men Study; Rancho Bernardo Study; and Study of Osteoporotic Fractures. Participants included in these analyses were aged 65 and older and had measures of body mass index, appendicular lean mass, grip strength, and gait speed. The prevalence of sarcopenia and agreement proportions was higher in women than men. The lowest prevalence was observed with the FNIH criteria (1.3% men and 2.3% women) compared with the International Working Group and the European Working Group for Sarcopenia in Older Persons (5.1% and 5.3% in men and 11.8% and 13.3% in women, respectively). The positive percent agreements between the FNIH criteria and other criteria were low, ranging from 7% to 32% in men and 5% to 19% in women. However, the negative percent agreement were high (all > 95%). The FNIH criteria result in a more conservative operational definition of sarcopenia, and the prevalence was lower compared with other proposed criteria. Agreement for diagnosing sarcopenia was low, but agreement for ruling out sarcopenia was very high. Consensus on the operational criteria for the diagnosis of sarcopenia is much needed to characterize populations for study and to identify adults for treatment. C1 [Dam, Thuy-Tien] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Peters, Katherine W.; Cawthon, Peggy M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Fragala, Maren] Univ Cent Florida, Dept Educ & Human Sci, Orlando, FL 32816 USA. [Harris, Tamara B.; Ferrucci, Luigi] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [McLean, Robert; Kiel, Douglas P.] Hebrew Senior Life, Inst Aging Res, Boston, MA USA. [McLean, Robert; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [McLean, Robert; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA. [Shardell, Michelle; Alley, Dawn E.; Guralnik, Jack] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Kenny, Anne] Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA. [Kritchevsky, Steve] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Kritchevsky, Steve] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27109 USA. [Vassileva, Maria T.] Fdn Natl Inst Hlth, Biomarkers Consortium, Bethesda, MD USA. [Studenski, Stephanie] Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15260 USA. RP Dam, TT (reprint author), Columbia Univ, 5141 Broadway Ave,3 Field West,Room 13, New York, NY 10034 USA. EM td2265@columbia.edu OI Kiel, Douglas/0000-0001-8474-0310 FU National Institute on Aging [U13AG04158, P30 AG024827, K23 AG040168]; Food and Drug Administration; Foundation of the National Institute of Health (FNIH); Abbot Nutrition; Amgen; Eli Lilly; Merck; Novartis; Dairy Research Institute; NIH, National Institute on Aging FX Funding support for the conference and the work of the consortium was provided by the National Institute on Aging (U13AG04158 and P30 AG024827), the Food and Drug Administration, and through grants from the Foundation of the National Institute of Health (FNIH) made possible by funding from Abbot Nutrition, Amgen, Eli Lilly, Merck, Novartis, and the Dairy Research Institute. This research was supported in part by the Intramural Program of the NIH, National Institute on Aging. Additional acknowledgments for each contributing cohort and members of the FNIH Sarcopenia Project can be found in an online supplement. Dr. Dam was supported by the National Institute on Aging through grant number K23 AG040168. NR 36 TC 81 Z9 83 U1 2 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2014 VL 69 IS 5 BP 584 EP 590 DI 10.1093/gerona/glu013 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AF5EY UT WOS:000334738000011 PM 24737561 ER PT J AU Correa-de-Araujo, R Hadley, E AF Correa-de-Araujo, Rosaly Hadley, Evan TI Skeletal Muscle Function Deficit: A New Terminology to Embrace the Evolving Concepts of Sarcopenia and Age-Related Muscle Dysfunction SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Sarcopenia; Skeletal muscle; Muscle weakness; Muscle strength; Muscle function; Skeletal muscle function deficit; Deficit ID OLDER PERSONS; CONSENSUS; MEXICO AB Concerns remain as to the best terminology to embrace sarcopenias evolving conceptualization. Many of these concerns stem from the fact that age-related decrements in muscle performance associated with physical impairment are only partially explained by decreases in muscle mass and that other pathophysiologic factors contribute to age-related impairments in muscle performance. Review of literature on the evolving conceptualization of sarcopenia since its early definition in 1989 and concerns with terminology. Early definitions of sarcopenia were based solely on muscle mass in relationship to the range of muscle within a reference population. Subsequent definitions added performance criteria to muscle mass alone. The Foundation for the National Institutes of Health Sarcopenia Project identified criteria for clinically relevant low muscle strength (weakness) and low lean mass. Progress on the sarcopenias evolving definitions has not been accompanied by recommendations on specific terminologies that address the lack of sufficient specificity from the use of an anatomic term to define a functional condition with numerous now known nonanatomic contributory factors. Skeletal Muscle Function Deficit is a broader construct that accommodates a set of diagnoses that includes both sarcopenia and other age-related muscle dysfunctions. Skeletal Muscle Function Deficit is proposed as a new terminology to embrace the evolving conceptualization of sarcopenia and other age-related muscle dysfunctions. It comprises a variety of contributory etiologies and has the potential to provide a framework for developing diagnostic categories that are useful for both clinical practice and research. C1 [Correa-de-Araujo, Rosaly; Hadley, Evan] NIA, US Dept Hlth & Human Serv, Div Geriatr & Clin Gerontol, NIH, Bethesda, MD 20892 USA. RP Correa-de-Araujo, R (reprint author), NIA, US Dept Hlth & Human Serv, Div Geriatr & Clin Gerontol, NIH, 7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM Rosaly.correa-de-araujo@nih.gov NR 15 TC 23 Z9 23 U1 1 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2014 VL 69 IS 5 BP 591 EP 594 DI 10.1093/gerona/glt208 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AF5EY UT WOS:000334738000012 PM 24737562 ER PT J AU Ahn, K Gotay, N Andersen, TM Anvari, AA Gochman, P Lee, Y Sanders, S Guha, S Darvasi, A Glessner, JT Hakonarson, H Lencz, T State, MW Shugart, YY Rapoport, JL AF Ahn, K. Gotay, N. Andersen, T. M. Anvari, A. A. Gochman, P. Lee, Y. Sanders, S. Guha, S. Darvasi, A. Glessner, J. T. Hakonarson, H. Lencz, T. State, M. W. Shugart, Y. Y. Rapoport, J. L. TI High rate of disease-related copy number variations in childhood onset schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE CNV; genetics; neurodevelopment; schizophrenia ID AUTISM SPECTRUM DISORDERS; HIDDEN-MARKOV MODEL; SNP GENOTYPING DATA; RECURRENT MICRODELETIONS; DEVELOPMENTAL DELAY; INCREASE RISK; DOUBLE-BLIND; DELETIONS; VARIANTS; 16P11.2 AB Copy number variants (CNVs) are risk factors in neurodevelopmental disorders, including autism, epilepsy, intellectual disability (ID) and schizophrenia. Childhood onset schizophrenia (COS), defined as onset before the age of 13 years, is a rare and severe form of the disorder, with more striking array of prepsychotic developmental disorders and abnormalities in brain development. Because of the well-known phenotypic variability associated with pathogenic CNVs, we conducted whole genome genotyping to detect CNVs and then focused on a group of 46 rare CNVs that had well-documented risk for adult onset schizophrenia (AOS), autism, epilepsy and/or ID. We evaluated 126 COS probands, 69 of which also had a healthy full sibling. When COS probands were compared with their matched related controls, significantly more affected individuals carried disease-related CNVs (P = 0.017). Moreover, COS probands showed a higher rate than that found in AOS probands (P < 0.0001). A total of 15 (11.9%) subjects exhibited at least one such CNV and four of these subjects (26.7%) had two. Five of 15 (4.0% of the sample) had a 2.5-3Mb deletion mapping to 22q11.2, a rate higher than that reported for adult onset (0.3-1%) (P < 0.001) or autism spectrum disorder and, indeed, the highest rate reported for any clinical population to date. For one COS subject, a duplication found at 22q13.3 had previously only been associated with autism, and for four patients CNVs at 8q11.2, 10q22.3, 16p11.2 and 17q21.3 had only previously been associated with ID. Taken together, these findings support the well-known pleiotropic effects of these CNVs suggesting shared abnormalities early in brain development. Clinically, broad CNV-based population screening is needed to assess their overall clinical burden. C1 [Ahn, K.; Gotay, N.; Andersen, T. M.; Anvari, A. A.; Gochman, P.; Lee, Y.; Rapoport, J. L.] NIMH, Childhood Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Sanders, S.; State, M. W.] Yale Univ, Sch Med, Dept Genet, Program Neurogenet,Child Study Ctr,Dept Psychiat, New Haven, CT 06510 USA. [Guha, S.; Lencz, T.] Zucker Hillside Hosp, Glen Oaks, NY USA. [Darvasi, A.] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. [Glessner, J. T.; Hakonarson, H.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Shugart, Y. Y.] NIMH, Unit Stat Genom, NIH, Bethesda, MD 20892 USA. RP Rapoport, JL (reprint author), NIMH, Childhood Psychiat Branch, NIH, 10 Ctr Dr,Room 3N202,MSC 1600, Bethesda, MD 20892 USA. EM rapoporj@mail.nih.gov RI Lencz, Todd/J-3418-2014; OI Lencz, Todd/0000-0001-8586-338X; Guha, Saurav/0000-0002-0620-5408; Sanders, Stephan/0000-0001-9112-5148 FU Intramural NIH HHS [Z01 MH002581-17] NR 50 TC 28 Z9 28 U1 4 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 2014 VL 19 IS 5 BP 568 EP 572 DI 10.1038/mp.2013.59 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AF7VY UT WOS:000334924300009 PM 23689535 ER PT J AU Zhang, F Fuss, IJ Yang, Z Strober, W AF Zhang, F. Fuss, I. J. Yang, Z. Strober, W. TI Transcription of ROR gamma t in developing Th17 cells is regulated by E-proteins SO MUCOSAL IMMUNOLOGY LA English DT Article ID LYMPHOCYTE DEVELOPMENT; DIFFERENTIATION; T(H)17; ID3; LINEAGE; RECEPTOR; DISTINCT; IL-21; BETA; E2A AB In the present study we investigated the molecular mechanisms regulating the expression of RAR-related orphan receptor gamma t (ROR gamma t), the central factor controlling interleukin (IL)-17 transcription and Th17 differentiation. In key studies, we found that cells from mice with major deletions of E-protein transcription factors, E2A and HEB, display greatly reduced ROR gamma t/IL-17 expression and that E-protein-deficient mice exhibit greatly diminished IL-17-dependent inflammation in experimental allergic encephalitis models. In additional studies, we unexpectedly found that cells from mice with deletion of Id3, a protein that inhibits E-protein binding to DNA, display diminished ROR gamma t/IL-17 expression and mice deficient in this protein exhibit decreased Th17-mediated inflammation in a cell-transfer colitis model. The explanation of these initially paradoxical findings came from studies showing that Id3 deficiency leads to increased IL-4-induced GATA-3 expression, the latter a negative regulator of ROR gamma t transcription; thus, increased Id3 expression likely has a net positive effect on ROR gamma t expression via its inhibition of IL-4 production. Finally, we found that both E-proteins and Id3 are upregulated in tandem by the cytokines that induce Th17 differentiation, transforming growth factor-beta, and IL-6, implying that these transcription factors are critical regulators of Th17 induction. C1 [Zhang, F.; Fuss, I. J.; Yang, Z.; Strober, W.] NIAID, Mucosal Immun Sect, Lab Host Def, NIH, Bethesda, MD 20892 USA. RP Zhang, F (reprint author), NIAID, Mucosal Immun Sect, Lab Host Def, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM zhangfp@im.ac.cn; Wstrober@niaid.nih.go FU Intramural NIH HHS [Z01 AI000354-25] NR 27 TC 8 Z9 9 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD MAY PY 2014 VL 7 IS 3 BP 521 EP 532 DI 10.1038/mi.2013.69 PG 12 WC Immunology SC Immunology GA AF7VT UT WOS:000334923700008 PM 24064669 ER PT J AU Prodger, JL Hirbod, T Kigozi, G Nalugoda, F Reynolds, SJ Galiwango, R Shahabi, K Serwadda, D Wawer, MJ Gray, RH Kaul, R AF Prodger, J. L. Hirbod, T. Kigozi, G. Nalugoda, F. Reynolds, S. J. Galiwango, R. Shahabi, K. Serwadda, D. Wawer, M. J. Gray, R. H. Kaul, R. CA Rakai Genital Immunology Res Grp TI Immune correlates of HIV exposure without infection in foreskins of men from Rakai, Uganda SO MUCOSAL IMMUNOLOGY LA English DT Article ID COMMERCIAL SEX WORKERS; T-CELL-ACTIVATION; FEMALE GENITAL-TRACT; MALE CIRCUMCISION; IMMUNOGLOBULIN-A; UNINFECTED INDIVIDUALS; MUCOSAL; ACQUISITION; EXPRESSION; IGA AB Human immunodeficiency virus (HIV) susceptibility is heterogenous, with some HIV-exposed but seronegative (HESN) individuals remaining uninfected despite repeated exposure. Previous studies in the cervix have shown that reduced HIV susceptibility may be mediated by immune alterations in the genital mucosa. However, immune correlates of HIV exposure without infection have not been investigated in the foreskin. We collected sub-preputial swabs and foreskin tissue from HESN (n = 20) and unexposed control (n = 57) men undergoing elective circumcision. Blinded investigators assayed swabs for HIV-neutralizing IgA, innate antimicrobial peptides, and cytokine levels. Functional T-cell subsets from foreskin tissue were assessed by flow cytometry. HESN foreskins had elevated alpha-defensins (3,027 vs. 1,795pg ml(-1), P = 0.011) and HIV-neutralizing IgA(50.0 vs. 13.5% of men, P = 0.019). Foreskin tissue from HESN men contained a higher density of CD3 T cells (151.9 vs. 69.9 cells mm(-2), P = 0.018), but a lower proportion of these was Th17 cells (6.12 vs. 8.04% of CD4 T cells, P = 0.007), and fewer produced tumor necrosis factor a (TNF alpha) (34.3 vs. 41.8% of CD4 T cells, P = 0.037; 36.9 vs. 45.7% of CD8 T cells, P = 0.004). A decrease in the relative abundance of susceptible CD4 T cells and local TNFa production, in combination with HIV-neutralizing IgA and alpha-defensins, may represent a protective immune milieu at a site of HIV exposure. C1 [Prodger, J. L.; Shahabi, K.; Kaul, R.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Hirbod, T.] Dept Med, Solna, Sweden. [Hirbod, T.] Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. [Kigozi, G.; Nalugoda, F.; Reynolds, S. J.; Galiwango, R.; Serwadda, D.; Wawer, M. J.; Gray, R. H.; Kaul, R.] Rakai Hlth Sci Program, Kalisizo, Uganda. [Reynolds, S. J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Reynolds, S. J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Serwadda, D.] Makerere Univ, Inst Publ Hlth, Kampala, Uganda. [Wawer, M. J.; Gray, R. H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Prodger, JL (reprint author), Univ Toronto, Dept Med, Toronto, ON, Canada. EM jessica.prodger@utoronto.ca FU Bill and Melinda Gates Foundation [22006.03]; National Institutes of Health [R01AI087409-01A1, UO1AI51171, 1UO1AI075115-O1A1]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We would like to acknowledge STTARR at the Toronto MaRS Discovery District for assistance with CD3 image analysis and Mariethe Ehnlund at the Karolinska Institute for technical assistance. Funding was provided by the Bill and Melinda Gates Foundation, grant number 22006.03, and R01AI087409-01A1, UO1AI51171, and 1UO1AI075115-O1A1 from the National Institutes of Health. The study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 49 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD MAY PY 2014 VL 7 IS 3 BP 634 EP 644 DI 10.1038/mi.2013.83 PG 11 WC Immunology SC Immunology GA AF7VT UT WOS:000334923700018 PM 24150258 ER PT J AU Suwara, MI Green, NJ Borthwick, LA Mann, J Mayer-Barber, KD Barron, L Corris, PA Farrow, SN Wynn, TA Fisher, AJ Mann, DA AF Suwara, M. I. Green, N. J. Borthwick, L. A. Mann, J. Mayer-Barber, K. D. Barron, L. Corris, P. A. Farrow, S. N. Wynn, T. A. Fisher, A. J. Mann, D. A. TI IL-1 alpha released from damaged epithelial cells is sufficient and essential to trigger inflammatory responses in human lung fibroblasts SO MUCOSAL IMMUNOLOGY LA English DT Article ID BRONCHIOLITIS OBLITERANS SYNDROME; IDIOPATHIC PULMONARY-FIBROSIS; ENDOPLASMIC-RETICULUM STRESS; INJURY; COPD; PATHOGENESIS; INHIBITION; MECHANISMS; APOPTOSIS; PATHWAY AB Activation of the innate immune system plays a key role in exacerbations of chronic lung disease, yet the potential role of lung fibroblasts in innate immunity and the identity of epithelial danger signals (alarmins) that may contribute to this process are unclear. The objective of the study was to identify lung epithelial-derived alarmins released during endoplasmic reticulum stress (ER stress) and oxidative stress and evaluate their potential to induce innate immune responses in lung fibroblasts. We found that treatment of primary human lung fibroblasts (PHLFs) with conditioned media from damaged lung epithelial cells significantly upregulated interleukin IL-6, IL-8, monocyte chemotactic protein-1, and granulocyte macrophage colony-stimulating factor expression (P<0.05). This effect was reduced with anti-IL-1 alpha or IL-1Ra but not anti-IL-1 beta antibody. Costimulation with a Toll-like receptor 3 ligand, polyinosinic-polycytidylic acid (poly I:C), significantly accentuated the IL-1 alpha-induced inflammatory phenotype in PHLFs, and this effect was blocked with inhibitor of nuclear factor kappa-B kinase subunit beta and TGF beta-activated kinase-1 inhibitors. Finally, Il1r1-/- and Il1a -/- mice exhibit reduced bronchoalveolar lavage (BAL) neutrophilia and collagen deposition in response to bleomycin treatment. We conclude that IL-1 alpha plays a pivotal role in triggering proinflammatory responses in fibroblasts and this process is accentuated in the presence of double-stranded RNA. This mechanism may be important in the repeated cycles of injury and exacerbation in chronic lung disease. C1 [Suwara, M. I.; Green, N. J.; Borthwick, L. A.; Mann, J.; Corris, P. A.; Fisher, A. J.; Mann, D. A.] Newcastle Univ, Inst Cellular Med, Tissue Fibrosis & Repair Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Mayer-Barber, K. D.; Barron, L.; Wynn, T. A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Farrow, S. N.] GlaxoSmithKline, Resp Therapy Area, Stevenage, Herts, England. RP Mann, DA (reprint author), Newcastle Univ, Inst Cellular Med, Tissue Fibrosis & Repair Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. EM A.J.Fisher@newcastle.ac.uk; derek.mann@ncl.ac.uk FU National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals Foundation Trust; Newcastle University; Biotechnology and Biological Sciences Research Council; GlaxoSmithKline; Wellcome Trust [WT086755MA]; MRC [MR/K001949/1]; European Union FX The Research was supported by the National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals Foundation Trust and Newcastle University. This work was also supported by research grants from the Biotechnology and Biological Sciences Research Council and GlaxoSmithKline. Work in the laboratory of D. A. M. is also funded by a Wellcome Trust grant (WT086755MA) and MRC grant (MR/K001949/1). L. A. B. was funded by a European Union FP7 Marie Curie fellowship. A.J.F. was supported by a GlaxoSmithKline clinical fellowship award. NR 28 TC 38 Z9 40 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD MAY PY 2014 VL 7 IS 3 BP 684 EP 693 DI 10.1038/mi.2013.87 PG 10 WC Immunology SC Immunology GA AF7VT UT WOS:000334923700022 PM 24172847 ER PT J AU Huh, SY Min, JH Kim, W Kim, SH Kim, HJ Kim, BJ Kim, BJ Lee, KH AF Huh, So-Young Min, Ju-Hong Kim, Woojun Kim, Su-Hyun Kim, Ho Jin Kim, Byung-Jo Kim, Byoung Joon Lee, Kwang Ho TI The usefulness of brain MRI at onset in the differentiation of multiple sclerosis and seropositive neuromyelitis optica spectrum disorders SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE aquaporin-4; brain; onset; MRI; multiple sclerosis; Neuromyelitis optica ID CLINICALLY ISOLATED SYNDROMES; DIAGNOSTIC-CRITERIA; NATALIZUMAB THERAPY; FINGOLIMOD FTY720; ABNORMALITIES; MULTICENTER; AQUAPORIN-4; LESIONS; MS; ENHANCEMENT AB Background: Although neuromyelitis optica (NMO) is a central nervous system (CNS) autoimmune disease distinct from multiple sclerosis (MS). NMO and NMO spectrum disorder (NMOSD) sometimes show asymptomatic lesions on brain magnetic resonance imaging (MRI) at onset, and even present with symptomatic brain involvement. Objectives: We investigated whether brain MRI at onset can be helpful for the differentiation of MS and NMOSD. Methods: We retrospectively analyzed initial brain MRIs, performed within three months of onset, in patients with MS (n = 51) and anti-aquaporin4-antibody-positive patients with NMOSD (n = 67). Results: NMOSD patients met the Paty (37%) and Barkhof (13%) criteria, and the criteria of the European Magnetic Imaging in MS (MAGNIMS) study group (9%), for MS. Ovoid lesions perpendicular to the lateral ventricle, isolated juxtacortical lesions in U-fibers and isolated ovoid/round cortical lesions were found only in MS patients, whereas longitudinal corticospinal tract lesions, extensive hemispheric lesions, periependymal lesions surrounding the lateral ventricle and cervicomedullary lesions were found only in NMOSD patients. Conclusions: Our study suggests that it is difficult to differentiate MS from NMOSD by the fulfillment of the MRI criteria for MS on brain MRI at onset; however, the characteristic morphology of brain lesions is highly useful for the early differentiation of the two disorders. C1 [Huh, So-Young] Kosin Univ, Gospel Hosp, Coll Med, Dept Neurol, Pusan, South Korea. [Huh, So-Young; Kim, Woojun; Kim, Su-Hyun; Kim, Ho Jin] Natl Canc Ctr, Dept Neurol, Bethesda, MD USA. [Min, Ju-Hong; Kim, Byoung Joon; Lee, Kwang Ho] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul 135710, South Korea. [Kim, Woojun] Catholic Univ Korea, Dept Neurol, Seoul, South Korea. Univ Korea Hosp, Dept Neurol, Seoul, South Korea. RP Min, JH (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, 50 Ilwon Dong, Seoul 135710, South Korea. EM juhongm@gmail.com RI Kim, Byung Jo/A-5943-2012 OI Kim, Byung Jo/0000-0002-0445-7185 FU Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea [A080588-28]; Samsung Medical Center [SMR112102, CRO112042] FX This work was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A080588-28) and was also by grants of Samsung Medical Center (SMR112102 and CRO112042). NR 37 TC 17 Z9 21 U1 0 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD MAY PY 2014 VL 20 IS 6 BP 695 EP 704 DI 10.1177/1352458513506953 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AF7AN UT WOS:000334865900008 PM 24072726 ER PT J AU Sacks, DL AF Sacks, David L. TI Vaccines against tropical parasitic diseases: a persisting answer to a persisting problem SO NATURE IMMUNOLOGY LA English DT Article ID LONG-TERM IMMUNITY; T-CELL IMMUNITY; PROTECTIVE IMMUNITY; IRRADIATED SPOROZOITES; LEISHMANIA-MAJOR; MALARIA; MEMORY; IMMUNIZATION; CD8(+); MAINTENANCE C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sacks, DL (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM dsacks@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000494-21] NR 25 TC 15 Z9 15 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2014 VL 15 IS 5 BP 403 EP 405 DI 10.1038/ni.2853 PG 3 WC Immunology SC Immunology GA AF4FU UT WOS:000334667900001 PM 24747701 ER PT J AU Heikamp, EB Patel, CH Collins, S Waickman, A Oh, MH Sun, IH Illei, P Sharma, A Naray-Fejes-Toth, A Fejes-Toth, G Misra-Sen, J Horton, MR Powell, JD AF Heikamp, Emily B. Patel, Chirag H. Collins, Sam Waickman, Adam Oh, Min-Hee Sun, Im-Hong Illei, Peter Sharma, Archna Naray-Fejes-Toth, Aniko Fejes-Toth, Geza Misra-Sen, Jyoti Horton, Maureen R. Powell, Jonathan D. TI The AGC kinase SGK1 regulates T(H)1 and T(H)2 differentiation downstream of the mTORC2 complex SO NATURE IMMUNOLOGY LA English DT Article ID SELECTIVE ACTIVATION; UBIQUITIN LIGASE; T-CELLS; PHOSPHORYLATION; RICTOR; MICE; INFLAMMATION; EXPRESSION; CHANNEL; ASTHMA AB SGK1 is an AGC kinase that regulates the expression of membrane sodium channels in renal tubular cells in a manner dependent on the metabolic checkpoint kinase complex mTORC2. We hypothesized that SGK1 might represent an additional mTORC2dependent regulator of the differentiation and function of T cells. Here we found that after activation by mTORC2, SGK1 promoted T helper type 2 (T(H)2) differentiation by negatively regulating degradation of the transcription factor JunB mediated by the E3 ligase Nedd4-2. Simultaneously, SGK1 repressed the production of interferon-gamma (IFN-gamma) by controlling expression of the long isoform of the transcription factor TCF-1. Consistent with those findings, mice with selective deletion of SGK1 in T cells were resistant to experimentally induced asthma, generated substantial IFN-g in response to viral infection and more readily rejected tumors. C1 [Heikamp, Emily B.; Patel, Chirag H.; Waickman, Adam; Sun, Im-Hong; Powell, Jonathan D.] Johns Hopkins Univ Sch Med, Dept Oncol, Sidney Kimmel Comprehens Canc Res Ctr, Baltimore, MD 21218 USA. [Collins, Sam; Oh, Min-Hee; Horton, Maureen R.] Johns Hopkins Univ Sch Med, Dept Med, Baltimore, MD USA. [Illei, Peter] Johns Hopkins Univ Sch Med, Dept Pathol, Baltimore, MD USA. [Sharma, Archna; Misra-Sen, Jyoti] NIA, Immune Cells & Inflammat Sect, Immunol Lab, NIH, Baltimore, MD 21224 USA. [Naray-Fejes-Toth, Aniko; Fejes-Toth, Geza] Dartmouth Med Sch, Dept Physiol, Lebanon, NH USA. RP Powell, JD (reprint author), Johns Hopkins Univ Sch Med, Dept Oncol, Sidney Kimmel Comprehens Canc Res Ctr, Baltimore, MD 21218 USA. EM poweljo@jhmi.edu RI Heikamp, Emily/K-7158-2016; Sharma, Archna/R-9377-2016 OI Heikamp, Emily/0000-0002-4591-4477; Sharma, Archna/0000-0003-4745-0220 FU US National Institutes of Health [R01 AI77610, NHLBI P01HL010342, NHLBI R21HL111783, DK 41481, DK 58898]; American Asthma Foundation (J.D.P.); Intramural Research Program of the NIH; National Institute on Aging (J.M.S.); FAMRI Center of Excellence [108595]; American Medical Association (E.B.H.) FX We thank D. Pardoll, C. Gamper and members of the Powell Lab for discussions, and the Magnuson laboratory for Rictor-/-mice. Supported by the US National Institutes of Health (R01 AI77610 to J.D.P., NHLBI P01HL010342 and NHLBI R21HL111783 to M.R.H., DK 41481 to A.N.-F.-T. and DK 58898 to G.F.-T.), the American Asthma Foundation (J.D.P.), the Intramural Research Program of the NIH, National Institute on Aging (J.M.S.), the FAMRI Center of Excellence 108595 (M.R.H.) and the American Medical Association (E.B.H.). NR 41 TC 46 Z9 47 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2014 VL 15 IS 5 BP 457 EP + DI 10.1038/ni.2867 PG 10 WC Immunology SC Immunology GA AF4FU UT WOS:000334667900011 PM 24705297 ER PT J AU Caprioli, D Calu, D Shaham, Y AF Caprioli, Daniele Calu, Donna Shaham, Yavin TI Loss of phasic dopamine: a new addiction marker? SO NATURE NEUROSCIENCE LA English DT Editorial Material ID DRUG-ADDICTION; COCAINE USE; STRIATUM; BEHAVIOR; REWARD AB A study finds that the loss of phasic dopamine signal in ventral, but not dorsal, striatum predicts escalation of cocaine self-administration. We discuss the study's implications for addiction theory and treatment. C1 [Caprioli, Daniele; Calu, Donna; Shaham, Yavin] NIDA, Behav Neurosci Res Branch, Intramural Res Program, US Natl Inst Hlth,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Caprioli, D (reprint author), NIDA, Behav Neurosci Res Branch, Intramural Res Program, US Natl Inst Hlth,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI shaham, yavin/G-1306-2014; OI Calu, Donna/0000-0003-2377-9494 FU Intramural NIH HHS [ZIA DA000434-14] NR 16 TC 4 Z9 4 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2014 VL 17 IS 5 BP 644 EP 646 DI 10.1038/nn.3699 PG 4 WC Neurosciences SC Neurosciences & Neurology GA AF9DS UT WOS:000335016200004 PM 24883455 ER PT J AU Johnson, JO Pioro, EP Boehringer, A Chia, R Feit, H Renton, AE Pliner, HA Abramzon, Y Marangi, G Winborn, BJ Gibbs, JR Nalls, MA Morgan, S Shoai, M Hardy, J Pittman, A Orrell, RW Malaspina, A Sidle, KC Fratta, P Harms, MB Baloh, RH Pestronk, A Weihl, CC Rogaeva, E Zinman, L Drory, VE Borghero, G Mora, G Calvo, A Rothstein, JD Drepper, C Sendtner, M Singleton, AB Taylor, JP Cookson, MR Restagno, G Sabatelli, M Bowser, R Chio, A Traynor, BJ AF Johnson, Janel O. Pioro, Erik P. Boehringer, Ashley Chia, Ruth Feit, Howard Renton, Alan E. Pliner, Hannah A. Abramzon, Yevgeniya Marangi, Giuseppe Winborn, Brett J. Gibbs, J. Raphael Nalls, Michael A. Morgan, Sarah Shoai, Maryam Hardy, John Pittman, Alan Orrell, Richard W. Malaspina, Andrea Sidle, Katie C. Fratta, Pietro Harms, Matthew B. Baloh, Robert H. Pestronk, Alan Weihl, Conrad C. Rogaeva, Ekaterina Zinman, Lorne Drory, Vivian E. Borghero, Giuseppe Mora, Gabriele Calvo, Andrea Rothstein, Jeffrey D. Drepper, Carsten Sendtner, Michael Singleton, Andrew B. Taylor, J. Paul Cookson, Mark R. Restagno, Gabriella Sabatelli, Mario Bowser, Robert Chio, Adriano Traynor, Bryan J. CA ITALSGEN TI Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis SO NATURE NEUROSCIENCE LA English DT Article ID DOMINANT DISTAL MYOPATHY; NUCLEAR-MATRIX; PROTEIN; ALS; COMPLEXES AB MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Using exome sequencing, we identified mutations in MATR3 in ALS kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration. C1 [Johnson, Janel O.; Renton, Alan E.; Pliner, Hannah A.; Abramzon, Yevgeniya; Marangi, Giuseppe; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Pioro, Erik P.] Cleveland Clin, Neurol Inst, Neuromuscular Ctr, Dept Neurol, Cleveland, OH 44106 USA. [Boehringer, Ashley; Bowser, Robert] Barrow Neurol Inst, Div Neurol, Phoenix, AZ 85013 USA. [Chia, Ruth; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Feit, Howard] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA. [Marangi, Giuseppe] Univ Cattolica Sacro Cuore, Inst Med Genet, I-00168 Rome, Italy. [Winborn, Brett J.; Taylor, J. Paul] St Jude Childrens Res Hosp, Dept Cell & Mol Biol, Memphis, TN 38105 USA. [Gibbs, J. Raphael] NIA, Computat Biol Core, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Gibbs, J. Raphael; Morgan, Sarah; Shoai, Maryam; Hardy, John; Pittman, Alan] UCL, Inst Neurol, Dept Mol Neurosci, London, England. [Gibbs, J. Raphael; Morgan, Sarah; Shoai, Maryam; Hardy, John; Pittman, Alan] UCL, Inst Neurol, Reta Lila Weston Labs, London, England. [Nalls, Michael A.; Singleton, Andrew B.] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Orrell, Richard W.] UCL, Inst Neurol, Dept Clin Neurosci, London, England. [Malaspina, Andrea] Queen Mary Univ London, North East London & Essex Reg Motor Neuron Dis Ca, Blizard Inst, Ctr Neurosci & Trauma, London, England. [Fratta, Pietro] UCL, Dept Neurodegenerat Dis, London, England. [Harms, Matthew B.; Pestronk, Alan; Weihl, Conrad C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Baloh, Robert H.] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA. [Rogaeva, Ekaterina] Univ Toronto, Dept Med, Div Neurol, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. [Zinman, Lorne] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Internal Med, Div Neurol, Toronto, ON, Canada. [Drory, Vivian E.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Neurol, IL-69978 Tel Aviv, Israel. [Borghero, Giuseppe] Azienda Univ Osped Cagliari, Dept Neurol, Cagliari, Italy. [Borghero, Giuseppe] Univ Cagliari, Cagliari, Italy. [Mora, Gabriele] Salvatore Maugeri Fdn, ALS Ctr, Milan, Italy. [Calvo, Andrea; Chio, Adriano] Univ Turin, Rita Levi Montalcini Dept Neurosci, Turin, Italy. [Rothstein, Jeffrey D.; Traynor, Bryan J.] Johns Hopkins Univ, Dept Neurol, Brain Sci Inst, Baltimore, MD 21218 USA. [Drepper, Carsten; Sendtner, Michael] Univ Wurzburg, Inst Clin Neurobiol, D-97070 Wurzburg, Germany. [Drepper, Carsten] Univ Wurzburg, Dept Child & Adolescent Psychiat, D-97070 Wurzburg, Germany. [Restagno, Gabriella] Azienda Sanit Osped Osped Infantile Regina Marghe, Dept Clin Pathol, Mol Genet Unit, Turin, Italy. [Sabatelli, Mario] Catholic Univ, Neurol Inst, Rome, Italy. [Sabatelli, Mario] Insieme Contro Malattie Motoneurone Assoc ALS Res, Rome, Italy. RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM traynorb@mail.nih.gov RI Conforti, Francesca Luisa/K-8877-2016; Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Pittman, Alan/D-6231-2012; Pliner, Hannah/F-3608-2015; MANDRIOLI, JESSICA/K-7235-2016; Battistini, Stefania/N-2596-2015; QUATTRONE, Aldo/A-6734-2016; Calvo, Andrea/K-4141-2016; LOGROSCINO, GIANCARLO/K-5148-2016; Spataro, Rossella/B-3656-2016; Lunetta, Christian/K-9214-2016; Sendtner, Michael/J-1542-2012 OI Fratta, Pietro/0000-0002-8762-8188; Sabatelli, Mario/0000-0001-6635-4985; Conforti, Francesca Luisa/0000-0001-8364-1783; Chio, Adriano/0000-0001-9579-5341; Simone, Isabella Laura/0000-0002-7429-3091; Gambardella , Antonio/0000-0001-7384-3074; Morgan, Sarah/0000-0002-1734-4710; Pliner, Hannah/0000-0003-1484-6501; MANDRIOLI, JESSICA/0000-0002-9244-9782; Battistini, Stefania/0000-0003-2887-7624; QUATTRONE, Aldo/0000-0003-2001-957X; Calvo, Andrea/0000-0002-5122-7243; LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Spataro, Rossella/0000-0002-8910-3131; Lunetta, Christian/0000-0002-4788-1875; Sendtner, Michael/0000-0002-4737-2974 FU Intramural Research Programs of the US National Institutes of Health (NIH); National Institute on Aging [Z01-AG000949-02]; NINDS; Packard Center for ALS Research at Johns Hopkins; ALS Association; Ontario Research Fund; UK MND Association [11/6075]; Medical Research Council (MRC) UK; Wellcome Trust/MRC Joint Call in Neurodegeneration Award [WT089698]; MRC Neuromuscular Centre; UK National Institute for Health Research Biomedical Research Unit; Biomedical Research Centre; MRC/Motor Neuron Disease Association Lady Edith Wolfson fellowship; AriSLA-Italian Research Foundation for Amyotrophic Lateral Sclerosis; Italian Health Ministry; Fondazione Vialli e Mauro Onlus; Federazione Italiana Giuoco Calcio; Compagnia di San Paolo; European Community [259867]; EuroMOTOR; German Federal Ministry of Education and Research (BMBF); German Network for Motoneuron Disease [TP4]; NIH [NS061867]; Adelis Foundation FX DNA samples for this study were obtained in part from the National Institute of Neurological Disorders and Stroke (NINDS) repository at the Coriell Cell Repositories (http://www. coriell. org/). We thank the patients and research subjects who contributed samples for this study. This work was supported in part by the Intramural Research Programs of the US National Institutes of Health (NIH), National Institute on Aging (Z01-AG000949-02) and NINDS. The work was also supported by the Packard Center for ALS Research at Johns Hopkins (B.J.T.), ALS Association (B.J.T., A. Chio), Ontario Research Fund (E.R.), UK MND Association (J. H., R.W.O. grant 11/6075), Medical Research Council (MRC) UK (J. H.), Wellcome Trust/MRC Joint Call in Neurodegeneration Award (J. H., grant WT089698), MRC Neuromuscular Centre (J.H.), UK National Institute for Health Research Biomedical Research Unit (J.H.), Biomedical Research Centre (A. Pittman), MRC/Motor Neuron Disease Association Lady Edith Wolfson fellowship (P.F.), AriSLA-Italian Research Foundation for Amyotrophic Lateral Sclerosis (A. Chio, B.J.T.), Italian Health Ministry (Ricerca Sanitaria Finalizzata 2007, A. Chio), Fondazione Vialli e Mauro Onlus (A. Chio), Federazione Italiana Giuoco Calcio (A. Chio, M. Sabatelli, B.J.T.), Compagnia di San Paolo (A. Chio, G.R.), Adelis Foundation (V.E.D.), European Community's Health Seventh Framework Programme (FP7/2007-2013) under grant agreements 259867 (A. Chio, M. Sendtner, C.D.), EuroMOTOR (M. Sendtner), German Federal Ministry of Education and Research (BMBF) (M. Sendtner), German Network for Motoneuron Disease (M. Sendtner, grant TP4) and NIH grant NS061867 (R.B.). NR 17 TC 101 Z9 105 U1 8 U2 46 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2014 VL 17 IS 5 BP 664 EP + DI 10.1038/nn.3688 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AF9DS UT WOS:000335016200008 PM 24686783 ER PT J AU Widemann, BC Dombi, E Gillespie, A Wolters, PL Belasco, J Goldman, S Korf, BR Solomon, J Martin, S Salzer, W Fox, E Patronas, N Kieran, MW Perentesis, JP Reddy, A Wright, JJ Kim, A Steinberg, SM Balis, FM AF Widemann, Brigitte C. Dombi, Eva Gillespie, Andrea Wolters, Pamela L. Belasco, Jean Goldman, Stewart Korf, Bruce R. Solomon, Jeffrey Martin, Staci Salzer, Wanda Fox, Elizabeth Patronas, Nicholas Kieran, Mark W. Perentesis, John P. Reddy, Alyssa Wright, John J. Kim, AeRang Steinberg, Seth M. Balis, Frank M. TI Phase 2 randomized, flexible crossover, double-blinded, placebo-controlled trial of the farnesyltransferase inhibitor tipifarnib in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas SO NEURO-ONCOLOGY LA English DT Article DE neurofibromatosis type 1; phase 2 trial; plexiform neurofibroma; RAS signaling; trial design ID NERVE SHEATH TUMORS; SOLID TUMORS; I TRIAL; MAMMALIAN TARGET; TRANSFERASE INHIBITORS; RAS; RAPAMYCIN; NF1; GUIDELINES; MANAGEMENT AB RAS is dysregulated in neurofibromatosis type 1 (NF1) related plexiform neurofibromas (PNs). The activity of tipifarnib, which blocks RAS signaling by inhibiting its farnesylation, was tested in children and young adults with NF1 and progressive PNs. Patients aged 325 years with NF1-related PNs and imaging evidence of tumor progression were randomized in a double-blinded fashion to receive tipifarnib (200 mg/m(2) orally every 12 h) or placebo (phase A) and crossed over to the opposite treatment arm at the time of tumor progression (phase B). PN volumes were measured with MRI, and progression was defined as 20 volume increase. Time to progression (TTP) in phase A was the primary endpoint, and the trial was powered to detect whether tipifarnib doubled TTP compared with placebo. Toxicity, response, and quality of life were also monitored. Sixty-two patients were enrolled. Tipifarnib and placebo were well tolerated. On phase A, the median TTP was 10.6 months on the placebo arm and 19.2 months on the tipifarnib arm (P .12; 1-sided). Quality of life improved significantly compared with baseline on the tipifarnib arm but not on the placebo arm. Volumetric tumor measurement detected tumor progression earlier than conventional 2-dimensional (WHO) and 1-dimensional (RECIST) methods. Tipifarnib was well tolerated but did not significantly prolong TTP of PNs compared with placebo. The randomized, flexible crossover design and volumetric PN assessment provided a feasible and efficient means of assessing the efficacy of tipifarnib. The placebo arm serves as an historical control group for phase 2 single-arm trials directed at progressive PNs. C1 [Widemann, Brigitte C.; Dombi, Eva; Gillespie, Andrea; Wolters, Pamela L.; Martin, Staci; Fox, Elizabeth; Balis, Frank M.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Wright, John J.] NCI, Canc Therapy Evaluat Program, Invest Drug Branch, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Patronas, Nicholas] NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Belasco, Jean; Fox, Elizabeth; Balis, Frank M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Goldman, Stewart] Ann & Robert H Lurie Childrens Hosp, Chicago, IL USA. [Korf, Bruce R.] Univ Alabama Birmingham, Dept Genet, South Birmingham, AL USA. [Solomon, Jeffrey] Expert Image Anal LC, Potomac, MD USA. [Kieran, Mark W.] Dana Farber Childrens Hosp, Ctr Canc, Boston, MA USA. [Perentesis, John P.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Kim, AeRang] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Salzer, Wanda] US Army, Med Res & Mat Command, Ft Detrick, MD USA. [Reddy, Alyssa] Childrens Hosp Alabama, Birmingham, AL USA. RP Widemann, BC (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10 CRC,Room 1-5750,MSC 1101, Bethesda, MD 20892 USA. EM widemanb@mail.nih.gov OI Kieran, Mark/0000-0003-2184-7692 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; Department of Defense [MIPR 1LCDN91152] FX This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and by a Clinical Trial Award (MIPR 1LCDN91152) from the Department of Defense. NR 41 TC 20 Z9 22 U1 3 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2014 VL 16 IS 5 BP 707 EP 718 DI 10.1093/neuonc/nou004 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AF5HU UT WOS:000334745400011 PM 24500418 ER PT J AU Baumann, MH Bulling, S Benaderet, TS Saha, K Ayestas, MA Partilla, JS Ali, SF Stockner, T Rothman, RB Sandtner, W Sitte, HH AF Baumann, Michael H. Bulling, Simon Benaderet, Tova S. Saha, Kusumika Ayestas, Mario A. Partilla, John S. Ali, Syed F. Stockner, Thomas Rothman, Richard B. Sandtner, Walter Sitte, Harald H. TI Evidence for a Role of Transporter-Mediated Currents in the Depletion of Brain Serotonin Induced by Serotonin Transporter Substrates SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin (5-HT) release; 5-HT depletion; 5-HT transporter (SERT); SERT substrate; SERT-mediated current ID INCREASES EXTRACELLULAR SEROTONIN; PRIMARY PULMONARY-HYPERTENSION; VALVULAR HEART-DISEASE; RAT-BRAIN; D-FENFLURAMINE; P-CHLOROAMPHETAMINE; IN-VIVO; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SUBSTITUTED AMPHETAMINES; NEUROTOXICITY PROFILES AB Serotonin (5-HT) transporter (SERT) substrates like fenfluramine and 3,4-methylenedioxymethamphetamine cause long-term depletion of brain 5-HT, while certain other substrates do not. The 5-HT deficits produced by SERT substrates are dependent upon transporter proteins, but the exact mechanisms responsible are unclear. Here, we compared the pharmacology of several SERT substrates: fenfluramine, d-fenfluramine, 1-(m-chlorophenyl)piperazine (mCPP) and 1-(m-trifluoromethylphenyl)piperainze (TFMPP), to establish relationships between acute drug mechanisms and the propensity for long-term 5-HT depletions. In vivo microdialysis was carried out in rat nucleus accumbens to examine acute 5-HT release and long-term depletion in the same subjects. In vitro assays were performed to measure efflux of [H-3]5-HT in rat brain synaptosomes and transporter-mediated ionic currents in SERT-expressing Xenopus oocytes. When administered repeatedly to rats (6 mg/kg, i.p., four doses), all drugs produce large sustained elevations in extracellular 5-HT (>5-fold) with minimal effects on dopamine. Importantly, 2 weeks after dosing, only rats exposed to fenfluramine and d-fenfluramine display depletion of brain 5-HT. All test drugs evoke fluoxetine-sensitive efflux of [H-3]5-HT from synaptosomes, but d-fenfluramine and its bioactive metabolite d-norfenfluramine induce significantly greater SERT-mediated currents than phenylpiperazines. Our data confirm that drug-induced 5-HT release probably does not mediate 5-HT depletion. However, the magnitude of transporter-mediated inward current may be a critical factor in the cascade of events leading to 5-HT deficits. This hypothesis warrants further study, especially given the growing popularity of designer drugs that target SERT. C1 [Baumann, Michael H.; Benaderet, Tova S.; Ayestas, Mario A.; Partilla, John S.; Rothman, Richard B.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA. [Bulling, Simon; Saha, Kusumika; Stockner, Thomas; Sandtner, Walter; Sitte, Harald H.] Med Univ Vienna, Inst Pharmacol, Ctr Physiol & Pharmacol, A-1090 Vienna, Austria. [Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Sitte, HH (reprint author), Med Univ Vienna, Inst Pharmacol, Ctr Physiol & Pharmacol, Waehringerstr 13 A, A-1090 Vienna, Austria. EM harald.sitte@meduniwien.ac.at RI Stockner, Thomas/A-9509-2014; OI Stockner, Thomas/0000-0002-7071-8283; Sitte, Harald/0000-0002-1339-7444 FU Intramural Research Program of the NIDA; NIH; Austrian Research Fund/FWF [F3506, W1232]; [DA000523-05] FX This research was supported by the Intramural Research Program of the NIDA, NIH, DA000523-05 to MHB and the Austrian Research Fund/FWF grants F3506 and W1232 to HHS. We are indebted to Klaus Schicker for valuable comments on the manuscript. NR 69 TC 9 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2014 VL 39 IS 6 BP 1355 EP 1365 DI 10.1038/npp.2013.331 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AF2RV UT WOS:000334560600007 PM 24287719 ER PT J AU Grant, PJ Joseph, LA Farmer, CA Luckenbaugh, DA Lougee, LC Zarate, CA Swedo, SE AF Grant, Paul J. Joseph, Lisa A. Farmer, Cristan A. Luckenbaugh, David A. Lougee, Lorraine C. Zarate, Carlos A., Jr. Swedo, Susan E. TI 12-Week, Placebo-Controlled Trial of Add-on Riluzole in the Treatment of Childhood-Onset Obsessive-Compulsive Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE mood/anxiety/stress disorders; psychiatry and behavioral sciences; clinical pharmacology/clinical trials; psychopharmacology; riluzole; obsessive-compulsive disorder ID OF-THE-LITERATURE; AUTISTIC DISORDER; CHILDREN; ADOLESCENTS; METAANALYSIS; RELIABILITY; VALIDITY; SCALE; PHARMACOTHERAPY; SCHEDULE AB Many children with childhood-onset obsessive compulsive disorder (OCD) fail to respond adequately to standard therapies. Evidence from preclinical and clinical studies suggests that the glutamatergic neurotransmitter system might be an alternative treatment target. This study examined the efficacy of riluzole, a glutamatergic modulator, as an adjunctive therapy for children with treatment-resistant OCD. In a 12-week, double-blind, placebo-controlled study, 60 treatment-resistant children and adolescents (mean age=14.5 +/- 2.4 years), with moderate to severe OCD (mean Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)=28.2 +/- 3.7), 17 of whom also had concomitant autism spectrum disorder, were randomized to receive riluzole (final dose of 100 mg/day) or placebo in addition to the existing treatment regimen. Fifty-nine subjects completed the randomized trial. Primary outcome measures were changes on the CY-BOCS, the Clinical Global Impressions Scale, and the Children's Global Assessment Scale. Riluzole was fairly well tolerated, although it was associated with one case of pancreatitis and five instances of slight increases in transaminases. All subjects showed significant reductions in CY-BOCS scores during treatment; however, there was no significant difference between placebo and riluzole on any of the primary or secondary outcome measures. The study failed to demonstrate superiority of riluzole over placebo as an adjunctive treatment for children with childhood-onset OCD. However, future studies may show benefits for less treatment-refractory children with fewer concomitant medications. C1 [Grant, Paul J.; Joseph, Lisa A.; Farmer, Cristan A.; Lougee, Lorraine C.; Swedo, Susan E.] NIMH, Pediat & Dev Neurosci Branch, NIH, Bethesda, MD 20892 USA. [Luckenbaugh, David A.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. RP Swedo, SE (reprint author), NIMH, Pediat & Dev Neurosci Branch, NIH, 10 Ctr Dr MSC 1255,Bldg 10,Room 1C250, Bethesda, MD 20892 USA. EM swedos@mail.nih.gov FU Intramural Program of the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) [1ZIAMH002913] FX This research (protocol 05-M-0225) was supported by the Intramural Program of the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH; Grant # 1ZIAMH002913). ClinicalTrials.gov identifier NCF00251303. NR 32 TC 8 Z9 10 U1 6 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2014 VL 39 IS 6 BP 1453 EP 1459 DI 10.1038/npp.2013.343 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AF2RV UT WOS:000334560600016 PM 24356715 ER PT J AU Ginexi, EM Riley, W Atienza, AA Mabry, PL AF Ginexi, Elizabeth M. Riley, William Atienza, Audie A. Mabry, Patricia L. TI The Promise of Intensive Longitudinal Data Capture for Behavioral Health Research SO NICOTINE & TOBACCO RESEARCH LA English DT Editorial Material ID ECOLOGICAL MOMENTARY ASSESSMENT; CESSATION; QUITTERS; SMOKERS AB Advances in technology and the associated cultural norms, especially the advent of the smartphone, offer an unprecedented opportunity to collect data on relevant health behaviors and experiences unobtrusively at a greater frequency and in greater volumes than ever before. This special issue will acquaint the readership of Nicotine and Tobacco Research with the potential for intensive longitudinal data and will illustrate some innovative analytic techniques for addressing research questions associated with this type of complex data. This introductory article will provide a brief history of the analytic techniques for intensive longitudinal data and will point to some resources that support and enable the use of these techniques. C1 [Ginexi, Elizabeth M.; Riley, William; Atienza, Audie A.] NCI, NIH, Bethesda, MD 20892 USA. [Mabry, Patricia L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Ginexi, EM (reprint author), NCI, Div Canc Control & Populat Sci, Behav Res Program, Room 3E564,MSC 9761,9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM lginexi@mail.nih.gov NR 18 TC 3 Z9 3 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAY PY 2014 VL 16 SU 2 BP S73 EP S75 DI 10.1093/ntr/ntt273 PG 3 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA AF4JS UT WOS:000334678700002 PM 24711629 ER PT J AU Fakhry, C Psyrri, A Chaturvedhi, A AF Fakhry, Carole Psyrri, Amanda Chaturvedhi, Anil TI HPV and head and neck cancers: State-of-the-science SO ORAL ONCOLOGY LA English DT Editorial Material ID SQUAMOUS-CELL CARCINOMAS; HUMAN-PAPILLOMAVIRUS; OROPHARYNGEAL CANCER; UNITED-STATES; RETINOBLASTOMA PROTEIN; ORAL-CAVITY; RISK-FACTOR; PHENOTYPE; INFECTION; PROFILES C1 [Fakhry, Carole] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Psyrri, Amanda] Attikon Univ Hosp, Athens, Greece. [Chaturvedhi, Anil] NCI, Bethesda, MD 20892 USA. RP Fakhry, C (reprint author), Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 39 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD MAY PY 2014 VL 50 IS 5 BP 353 EP 355 DI 10.1016/j.oraloncology.2014.03.010 PG 3 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA AF3AK UT WOS:000334583600007 PM 24726207 ER PT J AU Chen, B Yoon, JS Hu, BR Basta, M AF Chen, Bo Yoon, Jeong Seon Hu, Bingren Basta, Milan TI High-dose intravenous immunoglobulin exerts neuroprotective effect in the rat model of neonatal asphyxia SO PEDIATRIC RESEARCH LA English DT Article ID ISCHEMIC-STROKE; IMMUNE DAMAGE; BRAIN-INJURY; CELL-DEATH; ACTIVATION; PROTECTS; SYSTEM AB BACKGROUND: Neonatal asphyxia is one of the leading causes of death in newborn and permanent neurological disabilities in surviving children. The underlying hypoxic-ischemic (HI) injury triggers an inflammatory response lading to neuronal damage. Here, we tested the hypothesis that high-dose intravenous immunoglobulin (IVIG) could exert immunomodulatory effect in rat pups subjected to HI injury. METHODS: HI injury was induced in 7-d-old pups by ligating the common carotid artery followed by exposure to 8% oxygen for 2 h. Brain infarction was evaluated by imaging stained coronal brain sections. Neurological deficits were assessed in weeks 1 through 4 after HI. Western blotting and immunohistochemistry were used to assess complement fragment deposition in the brain tissue. RESULTS: Treatment with IVIG at 2 g/kg significantly and in a dose-responsive manner reduced brain infarction size as well as mortality and neurological deficits caused by HI. Anatomical and functional improvements in IVIG-treated pups correlated with decreased deposition of C3b complement fragments in the injured brain hemisphere. CONCLUSION: IVIG significantly improved the outcome of HI injury in rat pups and could potentially be used for the treatment of human neonatal asphyxia to target proinflammatory complement fragments. C1 [Chen, Bo; Hu, Bingren] Univ Maryland, Sch Med, Dept Anesthesiol, Shock Trauma & Anesthesiol Res Ctr, Baltimore, MD 21201 USA. [Yoon, Jeong Seon] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Basta, Milan] BioVisions Inc, Potomac, MD 20854 USA. RP Basta, M (reprint author), BioVisions Inc, Potomac, MD 20854 USA. EM basta.milan@gmail.com OI Basta, Milan/0000-0001-5958-9241 FU Investigator Initiated Study (IIS) Award from Baxter Healthcare (Westlake Village, CA) FX This study was supported by Investigator Initiated Study (IIS) Award from Baxter Healthcare (Westlake Village, CA). NR 20 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 2014 VL 75 IS 5 BP 612 EP 617 DI 10.1038/pr2014.12 PG 6 WC Pediatrics SC Pediatrics GA AF6JL UT WOS:000334821200005 PM 24488088 ER PT J AU Newburg, DS Grave, G AF Newburg, David S. Grave, Gilman TI Recent advances in human milk glycobiology SO PEDIATRIC RESEARCH LA English DT Editorial Material ID TANDEM MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; FED INFANTS; OLIGOSACCHARIDES; MICROARRAYS; LIBRARY; GLYCOME C1 [Newburg, David S.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. [Grave, Gilman] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Growth & Nutr Branch, NIH, Bethesda, MD USA. RP Newburg, DS (reprint author), Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. EM david.newburg@bc.edu FU NIAID NIH HHS [U01 AI075563, AI075563]; NICHD NIH HHS [HD013021, HD059140, HD061930, P01 HD013021, R01 HD059140, R01 HD061930] NR 31 TC 10 Z9 11 U1 0 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 2014 VL 75 IS 5 BP 675 EP 679 DI 10.1038/pr.2014.24 PG 5 WC Pediatrics SC Pediatrics GA AF6JL UT WOS:000334821200015 PM 24522101 ER PT J AU Widemann, BC Schwartz, S Jayaprakash, N Christensen, R Pui, CH Chauhan, N Daugherty, C King, TR Rush, JE Howard, SC AF Widemann, Brigitte C. Schwartz, Stefan Jayaprakash, Nalini Christensen, Robbin Pui, Ching-Hon Chauhan, Nikhil Daugherty, Claire King, Thomas R. Rush, Janet E. Howard, Scott C. TI Efficacy of Glucarpidase (Carboxypeptidase G2) in Patients with Acute Kidney Injury After High-Dose Methotrexate Therapy SO PHARMACOTHERAPY LA English DT Article DE glucarpidase; acute kidney injury; carboxypeptidase; methotrexate ID INDUCED RENAL DYSFUNCTION; HIGH-FLUX HEMODIALYSIS; LEUCOVORIN RESCUE; CANCER-PATIENTS; NEPHROTOXICITY; TOXICITY; THYMIDINE; ACID; PHARMACOKINETICS; PHARMACOLOGY AB Study Objective Because the incidence rate of renal impairment is 2-10% for patients treated with high-dose methotrexate and renal impairment develops in 0-12.4% of patients treated for osteosarcoma, we sought to evaluate the efficacy of glucarpidase, a recently approved drug that rapidly hydrolyzes methotrexate to inactive metabolites, which allows for nonrenal clearance in patients with delayed renal methotrexate elimination. Design Pooled analysis of efficacy data from four multicenter single-arm compassionate-use clinical trials using protocols from 1993 to 2007. Patients Of 476 patients with renal toxicity and delayed methotrexate elimination who were treated with intravenous glucarpidase for rescue after high-dose methotrexate, 169 patients had at least one preglucarpidase (baseline) plasma methotrexate concentration greater than 1 mu mol/L and one postglucarpidase methotrexate concentration measurement by high-performance liquid chromatography and were included in the efficacy analysis; renal recovery was assessed in 436 patients who had at least one recorded preglucarpidase and postglucarpidase serum creatinine concentration measurement. Measurements and Main Results Efficacy was defined as rapid and sustained clinically important reduction (RSCIR) in plasma methotrexate concentration, with a concentration of 1 mu mol/L or lower at all postglucarpidase determinations. Median age of efficacy-evaluable patients was 20years (range 5weeks-84years). Osteosarcoma (36%), non-Hodgkin lymphoma (27%), and acute lymphoblastic leukemia (20%) were the most frequent underlying diagnoses. Median preglucarpidase serum methotrexate was 11.7 mu mol/L. At the first (median 15minutes) through the last (median 40hours) postglucarpidase measurement, plasma methotrexate concentrations demonstrated consistent 99% median reduction. RSCIR was achieved by 83 (59%) of 140 patients. A total of 64% of patients with renal impairment greater than or equal to Common Terminology Criteria for Adverse Events grade 2 recovered to grade 0 or 1 at a median of 12.5days after glucarpidase administration. Conclusion Glucarpidase caused a clinically important 99% or greater sustained reduction of serum methotrexate levels and provided noninvasive rescue from methotrexate toxicity in renally impaired patients. C1 [Widemann, Brigitte C.; Jayaprakash, Nalini] NCI, Bethesda, MD 20892 USA. [Schwartz, Stefan] Charite, D-13353 Berlin, Germany. [Christensen, Robbin; Pui, Ching-Hon; Howard, Scott C.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Chauhan, Nikhil; Daugherty, Claire; King, Thomas R.; Rush, Janet E.] BTG Int Inc, W Conshohocken, PA 19428 USA. RP King, TR (reprint author), BTG Int Inc, Five Tower Bridge,Suite 800,300 Barr Harbor Dr, W Conshohocken, PA 19428 USA. EM thomas.king@btgplc.com FU BTG International Inc. FX Preparation of this manuscript for publication from the authors' original creation was sponsored by BTG International Inc. NR 34 TC 9 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY PY 2014 VL 34 IS 5 BP 427 EP 439 DI 10.1002/phar.1360 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF7VX UT WOS:000334924200005 PM 24132809 ER PT J AU Masaki, T Wang, Y DiGiovanna, JJ Khan, SG Raffeld, M Beltaifa, S Hornyak, TJ Darling, TN Lee, CCR Kraemer, KH AF Masaki, Taro Wang, Yun DiGiovanna, John J. Khan, Sikandar G. Raffeld, Mark Beltaifa, Senda Hornyak, Thomas J. Darling, Thomas N. Lee, Chyi-Chia R. Kraemer, Kenneth H. TI High frequency of PTEN mutations in nevi and melanomas from xeroderma pigmentosum patients SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE xeroderma pigmentosum; melanoma; PTEN; nevi; mTOR; DNA repair; UV carcinogenesis ID DNA-POLYMERASE-IOTA; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; METASTATIC MELANOMA; SKIN CARCINOGENESIS; GENETIC ALTERATIONS; DISTINCT SUBTYPES; MELANOCYTIC NEVI; MTOR PATHWAY; BRAF AB We examined nevi and melanomas in 10 xeroderma pigmentosum (XP) patients with defective DNA repair. The lesions had a lentiginous appearance with markedly increased numbers of melanocytes. Using laser capture microdissection, we performed DNA sequencing of 18 benign and atypical nevi and 75 melanomas (melanoma in situ and invasive melanomas). The nevi had a similar high frequency of PTEN mutations as melanomas [61% (11/18) versus 53% (39/73)]. Both had a very high proportion of UV-type mutations (occurring at adjacent pyrimidines) [91% (10/11) versus 92% (36/39)]. In contrast to melanomas in the general population, the frequency of BRAF mutations (11%, 7/61), NRAS mutations (21%, 13/62), and KIT mutations (21%, 6/28) in XP melanomas was lower than for PTEN. Phospho-S6 immunostaining indicated activation of the mTOR pathway in the atypical nevi and melanomas. Thus, the clinical and histological appearances and the molecular pathology of these UV-related XP nevi and melanomas were different from nevi and melanomas in the general population. C1 [Masaki, Taro; Wang, Yun; DiGiovanna, John J.; Khan, Sikandar G.; Hornyak, Thomas J.; Kraemer, Kenneth H.] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Masaki, Taro] Kobe Univ, Grad Sch Med, Div Dermatol, Kobe, Hyogo 657, Japan. [Wang, Yun] Peking Univ First Hosp, Dept Dermatol, Beijing, Peoples R China. [Raffeld, Mark; Beltaifa, Senda; Lee, Chyi-Chia R.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Hornyak, Thomas J.] Univ Maryland Med Ctr, Dept Dermatol, Baltimore, MD USA. [Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. RP Kraemer, KH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. EM kraemerk@nih.gov OI Darling, Thomas/0000-0002-5161-1974 NR 48 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 EI 1755-148X J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD MAY PY 2014 VL 27 IS 3 BP 454 EP 464 DI 10.1111/pcmr.12226 PG 11 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA AE7IM UT WOS:000334170900016 PM 24483290 ER PT J AU Gutierrez, N Eromobor, I Petrie, RJ Vedula, P Cruz, L Rodriguez, AJ AF Gutierrez, Natasha Eromobor, Itua Petrie, Ryan J. Vedula, Pavan Cruz, Lissette Rodriguez, Alexis J. TI The beta-actin mRNA zipcode regulates epithelial adherens junction assembly but not maintenance SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE RhoA and Src signaling; actin cytoskeleton regulation; actin mRNA zipcodes; adherens junction assembly; translation regulation ID CELL-CELL ADHESION; BREAST-CANCER CELLS; E-CADHERIN; MAMMALIAN-CELLS; RATE CONSTANTS; LIVING CELLS; CONTACTS; LOCALIZATION; DYNAMICS; RAC AB Epithelial cell-cell contact stimulates actin cytoskeleton remodeling to down-regulate branched filament polymerization-driven lamellar protrusion and subsequently to assemble linear actin filaments required for E-cadherin anchoring during adherens junction complex assembly. In this manuscript, we demonstrate that de novo protein synthesis, the beta-actin 3 ' UTR, and the beta-actin mRNA zipcode are required for epithelial adherens junction complex assembly but not maintenance. Specifically, we demonstrate that perturbing cell-cell contact-localized beta-actin monomer synthesis causes epithelial adherens junction assembly defects. Consequently, inhibiting beta-actin mRNA zipcode/ZBP1 interactions with beta-actin mRNA zipcode antisense oligonucleotides, to intentionally delocalize beta-actin monomer synthesis, is sufficient to perturb adherens junction assembly following epithelial cell-cell contact. Additionally, we demonstrate active RhoA, the signal required to drive zipcode-mediated beta-actin mRNA targeting, is localized at epithelial cell-cell contact sites in a beta-actin mRNA zipcode-dependent manner. Moreover, chemically inhibiting Src kinase activity prevents the local stimulation of beta-actin monomer synthesis at cell-cell contact sites while inhibiting epithelial adherens junction assembly. Together, these data demonstrate that epithelial cell-cell contact stimulates beta-actin mRNA zipcode-mediated monomer synthesis to spatially regulate actin filament remodeling, thereby controlling adherens junction assembly to modulate cell and tissue adhesion. C1 [Gutierrez, Natasha; Eromobor, Itua; Vedula, Pavan; Cruz, Lissette; Rodriguez, Alexis J.] Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA. [Petrie, Ryan J.] NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Rodriguez, AJ (reprint author), Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA. EM ajrod@andromeda.rutgers.edu FU NSF [0088668]; NIH [R25 60825-06]; Rutgers Research Exchange Program FX This work was supported by NSF # 0088668, NSF # 0538554, and NIH R25 60825-06 to N.G. and L.C., and the Rutgers Research Exchange Program to A.J.R. NR 42 TC 2 Z9 2 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 EI 1469-9001 J9 RNA JI RNA-Publ. RNA Soc. PD MAY PY 2014 VL 20 IS 5 BP 689 EP 701 DI 10.1261/rna.043208.113 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AF4JJ UT WOS:000334677800010 PM 24681968 ER PT J AU Yin, F Battiwalla, M Ito, S Feng, XM Chinian, F Melenhorst, JJ Koklanaris, E Sabatino, M Stroncek, D Samsel, L Klotz, J Hensel, NF Robey, PG Barrett, AJ AF Yin, Fang Battiwalla, Minoo Ito, Sawa Feng, Xingmin Chinian, Fariba Melenhorst, Jan Joseph Koklanaris, Eleftheria Sabatino, Marianna Stroncek, David Samsel, Leigh Klotz, Jeffrey Hensel, Nancy F. Robey, Pamela G. Barrett, A. John TI Bone Marrow Mesenchymal Stromal Cells to Treat Tissue Damage in Allogeneic Stem Cell Transplant Recipients: Correlation of Biological Markers with Clinical Responses SO STEM CELLS LA English DT Article DE Allogeneic stem cell transplantation; Graft-versus-host disease; Biomarkers; Mesenchymal stromal cell ID VERSUS-HOST-DISEASE; BIOMARKERS; THERAPY; BLOOD; DONOR AB Bone marrow mesenchymal stromal cells (BMSCs) have been used to treat acute graft-versus-host disease (GVHD) and other complications following allogeneic hematopoietic stem cell transplantation (SCT). We conducted a phase I trial using third party, early passage BMSCs for patients with steroid-refractory GVHD, tissue injury, or marrow failure following SCT to investigate safety and efficacy. To identify mechanisms of BMSC immunomodulation and tissue repair, patients were serially monitored for plasma GVHD biomarkers, cytokines, and lymphocyte phenotype. Ten subjects were infused a fixed dose of 2 x 10(6) BMSCs/kg intravenously weekly for three doses. There was no treatment-related toxicity (primary endpoint). Eight subjects were evaluable for response at 4 weeks after the last infusion. Five of the seven patients with steroid-refractory acute GVHD achieved a complete response, two of two patients with tissue injury (pneumomediastinum/pneumothorax) achieved resolution but there was no response in two subjects with delayed marrow failure. Rapid reductions in inflammatory cytokines were observed. Clinical responses correlated with a fall in biomarkers (Reg 3 alpha, CK18, and Elafin) relevant for the site of GVHD or tissue injury. The GVHD complete responders survived significantly longer and had higher baseline absolute lymphocyte and central memory CD4 and CD8 counts. Cytokine changes also segregated with survival. These results confirm that BMSCs are associated with rapid clinical and biomarker responses in GVHD and tissue injury. However, BMSCs were ineffective in patients with prolonged GVHD with lower lymphocyte counts, which suggest that effective GVHD control by BMSCs requires a relatively intact immune system. Stem Cells 2014;32:1278-1288 C1 [Yin, Fang; Battiwalla, Minoo; Ito, Sawa; Feng, Xingmin; Chinian, Fariba; Melenhorst, Jan Joseph; Koklanaris, Eleftheria; Klotz, Jeffrey; Hensel, Nancy F.; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Melenhorst, Jan Joseph] Univ Penn, Dept Pathol & Lab Med, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA USA. [Sabatino, Marianna; Stroncek, David] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Samsel, Leigh] NHLBI, Flow Cytometry Core, NIH, Bethesda, MD 20892 USA. [Robey, Pamela G.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. EM barrettjj@nhlbi.nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural Research Program of the National Heart Lung and Blood Institute; Intramural Research Program of the Clinical Center; Intramural Research Program of the National Institute of Dental and Craniofacial Research, NIH FX This research was supported by the Intramural Research Programs of the National Heart Lung and Blood Institute, the Clinical Center and the National Institute of Dental and Craniofacial Research, NIH. NR 17 TC 21 Z9 22 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD MAY PY 2014 VL 32 IS 5 BP 1278 EP 1288 DI 10.1002/stem.1638 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA AF3FP UT WOS:000334597200021 PM 24452962 ER PT J AU Humeniuk, R Koller, R Bies, J Aplan, P Wolff, L AF Humeniuk, Rita Koller, Richard Bies, Juraj Aplan, Peter Wolff, Linda TI Brief Report: Loss of p15Ink4b Accelerates Development of Myeloid Neoplasms in Nup98-HoxD13 Transgenic Mice SO STEM CELLS LA English DT Article DE p15Ink4b; Myeloproliferative disease; Acute myelogenous leukemia; Myelodysplastic syndromes; Nup98-HoxD13; Transgenic mouse ID TUMOR-SUPPRESSOR; MYELODYSPLASTIC SYNDROMES; BETHESDA PROPOSALS; LEUKEMIA; INACTIVATION; METHYLATION; HYPERMETHYLATION; CLASSIFICATION; P15(INK4B); P15 AB Homeostasis of hematopoietic stem and progenitor cells is a tightly regulated process. The disturbance of the balance in the hematopoietic progenitor pool can result in favorable conditions for development of diseases such as myelodysplastic syndromes and leukemia. It has been shown recently that mice lacking p15Ink4b have skewed differentiation of common myeloid progenitors toward the myeloid lineage at the expense of erythroid progenitors. The lack of p15INK4B expression in human leukemic blasts has been linked to poor prognosis and increased risk of myelodysplastic syndromes transformation to acute myeloid leukemia. However, the role of p15Ink4b in disease development is just beginning to be elucidated. This study examines the collaboration of the loss of p15Ink4b with Nup98-HoxD13 translocation in the development of hematological malignancies in a mouse model. Here, we report that loss of p15Ink4b collaborates with Nup98-HoxD13 transgene in the development of predominantly myeloid neoplasms, namely acute myeloid leukemia, myeloproliferative disease, and myelodysplastic syndromes. This mouse model could be a very valuable tool for studying p15Ink4b function in tumorigenesis as well as preclinical drug testing. Stem Cells 2014;32:1361-1366 C1 [Humeniuk, Rita; Koller, Richard; Bies, Juraj; Aplan, Peter; Wolff, Linda] NCI, NIH, Bethesda, MD 20892 USA. RP Wolff, L (reprint author), 37 Convent Dr, Bethesda, MD 20892 USA. EM wolffl@mail.nih.gov RI Aplan, Peter/K-9064-2016 NR 17 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD MAY PY 2014 VL 32 IS 5 BP 1361 EP 1366 DI 10.1002/stem.1635 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA AF3FP UT WOS:000334597200028 PM 24449168 ER PT J AU Iniguez, SD Riggs, LM Nieto, SJ Dayrit, G Zamora, NN Shawhan, KL Cruz, B Warren, BL AF Iniguez, Sergio D. Riggs, Lace M. Nieto, Steven J. Dayrit, Genesis Zamora, Norma N. Shawhan, Kristi L. Cruz, Bryan Warren, Brandon L. TI Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Article DE Anhedonia; animal model; anxiety; bullying; depression; forced swim test; juvenile; mood disorders ID UNPREDICTABLE MILD STRESS; ANIMAL-MODELS; MOOD DISORDERS; ADULTHOOD; ANXIETY; BEHAVIOR; RATS; BRAIN; ANTIDEPRESSANT; PREFERENCE AB Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35-44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7-12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression-and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence. C1 [Iniguez, Sergio D.; Riggs, Lace M.; Nieto, Steven J.; Dayrit, Genesis; Zamora, Norma N.; Shawhan, Kristi L.; Cruz, Bryan] Calif State Univ San Bernardino, Dept Psychol, San Bernardino, CA 92407 USA. [Warren, Brandon L.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. RP Iniguez, SD (reprint author), Calif State Univ San Bernardino, Dept Psychol, 5500 Univ Pkwy, San Bernardino, CA 92407 USA. EM iniguez@csusb.edu RI Iniguez, Sergio/J-2410-2015 FU National Institutes of Health (NIH); National Institute on Drug Abuse [R24DA033877]; California State University Program for Education and Research in Biotechnology grant; Associated Students Incorporated grants from CSUSB FX The National Institutes of Health (NIH) provided funding for this study. The NIH had no involvement in the design of the study, data collection process, or interpretation of the results. The funding sources did not play any role in writing the research manuscript or the decision to submit the paper for publication. This work was supported by a grant from the National Institute on Drug Abuse (R24DA033877 to SDI), a California State University Program for Education and Research in Biotechnology grant (to SDI), and the Associated Students Incorporated grants from CSUSB (to LMR, SJN, GD, NNZ, KLS, and BC). NR 56 TC 23 Z9 23 U1 2 U2 25 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1025-3890 EI 1607-8888 J9 STRESS JI Stress PD MAY PY 2014 VL 17 IS 3 BP 247 EP 255 DI 10.3109/10253890.2014.910650 PG 9 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA AF8BQ UT WOS:000334940500006 PM 24689732 ER PT J AU Al-Awadi, AR Al-Kuhlani, A Breman, JG Doumbo, O Eberhard, ML Guiguemde, RT Magnussen, P Molyneux, DH Nadim, A AF Al-Awadi, Abdul R. Al-Kuhlani, Abdulhakim Breman, Joel G. Doumbo, Ogobara Eberhard, Mark L. Guiguemde, Robert T. Magnussen, Pascal Molyneux, David H. Nadim, Abolhassan TI Guinea worm (Dracunculiasis) eradication: update on progress and endgame challenges SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Editorial Material DE Dracunculiasis; Dracunculus medinensis Guinea worm; Eradication ID INSIGNIS NEMATODA; DRACUNCULOIDEA; CERTIFICATION; DISEASE AB The International Commission for the Certification of Dracunculiasis Eradication (ICCDE) met in December to review progress towards eradication. The status of the programme was presented by WHO and The Carter Center, Atlanta. The Commission received reports from international certification teams that Cote dIvoire, Niger and Nigeria were free of transmission and should be certified, while four countries, namely Chad, Ethiopia, Mali and South Sudan, remained endemic. The Commission certified that Somalia and South Africa were free of transmission. During 2013, there was a decline of about 78 in the numbers of cases reported in South Sudan. A report of the perplexing dracunculiasis epidemiology in Chad was also discussed, where dogs have been found to be infected with Dracunculus medinensis. C1 [Al-Awadi, Abdul R.] Islamic Org Med Sci, Sulibikhat 90803, Kuwait. [Al-Kuhlani, Abdulhakim] Minist Publ Hlth & Populat, Sect PHC, Sanaa, Yemen. [Breman, Joel G.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Doumbo, Ogobara] Univ Mali, Fac Med, Dept Epidemiol Affect Parasitaires, Bamako, Mali. [Eberhard, Mark L.] Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Atlanta, GA 30333 USA. [Guiguemde, Robert T.] Univ Bobo Dioulasso, Burkina Natl Acad Sci, Bobo Dioulasso 01, Burkina Faso. [Magnussen, Pascal] Univ Copenhagen, Inst Vet Dis, Biol Sect Parasitol & Aquat Dis, DK-1781 Frederiksberg C, Denmark. [Molyneux, David H.] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. RP Molyneux, DH (reprint author), Univ Liverpool, Liverpool Sch Trop Med, Pembroke Pl, Liverpool L3 5QA, Merseyside, England. EM david.molyneux@liv.ac.uk NR 11 TC 12 Z9 12 U1 11 U2 45 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0035-9203 EI 1878-3503 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD MAY PY 2014 VL 108 IS 5 BP 249 EP 251 DI 10.1093/trstmh/tru039 PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AF5LE UT WOS:000334754200002 PM 24699360 ER PT J AU Post, RM Leverich, GS Kupka, R Keck, P McElroy, S Altshuler, L Frye, MA Luckenbaugh, DA Rowe, M Grunze, H Suppes, T Nolen, WA AF Post, R. M. Leverich, G. S. Kupka, R. Keck, P., Jr. McElroy, S. Altshuler, L. Frye, M. A. Luckenbaugh, D. A. Rowe, M. Grunze, H. Suppes, T. Nolen, W. A. TI Increased parental history of bipolar disorder in the United States: association with early age of onset SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE assortative mating; bipolar disorder; childhood onset bipolar disorder; genetics ID ASTERISK-D-CHILD; MATERNAL DEPRESSION; MENTAL-DISORDERS; OUTPATIENTS; RISK; RATINGS AB Objective Early-onset bipolar (BP) disorder and other poor prognosis characteristics are more prevalent in patients from the United States than from the Netherlands and Germany (abbreviated as Europe). We explored the impact of parental loading for affective illness on onset and other characteristics of BP disorder. Method Parental history for unipolar (UP) and bipolar (BP) depression and course of illness characteristics were obtained from self-report in adults (average age 42) with BP disorder. Illness characteristics were examined by chi(2) and multinomial logistic regression in relationship to the degree of parental loading: i) both parents negative; ii) one UP disorder; iii) one with BP disorder; and iv) both affected. Results After controlling for many poor prognosis factors, compared with those from Europe, patients from the United States had more iii) one parent with BP disorder and iv) both parents affected. An early age of onset of BP disorder was independently associated with this increased parental loading for affective disorder. Conclusion Parental history of BP disorder and both parents with a mood disorder were more common in the United States than Europe and were associated with an early onset of bipolar disorder and other poor prognosis characteristics. These findings deserve replication and exploration of the potential mechanisms involved and their therapeutic implications. C1 [Post, R. M.; Leverich, G. S.; Rowe, M.] Bipolar Collaborat Network, Bethesda, MD 20814 USA. [Post, R. M.] George Washington Univ, Dept Psychiat & Behav Sci, Washington, DC USA. [Kupka, R.] Vrije Univ Amsterdam, Dept Psychiat, Med Ctr, Amsterdam, Netherlands. [Keck, P., Jr.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. [Keck, P., Jr.; McElroy, S.] Lindner Ctr HOPE, Mason, OH USA. [McElroy, S.] Univ Cincinnati, Coll Med, Biol Psychiat Program, Cincinnati, OH USA. [Altshuler, L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Altshuler, L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, West Los Angeles Healthcare Ctr, Los Angeles, CA USA. [Frye, M. A.] Mayo Clin, Dept Psychiat, Rochester, MI USA. [Luckenbaugh, D. A.] NIMH, NIH, Bethesda, MD 20892 USA. [Grunze, H.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Suppes, T.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Suppes, T.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Nolen, W. A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. RP Post, RM (reprint author), Bipolar Collaborat Network, 5415 W Cedar Lane 201B, Bethesda, MD 20814 USA. EM robert.post@speakeasy.net OI Grunze, Heinz/0000-0003-4712-8979 FU AstraZeneca; Alkermes; Cephalon; GlaxoSmithKline; Eli Lilly; Marriott Foundation; National Institute of Mental Health; National Institute of Drug Abuse; Orexigen; Pfizer Inc.; Shire; Abbott; Bristol-Myers Squibb; Forest; Jazz; Takeda; Johnson & Johnson Pharmaceutical Research Development; Sepracor; Takeda Pharmaceuticals North America, Inc.; H. Lundbeck A/S; Sunovion Pharmaceuticals Inc.; Pfizer; Astra-Zeneca; Bial; Janssen-Cilag; Sanofi-Aventis; Servier; United BioSource Corporation; Netherlands Organization for Health Research and Development; European Union; Stanley Medical Research Institute; Wyeth FX Dr. Kupka has received research grants from AstraZeneca and honoraria from Eli Lilly, Janssen-Cilag, Bristol-Myers Squibb, and AstraZeneca.; Dr. Keck is employed by the University of Cincinnati College of Medicine and University of Cincinnati Physicians. Dr. Keck is a principal or coinvestigator on research studies sponsored by Alkermes, AstraZeneca, Cephalon, GlaxoSmithKline, Eli Lilly, Marriott Foundation, the National Institute of Mental Health, the National Institute of Drug Abuse, Orexigen, Pfizer Inc., and Shire, and has been reimbursed for consulting to, in the past 2 years, Bristol-Myers-Squibb, Teva, Otsuka, Forest, Merck, Sunovion, Alkermes, and Shire. Dr. Keck is also inventor on US Patent No. 6,387,956: Shapira NA, Goldsmith TD, Keck PE Jr (University of Cincinnati), Methods of Treating Obsessive-Compulsive Spectrum Disorder Comprises the Step of Administering an Effective Amount of Tramadol to an Individual; filed March 25, 1999; approved May 14, 2002.; Dr. McElroy is a consultant to or member of the scientific advisory boards of Eli Lilly and Schering-Plough and is a principal or coinvestigator on research studies sponsored by Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Jazz, the Marriott Foundation, the National Institute of Mental Health, Orexigen, Shire, and Takeda. Dr. McElroy is also inventor on US Patent No. 6,323,236, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and, along with the patent's assignee, the University of Cincinnati, has received payments from Johnson & Johnson Pharmaceutical Research & Development, which has exclusive rights under the patent.; Dr. Altshuler has received past funding from Sepracor (advisory board honoraria, January 2010), and Eli Lilly (consultant, September 2010) and past and potential future funding from Takeda Pharmaceuticals North America, Inc., and H. Lundbeck A/S (advisory board honoraria, October 2012) and Sunovion Pharmaceuticals Inc. (advisory board honoraria, January 2013).; Dr. Frye has received grant support from Pfizer (drug supply: varenicline), has been a consultant to Cephalon, Dainippon Sumitomo, Ortho McNeil/Janssen, Johnson & Johnson, Schering-Plough, and Pfizer, and has participated in supported CME activities for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Otsuka, Pfizer, and Schering-Plough.; Dr. Grunze has received grant/research support, consulting fees, and honoraria within the last 3 years from Astra-Zeneca, Bial, Bristol-Myers Squibb, Eli Lilly, Lundbeck, Janssen-Cilag, Sanofi-Aventis, Servier, United BioSource Corporation.; Dr. Nolen has received grants from The Netherlands Organization for Health Research and Development, the European Union, The Stanley Medical Research Institute, AstraZeneca, Eli Lilly, GlaxoSmithKline, and Wyeth; has received honoraria or speaker's fees from AstraZeneca, Eli Lilly, Pfizer, Servier, and Wyeth; and has served on the advisory boards of AstraZeneca, Cyberonics, Pfizer, and Servier. NR 25 TC 19 Z9 19 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X EI 1600-0447 J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD MAY PY 2014 VL 129 IS 5 SI SI BP 375 EP 382 DI 10.1111/acps.12208 PG 8 WC Psychiatry SC Psychiatry GA AE8AP UT WOS:000334221600006 PM 24138298 ER PT J AU Barranger, JA Brady, RO Grabowski, GA Mankin, H Mistry, PK Weinreb, NJ AF Barranger, John A. Brady, Roscoe O. Grabowski, Gregory A. Mankin, Henry Mistry, Pramod K. Weinreb, Neal J. TI Position statement: National Gaucher Foundation Medical Advisory Board, January 7, 2014 SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material ID ENZYME REPLACEMENT THERAPY; VELAGLUCERASE ALPHA; SKELETAL MANIFESTATIONS; TALIGLUCERASE ALPHA; DISEASE PATIENTS; TYPE-1; IMIGLUCERASE; EXPERIENCE; GLUCOCEREBROSIDASE; IMPROVEMENT C1 [Barranger, John A.] Lysosomal Storage Dis Clin Care Network, Pittsburgh, PA USA. [Brady, Roscoe O.] NIH, Bethesda, MD 20892 USA. [Grabowski, Gregory A.] Synageva BioPharma, Lexington, MA USA. [Mankin, Henry] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. [Mistry, Pramod K.] Yale Univ, Sch Med, New Haven, CT USA. [Weinreb, Neal J.] Univ Res Fdn Lysosomal Storage Dis, Coral Springs, FL USA. RP Weinreb, NJ (reprint author), 8170 Royal Palm Blvd, Coral Springs, FL 33065 USA. EM boneal@winning.com NR 31 TC 2 Z9 2 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2014 VL 89 IS 5 BP 457 EP 458 DI 10.1002/ajh.23687 PG 2 WC Hematology SC Hematology GA AE9MN UT WOS:000334332000002 PM 24488939 ER PT J AU Scheinberg, P Townsley, D Dumitriu, B Scheinberg, P Weinstein, B Rios, O Wu, CO Young, NS AF Scheinberg, Phillip Townsley, Danielle Dumitriu, Bogdan Scheinberg, Priscila Weinstein, Barbara Rios, Olga Wu, Colin O. Young, Neal S. TI Horse antithymocyte globulin as salvage therapy after rabbit antithymocyte globulin for severe aplastic anemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; HIGH-DOSE CYCLOPHOSPHAMIDE; ANTI-THYMOCYTE GLOBULIN; IMMUNOSUPPRESSIVE THERAPY; CYCLOSPORINE; CHILDREN; ATG AB The effectiveness of salvage therapy for aplastic anemia patients unresponsive to initial rabbit antithymocyte globulin (r-ATG) or cyclophosphamide is not known. We investigated the administration of standard horse ATG (h-ATG) plus cyclosporine (CsA) in patients who were refractory to initial r-ATG/CsA (n = 19) or cyclophosphamide/CsA (n = 6) (registered at as NCT00944749). The primary endpoint was hematologic response at 3 months and was defined as no longer meeting the criteria for severe aplastic anemia. Of the 19 patients who received r-ATG as initial therapy, 4 (21%) achieved a hematologic response by 3 months, and of the 6 patients who received cyclophosphamide, only 1 (17%) responded by 6 months. Among the responders there were no cases of relapse, and in nonresponders 2 patients evolved to monosomy 7. The overall survival for the cohort at 3 years was 68% (95% CI, 50-91%). These results suggest that only a minority can be successfully salvaged after receiving as first therapy either r-ATG or cyclophosphamide. Although h-ATG may be utilized in the salvage setting, the overall response rate probably will be lower than when h-ATG is used as initial treatment. Am. J. Hematol. 89:467-469, 2014. (c) Published 2014. C1 [Scheinberg, Phillip; Townsley, Danielle; Dumitriu, Bogdan; Scheinberg, Priscila; Weinstein, Barbara; Rios, Olga; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Scheinberg, Phillip] Beneficencia Portuguesa, Hosp Sao Jose, Ctr Oncol, Hematol Serv, Sao Paulo, Brazil. [Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Scheinberg, P (reprint author), Rua Martiniano de Carvalho, BR-01321001 Sao Paulo, Brazil. EM scheinbp@gmail.com OI Scheinberg, Phillip/0000-0002-9047-4538 FU NIH, National Heart, Lung, and Blood Institute FX This research was supported by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute. NR 20 TC 7 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2014 VL 89 IS 5 BP 467 EP 469 DI 10.1002/ajh.23669 PG 3 WC Hematology SC Hematology GA AE9MN UT WOS:000334332000004 PM 24415649 ER PT J AU Prasad, V Shea, N AF Prasad, Vinay Shea, Neal TI Open Access Publication, Journal Policy, and Scientific Community Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Shea, Neal] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 2 TC 2 Z9 2 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD MAY PY 2014 VL 127 IS 5 DI 10.1016/j.amjmed.2014.01.030 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AF1XL UT WOS:000334507100008 PM 24560327 ER PT J AU Terrault, N Reddy, KR Poordad, F Curry, M Schiano, T Johl, J Shaikh, O Dove, L Shetty, K Millis, M Schiff, E Regenstein, F Barnes, D Barin, B Peters, M Roland, M Stock, P AF Terrault, N. Reddy, K. R. Poordad, F. Curry, M. Schiano, T. Johl, J. Shaikh, O. Dove, L. Shetty, K. Millis, M. Schiff, E. Regenstein, F. Barnes, D. Barin, B. Peters, M. Roland, M. Stock, P. CA HIVTR Investigators TI Peginterferon and Ribavirin for Treatment of Recurrent Hepatitis C Disease in HCV- HIV Coinfected Liver Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Sustained virologic response; histologic response; antiviral therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; MULTICENTER EXPERIENCE; PEGYLATED-INTERFERON; PLUS RIBAVIRIN; SURVIVAL; EFFICACY; SAFETY AB Achievement of a sustained virologic response (SVR) with antiviral therapy significantly improves graft survival in hepatitis C virus (HCV) monoinfected liver transplant (LT) patients. Risks and benefits of HCV therapy in HCV-human immunodeficiency virus (HIV) coinfected LT recipients are not well established. Among 89 HCV-HIV LT recipients in the HIVTR cohort, 39 (23% Black, 79% genotype 1, 83% fibrosis stage1) were treated with peginterferon-a2a or a2b plus ribavirin for a median 363 days (14-1373). On intent-to-treat basis, 22% (95% CI: 10-39) and 14% (95% CI: 5-30) achieved an end-of-treatment response (EOTR) and SVR, respectively. By per-protocol analysis (completed 48 weeks of therapydose reductions), 42% and 26% had EOTR and SVR, respectively. Severe adverse events occurred in 85%, with 26% hospitalized with infections and 13% developing acute rejection. Early discontinuations and dose reductions occurred in 38% and 82%, respectively, despite use of growth factors in 85%. Eighteen of 39 treated patients (46%) subsequently died/had graft loss, with 10 (26%) attributed to recurrent HCV. In conclusion, SVR rates are low and tolerability is poor in HCV-HIV coinfected transplant recipients treated with peginterferon and ribavirin. These results highlight the critical need for better tolerated and more efficacious HCV therapies for HCV-HIV coinfected transplant recipients. The authors show that treatment of HCV-HIV coinfected transplant recipients with peginterferon and ribavirin yielded sustained virology responses in only 14% and with high rates of dose reductions (85%), early discontinuation (38%), and severe adverse events (85%). C1 [Terrault, N.; Peters, M.; Roland, M.] Univ Calif San Francisco, Dept Med, Div Gastroenterol & Hepatol, San Francisco, CA 94143 USA. [Reddy, K. R.] Univ Penn, Dept Med, Div Gastoenterol & Hepatol, Philadelphia, PA 19104 USA. [Poordad, F.] Univ Texas Hlth Sci Ctr San Antonio, Texas Liver Inst, Univ Transplant Ctr, San Antonio, TX 78229 USA. [Curry, M.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Schiano, T.] Mt Sinai SOM, Div Liver Dis, Dept Med, New York, NY USA. [Johl, J.] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. [Shaikh, O.] Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Dove, L.] Columbia Univ, Dept Med, New York, NY USA. [Shetty, K.] Georgetown Univ, Dept Surg, Washington, DC USA. [Millis, M.] Univ Chicago, Dept Surg, Chicago, IL 60637 USA. [Schiff, E.] Univ Miami, Dept Med, Div Hepatol, Miami, FL USA. [Regenstein, F.] Tulane Univ, Dept Med, New Orleans, LA 70118 USA. [Barnes, D.] Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA. [Barin, B.] EMMES Corp, Rockville, MD USA. [Stock, P.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. RP Terrault, N (reprint author), Univ Calif San Francisco, Dept Med, Div Gastroenterol & Hepatol, San Francisco, CA 94143 USA. EM norah.terrault@ucsf.edu FU solid organ transplantation in HIV: Multi-Site Study [AI052748]; National Institute of Allergy and Infectious Diseases FX This work was supported by the solid organ transplantation in HIV: Multi-Site Study (AI052748) funded by the National Institute of Allergy and Infectious Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. We want to thank Rodney Rogers from the University of California, San Francisco for this expert coordination of the study consortium. We want to thank all of the solid organ transplantation in HIV: Multi-Site Study investigators and coordinators for their hard work and dedication to the study and subjects. A complete list can be found in the online materials for this article. NR 14 TC 12 Z9 12 U1 0 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2014 VL 14 IS 5 BP 1129 EP 1135 DI 10.1111/ajt.12668 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA AF0LG UT WOS:000334404900018 PM 24636466 ER PT J AU Wirth, EK Bharathi, BS Hatfield, D Conrad, M Brielmeier, M Schweizer, U AF Wirth, Eva K. Bharathi, B. Suman Hatfield, Dolph Conrad, Marcus Brielmeier, Markus Schweizer, Ulrich TI Cerebellar Hypoplasia in Mice Lacking Selenoprotein Biosynthesis in Neurons SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE Selenium; Brain; Gpx4; Cell death; Proliferation ID PROGRESSIVE CEREBELLOCEREBRAL ATROPHY; APOLIPOPROTEIN-E RECEPTOR-2; NEUROLOGICAL DYSFUNCTION; BRAIN SELENIUM; CELL-DEATH; MOUSE; GENE; SELENOCYSTEINE; EXPRESSION; DELETION AB Selenium exerts many, if not most, of its physiological functions as a selenocysteine moiety in proteins. Selenoproteins are involved in many biochemical processes including regulation of cellular redox state, calcium homeostasis, protein biosynthesis, and degradation. A neurodevelopmental syndrome called progressive cerebello-cortical atrophy (PCCA) is caused by mutations in the selenocysteine synthase gene, SEPSECS, demonstrating that selenoproteins are essential for human brain development. While we have shown that selenoproteins are required for correct hippocampal and cortical interneuron development, little is known about the functions of selenoproteins in the cerebellum. Therefore, we have abrogated neuronal selenoprotein biosynthesis by conditional deletion of the gene encoding selenocysteyl tRNA([Ser]Sec) (gene symbol Trsp). Enzymatic activity of cellular glutathione peroxidase and cytosolic thioredoxin reductase is reduced in cerebellar extracts from Trsp-mutant mice. These mice grow slowly and fail to gain postural control or to coordinate their movements. Histological analysis reveals marked cerebellar hypoplasia, associated with Purkinje cell death and decreased granule cell proliferation. Purkinje cell death occurs along parasagittal stripes as observed in other models of Purkinje cell loss. Neuron-specific inactivation of glutathione peroxidase 4 (Gpx4) used the same Cre driver phenocopies tRNA([Ser]Sec) mutants in several aspects: cerebellar hypoplasia, stripe-like Purkinje cell loss, and reduced granule cell proliferation. Parvalbumin-expressing GABAergic interneurons (stellate and/or basket cells) are virtually absent in tRNA([Ser]Sec)-mutant mice, while some remained in Gpx4-mutant mice. Our data show that selenoproteins are specifically required in postmitotic neurons of the developing cerebellum, thus providing a rational explanation for cerebellar hypoplasia as occurring in PCCA patients. C1 [Wirth, Eva K.; Bharathi, B. Suman; Schweizer, Ulrich] Charite, Inst Expt Endokrinol, D-13353 Berlin, Germany. [Hatfield, Dolph] NIH, Mouse Canc Genet Program, Ctr Canc Res, Bethesda, MD 20892 USA. [Conrad, Marcus] Helmholtz Zentrum Munchen, Inst Dev Genet, D-85764 Munich, Germany. [Brielmeier, Markus] Helmholtz Zentrum Munchen, Abt Vergleichende Med, D-85764 Neuherberg, Germany. [Schweizer, Ulrich] Univ Bonn, Inst Biochem & Mol Biol, D-53115 Bonn, Germany. RP Schweizer, U (reprint author), Univ Bonn, Inst Biochem & Mol Biol, Nussallee 11, D-53115 Bonn, Germany. EM uschweiz@uni-bonn.de RI Brielmeier, Markus/M-7352-2014; OI Brielmeier, Markus/0000-0002-8715-869X; Wirth, Eva Katrin/0000-0002-0491-9941; Conrad, Marcus/0000-0003-1140-5612; Schweizer, Ulrich/0000-0003-1380-4780 FU Deutsche Forschungsgemeinschaft DFG [Schw914/2-1]; Charite-Universitatsmedizin Berlin FX The authors thank Silke Kappler for technical assistance and Dr. Richard Hawkes for zebrin II antibody. The study was funded by Deutsche Forschungsgemeinschaft DFG Schw914/2-1 and Charite-Universitatsmedizin Berlin. NR 28 TC 14 Z9 14 U1 0 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0163-4984 EI 1559-0720 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD MAY PY 2014 VL 158 IS 2 BP 203 EP 210 DI 10.1007/s12011-014-9920-z PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AF1US UT WOS:000334500000010 PM 24599700 ER PT J AU Hoang, AN Agarwal, PK Walton-Diaz, A Wood, CG Metwalli, AR Kassouf, W Brown, GA Black, PC Urbauer, DL Grossman, HB Dinney, CPN Kamat, AM AF Hoang, Anthony N. Agarwal, Piyush K. Walton-Diaz, Annerleim Wood, Christopher G. Metwalli, Adam R. Kassouf, Wassim Brown, Gordon A. Black, Peter C. Urbauer, Diana L. Grossman, H. Barton Dinney, Colin P. N. Kamat, Ashish M. TI Clinical significance of ureteric 'skip lesions' at the time of radical cystectomy: the M.D. Anderson experience and literature review SO BJU INTERNATIONAL LA English DT Article DE ureteral margin; cystectomy; bladder cancer; ureteral urothelial carcinoma; upper tract recurrence ID FROZEN-SECTION ANALYSIS; TRANSITIONAL-CELL CARCINOMA; BLADDER-CANCER; IN-SITU; MARGINS; INVOLVEMENT AB Objective To assess the incidence and clinical significance of 'skip lesions' that are present in proximal but not in distal ureteric sections, which are occasionally found during the pathological examination of ureteric margins during radical cystectomy (RC). Patients and Methods We identified 660 patients who underwent a RC and had at least two permanent margins for a given ureter. In all, 1173 ureters were analysed and classified as follows: 'normal' (no tumour, reactive atypia, mild or moderate dysplasia) or 'abnormal' (severe dysplasia, carcinoma in situ (CIS), or tumour). Transitions from 'normal' distal pathology to 'abnormal' on proximal section(s) determined frequency of skip lesions. Fisher's exact test and the log-rank test were used to study correlations. Results Ureteric skip lesions were found in 4.8% patients (2.9% ureters). Pathology of skip lesions was CIS in 55.9%, transitional cell carcinoma in 23.5% and severe dysplasia in 20.6%. Skip lesions were associated with lymphovascular invasion (34.4% vs 13.7%, P = 0.004) and advanced pT stage (P = 0.007). On multivariate analysis, skip lesions correlated with lower median overall survival (OS) (inestimable vs 8.2 years, P = 0.014) in patients with pT0 or pTa disease and a trend towards lower OS (2.7 vs 8.8 years, P = 0.066) in pTis disease. Concordance between frozen distal margin and permanent proximal margin varied; sensitivity was 80% in those without and 20% in those with skip lesions. Conclusions The presence of a ureteric skip lesion may be associated with lower survival in patients with pT0, pTa or pTis urothelial carcinoma. Thus, while uncommon, ureteric skip lesions should be reported in pathological findings. C1 [Hoang, Anthony N.; Agarwal, Piyush K.; Walton-Diaz, Annerleim; Metwalli, Adam R.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Wood, Christopher G.; Kassouf, Wassim; Brown, Gordon A.; Black, Peter C.; Grossman, H. Barton; Dinney, Colin P. N.; Kamat, Ashish M.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Urbauer, Diana L.] Univ Texas MD Anderson Canc Ctr, Div Quantitat Sci, Houston, TX 77030 USA. RP Kamat, AM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Urol, Unit 1373, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM akamat@mdanderson.org OI Agarwal, Piyush/0000-0002-6042-6834 FU M. D. Anderson Cancer Center Bladder SPORE [5P50CA091846-03]; Department of Urology T32 Training Grant FX This research was supported by the M. D. Anderson Cancer Center Bladder SPORE (5P50CA091846-03) and a Department of Urology T32 Training Grant NR 12 TC 6 Z9 6 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD MAY PY 2014 VL 113 IS 5B SI SI BP E28 EP E33 DI 10.1111/bju.12344 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AF4LA UT WOS:000334682300003 PM 24053608 ER PT J AU Lai, GY Giovannucci, EL Pollak, MN Peskoe, SB Stampfer, MJ Willett, WC Platz, EA AF Lai, Gabriel Y. Giovannucci, Edward L. Pollak, Michael N. Peskoe, Sarah B. Stampfer, Meir J. Willett, Walter C. Platz, Elizabeth A. TI Association of C-peptide and leptin with prostate cancer incidence in the Health Professionals Follow-up Study SO CANCER CAUSES & CONTROL LA English DT Article DE Prostate cancer; C-peptide; Leptin; Nested case-control study; Risk ID PROSPECTIVE RISK-FACTOR; GROWTH-FACTOR-I; INSULIN-RESISTANCE; DIABETES-MELLITUS; SUBSEQUENT RISK; PLASMA LEPTIN; PSA ERA; OBESITY; ADIPONECTIN; BIOMARKERS AB Hyperinsulinemia is hypothesized to influence prostate cancer risk. Thus, we evaluated the association of circulating C-peptide, which is a marker of insulin secretion, and leptin, which is secreted in response to insulin and influences insulin sensitivity, with prostate cancer risk. We identified prostate cancer cases (n = 1,314) diagnosed a mean of 5.4 years after blood draw and matched controls (n = 1,314) in the Health Professionals Follow-up Study. Plasma C-peptide and leptin concentrations were measured by ELISA. Odds ratios (ORs) and 95 % confidence intervals (CI) were estimated taking into account the matching factors age and history of a PSA test before blood draw and further adjusting for body mass index, diabetes, and other factors. Neither C-peptide (quartile [Q]4 vs. Q1: OR 1.05, 95 % CI 0.82-1.34, p-trend = 0.95) nor leptin (Q4 vs. Q1: OR 0.85, 95 % CI 0.65-1.12, p-trend = 0.14) was associated with prostate cancer risk. Further, neither was associated with risk of advanced or lethal disease (n = 156 cases; C-peptide: Q4 vs. Q1, OR 1.18, 95 % CI 0.69-2.03, p-trend = 0.78; leptin: Q4 vs. Q1, OR 0.74, 95 % CI 0.41-1.36, p-trend = 0.34). In this large prospective study, circulating C-peptide and leptin concentrations were not clearly associated with risk of prostate cancer overall or aggressive disease. Well into the PSA era, our findings do not appear to be supportive of the hypothesis that hyperinsulinemia influences risk of total or aggressive prostate cancer. C1 [Lai, Gabriel Y.; Peskoe, Sarah B.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Bethesda, MD 21205 USA. [Lai, Gabriel Y.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA. [Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.] Harvard Univ, Sch Med, Dept Med, Channing Div Network Med, Boston, MA USA. [Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Pollak, Michael N.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Pollak, Michael N.] McGill Univ, Jewish Gen Hosp, Lady David Inst Med Res, Montreal, PQ H3T 1E2, Canada. [Platz, Elizabeth A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Platz, Elizabeth A.] James Buchanan Brady Urol Inst, Baltimore, MD USA. [Platz, Elizabeth A.] Johns Hopkins Sch Med, Dept Urol, Baltimore, MD USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Rm E6132,615 N Wolfe St, Bethesda, MD 21205 USA. EM eplatz@jhsph.edu FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services [R01 CA55075, R01 CA141298, R01 CA133891, T32 CA009314] FX We would like to thank the participants and staff of the Health Professionals Follow-up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. In addition, this study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Certain data used in this publication were obtained from the DPH. The authors assume full responsibility for analyses and interpretation of these data. We also thank Yuzhen Tao in the Dr. Pollak's laboratory for running the assays. This work was funded by Public Health Service research Grants R01 CA55075, R01 CA141298, and R01 CA133891 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. Gabriel Lai was supported by a National Research Service Award T32 CA009314 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 36 TC 9 Z9 9 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2014 VL 25 IS 5 BP 625 EP 632 DI 10.1007/s10552-014-0369-3 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AF0MU UT WOS:000334409500009 PM 24664287 ER PT J AU Rieder, D Ploner, C Krogsdam, AM Stocker, G Fischer, M Scheideler, M Dani, C Amri, EZ Mueller, WG McNally, JG Trajanoski, Z AF Rieder, Dietmar Ploner, Christian Krogsdam, Anne M. Stocker, Gernot Fischer, Maria Scheideler, Marcel Dani, Christian Amri, Ez-Zoubir Mueller, Waltraud G. McNally, James G. Trajanoski, Zlatko TI Co-expressed genes prepositioned in spatial neighborhoods stochastically associate with SC35 speckles and RNA polymerase II factories SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE Nuclear organization; Spatial gene positioning; Splicing speckles; Transcription factories ID TRANSCRIPTION FACTORIES; CHROMATIN-STRUCTURE; DROSOPHILA GENOME; NUCLEAR SPECKLES; HUMAN-CELLS; ORGANIZATION; CLUSTERS; DOMAINS; ELONGATION; EXPRESSION AB Chromosomally separated, co-expressed genes can be in spatial proximity, but there is still debate about how this nuclear organization is achieved. Proposed mechanisms include global genome organization, preferential positioning of chromosome territories, or gene-gene sharing of various nuclear bodies. To investigate this question, we selected a set of genes that were co-expressed upon differentiation of human multipotent stem cells. We applied a novel multi-dimensional analysis procedure which revealed that prior to gene expression, the relative position of these genes was conserved in nuclei. Upon stem cell differentiation and concomitant gene expression, we found that co-expressed genes were closer together. In addition, we found that genes in the same 1-mu m-diameter neighborhood associated with either the same splicing speckle or to a lesser extent with the same transcription factory. Dispersal of speckles by overexpression of the serine-arginine (SR) protein kinase cdc2-like kinase Clk2 led to a significant drop in the number of genes in shared neighborhoods. We demonstrate quantitatively that the frequencies of speckle and factory sharing can be explained by assuming stochastic selection of a nuclear body within a restricted sub-volume defined by the original global gene positioning present prior to gene expression. We conclude that the spatial organization of these genes is a two-step process in which transcription-induced association with nuclear bodies enhances and refines a pre-existing global organization. C1 [Rieder, Dietmar; Krogsdam, Anne M.; Stocker, Gernot; Fischer, Maria; Trajanoski, Zlatko] Med Univ Innsbruck, Div Bioinformat, Bioctr, A-6020 Innsbruck, Austria. [Ploner, Christian] Med Univ Innsbruck, Dept Plast Reconstruct & Aesthet Surg, A-6020 Innsbruck, Austria. [Scheideler, Marcel] Graz Univ Technol, Inst Genom & Bioinformat, A-8010 Graz, Austria. [Dani, Christian; Amri, Ez-Zoubir] Univ Nice Sophia Antipolis, CNRS, Inst Dev Biol & Canc, Fac Med, F-06189 Nice, France. [Mueller, Waltraud G.; McNally, James G.] NCI, NIH, Lab Receptor Biol & Gene Express, Bethesda, MD USA. RP Trajanoski, Z (reprint author), Med Univ Innsbruck, Div Bioinformat, Bioctr, Innrain 80, A-6020 Innsbruck, Austria. EM zlatko.trajanoski@i-med.ac.at RI DANI, Christian/G-3639-2014; OI Dani, Christian/0000-0003-3228-0230; amri, Ez-Zoubir/0000-0001-8426-5396 FU Austrian Federal Ministry for Science and Research; Austrian Science Funds FX This work was supported by the Austrian Federal Ministry for Science and Research, Project GEN-AU BIN and the Austrian Science Funds, Projects SFB Lipotoxicity and SFB Cell proliferation and cell death in tumors. We thank Martina Wick, Claudia Neuhold, and Nicole Golob for support in the lab, and Hubert Hackl for statistical advice and valuable comments. NR 68 TC 14 Z9 14 U1 0 U2 7 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X EI 1420-9071 J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAY PY 2014 VL 71 IS 9 BP 1741 EP 1759 DI 10.1007/s00018-013-1465-3 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AF0RM UT WOS:000334421700011 PM 24026398 ER PT J AU Wirth, CC Glushakova, S Scheuermayer, M Repnik, U Garg, S Schaack, D Kachman, MM Weissbach, T Zimmerberg, J Dandekar, T Griffiths, G Chitnis, CE Singh, S Fischer, R Pradel, G AF Wirth, Christine C. Glushakova, Svetlana Scheuermayer, Matthias Repnik, Urska Garg, Swati Schaack, Dominik Kachman, Marika M. Weissbach, Tim Zimmerberg, Joshua Dandekar, Thomas Griffiths, Gareth Chitnis, Chetan E. Singh, Shailja Fischer, Rainer Pradel, Gabriele TI Perforin-like protein PPLP2 permeabilizes the red blood cell membrane during egress of Plasmodium falciparum gametocytes SO CELLULAR MICROBIOLOGY LA English DT Article ID MALARIA PARASITE RELEASE; INFECTED ERYTHROCYTES; PORE FORMATION; OSMIOPHILIC BODIES; XANTHURENIC ACID; MOSQUITO MIDGUT; HOST; TRANSMISSION; COMPLEMENT; GENE AB Egress of malaria parasites from the host cell requires the concerted rupture of its enveloping membranes. Hence, we investigated the role of the plasmodial perforin-like protein PPLP2 in the egress of Plasmodium falciparum from erythrocytes. PPLP2 is expressed in blood stage schizonts and mature gametocytes. The protein localizes in vesicular structures, which in activated gametocytes discharge PPLP2 in a calcium-dependent manner. PPLP2 comprises a MACPF domain and recombinant PPLP2 has haemolytic activities towards erythrocytes. PPLP2-deficient [PPLP2(-)] merozoites show normal egress dynamics during the erythrocytic replication cycle, but activated PPLP2(-) gametocytes were unable to leave erythrocytes and stayed trapped within these cells. While the parasitophorous vacuole membrane ruptured normally, the activated PPLP2(-) gametocytes were unable to permeabilize the erythrocyte membrane and to release the erythrocyte cytoplasm. In consequence, transmission of PPLP2(-) parasites to the Anopheles vector was reduced. Pore-forming equinatoxin II rescued both PPLP2(-) gametocyte exflagellation and parasite transmission. The pore sealant Tetronic 90R4, on the other hand, caused trapping of activated wild-type gametocytes within the enveloping erythrocytes, thus mimicking the PPLP2(-) loss-of-function phenotype. We propose that the haemolytic activity of PPLP2 is essential for gametocyte egress due to permeabilization of the erythrocyte membrane and depletion of the erythrocyte cytoplasm. C1 [Wirth, Christine C.; Weissbach, Tim; Fischer, Rainer; Pradel, Gabriele] Rhein Westfal TH Aachen, Inst Mol Biotechnol, D-52074 Aachen, Germany. [Glushakova, Svetlana; Kachman, Marika M.; Zimmerberg, Joshua] Eunice Kennedy Schriver Natl Inst Child Hlth & Hu, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Scheuermayer, Matthias] Univ Wurzburg, Res Ctr Infect Dis, D-97080 Wurzburg, Germany. [Repnik, Urska; Griffiths, Gareth] Univ Oslo, Dept Biosci, N-0316 Oslo, Norway. [Garg, Swati; Chitnis, Chetan E.; Singh, Shailja] Int Ctr Genet Engn & Biotechnol ICGEB, Malaria Grp, New Delhi 110067, India. [Schaack, Dominik; Dandekar, Thomas] Univ Wurzburg, Dept Bioinformat, D-97074 Wurzburg, Germany. [Singh, Shailja] Shiv Nadar Univ, Dept Life Sci, Tehsil Dadri 203207, Gautam Budh Nag, India. [Fischer, Rainer; Pradel, Gabriele] Fraunhofer Inst Mol Biol & Appl Ecol, D-50274 Aachen, Germany. RP Pradel, G (reprint author), Rhein Westfal TH Aachen, Inst Mol Biotechnol, Worringerweg 1, D-52074 Aachen, Germany. EM gabriele.pradel@molbiotech.rwth-aachen.de RI WeiSSbach, Tim/L-1575-2015; Dandekar, Thomas/A-4431-2017 OI Dandekar, Thomas/0000-0003-1886-7625 FU Deutsche Forschungsgemeinschaft [SPP1580] FX We thank Inga Siden-Kiamos (FORTH Institute of Molecular Biology and Biotechnology Crete) for helpful discussions. We are grateful to Gregor Anderluh (University of Ljubljana) for providing equinatoxin II, to Pietro Alano (Istituto Superiore di Sanita Rome) for providing parasite line Pfg377(-) and to Kim Williamson (Loyola University Chicago) for providing vector pIH. We further thank the team of Georg Krohne (University of Wurzburg) and the Electron Microscopy Unit for Biological Sciences (University of Oslo) for support with the electron microscopy-related work. The authors acknowledge funding by the priority programme SPP1580 of the Deutsche Forschungsgemeinschaft (G.P. and G.G.). NR 73 TC 24 Z9 24 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 EI 1462-5822 J9 CELL MICROBIOL JI Cell Microbiol. PD MAY PY 2014 VL 16 IS 5 SI SI BP 709 EP 733 DI 10.1111/cmi.12288 PG 25 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA AE9IF UT WOS:000334320800011 PM 24602217 ER PT J AU Ippolito, E Farsetti, P Boyce, AM Corsi, A De Maio, F Collins, MT AF Ippolito, Ernesto Farsetti, Pasquale Boyce, Alison M. Corsi, Alessandro De Maio, Fernando Collins, Michael T. TI Radiographic Classification of Coronal Plane Femoral Deformities in Polyostotic Fibrous Dysplasia SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MCCUNE-ALBRIGHT SYNDROME; MECHANICAL AXIS DEVIATION; STIMULATORY G-PROTEIN; ACTIVATING MUTATIONS; NATURAL-HISTORY; PROXIMAL PART; LOWER-LIMBS; BONE; FEMUR; ABNORMALITIES AB Fibrous dysplasia of bone is a skeletal dysplasia with a propensity to affect the femur in its polyostotic form, leading to deformity, fracture, and pain. The proximal femur is most commonly involved with a tendency to distal progression, thereby producing the typical shepherd's crook deformity. However, there are few data on the spectrum and progression of femoral deformities in polyostotic fibrous dysplasia. The purposes of this study were (1) to develop a radiographic classification for polyostotic fibrous dysplasia; (2) to test this classification's intra- and interobserver reliability; and (3) to characterize the radiographic progression of polyostotic fibrous dysplasia in a population of patients with the condition who were treated with a variety of approaches at several centers. We retrospectively reviewed radiographs of 127 femurs from 84 adult patients affected by polyostotic fibrous dysplasia. Fifty-nine femurs had undergone one or more operations. The radiographs were evaluated in the coronal plane for neck-shaft angle and angular deformities along the whole femoral shaft down to the distal epiphysis. Four observers evaluated each film two times at intervals; intra- and interobserver reliability testing was performed using the kappa statistic. Eighty-nine femurs (70%) were available for followup to evaluate for progression at a mean of 10 years (range, 6-20 years). Six reproducible patterns of deformity were identified in both untreated and operated femurs: type 1 (24%), normal neck-shaft angle with altered shape of the proximal femur; type 2 (6%), isolated coxa valga with neck-shaft angle > 140A degrees; type 3 (7%), isolated coxa vara with neck-shaft angle < 120A degrees; type 4 (20%), lateral bowing of the proximal half of the femur associated with normal neck-shaft angle; type 5 (14%), like in type 4 but associated with coxa valga; and type 6 (29%), like in type 4 but associated with coxa vara. Interobserver and intraoberver kappa values were excellent, ranging from 0.83 to 0.87. In 46 of the 89 femurs (52%) for which longitudinal radiographic documentation was available, there was progressive worsening of the original deformity, although the pattern remained the same; types 1 and 2 tended not to progress, whereas types 3 to 6 did. A reproducible radiographic classification of polyostotic fibrous dysplasia-associated femoral deformities is proposed, which can serve as a tool for assessing and treating these deformities. After reviewing the radiographs of 127 femurs, we identified six reproducible patterns of femoral deformities. Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Ippolito, Ernesto; Farsetti, Pasquale; De Maio, Fernando] Univ Roma Tor Vergata, Dept Orthopaed Surg, PTV, I-00133 Rome, Italy. [Boyce, Alison M.; Collins, Michael T.] NIH, Bethesda, MD 20892 USA. [Corsi, Alessandro] Univ Roma La Sapienza, Dept Mol Med, I-00185 Rome, Italy. RP Ippolito, E (reprint author), Univ Roma Tor Vergata, Dept Orthopaed Surg, PTV, Viale Oxford 81, I-00133 Rome, Italy. EM ippolito@med.uniroma2.it NR 23 TC 9 Z9 9 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 2014 VL 472 IS 5 BP 1558 EP 1567 DI 10.1007/s11999-013-3380-1 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AE7LV UT WOS:000334180400032 PM 24249535 ER PT J AU Kennard, BD Brown, LT Hawkins, L Risi, A Radcliffe, J Emslie, GJ Mayes, TL King, JD Foxwell, AA Buyukdura, J Bethel, J Naar-King, S Xu, JH Lee, SS Garvie, P London, C Tanney, M Thornton, S AF Kennard, Beth D. Brown, Larry T. Hawkins, Linda Risi, Andrea Radcliffe, Jerilynn Emslie, Graham J. Mayes, Taryn L. King, Jessica D. Foxwell, Aleksandra A. Buyukdura, Jeylan Bethel, James Naar-King, Sylvie Xu, Jiahong Lee, Sonia S. Garvie, Patricia London, Carla Tanney, Mary Thornton, Sarah CA Adolescent Trials Network HIV AIDS TI Development and Implementation of Health and Wellness CBI for Individuals With Depression and HIV SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE cognitive behavioral therapy; major depressive disorder; HIV; adherence; health ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; MEDICATION ADHERENCE; ADOLESCENT DEPRESSION; QUICK INVENTORY; CHILDREN; PSYCHOTHERAPY; DISORDERS; SYMPTOMATOLOGY; MANAGEMENT AB Rates of depression are reported to be between 22% to 33% in adults with HIV, which is double that of the general population. Depression negatively affects treatment adherence and health outcomes of those with medical illnesses. Further, it has been shown in adults that reducing depression may improve both adherence and health outcomes. To address the issues of depression, and nonadherence, Health and Wellness (H&W) cognitive behavioral therapy (CBT) and medication management (MM) treatment strategies have been developed specifically for youth living with both HIV and depression. H&W CBT is based on other studies with uninfected youth and upon research on adults with HIV. H&W CBT uses problem solving, motivational interviewing and cognitive-behavioral strategies to decrease adherence obstacles and increase wellness. The intervention is delivered in 14 planned sessions over a 6-month period, with three different stages of CBT. This paper summarizes the feasibility and acceptability data from an open depression trial with 8 participants, 16 to 24 years of age, diagnosed with HIV and with a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of depression, conducted at two treatment sites in the Adolescent Trials Network (ATN). Both therapists and subjects completed a Session Evaluation Form (SPF) after each session, and results were strongly favorable. Results from The Quick Inventory of Depressive Symptomatology Clinician (QEDS-C) also showed noteworthy improvement in depression severity. A clinical case vignette illustrates treatment response. Further research will examine the use of H&W CBT in a larger trial of youth diagnosed with both HIV and depression. C1 [Kennard, Beth D.; Emslie, Graham J.; Mayes, Taryn L.; King, Jessica D.; Foxwell, Aleksandra A.; Buyukdura, Jeylan] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Brown, Larry T.] Brown Univ, Rhode Isl Hosp, Providence, RI 02912 USA. [Hawkins, Linda; Radcliffe, Jerilynn; Tanney, Mary] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Hawkins, Linda; Radcliffe, Jerilynn; Tanney, Mary] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Risi, Andrea] Univ S Florida, Silver Child Dev Ctr, Tampa, FL 33620 USA. [Bethel, James; Xu, Jiahong; Thornton, Sarah] WESTAT Corp, Rockville, MD 20850 USA. [Naar-King, Sylvie] Wayne State Univ, Detroit, MI 48202 USA. [Lee, Sonia S.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. [Garvie, Patricia; London, Carla] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Kennard, BD (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM beth.kennard@utsouthwestern.edu FU NICHD NIH HHS [U01 HD040533, U01 HD040474, U01 HD040481] NR 31 TC 6 Z9 6 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 EI 1878-187X J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD MAY PY 2014 VL 21 IS 2 BP 237 EP 246 PG 10 WC Psychology, Clinical SC Psychology GA AE7AZ UT WOS:000334150400013 PM 24795524 ER PT J AU Verkoczy, L Diaz, M AF Verkoczy, Laurent Diaz, Marilyn TI Autoreactivity in HIV-1 broadly neutralizing antibodies: implications for their function and induction by vaccination SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE immune tolerance; autoreactivity; polyreactivity; broadly neutralizing antibodies; somatic hypermutation ID B-CELL RESPONSES; SYSTEMIC-LUPUS-ERYTHEMATOSUS; MEMBRANE-PROXIMAL REGION; MONOCLONAL-ANTIBODIES; ANTIRETROVIRAL THERAPY; POTENT NEUTRALIZATION; ENVELOPE PROTEIN; IMMUNOGEN DESIGN; STRUCTURAL BASIS; KNOCKIN MICE AB Purpose of review This review discusses progress in understanding the impact of immune tolerance on inducing broadly neutralizing antibodies (bnAbs), and how such knowledge can be incorporated into novel immunization approaches. Recent findings Over 120 bnAbs have now been isolated, all of which bear unusual features associated with host tolerance controls, but paradoxically may also be required for their function. Evidence that poly/autoreactivity of membrane proximal external region bnAbs can invoke such controls has been demonstrated by knock-in technology, highlighting its potential for studying the impact of tolerance in the generation of bnAb lineages to distinct HIV-1 envelope targets. The requirement for extensive affinity maturation in developing neutralization breadth/potency during infection is being examined, and similar studies in the setting of immunization will be aided by testing novel vaccine approaches in knock-in models that either selectively express reverted V(D)J rearrangements, or unrearranged germline segments, from which bnAb lineages originate. It is increasingly apparent that immune tolerance, sometimes invoked by self-reactivity that overlaps with bnAb epitope specificity, adds to a formidable set of roadblocks impeding bnAb induction. The path to an effective HIV-1 vaccine may thus benefit from a deeper understanding of host controls, including categorizing those that are unique or common at distinct bnAb targets, and ranking those most feasible to overcome by immunization. Ultimately, such emerging information will be critical to incorporate into new vaccine approaches that can be tested in human trials. C1 [Verkoczy, Laurent] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Diaz, Marilyn] NIEHS, Res Triangle Pk, NC 27709 USA. RP Verkoczy, L (reprint author), Duke Univ, Med Ctr, Duke Human Vaccine Inst, 2 Genome Court,3015 MSRBII Bldg, Durham, NC 27710 USA. EM laurent.verkoczy@duke.edu FU NIH, National Institute of Environmental Health Sciences, Division of Intramural Research [Z01 ES101603]; Center for HIV/AIDS Vaccine Immunogen-Discovery (CHAVI-ID) [UM1 AI100645]; NIH [R01 AI087202]; Collaboration for AIDS Discovery Vaccine Development Center grant from the Bill and Melinda Gates Foundation FX This work was supported by NIH, National Institute of Environmental Health Sciences, Division of Intramural Research project Z01 ES101603, the Center for HIV/AIDS Vaccine Immunogen-Discovery (CHAVI-ID) grant UM1 AI100645, NIH grant R01 AI087202 and a Collaboration for AIDS Discovery Vaccine Development Center grant from the Bill and Melinda Gates Foundation. NR 108 TC 18 Z9 19 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2014 VL 9 IS 3 BP 224 EP 234 DI 10.1097/COH.0000000000000049 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AE9BM UT WOS:000334298900005 PM 24714565 ER PT J AU Petrovas, C Koup, RA AF Petrovas, Constantinos Koup, Richard A. TI T follicular helper cells and HIV/SIV-specific antibody responses SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE simian immunodeficiency virus; T follicular helper cells; antibodies; HIV ID GERMINAL CENTER B; HIV-INFECTION; VIRAL-INFECTION; DENDRITIC CELLS; TFH CELLS; DIFFERENTIATION; ANTIGEN; EFFECTOR; GENERATION; EXPRESSION AB Purpose of review Here, we describe recent data on the characterization of follicular helper CD4 T cells (Tfh) and the dynamics of Tfh-B-cell interactions in HIV and simian immunodeficiency virus (SIV) infection and discuss important aspects of these interactions that need to be addressed in order to design more effective vaccines that elicit broadly neutralizing antibodies. Recent findings Mouse, nonhuman primate (NHP) and human Tfh cells share phenotypic, functional and molecular programs, which are regulated by local signals and spatiotemporal parameters. Chronic HIV/SIV infection results in accumulation of Tfh, germinal center B cells and circulating virus-specific immunoglobulins in some individuals. However, most HIV/SIV-infected individuals do not mount broadly neutralizing antibodies, pointing to functional defects in Tfh cells in chronic HIV/SIV infection. The susceptibility of particular CD4 T-cell populations to HIV/SIV infection within lymph nodes notably impacts upon the dynamics of Tfh-germinal center B-cell interactions. Some circulating CD4 T cells share certain characteristics with Tfh cells, however, their direct origin from germinal center Tfh cells is not clear. There are many ways in which HIV and SIV influence the complex signals and mechanisms regulating the development of Tfh cells and their interactions with germinal center B cells. Understanding the biology of Tfh cells will be necessary to appropriately recruit these cells during vaccination with the goal of stimulating a more broad and potent neutralizing antibody response. C1 [Petrovas, Constantinos; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Koup, RA (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM rkoup@mail.nih.gov FU Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health; Bill and Melinda Gates Foundation [OPP1032325] FX This research was supported by the Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health and CAVD grant #OPP1032325 from the Bill and Melinda Gates Foundation. NR 70 TC 11 Z9 11 U1 0 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2014 VL 9 IS 3 BP 235 EP 241 DI 10.1097/COH.0000000000000053 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AE9BM UT WOS:000334298900006 PM 24670319 ER PT J AU Ueda, Y Nishimura, J Murakami, Y Kajigaya, S Kinoshita, T Kanakura, Y Young, NS AF Ueda, Yasutaka Nishimura, Jun-ichi Murakami, Yoshiko Kajigaya, Sachiko Kinoshita, Taroh Kanakura, Yuzuru Young, Neal S. TI Paroxysmal nocturnal hemoglobinuria with copy number-neutral 6pLOH in GPI (+) but not in GPI (-) granulocytes SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE array comparative genomic hybridization; bone marrow failure syndromes; clonal evolution; loss of heterozygosity; paroxysmal nocturnal hemoglobinuria ID NATURAL-KILLER-CELLS; JAPANESE PATIENTS; MUTATION; ALLELES AB Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired bone marrow disorder caused by expansion of a clone of hematopoietic cells lacking glycosylphosphatidylinositol (GPI)-anchored membrane proteins. Multiple lines of evidence suggest immune attack on normal hematopoietic stem cells provides a selective growth advantage to PNH clones. Recently, frequent loss of HLA alleles associated with copy number-neutral loss of heterozygosity in chromosome 6p (CN-6pLOH) in aplastic anemia (AA) patients was reported, suggesting that AA hematopoiesis 'escaped' from immune attack by loss of HLA alleles. We report here the first case of CN-6pLOH in a Japanese PNH patient only in GPI-anchored protein positive (59%) granulocytes, but not in GPI-anchored protein negative (41%) granulocytes. CN-6pLOH resulted in loss of the alleles A*02:06-DRB1*15:01-DQB1*06:02, which have been reported to be dominant in Japanese PNH patients. Our patient had maintained nearly normal blood count for several years. Our case supports the hypothesis that a hostile immune environment drives selection of resistant hematopoietic cell clones and indicates that clonal evolution may occur also in normal phenotype (non-PNH) cells in some cases. C1 [Ueda, Yasutaka; Kajigaya, Sachiko; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Nishimura, Jun-ichi; Kanakura, Yuzuru] Osaka Univ, Grad Sch Med, Dept Hematol & Oncol, Osaka, Japan. [Murakami, Yoshiko; Kinoshita, Taroh] Osaka Univ, Microbial Dis Res Inst, Dept Immunoregulat, Osaka, Japan. [Murakami, Yoshiko; Kinoshita, Taroh] Osaka Univ, WPI Immunol Frontier Res Ctr, Dept Immunoglycobiol, Osaka, Japan. RP Ueda, Y (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10-CRC,Rm 3E-5216,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ueday2@nhlbi.nih.gov RI Kinoshita, Taroh/C-7353-2009 FU NIH; NHLBI; Ministry of Education, Culture, Sports, Science and Technology of Japan FX This research was supported by the Intramural Research Program of the NIH, the NHLBI, and in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors thank Satoru Hayashi for excellent technical assistance. NR 13 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 MAY PY 2014 VL 92 IS 5 BP 450 EP 453 DI 10.1111/ejh.12253 PG 4 WC Hematology SC Hematology GA AE8QX UT WOS:000334267500012 PM 24931618 ER PT J AU Cistaro, A Pagani, M Montuschi, A Calvo, A Moglia, C Canosa, A Restagno, G Brunetti, M Traynor, B Nobili, F Carrara, G Fania, P Lopiano, L Valentini, M Chio, A AF Cistaro, Angelina Pagani, Marco Montuschi, Anna Calvo, Andrea Moglia, Cristina Canosa, Antonio Restagno, Gabriella Brunetti, Maura Traynor, Bryan J. Nobili, Flavio Carrara, Giovanna Fania, Piercarlo Lopiano, Leonardo Valentini, M. Consuelo Chio, Adriano TI The metabolic signature of C9ORF72-related ALS: FDG PET comparison with nonmutated patients SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE Amyotrophic lateral sclerosis; C9ORF72 gene; FDG PET ID AMYOTROPHIC-LATERAL-SCLEROSIS; HEXANUCLEOTIDE REPEAT EXPANSION; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; CLINICAL CHARACTERISTICS; C9ORF72; SCHIZOPHRENIA; CRITERIA AB Recently, a GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene, located on chromosome 9p21 has been demonstrated to be the commonest cause of familial amyotrophic lateral sclerosis (ALS) and to account for 5 to 10 % of apparently sporadic ALS. Relatively little is known about the brain metabolism profile of patients carrying the expansion. Our aim was to identify the [F-18]FDG PET profile in ALS patients with the C9ORF72 expansion (C9ORF72-ALS). Fifteen C9ORF72-ALS patients were compared with 12 patients with ALS and comorbid frontotemporal dementia (FTD) without the C9ORF72 expansion (ALS-FTD) and 30 cognitively normal patients with ALS without mutations of ALS-related genes (sALS). The three groups were then cross-matched to 40 neurologically normal controls. All patients underwent FDG PET within 4 months of diagnosis. The C9ORF72-ALS patients compared with the sALS patients showed significant hypometabolism in the anterior and posterior cingulate cortex, insula, caudate and thalamus, the left frontal and superior temporal cortex, and hypermetabolism in the midbrain, bilateral occipital cortex, globus pallidus and left inferior temporal cortex. The ALS-FTD patients compared with the sALS patients showed more limited hypometabolic areas, including the orbitofrontal, prefrontal, anterior cingulate and insular cortex, and hypermetabolic areas, including the bilateral occipital cortex, the left precentral and postcentral cortex and superior temporal gyrus. The C9ORF72-ALS patients compared with the ALS-FTD patients showed hypometabolism in the left temporal cortex. ALS patients with the C9ORF72 hexanucleotide repeat expansion had a more widespread central nervous system involvement than ALS patients without genetic mutations, with or without comorbid FTD, consistent with their more severe clinical picture. C1 [Cistaro, Angelina; Fania, Piercarlo] IRMET SpA, Positron Emiss Tomog Ctr, Turin, Italy. [Pagani, Marco] CNR, Inst Cognit Sci & Technol, Rome, Italy. [Pagani, Marco] Karolinska Hosp, Dept Nucl Med, S-10401 Stockholm, Sweden. [Montuschi, Anna; Calvo, Andrea; Moglia, Cristina; Canosa, Antonio; Lopiano, Leonardo; Chio, Adriano] Univ Turin, Rita Levi Montalcini Dept Neurosci, Turin, Italy. [Calvo, Andrea; Lopiano, Leonardo; Chio, Adriano] Neurosci Inst Turin, Turin, Italy. [Restagno, Gabriella; Brunetti, Maura] Azienda Osped Citta Salute & Sci, Dept Clin Pathol, Mol Genet Unit, Turin, Italy. [Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Nobili, Flavio] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Clin Neurophysiol Unit, Genoa, Italy. [Carrara, Giovanna; Valentini, M. Consuelo] Azienda Osped Citta Salute & Sci, Dept Neuroradiol, Turin, Italy. [Chio, Adriano] ALS Ctr, Rita Levi Montalcini Dept Neurosci, I-10126 Turin, Italy. RP Chio, A (reprint author), ALS Ctr, Rita Levi Montalcini Dept Neurosci, I-10126 Turin, Italy. EM achio@usa.net RI Calvo, Andrea/K-4141-2016; Moglia, Cristina/K-4142-2016; OI Calvo, Andrea/0000-0002-5122-7243; Moglia, Cristina/0000-0001-7377-7222; Chio, Adriano/0000-0001-9579-5341 FU Compagnia di San Paolo, Programma Neuroscienze; Ministero della Salute (Ricerca Sanitaria Finalizzata) [RF-2010-2309849]; European Community [259867]; Intramural Research Programmes of the National Institutes of Health (NIH); National Institute on Aging [Z01-AG000949-02] FX We thank the patients and the neurologically normal controls for their collaboration in this study. This work was supported in part by Compagnia di San Paolo, Programma Neuroscienze 2008-2009 (to M. Consuelo Valentini and A. Calvo), Ministero della Salute (Ricerca Sanitaria Finalizzata, 2010, grant RF-2010-2309849) (to A. Chio) European Community's Health Seventh Framework Programme (FP7/2007-2013 under grant agreement 259867) (to A. Chio); The Intramural Research Programmes of the National Institutes of Health (NIH); National Institute on Aging (Z01-AG000949-02) (to Bryan J. Traynor). NR 41 TC 20 Z9 23 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 EI 1619-7089 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD MAY PY 2014 VL 41 IS 5 BP 844 EP 852 DI 10.1007/s00259-013-2667-5 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AF0QA UT WOS:000334417900005 PM 24445987 ER PT J AU Romagnuolo, J Cotton, PB Durkalski, V Pauls, Q Brawman-Mintzer, O Drossman, DA Mauldin, P Orrell, K Williams, AW Fogel, EL Tarnasky, PR Aliperti, G Freeman, ML Kozarek, RA Jamidar, PA Wilcox, CM Serrano, J Elta, GH AF Romagnuolo, Joseph Cotton, Peter B. Durkalski, Valerie Pauls, Qi Brawman-Mintzer, Olga Drossman, Douglas A. Mauldin, Patrick Orrell, Kyle Williams, April W. Fogel, Evan L. Tarnasky, Paul R. Aliperti, Giuseppe Freeman, Martin L. Kozarek, Richard A. Jamidar, Priya A. Wilcox, C. Mel Serrano, Jose Elta, Grace H. TI Can patient and pain characteristics predict manometric sphincter of Oddi dysfunction in patients with clinically suspected sphincter of Oddi dysfunction? SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID FINDINGS TYPE-I; ENDOSCOPIC SPHINCTEROTOMY; BOTULINUM TOXIN; RECURRENT PANCREATITIS; BILIARY SPHINCTER; CHOLECYSTECTOMY; PRESENTATIONS; SCINTIGRAPHY; INJECTION; EFFICACY AB Background: Biliopancreatic-type postcholecystectomy pain, without significant abnormalities on imaging and laboratory test results, has been categorized as "suspected" sphincter of Oddi dysfunction (SOD) type III. Clinical predictors of "manometric" SOD are important to avoid unnecessary ERCP, but are unknown. Objective: To assess which clinical factors are associated with abnormal sphincter of Oddi manometry (SOM). Design: Prospective, cross-sectional. Setting: Tertiary. Patients: A total of 214 patients with suspected SOD type III underwent ERCP and pancreatic SOM (pSOM; 85% dual SOM), at 7 U. S. centers (from August 2008 to March 2012) as part of a randomized trial. Interventions: Pain and gallbladder descriptors, psychosocial/functional disorder questionnaires. Main Outcome Measurements: Abnormal SOM findings. Univariate and multivariate analyses assessed associations between clinical characteristics and outcome. Results: The cohort was 92% female with a mean age of 38 years. Baseline pancreatic enzymes were increased in 5%; 9% had minor liver enzyme abnormalities. Pain was in the right upper quadrant (RUQ) in 90% (48% also epigastric); 51% reported daily abdominal discomfort. Fifty-six took narcotics an average of 33 days (of the past 90 days). Less than 10% experienced depression or anxiety. Functional disorders were common. At ERCP, 64% had abnormal pSOM findings (34% both sphincters, 21% biliary normal), 36% had normal pSOM findings, and 75% had at least abnormal 1 sphincter. Demographic factors, gallbladder pathology, increased pancreatobiliary enzymes, functional disorders, and pain patterns did not predict abnormal SOM findings. Anxiety, depression, and poorer coping were more common in patients with normal SOM findings (not significant on multivariate analysis). Limitations: Generalizability. Conclusions: Patient and pain factors and psychological comorbidity do not predict SOM results at ERCP in suspected type III SOD. (Clinical Trial registration number: NCT00688662.) C1 [Romagnuolo, Joseph; Cotton, Peter B.; Durkalski, Valerie; Pauls, Qi; Brawman-Mintzer, Olga; Mauldin, Patrick; Williams, April W.] Med Univ S Carolina, Charleston, SC 29425 USA. [Drossman, Douglas A.] Univ N Carolina, Chapel Hill, NC USA. [Orrell, Kyle; Tarnasky, Paul R.] Digest Hlth Associates Texas, Dallas, TX USA. [Fogel, Evan L.] Indiana Univ, Indianapolis, IN 46204 USA. [Aliperti, Giuseppe] Midwest Therapeut Endoscopy, St Louis, MO USA. [Freeman, Martin L.] Univ Minnesota, Minneapolis, MN USA. [Kozarek, Richard A.] Virginia Mason, Seattle, WA USA. [Jamidar, Priya A.] Yale Univ, New Haven, CT USA. [Wilcox, C. Mel] Univ Alabama Birmingham, Birmingham, AL USA. [Serrano, Jose] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. [Elta, Grace H.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Romagnuolo, J (reprint author), Med Univ S Carolina, Div Gastroenterol & Hepatol, 25 Courtenay Dr,ART 7100A, Charleston, SC 29425 USA. EM romagnuo@musc.edu FU NIDDK [U01 DK074739] FX All authors disclosed no financial relationships relevant to this publication. Supported by NIDDK grant U01 DK074739. NR 26 TC 4 Z9 4 U1 3 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2014 VL 79 IS 5 BP 765 EP 772 DI 10.1016/j.gie.2013.11.037 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AE9BQ UT WOS:000334299300014 PM 24472759 ER PT J AU Segars, JH Parrott, EC Nagel, JD Guo, XC Gao, XH Birnbaum, LS Pinn, VW Dixon, D AF Segars, James H. Parrott, Estella C. Nagel, Joan D. Guo, Xiaoxiao Catherine Gao, Xiaohua Birnbaum, Linda S. Pinn, Vivian W. Dixon, Darlene TI Proceedings from the Third National Institutes of Health International Congress on Advances in Uterine Leiomyoma Research: comprehensive review, conference summary and future recommendations SO HUMAN REPRODUCTION UPDATE LA English DT Review DE NIH conference summary and comprehensive review; uterine leiomyoma; fibroids; clinical treatment; basic research; conference recommendations ID PROGESTERONE-RECEPTOR MODULATOR; GONADOTROPIN-RELEASING-HORMONE; SMOOTH-MUSCLE-CELLS; RANDOMIZED-CONTROLLED-TRIAL; FOCUSED ULTRASOUND SURGERY; ENDOTHELIAL GROWTH-FACTOR; BLACK WOMENS HEALTH; REPRODUCTIVE-TRACT LEIOMYOMATA; TYROSINE KINASE INHIBITOR; FUMARATE-HYDRATASE GENE AB Uterine fibroids are the most common gynecologic tumors in women of reproductive age yet the etiology and pathogenesis of these lesions remain poorly understood. Age, African ancestry, nulliparity and obesity have been identified as predisposing factors for uterine fibroids. Symptomatic tumors can cause excessive uterine bleeding, bladder dysfunction and pelvic pain, as well as associated reproductive disorders such as infertility, miscarriage and other adverse pregnancy outcomes. Currently, there are limited noninvasive therapies for fibroids and no early intervention or prevention strategies are readily available. This review summarizes the advances in basic, applied and translational uterine fibroid research, in addition to current and proposed approaches to clinical management as presented at the Advances in Uterine Leiomyoma Research: 3rd NIH International Congress. Congress recommendations and a review of the fibroid literature are also reported. This review is a report of meeting proceedings, the resulting recommendations and a literature review of the subject. The research data presented highlights the complexity of uterine fibroids and the convergence of ethnicity, race, genetics, epigenetics and environmental factors, including lifestyle and possible socioeconomic parameters on disease manifestation. The data presented suggest it is likely that the majority of women with uterine fibroids will have normal pregnancy outcomes; however, additional research is warranted. As an alternative to surgery, an effective long-term medical treatment for uterine fibroids should reduce heavy uterine bleeding and fibroid/uterine volume without excessive side effects. This goal has not been achieved and current treatments reduce symptoms only temporarily; however, a multi-disciplined approach to understanding the molecular origins and pathogenesis of uterine fibroids, as presented in this report, makes our quest for identifying novel targets for noninvasive, possibly nonsystemic and effective long-term treatment very promising. The Congress facilitated the exchange of scientific information among members of the uterine leiomyoma research and health-care communities. While advances in research have deepened our knowledge of the pathobiology of fibroids, their etiology still remains incompletely understood. Further needs exist for determination of risk factors and initiation of preventive measures for fibroids, in addition to continued development of new medical and minimally invasive options for treatment. C1 [Segars, James H.; Guo, Xiaoxiao Catherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD 20892 USA. [Parrott, Estella C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Gynecol Hlth & Dis Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Nagel, Joan D.; Pinn, Vivian W.] NIH, Off Res Womens Hlth, Off Director, DHHS, Bethesda, MD 20892 USA. [Gao, Xiaohua; Dixon, Darlene] NIEHS, Natl Toxicol Program NTP Lab, NTP, NIH,DHHS, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.] NIEHS, Off Director, NTP, NIH,DHHS, Res Triangle Pk, NC 27709 USA. RP Dixon, D (reprint author), NIEHS, Natl Toxicol Program NTP Lab, NTP, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM dixon@niehs.nih.gov FU Intramural Research Program of the NIEHS; NTP, NIH; Office of Research on Women's Health, NIH; Reproductive Sciences Branch; Intramural Research Program in Reproductive and Adult Endocrinology, NICHD, NIH FX The Congress was supported, in part, by the Intramural Research Program of the NIEHS and NTP, NIH; the Office of Research on Women's Health, NIH and the Reproductive Sciences Branch and the Intramural Research Program in Reproductive and Adult Endocrinology, NICHD, NIH. NR 293 TC 27 Z9 29 U1 2 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1355-4786 EI 1460-2369 J9 HUM REPROD UPDATE JI Hum. Reprod. Update PD MAY-JUN PY 2014 VL 20 IS 3 BP 309 EP 333 DI 10.1093/humupd/dmt058 PG 25 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AF4IP UT WOS:000334675600001 PM 24401287 ER PT J AU Vera, DM Hora, RA Murillo, A Wong, JF Torre, AJ Wang, D Boulay, D Hancock, K Katz, JM Ramos, M Loayza, L Quispe, J Reaves, EJ Bausch, DG Chowell, G Montgomery, JM AF Vera, Delphis M. Hora, Ricardo A. Murillo, Anarina Wong, Juan F. Torre, Armando J. Wang, David Boulay, Darbi Hancock, Kathy Katz, Jacqueline M. Ramos, Mariana Loayza, Luis Quispe, Jose Reaves, Erik J. Bausch, Daniel G. Chowell, Gerardo Montgomery, Joel M. TI Assessing the impact of public health interventions on the transmission of pandemic H1N1 influenza a virus aboard a Peruvian navy ship SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE Disease outbreak; influenza; military personnel; Peru; ships; transmission ID SEROLOGIC ASSAYS; OUTBREAK; VESSEL AB Background Limited data exist on transmission dynamics and effectiveness of control measures for influenza in confined settings. Objectives To investigate the transmission dynamics of a 2009 pandemic H1N1 influenza A outbreak aboard a Peruvian Navy ship and quantify the effectiveness of the implemented control measures. Methods We used surveillance data and a simple stochastic epidemic model to characterize and evaluate the effectiveness of control interventions implemented during an outbreak of 2009 pandemic H1N1 influenza A aboard a Peruvian Navy ship. Results The serological attack rate for the outbreak was 49.1%, with younger cadets and low-ranking officers at greater risk of infection than older, higher-ranking officers. Our transmission model yielded a good fit to the daily time series of new influenza cases by date of symptom onset. We estimated a reduction of 54.4% in the reproduction number during the period of intense control interventions. Conclusion Our results indicate that the patient isolation strategy and other control measures put in place during the outbreak reduced the infectiousness of isolated individuals by 86.7%. Our findings support that early implementation of control interventions can limit the spread of influenza epidemics in confined settings. C1 [Vera, Delphis M.; Hora, Ricardo A.; Wong, Juan F.; Torre, Armando J.; Ramos, Mariana; Reaves, Erik J.; Bausch, Daniel G.] US Naval Med Res Unit 6, Lima, Peru. [Murillo, Anarina; Chowell, Gerardo] Arizona State Univ, Tempe, AZ USA. [Wang, David; Boulay, Darbi; Hancock, Kathy; Katz, Jacqueline M.; Montgomery, Joel M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Loayza, Luis; Quispe, Jose] Peruvian Navy, Lima, Peru. [Bausch, Daniel G.] Tulane Univ, New Orleans, LA 70118 USA. [Chowell, Gerardo] NIH, Bethesda, MD 20892 USA. RP Vera, DM (reprint author), US Naval Med Res Unit 6, 3230 Lima Pl, Washington, DC 20521 USA. EM delphisv@gmail.com FU Grant GEIS [I0308_11_LI]; [847705.82000.25GB.B0016] FX This work was supported and funded by work unit No. 847705.82000.25GB.B0016 and Grant GEIS I0308_11_LI entitled "Transmission dynamics of influenza outbreaks in military ships: Assessing the efficacy of control measures." NR 29 TC 6 Z9 6 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1750-2640 EI 1750-2659 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD MAY PY 2014 VL 8 IS 3 BP 353 EP 359 DI 10.1111/irv.12240 PG 7 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA AE6PS UT WOS:000334116600011 PM 24506160 ER PT J AU Katz, SI AF Katz, Stephen I. TI Unity in Action SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID INVESTIGATIVE DERMATOLOGY C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NIAMSD, NIH, Bldg 31,Room 4C32,31 Ctr Dr, Bethesda, MD 20892 USA. EM katzs@mail.nih.gov NR 5 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 IS 5 BP 1184 EP 1186 DI 10.1038/jid.2014.135 PG 3 WC Dermatology SC Dermatology GA AF2VJ UT WOS:000334570300002 PM 24732327 ER PT J AU Pos, Z Spivey, TL Liu, H Sommariva, M Chen, JG Wunderlich, JR Parisi, G Tomei, S Ayotte, BD Stroncek, DF Malek, JA Robbins, PF Rivoltini, L Maio, M Chouchane, L Wang, E Marincola, FM AF Pos, Zoltan Spivey, Tara L. Liu, Hui Sommariva, Michele Chen, Jinguo Wunderlich, John R. Parisi, Giulia Tomei, Sara Ayotte, Ben D. Stroncek, David F. Malek, Joel A. Robbins, Paul F. Rivoltini, Licia Maio, Michele Chouchane, Lotfi Wang, Ena Marincola, Francesco M. TI Longitudinal Study of Recurrent Metastatic Melanoma Cell Lines Underscores the Individuality of Cancer Biology SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID GENETIC-HETEROGENEITY; COPY NUMBER; EVOLUTION; BREAST; MUTATIONS; AMPLIFICATION; CARCINOMA; DELETIONS; TUMORS; TRIAL AB Recurrent metastatic melanoma provides a unique opportunity to analyze disease evolution in metastatic cancer. Here, we followed up eight patients with an unusually prolonged history of metastatic melanoma, who developed a total of 26 recurrences over several years. Cell lines derived from each metastasis were analyzed by comparative genomic hybridization and global transcript analysis. We observed that conserved, patient-specific characteristics remain stable in recurrent metastatic melanoma even after years and several recurrences. Differences among individual patients exceeded within-patient lesion variability, both at the DNA copy number (P<0.001) and RNA gene expression level (P<0.001). Conserved patient-specific traits included expression of several cancer/testis antigens and the c-kit proto-oncogene throughout multiple recurrences. Interestingly, subsequent recurrences of different patients did not display consistent or convergent changes toward a more aggressive disease phenotype. Finally, sequential recurrences of the same patient did not descend progressively from each other, as irreversible mutations such as homozygous deletions were frequently not inherited from previous metastases. This study suggests that the late evolution of metastatic melanoma, which markedly turns an indolent disease into a lethal phase, is prone to preserve case-specific traits over multiple recurrences and occurs through a series of random events that do not follow a consistent stepwise process. C1 [Pos, Zoltan; Spivey, Tara L.; Liu, Hui; Sommariva, Michele; Chen, Jinguo; Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Pos, Zoltan] Semmelweis Univ, Hungarian Acad Sci, Lendulet Expt & Translat Immun Res Grp, H-1085 Budapest, Hungary. [Pos, Zoltan] Semmelweis Univ, Dept Genet Cell & Immunobiol, H-1085 Budapest, Hungary. [Spivey, Tara L.] NIH, Clin Res Training Program CRTP, Bethesda, MD 20892 USA. [Spivey, Tara L.] Rush Univ, Med Ctr, Dept Gen Surg, Chicago, IL 60612 USA. [Sommariva, Michele] Univ Milan, Dept Biomed Sci Hlth, Milan, Italy. [Wunderlich, John R.; Robbins, Paul F.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Parisi, Giulia; Maio, Michele] Ctr Riferimento Oncol, Canc Bioimmunotherapy Unit, Avian, Italy. [Tomei, Sara; Malek, Joel A.] Weill Cornell Med Coll Qatar, Dept Genet Med, Doha, Qatar. [Ayotte, Ben D.] No Michigan Univ, Dept Biol, Marquette, MI 49855 USA. [Stroncek, David F.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD USA. [Rivoltini, Licia] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Chouchane, Lotfi] Weill Cornell Med Coll Qatar, Doha, Qatar. [Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar. RP Marincola, FM (reprint author), Sidra Med & Res Ctr, Res Branch, Doha, Qatar. EM fmarincola@sidra.org RI Pos, Zoltan/C-3623-2014; Sommariva, Michele/C-1174-2017; OI Pos, Zoltan/0000-0002-2574-7616; Sommariva, Michele/0000-0002-7622-0996; coral, sandra/0000-0002-1308-3082; Rivoltini, Licia/0000-0002-2409-6225 FU Associazione Italiana per la Ricerca sul Cancro [IG 11746]; Regione Toscana "Regional Health Research Program"; Hungarian Academy of Sciences "Lendulet" [LP2012-49/2012] FX The study was supported in part by Associazione Italiana per la Ricerca sul Cancro, IG 11746, Regione Toscana "Regional Health Research Program 2009," and the Hungarian Academy of Sciences "Lendulet" Grant LP2012-49/2012. NR 36 TC 0 Z9 0 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 IS 5 BP 1389 EP 1396 DI 10.1038/jid.2013.495 PG 8 WC Dermatology SC Dermatology GA AF2VJ UT WOS:000334570300030 PM 24270663 ER PT J AU Okiyama, N Sugihara, T Yokozeki, H Kohsaka, H AF Okiyama, N. Sugihara, T. Yokozeki, H. Kohsaka, H. TI Murine models of autoimmune myositis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 3rd International Conference on Cutaneous Lupus Erythematosus CY MAY 06-08, 2013 CL Edinburgh, SCOTLAND C1 [Okiyama, N.; Sugihara, T.; Kohsaka, H.] Tokyo Med & Dent Univ, Dept Med & Rheumatol, Tokyo, Japan. [Okiyama, N.; Yokozeki, H.] Tokyo Med & Dent Univ, Dept Dermatol, Tokyo, Japan. [Okiyama, N.] NCI, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 IS 5 BP 1488 EP 1488 PG 1 WC Dermatology SC Dermatology GA AF2VJ UT WOS:000334570300076 ER PT J AU Barsell, AB Allawh, R Xiong, M Tamura, D Collins, M Steinberg, SM Khan, SG Hill, S Kraemer, KH DiGiovanna, II AF Barsell, A. B. Allawh, R. Xiong, M. Tamura, D. Collins, M. Steinberg, S. M. Khan, S. G. Hill, S. Kraemer, K. H. DiGiovanna, I. I. TI Bone abnormalities in trichothiodystrophy: Central osteosclerosis is a prognostic marker for increased risk of early death SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Barsell, A. B.; Allawh, R.; Xiong, M.; Tamura, D.; Steinberg, S. M.; Khan, S. G.; Kraemer, K. H.; DiGiovanna, I. I.] NCI, Bethesda, MD 20892 USA. [Barsell, A. B.; Allawh, R.] George Wash Univ Sch Med, Washington, DC USA. [Xiong, M.] Brown Univ Sch Med, Providence, RI USA. [Hill, S.] NIH, Bethesda, MD 20892 USA. [Collins, M.] NICDR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 428 BP S75 EP S75 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400427 ER PT J AU Cataisson, C Salcedo, R Shibuya, K Naik, S Wright, L Trinchieri, G Yuspa, SH AF Cataisson, C. Salcedo, R. Shibuya, K. Naik, S. Wright, L. Trinchieri, G. Yuspa, S. H. TI MyD88 signaling in both keratinocytes and T-cells contribute to skin carcinogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Cataisson, C.; Shibuya, K.; Wright, L.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Naik, S.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. [Salcedo, R.; Trinchieri, G.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 186 BP S32 EP S32 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400187 ER PT J AU Glatz, M Stone, K Milner, JD Kong, HH AF Glatz, M. Stone, K. Milner, J. D. Kong, H. H. TI Altered skin microbial communities associated with wet wrap therapy for severe eczema SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Glatz, M.; Kong, H. H.] NCI, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Stone, K.; Milner, J. D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 623 BP S109 EP S109 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400621 ER PT J AU Harden, JL Lewis, SM Pierson, KC Suarez-Farinas, M Lentini, T Ortenzio, F Zaba, LC Goldbach-Mansky, R Bowcock, AM Lowes, MA AF Harden, J. L. Lewis, S. M. Pierson, K. C. Suarez-Farinas, M. Lentini, T. Ortenzio, F. Zaba, L. C. Goldbach-Mansky, R. Bowcock, A. M. Lowes, M. A. TI CARD14 expression in dermal endothelial cells in psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Harden, J. L.; Lewis, S. M.; Pierson, K. C.; Suarez-Farinas, M.; Lentini, T.; Ortenzio, F.; Zaba, L. C.; Lowes, M. A.] Rockefeller Univ, Lab Investigat Dermatol, New York, NY 10021 USA. [Suarez-Farinas, M.] Rockefeller Univ, Ctr Clin & Translat Sci, New York, NY 10021 USA. [Goldbach-Mansky, R.] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA. [Bowcock, A. M.] Univ London Imperial Coll Sci Technol & Med, London, England. RI Suarez-Farinas, Mayte/I-3558-2012 OI Suarez-Farinas, Mayte/0000-0001-8712-3553 NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 119 BP S21 EP S21 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400120 ER PT J AU Heller, ER Khan, SG Tamura, D DiGiovanna, JJ Kraemer, KH AF Heller, E. R. Khan, S. G. Tamura, D. DiGiovanna, J. J. Kraemer, K. H. TI Mutations in TTDN1 are associated with a unique trichothiodystrophy phenotype SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Heller, E. R.; Khan, S. G.; Tamura, D.; DiGiovanna, J. J.; Kraemer, K. H.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 432 BP S75 EP S75 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400431 ER PT J AU Kim, J Duverger, O Hwang, J Morasso, M AF Kim, J. Duverger, O. Hwang, J. Morasso, M. TI Impact of DIx3 deficiency in isthmus/infundibulum for hair shaft development SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Kim, J.; Duverger, O.; Hwang, J.; Morasso, M.] NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 244 BP S42 EP S42 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400244 ER PT J AU Kim, J Ogawa, Y Siebenlist, U Udey, MC Morass, M AF Kim, J. Ogawa, Y. Siebenlist, U. Udey, M. C. Morass, M. TI IL-17A regulates inflammation in Dlx3-deficient murine skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Kim, J.; Morass, M.] NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. [Ogawa, Y.; Udey, M. C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Siebenlist, U.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 121 BP S21 EP S21 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400122 ER PT J AU Klover, P Thangapazham, R Kato, J Wang, J Li, S Anderson, SA Hoffmann, V McCart, E Nathan, N Moss, J Darling, TN AF Klover, P. Thangapazham, R. Kato, J. Wang, J. Li, S. Anderson, S. A. Hoffmann, V. McCart, E. Nathan, N. Moss, J. Darling, T. N. TI Sirolimus normalizes skin and dramatically reduces internal tumors in a mouse model of tuberous sclerosis complex (TSC) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Klover, P.; Thangapazham, R.; Wang, J.; Li, S.; McCart, E.; Nathan, N.; Darling, T. N.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Kato, J.; Nathan, N.; Moss, J.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Anderson, S. A.; Hoffmann, V.] NIH, Diagnost & Res Serv Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 454 BP S79 EP S79 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400453 ER PT J AU Kuschal, C DiGiovanna, JJ Tamura, D Khan, SG Edelman, D Meltzer, P Soppet, D Stephens, R Kraemer, KH AF Kuschal, C. DiGiovanna, J. J. Tamura, D. Khan, S. G. Edelman, D. Meltzer, P. Soppet, D. Stephens, R. Kraemer, K. H. TI Identification of novel susceptibility genes in trichothiodystrophy and xeroderma pigmentosum patients by use of exome sequencing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Kuschal, C.; DiGiovanna, J. J.; Tamura, D.; Khan, S. G.; Kraemer, K. H.] NCI, Derm Br, Bethesda, MD 20892 USA. [Edelman, D.; Meltzer, P.] NCI, Genet Br, Bethesda, MD 20892 USA. [Soppet, D.; Stephens, R.] NCI, Adv Biomed Comp Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 187 BP S32 EP S32 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400188 ER PT J AU Lessard, JC Kalinin, A Stepp, M Morasso, M AF Lessard, J. C. Kalinin, A. Stepp, M. Morasso, M. TI A role for the calcium-binding protein Calm4 in cell migration and wound healing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Lessard, J. C.; Kalinin, A.; Morasso, M.] NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. [Stepp, M.] George Washington Univ, Sch Med, Dept Anat & Cell Biol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 766 BP S134 EP S134 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400763 ER PT J AU Li, L Flower, B Yuspa, SH AF Li, L. Flower, B. Yuspa, S. H. TI IKK16 inhibits activation NF-kappa B and reduces expression of proinflammatory chemokines in keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Li, L.; Flower, B.; Yuspa, S. H.] NCI, LCBG, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 136 BP S23 EP S23 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400137 ER PT J AU Lim, YH Ovejero, D Sugarman, J Eichenfield, L Levy, M Collins, M Choate, KA AF Lim, Y. H. Ovejero, D. Sugarman, J. Eichenfield, L. Levy, M. Collins, M. Choate, K. A. TI Somatic activating mutations in HRAS and NRAS cause cutaneous skeletal hypophosphatemic syndrome SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Lim, Y. H.; Choate, K. A.] Yale Univ, Sch Med, New Haven, CT USA. [Ovejero, D.; Collins, M.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Sugarman, J.] UCSF, San Francisco, CA USA. [Eichenfield, L.] Univ Calif San Diego, San Diego, CA USA. [Levy, M.] Dell Childrens Med Ctr, Austin, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 467 BP S81 EP S81 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400466 ER PT J AU Mascia, F Schloemann, D Michalowski, A Yuspa, S AF Mascia, F. Schloemann, D. Michalowski, A. Yuspa, S. TI Transcriptional snapshot of the early consequences of EGFR ablation in the epidermis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Mascia, F.; Schloemann, D.; Michalowski, A.; Yuspa, S.] NCI, LCBG, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 129 BP S22 EP S22 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400130 ER PT J AU Naik, HB Steinberg, SM Kong, HH Cowen, EW AF Naik, H. B. Steinberg, S. M. Kong, H. H. Cowen, E. W. TI Botulinum toxin improves quality of life and may ameliorate pain associated with cutaneous leiomyomas SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Naik, H. B.; Steinberg, S. M.; Kong, H. H.; Cowen, E. W.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 533 BP S93 EP S93 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400532 ER PT J AU Nakrani, R Glatz, M Booher, C Steinberg, SM Kong, HH AF Nakrani, R. Glatz, M. Booher, C. Steinberg, S. M. Kong, H. H. TI Subjective component of SCORAD provides unique information when assessing atopic dermatitis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Nakrani, R.; Glatz, M.; Booher, C.; Steinberg, S. M.; Kong, H. H.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 326 BP S56 EP S56 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400325 ER PT J AU Okiyama, N Katz, SI AF Okiyama, N. Katz, S. I. TI Programmed cell death1 (PD-1) regulates the effector function of autoimmune CD8 T cells via the ligands expressed on target epidermal cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Okiyama, N.; Katz, S. I.] NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 018 BP S3 EP S3 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400019 ER PT J AU Ouchi, T Udey, MC AF Ouchi, T. Udey, M. C. TI EpCAM expressed by epidermal Langerhans cells modulates topical immunization to proteins SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Ouchi, T.; Udey, M. C.] NCI, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 021 BP S4 EP S4 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400022 ER PT J AU Palazzo, E Kellett, MD Gormley, A Bible, PW Pietroni, V Radoja, N Blumenberg, M Kim, J Cataisson, C Morasso, M AF Palazzo, E. Kellett, M. D. Gormley, A. Bible, P. W. Pietroni, V. Radoja, N. Blumenberg, M. Kim, J. Cataisson, C. Morasso, M. TI DIx3-PKC interplay drives skin differentiation by controlling cell cycle in keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Palazzo, E.; Kellett, M. D.; Gormley, A.; Bible, P. W.; Pietroni, V.; Radoja, N.; Kim, J.; Morasso, M.] NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. [Cataisson, C.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Blumenberg, M.] NYU, Dept Dermatol, New York, NY 10016 USA. RI Palazzo, Elisabetta/J-5287-2016 OI Palazzo, Elisabetta/0000-0002-0812-5524 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 380 BP S66 EP S66 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400379 ER PT J AU Sargen, MR Kanetsky, PA Newton-Bishop, J Hayward, N Mann, G Gruis, N Tucker, M Goldstein, A Bianchi-Scarra, G Puig, S Elder, DE AF Sargen, M. R. Kanetsky, P. A. Newton-Bishop, J. Hayward, N. Mann, G. Gruis, N. Tucker, M. Goldstein, A. Bianchi-Scarra, G. Puig, S. Elder, D. E. TI Histological features of superficial spreading melanoma are associated with and predictive of CDKN2A germline mutations SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Sargen, M. R.; Elder, D. E.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Sargen, M. R.; Kanetsky, P. A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Newton-Bishop, J.] Univ Leeds, Leeds, W Yorkshire, England. [Hayward, N.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Mann, G.] Westmead Millennium Inst, Sydney, NSW, Australia. [Gruis, N.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Tucker, M.; Goldstein, A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bianchi-Scarra, G.] Univ Genoa, Genoa, Italy. [Puig, S.] Univ Hosp Clin Barcelona, Barcelona, Spain. RI Tucker, Margaret/B-4297-2015; hayward, nicholas/C-1367-2015 OI hayward, nicholas/0000-0003-4760-1033 NR 0 TC 0 Z9 0 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 690 BP S121 EP S121 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400688 ER PT J AU Tsuji, G Okiyama, N Villarroel, V Katz, SI AF Tsuji, G. Okiyama, N. Villarroel, V. Katz, S. I. TI Epigenetic modulation via histone deacetylase (HDAC) 6 inhibition impairs CD8 T cell functions during skin inflammation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Tsuji, G.; Okiyama, N.; Villarroel, V.; Katz, S. I.] NCI, Derm Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 020 BP S4 EP S4 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400021 ER PT J AU Xiao, Y Williams, JS Brownell, I AF Xiao, Y. Williams, J. S. Brownell, I. TI Sonic hedgehog signaling is essential for touch dome Merkel cell development SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Xiao, Y.; Williams, J. S.; Brownell, I.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 277 BP S47 EP S47 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400276 ER PT J AU Xiao, Y Williams, JS Brownell, I AF Xiao, Y. Williams, J. S. Brownell, I. TI Hedgehog signaling creates a perineural stem cell niche essential for maintaining sensory touch domes in skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Xiao, Y.; Williams, J. S.; Brownell, I.] NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 246 BP S42 EP S42 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400246 ER PT J AU Zuo, RC Kuzmina, Z Naik, HB Pavletic, SZ Cowen, EW AF Zuo, R. C. Kuzmina, Z. Naik, H. B. Pavletic, S. Z. Cowen, E. W. TI Serum autoantibodies and cutaneous autoimmunity in chronic graft-versus-host disease SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Zuo, R. C.; Kuzmina, Z.; Naik, H. B.; Pavletic, S. Z.; Cowen, E. W.] NCI CCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2014 VL 134 SU 1 MA 068 BP S12 EP S12 PG 1 WC Dermatology SC Dermatology GA AF2RT UT WOS:000334560400069 ER PT J AU Miyagi, E Kao, S Yedavalli, V Strebel, K AF Miyagi, Eri Kao, Sandra Yedavalli, Venkat Strebel, Klaus TI CBF beta Enhances De Novo Protein Biosynthesis of Its Binding Partners HIV-1 Vif and RUNX1 and Potentiates the Vif-Induced Degradation of APOBEC3G SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 VIF; ANTIVIRAL ACTIVITY; VIRAL INFECTIVITY; ENZYME APOBEC3G; IDENTIFICATION; DOMAIN; GAG; TRANSCRIPTION; PROTEASOME AB Vif is a lentiviral accessory protein that regulates viral infectivity in part by inducing proteasomal degradation of APOBEC3G (A3G). Recently, CBF beta was found to facilitate Vif-dependent degradation of A3G. However, the exact role of CBF beta remains unclear. Several studies noted reduced Vif expression in CBF beta knockdown cells while others saw no significant impact of CBF beta on Vif stability. Here, we confirmed that CBF beta increases Vif steady-state levels. CBF beta affected expression of neither viral Gag nor Vpu protein, indicating that CBF beta regulates Vif expression posttranscriptionally. Kinetic studies revealed effects of CBF beta on both metabolic stability and the rate of Vif biosynthesis. These effects were dependent on the ability of CBF beta to interact with Vif. Importantly, at comparable Vif levels, CBF beta further enhanced A3G degradation, suggesting that CBF beta facilitates A3G degradation by increasing the levels of Vif and by independently augmenting the ability of Vif to target A3G for degradation. CBF beta also increased expression of RUNX1 by enhancing RUNX1 biosynthesis. Unlike Vif, however, CBF beta had no detectable effect on RUNX1 metabolic stability. We propose that CBF beta acts as a chaperone to stabilize Vif during and after synthesis and to facilitate interaction of Vif with cellular cofactors required for the efficient degradation of A3G. C1 [Miyagi, Eri; Kao, Sandra; Yedavalli, Venkat; Strebel, Klaus] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. EM kstrebel@nih.gov FU NIH, NIAID FX This work was supported by the Intramural Research Program of the NIH, NIAID, to K.S. NR 65 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2014 VL 88 IS 9 BP 4839 EP 4852 DI 10.1128/JVI.03359-13 PG 14 WC Virology SC Virology GA AE9TT UT WOS:000334353900021 PM 24522927 ER PT J AU Tabler, CO Lucera, MB Haqqani, AA McDonald, DJ Migueles, SA Connors, M Tilton, JC AF Tabler, Caroline O. Lucera, Mark B. Haqqani, Aiman A. McDonald, David J. Migueles, Stephen A. Connors, Mark Tilton, John C. TI CD4(+) Memory Stem Cells Are Infected by HIV-1 in a Manner Regulated in Part by SAMHD1 Expression SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELLS; ANTIRETROVIRAL THERAPY; 2 SUBSETS; NAIVE; LYMPHOCYTES; ENTRY; DIFFERENTIATION; IDENTIFICATION; PERSISTENCE AB CD4(+) and CD8(+) memory T cells with stem cell-like properties (TSCM cells) have been identified in mice, humans, and nonhuman primates and are being investigated for antitumor and antiviral vaccines and immunotherapies. Whether CD4(+) TSCM cells are infected by human immunodeficiency virus (HIV) was investigated by using a combination HIV reporter virus system in vitro and by direct staining for HIV p24 antigen ex vivo. A proportion of TSCM cells were found to express the HIV coreceptors CCR5 and CXCR4 and were infected by HIV both in vitro and in vivo. Analysis of viral outcome following fusion using the combination reporter virus system revealed that TSCM cells can become productively or latently infected, although the vast majority of TSCM cells are abortively infected. Knockdown of the HIV restriction factor SAMHD1 using Vpx-containing simian immunodeficiency virus (SIV) virion-like particles enhanced the productive infection of TSCM cells, indicating that SAMHD1 contributes to abortive infection in these cells. These results demonstrate that CD4(+) TSCM cells are targets for HIV infection, that they become productively or latently infected at low levels, and that SAMHD1 expression promotes abortive infection of this important memory cell subset. C1 [Tabler, Caroline O.; Lucera, Mark B.; Haqqani, Aiman A.; Tilton, John C.] Case Western Reserve Univ, Case Ctr Prote & Bioinformat, Cleveland, OH 44106 USA. [McDonald, David J.] Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. [Migueles, Stephen A.; Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Tilton, JC (reprint author), Case Western Reserve Univ, Case Ctr Prote & Bioinformat, Cleveland, OH 44106 USA. EM jct63@case.edu FU Case Western Reserve University/University Hospitals Center for AIDS Research (NIH) [P30 AI036219]; Foundation for AIDS Research (amfAR) [108257-51-RGRL] FX This work was supported by the Case Western Reserve University/University Hospitals Center for AIDS Research (NIH grant P30 AI036219) and by Foundation for AIDS Research (amfAR) research grant 108257-51-RGRL. NR 48 TC 9 Z9 11 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2014 VL 88 IS 9 BP 4976 EP 4986 DI 10.1128/JVI.00324-14 PG 11 WC Virology SC Virology GA AE9TT UT WOS:000334353900032 PM 24554663 ER PT J AU Marshall, LJ Ferenczy, MW Daley, EL Jensen, PN Ryschkewitsch, CF Major, EO AF Marshall, Leslie J. Ferenczy, Michael W. Daley, Elizabeth L. Jensen, Peter N. Ryschkewitsch, Caroline F. Major, Eugene O. TI Lymphocyte Gene Expression and JC Virus Noncoding Control Region Sequences Are Linked with the Risk of Progressive Multifocal Leukoencephalopathy SO JOURNAL OF VIROLOGY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; SPI-B; MULTIPLE-SCLEROSIS; TRANSCRIPTION FACTOR; HUMAN BRAIN; REGULATORY REGION; BINDING SITES; NATALIZUMAB; VARIANTS; PROTEIN AB Progressive multifocal leukoencephalopathy (PML)-derived noncoding control region (NCCR) sequences permitted greater early viral gene expression than kidney-associated NCCR sequences. This was driven in part by binding of the transcription factor Spi-B to unique PML-associated Spi-B binding sites. Spi-B is upregulated in developing B cells in response to natalizumab therapy, a known risk factor for PML. Naturally occurring JCV sequence variation, together with drug treatment-induced cellular changes, may synergize to create an environment leading to an increased risk of PML. C1 [Marshall, Leslie J.; Ferenczy, Michael W.; Daley, Elizabeth L.; Jensen, Peter N.; Ryschkewitsch, Caroline F.; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Ferenczy, MW (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM michael.ferenczy@.nih.gov; majorg@ninds.nih.gov FU NIH Office of AIDS Research; Division of Intramural Research of the NINDS FX M.W.F. was supported in part by the Intramural AIDS Research Fellowship from the NIH Office of AIDS Research. The LMMN is supported by the Division of Intramural Research of the NINDS. NR 30 TC 18 Z9 18 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2014 VL 88 IS 9 BP 5177 EP 5183 DI 10.1128/JVI.03221-13 PG 7 WC Virology SC Virology GA AE9TT UT WOS:000334353900049 PM 24554653 ER PT J AU Wieland, SF Asabe, S Engle, RE Purcell, RH Chisari, FV AF Wieland, S. F. Asabe, S. Engle, R. E. Purcell, R. H. Chisari, F. V. TI Limited Hepatitis B Virus Replication Space in the Chronically Hepatitis C Virus-Infected Liver SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSGENIC MICE; GENOMIC ANALYSIS; VIRAL CLEARANCE; HOST RESPONSE; HUH-7 CELLS; CHIMPANZEES; INTERFERON; EXPRESSION; COINFECTION; DISEASE AB We compared the kinetics and magnitude of hepatitis B virus (HBV) infection in hepatitis C virus (HCV)-naive and chronically HCV-infected chimpanzees in whose livers type I interferon-stimulated gene (ISG) expression is strongly induced. HBV infection was delayed and attenuated in the HCV-infected animals, and the number of HBV-infected hepatocytes was drastically reduced. These results suggest that establishment of HBV infection and its replication space is limited by the antiviral effects of type I interferon in the chronically HCV-infected liver. C1 [Wieland, S. F.; Asabe, S.; Chisari, F. V.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Engle, R. E.; Purcell, R. H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Wieland, SF (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM swieland@scripps.edu OI Chisari, Francis/0000-0002-4832-1044 FU NIH [N01-AI-52705, N01-AI-45180, N01-CO-56000]; Intramural Research Program of the NIAID, NIH; Sam and Rose Stein Charitable Trust; [AI20001]; [CA76403] FX This study was supported by grants AI20001 and CA76403, by contracts N01-AI-52705, N01-AI-45180, and N01-CO-56000 from the NIH, by the Intramural Research Program of the NIAID, NIH, and by the Sam and Rose Stein Charitable Trust. NR 30 TC 4 Z9 4 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2014 VL 88 IS 9 BP 5184 EP 5188 DI 10.1128/JVI.03553-13 PG 5 WC Virology SC Virology GA AE9TT UT WOS:000334353900050 PM 24522924 ER PT J AU Joedicke, JJ Zelinskyy, G Dittmer, U Hasenkrug, KJ AF Joedicke, Jara J. Zelinskyy, Gennadiy Dittmer, Ulf Hasenkrug, Kim J. TI CD8(+) T Cells Are Essential for Controlling Acute Friend Retrovirus Infection in C57BL/6 Mice SO JOURNAL OF VIROLOGY LA English DT Letter ID ABSENCE C1 [Joedicke, Jara J.; Zelinskyy, Gennadiy; Dittmer, Ulf] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Essen, Germany. [Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Hasenkrug, KJ (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM khasenkrug@nih.gov NR 9 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2014 VL 88 IS 9 BP 5200 EP 5201 DI 10.1128/JVI.00312-14 PG 2 WC Virology SC Virology GA AE9TT UT WOS:000334353900053 PM 24707025 ER PT J AU Lesma, G Sacchetti, A Bai, RL Basso, G Bortolozzi, R Hamel, E Silvani, A Vaiana, N Viola, G AF Lesma, Giordano Sacchetti, Alessandro Bai, Rouli Basso, Giuseppe Bortolozzi, Roberta Hamel, Ernest Silvani, Alessandra Vaiana, Nadia Viola, Giampietro TI Hemiasterlin analogues incorporating an aromatic, and heterocyclic type C-terminus: design, synthesis and biological evaluation SO MOLECULAR DIVERSITY LA English DT Article DE Hemiasterlin; Antimitotic peptides; Tubulin; Cytotoxicity; Dynamic resolution ID SPONGE PRODUCT HEMIASTERLIN; CYTOTOXIC PEPTIDES; TRIPEPTIDE HEMIASTERLIN; MICROTUBULE INHIBITORS; ANTIMICROTUBULE AGENT; TUBULIN INHIBITORS; NATURAL-PRODUCTS; P-GLYCOPROTEIN; BINDING-SITE; HTI-286 AB A representative series of structural analogs of the antimitotic tripeptides hemiasterlins have been designed and synthesized, as potential inhibitors of tubulin polymerization. Relying also on a computational approach, we aimed to explore unknown extensive changes at the C-fragment, by incorporating the conformationally required double bond into five- and six-membered rings. Key steps of the synthetic strategy are a dynamic resolution affording the A-fragment in 97 % ee and the preparation of six new cyclic C fragments, all potentially able to interact with tubulin by means of H bonds. Unexpectedly, biological evaluation of these analogs did not provide evidences neither for cytotoxic effect nor for inhibition of tubulin polymerization. C1 [Lesma, Giordano; Silvani, Alessandra; Vaiana, Nadia] Univ Milan, Dipartimento Chim, I-20133 Milan, Italy. [Sacchetti, Alessandro] Politecn Milan, Dipartimento Chim Mat & Ing Chim Giulio Natta, I-20133 Milan, Italy. [Bai, Rouli; Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA. [Basso, Giuseppe; Bortolozzi, Roberta; Viola, Giampietro] Univ Padua, Dipartimento Salute Donna & Bambino, I-35128 Padua, Italy. RP Silvani, A (reprint author), Univ Milan, Dipartimento Chim, Via Golgi 19, I-20133 Milan, Italy. EM alessandro.sacchetti@polimi.it; hamele@dc37a.nci.nih.gov; alessandra.silvani@unimi.it; giampietro.viola.1@unipd.it RI Viola, Giampietro/I-4095-2012; Bortolozzi, Roberta/D-4950-2015; silvani, alessandra/B-3742-2013; Lesma, Giordano/P-1516-2016; OI Viola, Giampietro/0000-0001-9329-165X; Bortolozzi, Roberta/0000-0002-3357-4815; silvani, alessandra/0000-0002-0397-2636; Lesma, Giordano/0000-0002-3897-0008; BASSO, GIUSEPPE/0000-0002-2634-9302; sacchetti, alessandro/0000-0002-4830-0825 FU Intramural NIH HHS [Z99 CA999999] NR 38 TC 2 Z9 2 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1381-1991 EI 1573-501X J9 MOL DIVERS JI Mol. Divers. PD MAY PY 2014 VL 18 IS 2 BP 357 EP 373 DI 10.1007/s11030-014-9507-9 PG 17 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA AE8WC UT WOS:000334282700010 PM 24500310 ER PT J AU Kang, PB Gooch, CL McDermott, MP Darras, BT Finkel, RS Yang, ML Sproule, DM Chung, WK Kaufmann, P de Vivo, DC AF Kang, Peter B. Gooch, Clifton L. McDermott, Michael P. Darras, Basil T. Finkel, Richard S. Yang, Michele L. Sproule, Douglas M. Chung, Wendy K. Kaufmann, Petra de Vivo, Darryl C. CA Muscle Study Grp Pediat Neuromuscular Clinical Res TI THE MOTOR NEURON RESPONSE TO SMN1 DEFICIENCY IN SPINAL MUSCULAR ATROPHY SO MUSCLE & NERVE LA English DT Article DE compound motor action potential; electrophysiology; motor neuron disease; motor unit number estimation; spinal muscular atrophy ID PLACEBO-CONTROLLED TRIAL; ADULT ZEBRAFISH; DOUBLE-BLIND; CHILDREN; INJURY; SCALE; CORD; SMA; REGENERATION; DISEASES AB Introduction: The purpose of this study was to measure and analyze motor unit number estimation (MUNE) values longitudinally in spinal muscular atrophy (SMA). Methods: Sixty-two children with SMA types 2 and 3 were observed prospectively for up to 42 months. Longitudinal electrophysiological data were collected, including compound motor action potential (CMAP), single motor unit action potential (SMUP), and MUNE. Results: Significant motor neuron loss and compensatory collateral reinnervation were noted at baseline. Over time, there was a significant mean increase in MUNE (4.92 units/year, P=0.009), a mean decrease in SMUP amplitude (-6.32 V/year, P=0.10), and stable CMAP amplitude. Conclusions: The unexpected longitudinal results differ from findings in amyotrophic lateral sclerosis studies, perhaps indicating that compensatory processes in SMA involve new motor unit development. A better understanding of the mechanisms of motor unit decline and compensation in SMA is important for assessing novel therapeutic strategies and for providing key insights into disease pathophysiology. Muscle Nerve49: 636-644, 2014 C1 [Kang, Peter B.; Darras, Basil T.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Kang, Peter B.; Darras, Basil T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gooch, Clifton L.; Sproule, Douglas M.; Kaufmann, Petra; de Vivo, Darryl C.] Columbia Univ, Dept Neurol, New York, NY USA. [Gooch, Clifton L.] Univ S Florida, Dept Neurol, Coll Med, Tampa, FL 33620 USA. [McDermott, Michael P.] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USA. [McDermott, Michael P.] Univ Rochester, Dept Neurol, Rochester, NY USA. [Finkel, Richard S.; Yang, Michele L.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Finkel, Richard S.] Nemours Childrens Hosp, Div Neurol, Orlando, FL USA. [Yang, Michele L.] Childrens Hosp Colorado, Div Neurol, Aurora, CO USA. [Chung, Wendy K.] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Chung, Wendy K.] Columbia Univ, Dept Med, New York, NY USA. [Kaufmann, Petra] NINDS, Bethesda, MD 20892 USA. RP Kang, PB (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM pbkang@ufl.edu RI Gooch, Clifton/M-1874-2016 OI Gooch, Clifton/0000-0002-2210-2038 FU Spinal Muscular Atrophy Foundation; CTSA from NCRR/NIH [UL1 RR024156, UL1-RR-024134]; NSADA K12 program (NINDS training grant); Harvard University [UL1 RR025755-01]; Harvard Catalyst Clinical and Translational Science Center, from NCRR/NIH FX This study was funded by the Spinal Muscular Atrophy Foundation. Additional clinical research support was provided to Columbia University through the CTSA (UL1 RR024156) from NCRR/NIH and the NSADA K12 program (NINDS training grant); to The Children's Hospital of Philadelphia through the CTSA (UL1-RR-024134) from NCRR/NIH; and to Harvard University (UL1 RR025755-01), Harvard Catalyst Clinical and Translational Science Center, from NCRR/NIH. NR 32 TC 10 Z9 10 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD MAY PY 2014 VL 49 IS 5 BP 636 EP 644 DI 10.1002/mus.23967 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AF0TK UT WOS:000334426800003 PM 23893312 ER PT J AU Mendez, ML Romero, AI Rajal, VB Castro, EF Calvo, JI Palacio, L Hernandez, A AF Mendez, Mercedes L. Romero, Analia I. Rajal, Veronica B. Castro, Elza F. Calvo, Jose I. Palacio, Laura Hernandez, Antonio TI Properties of polyethersulfone ultrafiltration membranes modified with polyethylene glycols SO POLYMER ENGINEERING AND SCIENCE LA English DT Article ID PHASE-INVERSION MEMBRANES; LIQUID DISPLACEMENT POROSIMETRY; NATURAL ORGANIC-MATTER; MOLECULAR-WEIGHT; UF MEMBRANES; POLYSULFONE MEMBRANES; STRUCTURAL-PROPERTIES; ASYMMETRIC MEMBRANES; SURFACE MODIFICATION; TRANSPORT-PROPERTIES AB Polyethersulfone ultrafiltration membranes have been prepared using polyethylene glycols (PEGs) of 400, 1000, and 10,000 gmol, as additive with dimethylacetamide as solvent. Infrared analysis proves that PEG leaves almost completely the surface of the membranes after 24 h of water immersion. Scanning electron microscopy, contact angle, and liquid-liquid displacement porometry have been used to characterize the membrane morphology, surface hydrophilicity and porous structure. The relative flux reduction factor, flux, retention-of PEG (20,000 and 35,000 g/mol) and bovine serum albumin (67,000 g/mol)-and pure water permeability have been measured for the membranes. Results show that the addition of PEG increases slightly hydrophilicity and decreases pore size and narrows the corresponding pore size distribution while thickening the skin layer, in spite of the fast disappearance of the added PEG form the membrane surface. The resulting flux and pure water permeability are higher when middle size PEGs are added but decrease again when very high molecular weight (MW) PEGs are added. Retention decreases initially for increasing MWs of PEG although for very long PEG chains (MW of 10,000 g/mol) retention increases again. After filtration, the membranes with PEG added showed a lower relative flux reduction that decreases for increasing MW of the added PEGs. (c) 2013 Society of Plastics Engineers. POLYM. ENG. SCI., 54:1211-1221, 2014. (c) 2013 Society of Plastics Engineers C1 [Mendez, Mercedes L.; Romero, Analia I.; Rajal, Veronica B.; Castro, Elza F.] UNSa, Fac Ingn, Inst Invest Ind Quim, RA-4400 Salta, Argentina. [Rajal, Veronica B.] Univ Calif Davis, Fogarty Int Ctr, Davis, CA 95616 USA. [Calvo, Jose I.; Palacio, Laura; Hernandez, Antonio] Univ Valladolid, SMAP, E-47071 Valladolid, Spain. RP Hernandez, A (reprint author), Univ Valladolid, SMAP, Paseo Belen 7,Campus Miguel Delibes, E-47071 Valladolid, Spain. EM tonhg@termo.uva.es RI Hernandez, Antonio/B-4622-2012; Palacio, Laura/I-7552-2014 OI Hernandez, Antonio/0000-0002-2475-5681; Palacio, Laura/0000-0001-9886-9553 FU ANPCyT [PICTO 36716]; CIUNSa [1469/0]; Junta de Castilla y Leon [VA324A11nd GR18] FX Contract grant sponsor: ANPCyT; contract grant number: PICTO 36716; contract grant sponsor: CIUNSa; contract grant number: 1469/0; contract grant sponsor: Junta de Castilla y Leon (to Spanish authors); contract grant numbers: VA324A11nd GR18. NR 50 TC 3 Z9 4 U1 2 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0032-3888 EI 1548-2634 J9 POLYM ENG SCI JI Polym. Eng. Sci. PD MAY PY 2014 VL 54 IS 5 BP 1211 EP 1221 DI 10.1002/pen.23637 PG 11 WC Engineering, Chemical; Polymer Science SC Engineering; Polymer Science GA AF0ID UT WOS:000334396600025 ER PT J AU Baker, CM Best, RB AF Baker, Christopher M. Best, Robert B. TI Insights into the binding of intrinsically disordered proteins from molecular dynamics simulation SO WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE LA English DT Review ID IMPLICIT SOLVENT MODELS; ENERGY LANDSCAPE THEORY; EMPIRICAL FORCE-FIELDS; FLY-CASTING MECHANISM; TRANSITION-STATE; CONFORMATIONAL SELECTION; INDUCED FIT; FOLDING SIMULATIONS; INTERMOLECULAR INTERACTIONS; UNSTRUCTURED PROTEINS AB Intrinsically disordered proteins (IDPs) are a class of protein that, in the native state, possess no well-defined secondary or tertiary structure, existing instead as dynamic ensembles of conformations. They are biologically important, with approximately 20% of all eukaryotic proteins disordered, and found at the heart of many biochemical networks. To fulfil their biological roles, many IDPs need to bind to proteins and/or nucleic acids. And although unstructured in solution, IDPs typically fold into a well-defined three-dimensional structure upon interaction with a binding partner. The flexibility and structural diversity inherent to IDPs makes this coupled folding and binding difficult to study at atomic resolution by experiment alone, and computer simulation currently offers perhaps the best opportunity to understand this process. But simulation of coupled folding and binding is itself extremely challenging; these molecules are large and highly flexible, and their binding partners, such as DNA or cyclins, are also often large. Therefore, their study requires either simplified representations, advanced enhanced sampling schemes, or both. It is not always clear that existing simulation techniques, optimized for studying folded proteins, are well suited to IDPs. In this article, we examine the progress that has been made in the study of coupled folding and binding using molecular dynamics simulation. We summarize what has been learnt, and examine the state of the art in terms of both methodologies and models. We also consider the lessons to be learnt from advances in other areas of simulation and highlight the issues that remain of be addressed. C1 [Baker, Christopher M.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. [Best, Robert B.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Best, RB (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM robertbe@helix.nih.gov RI Best, Robert/H-7588-2016 OI Best, Robert/0000-0002-7893-3543 FU FEBS Return to Europe Fellowship; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH) FX C.M.B. is supported by a FEBS Return to Europe Fellowship. R.B.B. is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH). NR 172 TC 21 Z9 21 U1 9 U2 84 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1759-0876 EI 1759-0884 J9 WIRES COMPUT MOL SCI JI Wiley Interdiscip. Rev.-Comput. Mol. Sci. PD MAY PY 2014 VL 4 IS 3 BP 182 EP 198 DI 10.1002/wcms.1167 PG 17 WC Chemistry, Multidisciplinary; Mathematical & Computational Biology SC Chemistry; Mathematical & Computational Biology GA AF2DG UT WOS:000334522200002 ER PT J AU Baron, SL Steege, AL Hughes, JT Beard, SD AF Baron, Sherry L. Steege, Andrea L. Hughes, Joseph T., Jr. Beard, Sharon D. TI Introduction to a special issue: Eliminating health and safety inequities at work SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Editorial Material C1 [Baron, Sherry L.] CUNY, Queens Coll, Ctr Biol Nat Syst, Flushing, NY USA. [Steege, Andrea L.] Ctr Dis Control & Prevent, Natl Inst Occupat Safety & Hlth, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH USA. [Hughes, Joseph T., Jr.; Beard, Sharon D.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Baron, SL (reprint author), Queens Coll Remsen 311,65-30 Kissena Blvd, Flushing, NY 11367 USA. EM sbaron@qc.cuny.edu RI Steege, Andrea/H-8900-2016 OI Steege, Andrea/0000-0001-5665-2559 NR 6 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 EI 1097-0274 J9 AM J IND MED JI Am. J. Ind. Med. PD MAY PY 2014 VL 57 IS 5 SI SI BP 493 EP 494 DI 10.1002/ajim.22321 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AE4NM UT WOS:000333959200001 PM 24687420 ER PT J AU Baron, SL Beard, S Davis, LK Delp, L Forst, L Kidd-Taylor, A Liebman, AK Linnan, L Punnett, L Welch, LS AF Baron, Sherry L. Beard, Sharon Davis, Letitia K. Delp, Linda Forst, Linda Kidd-Taylor, Andrea Liebman, Amy K. Linnan, Laura Punnett, Laura Welch, Laura S. TI Promoting integrated approaches to reducing health inequities among low-income workers: Applying a social ecological framework SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Review DE total worker health; disparities; low-income workers; health inequities ID BODY-MASS INDEX; FRANCISCOS CHINATOWN RESTAURANTS; RANDOMIZED CONTROLLED-TRIAL; TIME PHYSICAL-ACTIVITY; PARTICIPATORY RESEARCH; OCCUPATIONAL-HEALTH; RISK-FACTORS; ENVIRONMENTAL-HEALTH; SOCIOECONOMIC-STATUS; BLOOD-PRESSURE AB Background Nearly one of every three workers in the United States is low-income. Low-income populations have a lower life expectancy and greater rates of chronic diseases compared to those with higher incomes. Low- income workers face hazards in their workplaces as well as in their communities. Developing integrated public health programs that address these combined health hazards, especially the interaction of occupational and non-occupational risk factors, can promote greater health equity. Methods We apply a social-ecological perspective in considering ways to improve the health of the low-income working population through integrated health protection and health promotion programs initiated in four different settings: the worksite, state and local health departments, community health centers, and community-based organizations. Results Examples of successful approaches to developing integrated programs are presented in each of these settings. These examples illustrate several complementary venues for public health programs that consider the complex interplay between work-related and non work-related factors, that integrate health protection with health promotion and that are delivered at multiple levels to improve health for low-income workers. Conclusions Whether at the workplace or in the community, employers, workers, labor and community advocates, in partnership with public health practitioners, can deliver comprehensive and integrated health protection and health promotion programs. Recommendations for improved research, training, and coordination among health departments, health practitioners, worksites and community organizations are proposed. Am. J. Ind. Med. 57:539-556, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Baron, Sherry L.] NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. [Beard, Sharon] NIEHS, Worker Educ & Training Branch, Res Triangle Pk, NC 27709 USA. [Davis, Letitia K.] Massachusetts Dept Publ Hlth, Occupat Hlth Surveillance Program, Boston, MA USA. [Delp, Linda] Univ Calif Los Angeles, Labor Occupat Safety & Hlth Program, Los Angeles, CA USA. [Forst, Linda] Univ Illinois, Sch Publ Hlth, Chicago, IL USA. [Kidd-Taylor, Andrea] Morgan State Univ, Dept Hlth Policy & Management, Baltimore, MD 21239 USA. [Liebman, Amy K.] Migrant Clin Network, Environm & Occupat Hlth Initiat, Quantico, VA USA. [Linnan, Laura] Univ N Carolina, Gillings Sch Publ Hlth, Chapel Hill, NC USA. [Punnett, Laura] Univ Massachusetts Lowell, Dept Work Environm, Lowell, MA USA. [Punnett, Laura] Univ Massachusetts Lowell, Ctr Women & Work, Lowell, MA USA. [Welch, Laura S.] CPWR Ctr Construct Res & Training, Silver Spring, MD USA. RP Baron, SL (reprint author), NIOSH, 4676 Columbia Pkwy R-17, Cincinnati, OH 45226 USA. EM slb8@cdc.gov FU Intramural NIH HHS [Z99 ES999999]; NIEHS NIH HHS [U45 ES006173] NR 124 TC 21 Z9 21 U1 7 U2 48 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 EI 1097-0274 J9 AM J IND MED JI Am. J. Ind. Med. PD MAY PY 2014 VL 57 IS 5 SI SI BP 539 EP 556 DI 10.1002/ajim.22174 PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AE4NM UT WOS:000333959200005 PM 23532780 ER PT J AU Lee, D Schroeder, JR Karschner, EL Goodwin, RS Hirvonen, J Gorelick, DA Huestis, MA AF Lee, Dayong Schroeder, Jennifer R. Karschner, Erin L. Goodwin, Robert S. Hirvonen, Jussi Gorelick, David A. Huestis, Marilyn A. TI Cannabis withdrawal in chronic, frequent cannabis smokers during sustained abstinence within a closed residential environment SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID 2-DIMENSIONAL GAS-CHROMATOGRAPHY; ADULTS SEEKING TREATMENT; ORAL FLUID; SIMULTANEOUS QUANTIFICATION; MARIJUANA DEPENDENCE; MASS-SPECTROMETRY; WHOLE-BLOOD; SYMPTOMS; QUESTIONNAIRE; INPATIENT AB Objectives Chronic, frequent cannabis smokers may experience residual and offset effects, withdrawal, and craving when abstaining from the drug. We characterized the prevalence, duration, and intensity of these effects in chronic frequent cannabis smokers during abstinence on a closed research unit. Methods Non-treatment-seeking participants (N = 29 on admission, 66% and 34% remaining after 2 and 4 weeks) provided subjective effects data. A battery of five instruments was computer-administered daily to measure psychological, sensory, and physical symptoms associated with cannabinoid intoxication and withdrawal. Plasma and oral fluid specimens were concurrently collected and analyzed for cannabinoids. Outcome variables were evaluated as change from admission (Day 0) with regression models. Results Most abstinence effects, including irritability and anxiety were greatest on Days 0-3 and decreased thereafter. Cannabis craving significantly decreased over time, whereas decreased appetite began to normalize on Day 4. Strange dreams and difficulty getting to sleep increased over time, suggesting intrinsic sleep problems in chronic cannabis smokers. Symptoms likely induced by residual drug effects were at maximum intensity on admission and positively correlated with plasma and oral fluid cannabinoid concentrations on admission but not afterward; these symptoms showed overall prevalence higher than cannabis withdrawal symptoms. Conclusions The combined influence of residual/offset drug effects, withdrawal, and craving was observed in chronic cannabis smokers during monitored abstinence. Abstinence symptoms were generally more intense in the initial phase, implying importance of early intervention in cannabis quit attempts. Sleep disturbance persisting for an extended period suggests that hypnotic medications could be beneficial in treating cannabis dependence. (Am J Addict 2014;23:234-242) C1 [Lee, Dayong; Karschner, Erin L.; Goodwin, Robert S.; Gorelick, David A.; Huestis, Marilyn A.] NIDA, NIH, Baltimore, MD 21224 USA. [Schroeder, Jennifer R.] NIDA, Off Clin Director, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Hirvonen, Jussi] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Huestis, MA (reprint author), NIDA, IRP, NIH, Biomed Res Ctr, 251 Bayview Blvd Suite 200,Room 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [ZIA DA000412-12, ZIA DA000412-13, ZIA DA000413-12, ZIA DA000413-13]; NIDA NIH HHS [R01 DA025044] NR 35 TC 9 Z9 9 U1 4 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD MAY PY 2014 VL 23 IS 3 BP 234 EP 242 DI 10.1111/j.1521-0391.2014.12088.x PG 9 WC Substance Abuse SC Substance Abuse GA AF0RD UT WOS:000334420800006 PM 24724880 ER PT J AU Gomar, JJ Gordon, ML Dickinson, D Kingsley, PB Ulug, AM Keehlisen, L Huet, S Buthorn, JJ Koppel, J Christen, E Conejero-Goldberg, C Davies, P Goldberg, TE AF Gomar, Jesus J. Gordon, Marc L. Dickinson, Dwight Kingsley, Peter B. Ulug, Aziz M. Keehlisen, Lynda Huet, Sarah Buthorn, Justin J. Koppel, Jeremy Christen, Erica Conejero-Goldberg, Concepcion Davies, Peter Goldberg, Terry E. TI APOE Genotype Modulates Proton Magnetic Resonance Spectroscopy Metabolites in the Aging Brain SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Aging; APOE genotype; cognitive function; neurodegeneration; proton magnetic resonance spectroscopy; structural equation modeling ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; N-ACETYLASPARTATE; EPSILON-4 ALLELE; H-1 MRS; DEMENTIA; RISK; GENE; NEUROBIOLOGY AB Background: Proton magnetic resonance spectroscopy (H-1-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer's disease. Additionally, we examined these measures in relation to cognition. Methods: We studied a cohort of 112 normal adults between 50 and 86 years old who were genotyped for APOE genetic polymorphism. Measurements of H-1-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures of general cognitive functioning, memory, executive function, semantic fluency, and speed of processing were also obtained. Results: General linear model analysis demonstrated that older APOE E4 carriers had significantly higher choline/creatine and myoinositol/creatine ratios than APOE E3 homozygotes. Structural equation modeling resulted in a model with an excellent goodness of fit and in which the APOE x age interaction and APOE status each had a significant effect on H-1-MRS metabolites (choline/creatine and myo-inositol/creatine). Furthermore, the APOE x age variable modulation of cognition was mediated by H-1-MRS metabolites. Conclusions: In a healthy aging normal population, choline/creatine and myo-inositol/creatine ratios were significantly increased in APOE E4 carriers, suggesting the presence of neuroinflammatory processes and greater membrane turnover in older carriers. Structural equation modeling analysis confirmed these possible neurodegenerative markers and also indicated the mediator role of these metabolites on cognitive performance among older APOE E4 carriers. C1 [Gomar, Jesus J.; Gordon, Marc L.; Keehlisen, Lynda; Huet, Sarah; Buthorn, Justin J.; Koppel, Jeremy; Christen, Erica; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E.] Feinstein Inst Med Res, Litwin Zucker Res Ctr, Manhasset, NY 11030 USA. [Gomar, Jesus J.] FIDMAG Hermanas Hosp, St Boi De Llobregat, Spain. [Gordon, Marc L.; Ulug, Aziz M.; Koppel, Jeremy; Davies, Peter; Goldberg, Terry E.] Hofstra North Shore Long Isl Jewish Sch Med, Hempstead, NY USA. [Dickinson, Dwight] NIMH, NIH, Bethesda, MD 20892 USA. [Kingsley, Peter B.] N Shore Univ Hosp, Dept Radiol, Manhasset, NY USA. [Ulug, Aziz M.] Feinstein Inst Med Res, Susan & Leonard Feinstein Ctr Neurosci, Manhasset, NY 11030 USA. RP Goldberg, TE (reprint author), Feinstein Inst Med Res, Litwin Zucker Res Ctr, 350 Community Dr, Manhasset, NY 11030 USA. EM tgoldber@nshs.edu RI Ulug, Aziz/F-6592-2011; OI Ulug, Aziz/0000-0002-2315-0322; Gomar, Jesus/0000-0002-6995-4270 FU Litwin-Zucker Research Center of the Feinstein Institute for Medical Research (North Shore-Long Island Jewish Health System); National Institutes of Health [RO1 AG038734]; Baxter; Eli Lilly; Forest Research Institute; Genentech; Merck; Applied Neurosolutions FX This study was supported by the Litwin-Zucker Research Center of the Feinstein Institute for Medical Research (North Shore-Long Island Jewish Health System) and National Institutes of Health (RO1 AG038734 to TEG).; Dr. Gordon has received research support from Baxter, Eli Lilly, Forest Research Institute, Genentech, and Merck and honoraria for consulting from Accera, Eli Lilly, GE Healthcare, and Noven Pharmaceuticals. Dr. Davies has received research support from and served as a consultant to Applied Neurosolutions. Dr. Goldberg receives royalties for the use of the Brief Assessment of Cognition in Schizophrenia in clinical trials. All other authors report no biomedical financial interests or potential conflicts of interest. NR 41 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 BP 686 EP 692 DI 10.1016/j.biopsych.2013.05.022 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KY UT WOS:000334102400005 PM 23831342 ER PT J AU Muse, J Emery, M Sambataro, F Lemaitre, H Tan, HY Chen, Q Kolachana, BS Das, S Callicott, JH Weinberger, DR Mattay, VS AF Muse, John Emery, Matthew Sambataro, Fabio Lemaitre, Herve Tan, Hao-Yang Chen, Qiang Kolachana, Bhaskar S. Das, Saumitra Callicott, Joseph H. Weinberger, Daniel R. Mattay, Venkata S. TI WWC1 Genotype Modulates Age-Related Decline in Episodic Memory Function Across the Adult Life Span SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Aging; episodic memory (EM); hippocampus; KIBRA; long-term potentiation (LTP); single nucleotide polymorphism (SNP); WWC1 ID KIBRA GENE VARIANTS; COGNITIVE FUNCTIONS; DECLARATIVE MEMORY; IMAGING GENETICS; WORKING-MEMORY; ARCHITECTURE; ASSOCIATION; PERFORMANCE AB Background: Episodic memory (EM) declines with age and the rate of decline is variable across individuals. A single nucleotide polymorphism (rs17070145) in the WWC1 gene that encodes the KIBRA protein critical for long-term potentiation and memory consolidation has previously been associated with EM performance, as well as differences in hippocampal engagement during EM tasks using functional magnetic resonance imaging (fMRI). In the current study, we explore the effect of this polymorphism on EM-related activity and cognitive performance across the adult life span using fMRI. Methods: Two hundred thirty-two healthy, Caucasian subjects (18-89 years) completed a battery of cognitive tests, as well as an EM task during an fMRI scan. Results: WWC1 T carriers had significantly better delayed recall performance than CC individuals (p=.006). The relationship between increasing age and recall scores (immediate and delayed) was also significantly different between WWC1 genotype groups (p=.01). In addition to the age-related decline in hippocampal formation (HF) activation (p<.05; false discovery rate(small volume correction-HF-region of interest)), we observed an age by WWC1 genotype interaction on HF activation during encoding and retrieval. The CC group showed a significant negative association between HF activity and increasing age, while no such association was observed in the T carrier group (left HF p=.04; r-z correlation difference during encoding and retrieval; right HF p=.0008; r-z correlation difference during retrieval). Conclusions: Our results show a dynamic relationship between rs17070145 polymorphism and increasing age on neuronal activity in the hippocampal region. C1 [Muse, John; Emery, Matthew; Sambataro, Fabio; Lemaitre, Herve; Tan, Hao-Yang; Chen, Qiang; Kolachana, Bhaskar S.; Das, Saumitra; Callicott, Joseph H.; Weinberger, Daniel R.; Mattay, Venkata S.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Muse, John; Tan, Hao-Yang; Chen, Qiang; Weinberger, Daniel R.; Mattay, Venkata S.] Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. RP Mattay, VS (reprint author), Lieber Inst Brain Dev, 855 North Wolfe St,Suite 300,3rd Floor, Baltimore, MD 21205 USA. EM anand.mattay@libd.org RI Sambataro, Fabio/E-3426-2010; OI Sambataro, Fabio/0000-0003-2102-416X; Lemaitre, Herve/0000-0002-5952-076X FU Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; Lieber institute of Brain Development, Baltimore, Maryland FX This work was supported by the Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, and The Lieber institute of Brain Development, Baltimore, Maryland. NR 22 TC 8 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 BP 693 EP 700 DI 10.1016/j.biopsych.2013.09.036 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KY UT WOS:000334102400006 PM 24290728 ER PT J AU Khincha, PP Wentzensen, IM Giri, N Alter, BP Savage, SA AF Khincha, Payal P. Wentzensen, Ingrid M. Giri, Neelam Alter, Blanche P. Savage, Sharon A. TI Response to androgen therapy in patients with dyskeratosis congenita SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE telomere; dyskeratosis congenita; androgen ID TELOMERE BIOLOGY DISORDERS; BONE-MARROW FAILURE; APLASTIC-ANEMIA; COMPONENT 1; LENGTH; MUTATIONS; STEROIDS; CANCER; CTC1 AB Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome and telomere biology disorder characterized by dysplastic nails, reticular skin pigmentation and oral leucoplakia. Androgens are a standard therapeutic option for bone marrow failure in those patients with DC who are unable to undergo haematopoietic stem cell transplantation, but there are no systematic data on its use in those patients. We evaluated haematological response and side effects of androgen therapy in 16 patients with DC in our observational cohort study. Untreated DC patients served as controls. Seventy percent of treated DC patients had a haematological response with red blood cell and/or platelet transfusion independence. The expected age-related decline in telomere length was noted in androgen-treated patients. All treated DC patients had at least one significant lipid abnormality. Additional treatment-related findings included a significant decrease in thyroid binding globulin, accelerated growth in pre-pubertal children and splenic peliosis in two patients. Liver enzymes were elevated in both androgen-treated and untreated patients, suggesting underlying liver involvement in DC. This study suggests that androgen therapy can be effectively used to treat bone marrow failure in DC, but that side effects need to be closely monitored. C1 [Khincha, Payal P.; Wentzensen, Ingrid M.; Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20850 USA. [Khincha, Payal P.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Wentzensen, Ingrid M.] Johns Hopkins Univ Hosp, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA. RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E 454, Bethesda, MD 20850 USA. EM savagesh@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU NIH [N02-CP-11019, N02-CP-65504, N02-CP-65501]; National Cancer Institute, National Institutes of Health FX We thank the patients, their families, and the referring clinicians for their valuable contributions to this study. Lisa Leathwood, RN, and Maureen Risch, RN, Westat, Inc. (NIH contracts N02-CP-11019, N02-CP-65504, and N02-CP-65501) provided outstanding study support. This work and the research of Drs. Khincha, Wentzensen, Giri, Alter and Savage were supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. We thank Charleen Adams, NCI, for help with FA-related data abstraction and Dr. Mark H. Greene, NCI, for his helpful comments. NR 29 TC 9 Z9 10 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2014 VL 165 IS 3 BP 349 EP 357 DI 10.1111/bjh.12748 PG 9 WC Hematology SC Hematology GA AE5LR UT WOS:000334031000010 PM 24666134 ER PT J AU Harmacek, L Watkins-Chow, DE Chen, JF Jones, KL Pavan, WJ Salbaum, JM Niswander, L AF Harmacek, Laura Watkins-Chow, Dawn E. Chen, Jianfu Jones, Kenneth L. Pavan, William J. Salbaum, J. Michael Niswander, Lee TI A unique missense allele of BAF155, a core BAF chromatin remodeling complex protein, causes neural tube closure defects in mice SO DEVELOPMENTAL NEUROBIOLOGY LA English DT Article DE neural tube defect; apoptosis; proliferation; Baf155msp3; epigenetic regulation ID DIFFERENTIAL EXPRESSION ANALYSIS; MAMMALIAN SWI/SNF COMPLEXES; MOUSE MYELENCEPHALIC BLEBS; PROTEASOMAL DEGRADATION; DNA METHYLTRANSFERASES; EMBRYONIC LETHALITY; BINDING PROTEIN; GENE-EXPRESSION; CELL; NEURULATION AB Failure of embryonic neural tube closure results in the second most common class of birth defects known as neural tube defects (NTDs). While NTDs are likely the result of complex multigenic dysfunction, it is not known whether polymorphisms in epigenetic regulators may be risk factors for NTDs. Here we characterized Baf155(msp3), a unique ENU-induced allele in mice. Homozygous Baf155(mps3) embryos exhibit highly penetrant exencephaly, allowing us to investigate the roles of an assembled, but malfunctional BAF chromatin remodeling complex in vivo at the time of neural tube closure. Evidence of defects in proliferation and apoptosis were found within the neural tube. RNA-Seq analysis revealed that surprisingly few genes showed altered expression in Baf155 mutant neural tissue, given the broad epigenetic role of the BAF complex, but included genes involved in neural development and cell survival. Moreover, gene expression changes between individual mutants were variable even though the NTD was consistently observed. This suggests that inconsistent gene regulation contributes to failed neural tube closure. These results shed light on the role of the BAF complex in the process of neural tube closure and highlight the importance of studying missense alleles to understand epigenetic regulation during critical phases of development. (c) 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 483-497, 2014 C1 [Harmacek, Laura; Chen, Jianfu; Niswander, Lee] Univ Colorado, Howard Hughes Med Inst, Dept Pediat, Childrens Hosp Colorado, Aurora, CO 80045 USA. [Harmacek, Laura; Chen, Jianfu; Niswander, Lee] Univ Colorado, Howard Hughes Med Inst, Grad Program Mol Biol, Childrens Hosp Colorado, Aurora, CO 80045 USA. [Watkins-Chow, Dawn E.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Jones, Kenneth L.] Univ Colorado, Dept Biochem & Mol Genet, Aurora, CO 80045 USA. [Salbaum, J. Michael] Pennington Biomed Res Ctr, Dept Regulat Gene Express, Baton Rouge, LA 70808 USA. RP Niswander, L (reprint author), Univ Colorado, Howard Hughes Med Inst, Dept Pediat, Childrens Hosp Colorado, Anschutz Med Campus, Aurora, CO 80045 USA. EM lee.niswander@ucdenver.edu RI Niswander, Lee/D-3976-2013; OI Watkins-Chow, Dawn/0000-0002-4355-0868 FU Department of Pediatrics, a Cancer Center Support [P30CA046934]; Bioinformatics Shared Resource; CCTSI FX Contract grant sponsor: Department of Pediatrics, a Cancer Center Support; contract grant number: P30CA046934.; Contract grant sponsor: the Bioinformatics Shared Resource, and the CCTSI. NR 61 TC 5 Z9 5 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-8451 EI 1932-846X J9 DEV NEUROBIOL JI Dev. Neurobiol. PD MAY PY 2014 VL 74 IS 5 BP 483 EP 497 DI 10.1002/dneu.22142 PG 15 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AE4ZR UT WOS:000333998100001 PM 24170322 ER PT J AU Germain, RN Gerner, MY Kastenmuller, W Laemmermann, T Torabi-Parizi, P Honda, T Egen, JG AF Germain, R. N. Gerner, M. Y. Kastenmueller, W. Laemmermann, T. Torabi-Parizi, P. Honda, T. Egen, J. G. TI Probing myeloid cell localization and function using dynamic intravital and highly multiplex static imaging methods SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 [Germain, R. N.; Gerner, M. Y.; Kastenmueller, W.; Laemmermann, T.; Torabi-Parizi, P.; Honda, T.; Egen, J. G.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 EI 1365-2362 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD MAY PY 2014 VL 44 SU 1 SI SI BP 13 EP 13 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE6DN UT WOS:000334080900035 ER PT J AU Fassl, SK Holzinger, D Vogl, T Gattorno, M Omenetti, A Chae, JJ Aksentijevich, I Roth, J Austermann, J AF Fassl, S. K. Holzinger, D. Vogl, T. Gattorno, M. Omenetti, A. Chae, J. J. Aksentijevich, I. Roth, J. Austermann, J. TI The molecular link between PSTPIP and MRP8/14 secretion in PSTPIP1-associated myeloid-related-proteinaemia inflammatory syndrome (PAMI) SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 [Fassl, S. K.; Holzinger, D.; Vogl, T.; Roth, J.; Austermann, J.] Univ Munster, Inst Immunol, D-48149 Munster, Germany. [Holzinger, D.] Univ Childrens Hosp Muenster, Dept Paediat Rheumatol & Immunol, Munster, Germany. [Gattorno, M.; Omenetti, A.] G Gaslini Sci Inst, Div Pediat 2, Genoa, Italy. [Chae, J. J.; Aksentijevich, I.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 EI 1365-2362 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD MAY PY 2014 VL 44 SU 1 SI SI BP 23 EP 23 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE6DN UT WOS:000334080900065 ER PT J AU Surewaard, BGJ Nijland, R Otto, M van Strijp, JAG Kubes, P AF Surewaard, B. G. J. Nijland, R. Otto, M. van Strijp, J. A. G. Kubes, P. TI Staphylococcal PSMs contribute to survival and killing post-phagocytosis SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 [Surewaard, B. G. J.; Nijland, R.; van Strijp, J. A. G.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Surewaard, B. G. J.; Kubes, P.] Univ Calgary, Dept Physiol & Pharmacol, Calvin Phoebe & Joan Snyder Inst Chron Dis, Calgary, AB T2N 1N4, Canada. [Otto, M.] NIH, Lab Human Bacterial Pathogenesis, Hamilton, MT USA. RI van Strijp, Jos/J-9549-2014 OI van Strijp, Jos/0000-0001-6253-0830 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 EI 1365-2362 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD MAY PY 2014 VL 44 SU 1 SI SI BP 33 EP 33 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AE6DN UT WOS:000334080900092 ER PT J AU Lee, NR Raznahan, A Wallace, GL Alexander-Bloch, A Clasen, LS Lerch, JP Giedd, JN AF Lee, Nancy Raitano Raznahan, Armin Wallace, Gregory L. Alexander-Bloch, Aaron Clasen, Liv S. Lerch, Jason P. Giedd, Jay N. TI Anatomical coupling among distributed cortical regions in youth varies as a function of individual differences in vocabulary abilities SO HUMAN BRAIN MAPPING LA English DT Article DE cerebral cortex; child; language; adolescent; magnetic resonance imaging; brain; semantics; cognition ID AUTOMATED 3-D EXTRACTION; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; MRI DATA; BRAIN; THICKNESS; CHILDREN; LANGUAGE; INTELLIGENCE; ACQUISITION AB Patient lesion and functional magnetic resonance imaging (fMRI) studies have provided convincing evidence that a distributed brain network subserves word knowledge. However, little is known about the structural correlates of this network within the context of typical development and whether anatomical coupling in linguistically relevant regions of cortex varies as a function of vocabulary skill. Here we investigate the association between vocabulary and anatomical coupling in 235 typically developing youth (ages 6-19 years) using structural MRI. The study's primary aim was to evaluate whether higher vocabulary performance was associated with greater vertex-level cortical thickness covariation in distributed regions of cortex known to be associated with word knowledge. Results indicate that better vocabulary skills are associated with greater anatomical coupling in several linguistically relevant regions of cortex, including the left inferior parietal (temporal-parietal junction), inferior temporal, middle frontal, and superior frontal gyri and the right inferior frontal and precentral gyri. Furthermore, in high vocabulary scorers, stronger coupling is found among these regions. Thus, complementing patient and fMRI studies, this is the first investigation to highlight the relevance of anatomical covariance within the cortex to vocabulary skills in typically developing youth, further elucidating the distributed nature of neural systems subserving word knowledge. Hum Brain Mapp 35:1885-1895, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Lee, Nancy Raitano; Raznahan, Armin; Wallace, Gregory L.; Alexander-Bloch, Aaron; Clasen, Liv S.; Giedd, Jay N.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Lerch, Jason P.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Lerch, Jason P.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. RP Lee, NR (reprint author), NIMH, NIH, 10 Ctr Dr,Bldg 10,4C110,MSC 1367, Bethesda, MD 20892 USA. EM lnancy@mail.nih.gov RI Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016; OI Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713; Alexander-Bloch, Aaron/0000-0001-6554-1893; Wallace, Gregory/0000-0003-0329-5054 FU National Institutes of Health, National Institute of Mental Health FX Contract grant sponsor: National Institutes of Health, National Institute of Mental Health (Intramural Research Program) NR 43 TC 9 Z9 9 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2014 VL 35 IS 5 BP 1885 EP 1895 DI 10.1002/hbm.22299 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AE5FB UT WOS:000334012100007 PM 23728856 ER PT J AU White, SF Brislin, SJ Sinclair, S Blair, JR AF White, Stuart F. Brislin, Sarah J. Sinclair, Stephen Blair, James R. TI Punishing unfairness: Rewarding or the organization of a reactively aggressive response? SO HUMAN BRAIN MAPPING LA English DT Article DE functional MRI; aggression; altruistic punishment; cognitive neuroscience; reactive aggression ID VENTROMEDIAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; ALTRUISTIC PUNISHMENT; NEURAL BASIS; FUNCTIONAL MRI; BASAL GANGLIA; STROOP TASK; SELECTION; CONFLICT; BRAIN AB Objectives The neural correlates of human cooperative behavior remain poorly understood. Previous work has suggested that increases in striatal activation while punishing unfair offers represents reward signaling. However, other regions are also implicated when punishing others, for example dorsomedial frontal cortex (dmFC), anterior insula cortex (AIC), and periaqueductal gray (PAG). Moreover, the response of other regions implicated in signaling reward, for example ventromedial prefrontal cortex (vmPFC) or posterior cingulate cortex (PCC), has not been systematically examined. Experimental Design: Functional magnetic resonance imaging utilizing parametric modulation was conducted on 21 healthy adults participating in a social exchange paradigm. Principal Observations: Participants showed significant positive modulation of activity as a function of delivered punishment in caudate, dmFC, AIC, and PAG; that is, higher punishments by participants of unsatisfactory offers were associated with increasing activity within these regions. However, participants showed significant negative modulation of activity as a function of delivered punishment in vmPFC and PCC; increases in punishment level by participants were associated with decreases in activity within these regions. Conclusions: The current data question whether caudate activity when punishing unfair offers should be considered to indicate the reward value of this punishment. Instead, this activity, in conjunction with activity within dmFC, AIC, and PAG, may represent the organization of an untypical, punishing response that represents a reactive aggressive response to provocation. Notably, an inverse, regulatory relationship between vmPFC and PAG activity has been previously implicated in the context of another stimulus for reactive aggression; looming threat (Mobbs et al. [2007]: Science 317:1079-1083). Hum Brain Mapp 35:2137-2147, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [White, Stuart F.; Sinclair, Stephen; Blair, James R.] NIMH, Sect Affect Cognit Neurosci, Bethesda, MD 20892 USA. [Brislin, Sarah J.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. RP White, SF (reprint author), NIMH, Sect Affect Cognit Neurosci, 9000 Rockville Pike,Bldg 15k,Room 300C, Bethesda, MD 20892 USA. EM whitesf@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health [1-ZIA-MH002860-08] FX Contract grant sponsor: The Intramural Research Program of the National Institute of Mental Health, National Institutes of Health; Contract grant number: 1-ZIA-MH002860-08. NR 52 TC 13 Z9 13 U1 7 U2 23 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 MAY PY 2014 VL 35 IS 5 BP 2137 EP 2147 DI 10.1002/hbm.22316 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AE5FB UT WOS:000334012100024 PM 23868733 ER PT J AU Bianciardi, M van Gelderen, P Duyn, JH AF Bianciardi, Marta van Gelderen, Peter Duyn, Jeff H. TI Investigation of BOLD fMRI resonance frequency shifts and quantitative susceptibility changes at 7 T SO HUMAN BRAIN MAPPING LA English DT Article DE fractional oxygen saturation; BOLD fMRI resonance frequency shifts; BOLD fMRI quantitative susceptibility changes; BOLD fMRI phase signal changes ID IN-VIVO; OXYGEN-METABOLISM; BLOOD; PHASE; MRI; SIGNAL; FLUCTUATIONS; ACTIVATION; COMPLEX; NOISE AB Although blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) experiments of brain activity generally rely on the magnitude of the signal, they also provide frequency information that can be derived from the phase of the signal. However, because of confounding effects of instrumental and physiological origin, BOLD related frequency information is difficult to extract and therefore rarely used. Here, we explored the use of high field (7 T) and dedicated signal processing methods to extract frequency information and use it to quantify and interpret blood oxygenation and blood volume changes. We found that optimized preprocessing improves detection of task-evoked and spontaneous changes in phase signals and resonance frequency shifts over large areas of the cortex with sensitivity comparable to that of magnitude signals. Moreover, our results suggest the feasibility of mapping BOLD quantitative susceptibility changes in at least part of the activated area and its largest draining veins. Comparison with magnitude data suggests that the observed susceptibility changes originate from neuronal activity through induced blood volume and oxygenation changes in pial and intracortical veins. Further, from frequency shifts and susceptibility values, we estimated that, relative to baseline, the fractional oxygen saturation in large vessels increased by 0.02-0.05 during stimulation, which is consistent to previously published estimates. Together, these findings demonstrate that valuable information can be derived from fMRI imaging of BOLD frequency shifts and quantitative susceptibility changes. Hum Brain Mapp 35:2191-2205, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Bianciardi, Marta; van Gelderen, Peter; Duyn, Jeff H.] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Bianciardi, Marta] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Bianciardi, Marta] Harvard Univ, Sch Med, Boston, MA USA. RP Bianciardi, M (reprint author), NINDS, AMRI, LFMI, NIH, Bldg 10,Rm B1D 723A MSC 1065, Bethesda, MD 20892 USA. EM bianciardim@mail.nih.gov FU National Institutes of Health; National Institute of Neurological Disorders and Stroke FX Contract grant sponsor: Intramural Research Program of the National Institutes of Health; Contract grant sponsor: National Institute of Neurological Disorders and Stroke. NR 34 TC 8 Z9 8 U1 1 U2 6 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 MAY PY 2014 VL 35 IS 5 BP 2191 EP 2205 DI 10.1002/hbm.22320 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AE5FB UT WOS:000334012100028 PM 23897623 ER PT J AU Grainger, JR Askenase, MH Guimont-Desrochers, F da Fonseca, DM Belkaid, Y AF Grainger, John R. Askenase, Michael H. Guimont-Desrochers, Fanny da Fonseca, Denise Morais Belkaid, Yasmine TI Contextual functions of antigen-presenting cells in the gastrointestinal tract SO IMMUNOLOGICAL REVIEWS LA English DT Review DE mucosal; macrophage; antigen-presenting cell; commensal; monocyte; pathogen; immune regulation; dendritic cell; Treg ID REGULATORY T-CELLS; GROWTH-FACTOR-BETA; CLASSICAL DENDRITIC CELLS; EFFACING BACTERIAL PATHOGENS; INTESTINAL LAMINA PROPRIA; RETINOIC-ACID; TOXOPLASMA-GONDII; INFLAMMATORY MONOCYTES; IMMUNE-SYSTEM; ORAL TOLERANCE AB The immune system of the gastrointestinal tract must be tightly regulated to limit pathologic responses toward innocuous antigens while simultaneously allowing for rapid development of effector responses against invading pathogens. Highly specialized antigen-presenting cell (APC) subsets present in the gut play a dominant role in balancing these seemingly disparate functions. In this review, we discuss new findings associated with the function of gut APCs and particularly the contextual role of these cells in both establishing tolerance to orally acquired antigens in the steady state and regulating acute inflammation during infection. C1 [Grainger, John R.; Askenase, Michael H.; Guimont-Desrochers, Fanny; da Fonseca, Denise Morais; Belkaid, Yasmine] NIAID, Program Barrier Immun & Repair, Mucosal Immunol Sect, Lab Parasit Dis,NIH, Bethesda, MD 20892 USA. [Askenase, Michael H.] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA. [da Fonseca, Denise Morais] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biochem & Immunol, BR-14049 Ribeirao Preto, Brazil. RP Belkaid, Y (reprint author), NIAID, Program Barrier Immun & Repair, Mucosal Immunol Sect, Lab Parasit Dis,NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov OI Grainger, John/0000-0002-4052-5923 FU Intramural NIH HHS [ZIA AI001132-03] NR 142 TC 14 Z9 14 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD MAY PY 2014 VL 259 IS 1 BP 75 EP 87 DI 10.1111/imr.12167 PG 13 WC Immunology SC Immunology GA AE5PR UT WOS:000334041600006 PM 24712460 ER PT J AU Shevach, EM Thornton, AM AF Shevach, Ethan M. Thornton, Angela M. TI tTregs, pTregs, and iTregs: similarities and differences SO IMMUNOLOGICAL REVIEWS LA English DT Review DE stability; IL-10; Helios; infectious tolerance; Treg cells; organ-specific autoimmunity ID REGULATORY T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TRANSCRIPTION FACTOR FOXP3; LATENT TGF-BETA; MHC CLASS-II; DENDRITIC CELLS; CUTTING EDGE; IN-VIVO; SURFACE EXPRESSION; REG CELLS AB Foxp3(+) T-regulatory cells (Tregs) are primarily generated in the thymus (tTreg), but also may be generated extrathymically at peripheral sites (pTreg), or induced in cell culture (iTreg) in the presence of transforming growth factor beta (TGF beta). A major unresolved issue is how these different populations of Tregs exert their suppressive function in vivo. We have developed novel systems in which the function of Tregs can be evaluated in vivo in normal mice. Our studies demonstrate that one prominent mechanism of action of polyclonal tTregs is to inhibit T-effector cell trafficking to the target organ, while antigen-specific iTregs primarily prevent T-cell priming by acting on antigen-presenting dendritic cells (DCs). Interleukin-10 (IL-10) plays an important role in the suppressive function of antigen-specific iTregs by controlling the expression of MARCH1 and CD83 on the DC. Activated tTregs may mediate infectious tolerance by delivery of cell surface-expressed TGF beta to naive responder T cells to generate pTregs. Manipulation of Treg function will require the ability to differentiate tTregs from pTregs and iTregs. The expression of the transcription factor Helios has proven to be a useful marker for the identification of stable tTregs in both mouse and human. C1 [Shevach, Ethan M.; Thornton, Angela M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Blg 10,RM 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases FX The studies described in this review were supported by funds from the Intramural Program of the National Institute of Allergy and Infectious Diseases. The authors would like to thank all members of the Cellular Immunology Section who contributed to these studies. The authors have no conflicts of interest to declare. NR 67 TC 87 Z9 90 U1 10 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD MAY PY 2014 VL 259 IS 1 BP 88 EP 102 DI 10.1111/imr.12160 PG 15 WC Immunology SC Immunology GA AE5PR UT WOS:000334041600007 PM 24712461 ER PT J AU Safdar, N Anderson, DJ Braun, BI Carling, P Cohen, S Donskey, C Drees, M Harris, A Henderson, DK Huang, SS Juthani-Mehta, M Lautenbach, E Linkin, DR Meddings, J Miller, LG Milstone, A Morgan, D Sengupta, S Varman, M Yokoe, D Zerr, DM AF Safdar, Nasia Anderson, Deverick J. Braun, Barbara I. Carling, Philip Cohen, Stuart Donskey, Curtis Drees, Marci Harris, Anthony Henderson, David K. Huang, Susan S. Juthani-Mehta, Manisha Lautenbach, Ebbing Linkin, Darren R. Meddings, Jennifer Miller, Loren G. Milstone, Aaron Morgan, Daniel Sengupta, Sharmila Varman, Meera Yokoe, Deborah Zerr, Danielle M. CA Soc Healthcare Epidemiology Amer TI The Evolving Landscape of Healthcare-Associated Infections: Recent Advances in Prevention and a Road Map for Research SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID SURGICAL-SITE INFECTIONS; VENTILATOR-ASSOCIATED PNEUMONIA; RANDOMIZED CONTROLLED-TRIAL; CARBAPENEMASE-PRODUCING ENTEROBACTERIACEAE; CATHETER-RELATED INFECTIONS; GENTAMICIN-COLLAGEN SPONGE; URINARY-TRACT-INFECTIONS; BLOOD-STREAM INFECTION; CRITICALLY-ILL ADULTS; INTENSIVE-CARE AB This white paper identifies knowledge gaps and new challenges in healthcare epidemiology research, assesses the progress made toward addressing research priorities, provides the Society for Healthcare Epidemiology of America (SHEA) Research Committee's recommendations for high-priority research topics, and proposes a road map for making progress toward these goals. It updates the 2010 SHEA Research Committee document, "Charting the Course for the Future of Science in Healthcare Epidemiology: Results of a Survey of the Membership of SHEA," which called for a national approach to healthcare-associated infections (HAIs) and a prioritized research agenda. This paper highlights recent studies that have advanced our understanding of HAIs, the establishment of the SHEA Research Network as a collaborative infrastructure to address research questions, prevention initiatives at state and national levels, changes in reporting and payment requirements, and new patterns in antimicrobial resistance. C1 [Safdar, Nasia] Univ Wisconsin, Div Infect Dis, William S Middleton Mem Vet Hosp, Madison, WI USA. [Anderson, Deverick J.] Duke Univ, Med Ctr, Dept Infect Dis, Durham, NC USA. [Braun, Barbara I.] Joint Commiss, Oak Brook Terrace, IL USA. [Carling, Philip] Boston Univ, Sch Med, Boston, MA 02118 USA. [Cohen, Stuart] Univ Calif Davis, Div Infect Dis, Sch Med Hosp Epidemiol & Infect Prevent, Sacramento, CA 95817 USA. [Donskey, Curtis] Louis Stokes Cleveland Vet Affairs Med Ctr, Cleveland, OH USA. [Drees, Marci] Christiana Care Hlth Syst, Newark, DE USA. [Harris, Anthony] Univ Maryland, Sch Med, EPH Genom Epidemiol & Clin Outcomes, Baltimore, MD 21201 USA. [Henderson, David K.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Huang, Susan S.] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. [Juthani-Mehta, Manisha] Yale Univ, Sch Med, Infect Dis Sect, New Haven, CT USA. [Lautenbach, Ebbing] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Linkin, Darren R.] Univ Penn, Philadelphia, PA 19104 USA. [Meddings, Jennifer] Univ Michigan, Ann Arbor, MI 48109 USA. [Miller, Loren G.] Harbor UCLA Med Ctr, Div Infect Dis, Torrance, CA 90509 USA. [Milstone, Aaron] Johns Hopkins Univ, Baltimore, MD USA. [Morgan, Daniel] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Morgan, Daniel] Vet Affairs Maryland Healthcare Syst, Baltimore, MD USA. [Sengupta, Sharmila] BLK Super Specialty Hosp, Dept Microbiol, Delhi, India. [Varman, Meera] Creighton Univ, Med Ctr, Omaha, NE USA. [Yokoe, Deborah] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Yokoe, Deborah] Harvard Univ, Sch Med, Boston, MA USA. [Zerr, Danielle M.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Zerr, Danielle M.] Seattle Childrens Res Inst, Seattle, WA USA. RP Safdar, N (reprint author), 600 Highland Ave,H4-574, Madison, WI 53792 USA. EM ns2@medicine.wisc.edu FU US Department of Veterans Affairs (VA); National Institutes of Health (NIH) [AG40669]; Centers for Disease Control and Prevention (CDC), Duke University/Duke Infection Control Outreach Network [U54CK000164]; NIH/National Institute of Allergy and Infectious Diseases (NIAID) Duke University [K23AI095357]; CDC/Duke University [U54CK000172-01]; The Joint Commission: Agency for Healthcare Research and Quality (AHRQ) [1R13HS022174-0112]; CDC National Institute for Occupational Safety and Health National Personal Protective Technology Laboratory; AHRQ; CDC; state of Pennsylvania; Doris Duke Charitable Foundation; University of Pennsylvania; Pennsylvania Department of Health; VA National Center for Patient Safety; NIH/National Institute of Nursing Research; CDC [1U54 CK000172-01]; NIH/NIAID; NIH/National Cancer Institute FX Potential conflicts of interest. N.S. reports research grants and/or contracts from the US Department of Veterans Affairs (VA) and the National Institutes of Health (NIH; AG40669). D.J.A. reports a financial relationship with UpToDate Online, a company involved in treatment of subjects, and having received research grants or contracts from the Centers for Disease Control and Prevention (CDC), Duke University/Duke Infection Control Outreach Network (U54CK000164), NIH/National Institute of Allergy and Infectious Diseases (NIAID) Duke University (K23AI095357), and CDC/Duke University (U54CK000172-01). B.I.B. reports having received research grants or contracts from The Joint Commission: Agency for Healthcare Research and Quality (AHRQ; 1R13HS022174-0112) and the CDC National Institute for Occupational Safety and Health National Personal Protective Technology Laboratory. P.C. reports being an advisor or consultant for Ecolab and holding patents, copyrights, or licenses from Steris. S.C. reports having received research grants or contracts from Viropharma, Merck, and Cubist for clinical trials in C. difficile infection. A.H. reports financial involvement with companies involved in the treatment of subjects and having served in an advisory or consultant role for Premier, Cubist, and UpToDate. S.S.H. reports leading a clinical trial in which participating hospitals receive contributed product from Sage. E.L. reports having received research grants or contracts from AHRQ, the CDC, and the state of Pennsylvania. D.R.L. reports having received research grants/contracts from Doris Duke Charitable Foundation, the University of Pennsylvania, and the Pennsylvania Department of Health. J.M. reports having received research grants or contracts from AHRQ, VA National Center for Patient Safety, and the NIH/National Institute of Nursing Research. L.G.M. reports having received research grant or contracts from Merck Harbor-UCLA and Cerexa and honoraria from Durata. A.M. reports a financial relationship with Sage Products, a company involved in the treatment of subjects, and past research support and research grants or contracts from the NIH. D.M. reports serving in an advisory or consultant role for Welch-Allyn. D.Y. reports having received research grants or contracts from the CDC (1U54 CK000172-01). D.M.Z. reports having received research grants or contracts from the NIH/NIAID and the NIH/National Cancer Institute. All other authors report no conflicts of interest relevant to this article. NR 77 TC 7 Z9 7 U1 1 U2 10 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAY 1 PY 2014 VL 35 IS 5 BP 480 EP 493 DI 10.1086/675821 PG 14 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AE4EI UT WOS:000333933900004 PM 24709716 ER PT J AU Leaver, CA AF Leaver, Cynthia A. TI Visiting Again? Subjective Well-Being of Children in Elementary School and Repeated Visits to School Health Nurses SO JOURNAL OF SCHOOL HEALTH LA English DT Article DE school nurse; student somatic complaints; predictors of school nurse visits; academic achievement ID MODEL; ADOLESCENTS; COMPLAINTS; YOUTH AB BACKGROUND Children with vague complaints are without chronic illness, and who repeatedly visit the school nurse may be at risk for limited academic success. This study compares student reports of subjective well-being between children who do and do not repeatedly visit the school nurse with vague complaints. METHODS Children in grades 4 through 6 completed the School Well-Being Profile-American English (SWBP-AE), a questionnaire with 4 well-being subscales: health status, school environment, social relationships, and school as a means of self-fulfillment. School nurses extracted data on clinic visits from clinic records. Logistic regression explored associations between well-being subscales and repeated visits to the school nurse. RESULTS Of the 320 students participating in the study, 33 (12.04%) students made repeated visits to the school nurse. Perception of health status (OR = 2.072; 95% CI = 1.037, 4.163) was the only significant (p < .05) predictor of repeated visits to the nurse. CONCLUSION Children with poor perception of their health status are more likely to repeatedly visit the school nurse. Children's perceptions of their school environment, social relationships, or school as a means of self-fulfillment are not statistically significant predictors of repeated visits to the school nurse. C1 NINR, NIH, Div Intramural Res, Bethesda, MD 20892 USA. RP Leaver, CA (reprint author), NINR, NIH, Div Intramural Res, 10 Ctr Dr,2-1339, Bethesda, MD 20892 USA. EM caleaver@cox.net FU Bravewell Collaborative FX The author would like to acknowledge the following individuals who have made significant contributions to the scientific content or technical support to this research project: Mary Paterson, RN, PhD, Ordinary Professor, The Catholic University of America, Washington, DC, Gwenyth R. Wallen, RN, PhD, Chief, Nursing Research and Translational Science, National Institutes of Health, Clinical Center, Bethesda Maryland, and Joan Austin, PhD, RN, FAAN, Consultant, National Institutes of Health, National Institute of Nursing Research. This research was completed while the author was a PhD student at The Catholic University of America, School of Nursing, Washington, DC. The author is currently a postdoctoral fellow at the National Institute of Nursing Research, National Institutes of Health sponsored by the Bravewell Collaborative. NR 29 TC 1 Z9 1 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4391 EI 1746-1561 J9 J SCHOOL HEALTH JI J. Sch. Health PD MAY PY 2014 VL 84 IS 5 BP 294 EP 301 DI 10.1111/josh.12150 PG 8 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA AE4QD UT WOS:000333966800002 PM 24707923 ER PT J AU Longchamps, RJ Abey, SK Martino, AC Henderson, WA AF Longchamps, R. J. Abey, S. K. Martino, A. C. Henderson, W. A. TI Letter: apoptosis and hepatic fibrosis in chronic hepatitis B - authors' reply SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Letter ID FIBROGENESIS; PATHOGENESIS C1 [Longchamps, R. J.; Abey, S. K.; Martino, A. C.; Henderson, W. A.] NINR, Digest Disorder Unit, Biobehav Branch, Div Intramural Res,Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Longchamps, RJ (reprint author), NINR, Digest Disorder Unit, Biobehav Branch, Div Intramural Res,Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. EM hendersw@mail.nih.gov FU Intramural NIH HHS [Z99 NR999999, ZIA NR000018-01, ZIA NR000018-02, ZIA NR000018-03, ZIA NR000018-04, ZIA NR000018-05]; NINR NIH HHS [ZIA NR000018] NR 6 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 EI 1365-2036 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD MAY PY 2014 VL 39 IS 9 BP 997 EP 997 DI 10.1111/apt.12715 PG 1 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA AD8ZA UT WOS:000333553000016 PM 24689349 ER PT J AU Chen, F Wang, Z Bhattacharyya, T AF Chen, Foster Wang, Zhong Bhattacharyya, Timothy TI Absence of femoral cortical thickening in long-term bisphosphonate users: Implications for atypical femur fractures SO BONE LA English DT Article DE Atypical femur fracture; Osteoporosis ID ASYMPTOMATIC PATIENTS; THERAPY AB The radiographs of patients on long term bisphosphonates with atypical femur fractures demonstrate markedly thick cortices at the site of the fracture. We conducted a prospective clinical study to determine if cortical thickening is increased in long term bisphosphonate users. We recruited 43 patients who had taken bisphosphonates for more than 5 years. A group of 45 healthy volunteers and 12 patients recently diagnosed with osteoporosis served as controls. We measured the cortical thickening as the ratio of femoral cortical thickness to diameter of the femur, and looked for cortical beaking. No difference in the cortical thickness ratio was observed between long term bisphosphonate users and osteoporotic controls (0.53 vs. 0.54, p = 0.659). No cases of cortical beaking were seen and no increase in thigh pain was observed. The power of the study was 95% to detect a 10% difference in cortical thickness ratio. We conclude that long term bisphosphonate use does not produce a generalized increase in subtrochanteric femoral cortical thickening in the majority of patients. (C) 2014 Published by Elsevier Inc. C1 [Chen, Foster; Wang, Zhong; Bhattacharyya, Timothy] NIAMSD, Clin & Invest Orthopaed Surg Unit, Unit Intramural Res Program, Bethesda, MD 20892 USA. RP Bhattacharyya, T (reprint author), NIAMS, Clin & Invest Orthopaed Surg Sect, Off Clin Director, 10 Ctr Dr,Bldg 10 CRC Room 4-2339, Bethesda, MD 20892 USA. EM Timothy.bhattacharyya@nih.gov FU Intramural NIH HHS [Z99 AR999999] NR 9 TC 11 Z9 11 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD MAY PY 2014 VL 62 BP 64 EP 66 DI 10.1016/j.bone.2014.01.011 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD6NU UT WOS:000333378300009 PM 24468718 ER PT J AU Ellingson, MS Wick, MJ White, WM Raymond, KM Saenger, AK Pichurin, PN Wassif, CA Porter, FD Babovic-Vuksanovic, D AF Ellingson, M. S. Wick, M. J. White, W. M. Raymond, K. M. Saenger, A. K. Pichurin, P. N. Wassif, C. A. Porter, F. D. Babovic-Vuksanovic, D. TI Pregnancy in an individual with mild Smith-Lemli-Opitz syndrome SO CLINICAL GENETICS LA English DT Letter ID CHOLESTEROL C1 [Ellingson, M. S.; Wick, M. J.; Pichurin, P. N.; Babovic-Vuksanovic, D.] Mayo Clin, Dept Med Genet, Rochester, MN 55902 USA. [Wick, M. J.; White, W. M.] Mayo Clin, Dept Obstet, Rochester, MN 55902 USA. [Raymond, K. M.; Saenger, A. K.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55902 USA. [Wassif, C. A.; Porter, F. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Babovic-Vuksanovic, D (reprint author), Mayo Clin, Dept Med Genet, 200 First St SW, Rochester, MN 55902 USA. EM dbabovic@mayo.edu OI Wassif, Christopher/0000-0002-2524-1420 FU Intramural NIH HHS [ZIA HD008825-06] NR 4 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9163 EI 1399-0004 J9 CLIN GENET JI Clin. Genet. PD MAY PY 2014 VL 85 IS 5 BP 495 EP 497 DI 10.1111/cge.12209 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA AD8UH UT WOS:000333540700016 PM 23790112 ER PT J AU Gamaletsou, MN Rammaert, B Bueno, MA Moriyama, B Sipsas, NV Kontoyiannis, DP Roilides, E Zeller, V Prinapori, R Taj-Aldeen, SJ Brause, B Lortholary, O Walsh, TJ AF Gamaletsou, Maria N. Rammaert, Blandine Bueno, Marimelle A. Moriyama, Brad Sipsas, Nikolaos V. Kontoyiannis, Dimitrios P. Roilides, Emmanuel Zeller, Valerie Prinapori, Roberta Taj-Aldeen, Saad J. Brause, Barry Lortholary, Olivier Walsh, Thomas J. TI Aspergillus osteomyelitis: Epidemiology, clinical manifestations, management, and outcome SO JOURNAL OF INFECTION LA English DT Article DE Aspergillus; Osteomyelitis ID CHRONIC GRANULOMATOUS-DISEASE; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; OF-THE-LITERATURE; RENAL-TRANSPLANT RECIPIENT; INVASIVE EXTERNAL OTITIS; CONTIGUOUS VERTEBRAL OSTEOMYELITIS; STERNAL WOUND INFECTIONS; AORTIC BYPASS GRAFT; EPIDURAL ABSCESS; FUNGAL-INFECTION AB Background: The epidemiology, pathogenesis, diagnosis, and management of Aspergillus osteomyelitis are not well understood. Methods: Protocol-defined cases of Aspergillus osteomyelitis published in the English literature were reviewed for comorbidities, microbiology, mechanisms of infection, clinical manifestations, radiological findings, inflammatory biomarkers, antifungal therapy, and outcome. Results: Among 180 evaluable patients, 127 (71%) were males. Possible predisposing medical conditions in 103 (57%) included pharmacological immunosuppression, primary immunodeficiency, and neutropenia. Seventy-three others (41%) had prior open fracture, trauma or surgery. Eighty (44%) followed a hematogenous mechanism, 58 (32%) contiguous infections, and 42 (23%) direct inoculation. Aspergillus osteomyelitis was the first manifestation of aspergillosis in 77%. Pain and tenderness were present in 80%. The most frequently infected sites were vertebrae (46%), cranium (23%), ribs (16%), and long bones (13%). Patients with vertebral Aspergillus osteomyelitis had more previous orthopedic surgery (19% vs 0%; P = 0.02), while those with cranial osteomyelitis had more diabetes mellitus (32% vs 8%; P = 0.002) and prior head/neck surgery (12% vs 0%; P = 0.02). Radiologic findings included osteolysis, soft-tissue extension, and uptake on T2-weighted images. Vertebral body Aspergillus osteomyelitis was complicated by spinal-cord compression in 47% and neurological deficits in 41%. Forty-four patients (24%) received only antifungal therapy, while 121 (67%) were managed with surgery and antifungal therapy. Overall mortality was 25%. Median duration of therapy was 90 days (range, 10-772 days). There were fewer relapses in patients managed with surgery plus antifungal therapy in comparison to those managed with antifungal therapy alone (8% vs 30%; P = 0.006). Conclusions: Aspergillus osteomyelitis is a debilitating infection affecting both immunocompromised and immunocompetent patients. The most common sites are vertebrae, ribs, and cranium. Based upon this comprehensive review, management of Aspergillus osteomyelitis optimally includes antifungal therapy and selective surgery to avoid relapse and to achieve a complete response. (C) 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved. C1 [Gamaletsou, Maria N.; Bueno, Marimelle A.; Brause, Barry; Walsh, Thomas J.] Cornell Univ, Weill Cornell Med Ctr, New York, NY 10021 USA. [Gamaletsou, Maria N.; Sipsas, Nikolaos V.] Univ Athens, Athens 11528, Greece. [Gamaletsou, Maria N.; Rammaert, Blandine; Sipsas, Nikolaos V.; Roilides, Emmanuel; Brause, Barry; Lortholary, Olivier; Walsh, Thomas J.] Hosp Special Surg, Ctr Osteoarticular Mycoses, New York, NY 10021 USA. [Gamaletsou, Maria N.; Rammaert, Blandine; Sipsas, Nikolaos V.; Roilides, Emmanuel; Brause, Barry; Lortholary, Olivier; Walsh, Thomas J.] Int Osteoarticular Mycoses Study Consortium, New York, NY USA. [Rammaert, Blandine; Lortholary, Olivier] Univ Paris 05, Sorbonne Paris Cite, Serv Malad Infect & Trop,Ctr Infectiol Necker Pas, Hop Necker Enfants Malad,APHP,Inst Imagine, Paris, France. [Rammaert, Blandine; Lortholary, Olivier] Inst Pasteur, Unite Mycol Mol, Paris, France. [Moriyama, Brad] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Roilides, Emmanuel] Aristotle Univ Thessaloniki, Fac Med, Sch Hlth Sci, Infect Dis Unit,Dept Pediat 3, GR-54006 Thessaloniki, Greece. [Roilides, Emmanuel] Hippokrateion Hosp, Thessaloniki, Greece. [Zeller, Valerie] Grp Hosp Diaconesses Croix St Simon, Osteoarticular Reference Ctr, Paris, France. [Prinapori, Roberta] Univ Genoa, San Martino Genoa Hosp, Dept Infect Dis, Genoa, Italy. [Taj-Aldeen, Saad J.] Hamad Med Corp, Dept Lab Med & Pathol, Mycol Unit, Doha, Qatar. RP Walsh, TJ (reprint author), Weill Cornell Med Ctr, Transplantat Oncol Infect Dis Program, 1300 York Ave,Rm A421, New York, NY 10065 USA. EM thw2003@med.cornell.edu FU National and Kapodistrian University of Athens; National Institutes of Health through an MD Anderson Cancer Center Support Grant [CA016672]; Save Our Sick Children Foundation Scholar Award; Sharpe Family Foundation Scholar Award in Pediatric Infectious Diseases FX This work was supported by the Special Account for Research Funds (to M.N.G., N.V.S.) of the National and Kapodistrian University of Athens; National Institutes of Health through an MD Anderson Cancer Center Support Grant (CA016672); Save Our Sick Children Foundation Scholar Award and the Sharpe Family Foundation Scholar Award in Pediatric Infectious Diseases (T.J.W.) NR 169 TC 16 Z9 16 U1 1 U2 11 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 EI 1532-2742 J9 J INFECTION JI J. Infect. PD MAY PY 2014 VL 68 IS 5 BP 478 EP 493 DI 10.1016/j.jinf.2013.12.008 PG 16 WC Infectious Diseases SC Infectious Diseases GA AE1XJ UT WOS:000333766200009 PM 24378282 ER PT J AU Louis, GMB Hediger, ML Bell, EM Kus, CA Sundaram, R McLain, AC Yeung, E Hills, EA Thoma, ME Druschel, CM AF Louis, Germaine M. Buck Hediger, Mary L. Bell, Erin M. Kus, Christopher A. Sundaram, Rajeshwari McLain, Alexander C. Yeung, Edwina Hills, Elaine A. Thoma, Marie E. Druschel, Charlotte M. TI Methodology for Establishing a Population-Based Birth Cohort Focusing on Couple Fertility and Children's Development, the Upstate KIDS Study SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE infertility; in vitro fertilization; children; fecundity; assisted reproductive technologies ID ASSISTED REPRODUCTIVE TECHNOLOGY; IN-VITRO FERTILIZATION; TERM HEALTH OUTCOMES; UNITED-STATES; STAGES QUESTIONNAIRES; INFERTILITY TREATMENT; PERINATAL OUTCOMES; CERTIFICATE DATA; MEDICAL HOME; VALIDITY AB Background Critical data gaps remain regarding infertility treatment and child development. We assessed the utility of a birth certificate registry for developing a population cohort aimed at answering such questions. Methods We utilised the Upstate New York livebirth registry (n = 201 063) to select births conceived with (n = 4024) infertility treatment or exposed infants, who were then frequency-matched by residence to a random sample of infants conceived without (n = 14 455) treatment or unexposed infants, 2008-10. Mothers were recruited at 2-4 months postpartum and queried about their reproductive histories, including infertility treatment for comparison with birth certificate data. Overall, 1297 (32%) mothers of exposed and 3692 of unexposed (26%) infants enrolled. Results Twins represented 22% of each infant group. The percentage of infants conceived with/without infertility treatment was similar whether derived from the birth registry or maternal report: 71% none, 16% drugs or intrauterine insemination, and 14% assisted reproductive technologies (ART). Concordant reporting between the two data sources was 93% for no treatment, 88% for ART, and 83% for fertility drugs, but differed by plurality. Exposed infants had slightly (P < 0.01) earlier gestations than unexposed infants (38.3 +/- 2.8 and 38.7 +/- 2.7 weeks, respectively) based upon birth certificates but not maternal report (38.7 +/- 2.7 and 38.7 +/- 2.9, respectively). Conversely, mean birthweight was comparable using birth certificates (3157 +/- 704 and 3194 +/- 679 g, respectively), but differed using maternal report (3167 +/- 692 and 3224 +/- 661, respectively P < 0.05). Conclusions The birth certificate registry is a suitable sampling framework as measured by concordance with maternally reported infertility treatment. Future efforts should address the impact of factors associated with discordant reporting on research findings. C1 [Louis, Germaine M. Buck; Hediger, Mary L.; Sundaram, Rajeshwari; Yeung, Edwina; Thoma, Marie E.] Div Intramural Populat Hlth Res, Rockville, MD USA. [Bell, Erin M.] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Albany, NY 12222 USA. [Bell, Erin M.; Hills, Elaine A.; Druschel, Charlotte M.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Albany, NY 12222 USA. [Kus, Christopher A.] New York State Dept Hlth, Div Family Hlth, Albany, NY USA. [Hills, Elaine A.; Druschel, Charlotte M.] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA. [McLain, Alexander C.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM louisg@mail.nih.gov RI Yeung, Edwina/F-5992-2015; OI Yeung, Edwina/0000-0002-3851-2613; McLain, Alexander/0000-0002-5475-0670; Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200700019C, HHSN275201200005C] FX Funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts HHSN267200700019C; HHSN275201200005C). The authors thank Kira Leishear and Patricia Moyer for their statistical programming assistance, and John Piddock and Larry Schoen for their assistance with vital registries. NR 44 TC 15 Z9 15 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 EI 1365-3016 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAY PY 2014 VL 28 IS 3 BP 191 EP 202 DI 10.1111/ppe.12121 PG 12 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA AE2KH UT WOS:000333801300003 ER PT J AU Stenberg, N Bresnahan, M Gunnes, N Hirtz, D Hornig, M Lie, KK Lipkin, WI Lord, C Magnus, P Reichborn-Kjennerud, T Schjolberg, S Suren, P Susser, E Svendsen, BK von Tetzchner, S Oyen, AS Stoltenberg, C AF Stenberg, Nina Bresnahan, Michaeline Gunnes, Nina Hirtz, Deborah Hornig, Mady Lie, Kari Kveim Lipkin, W. Ian Lord, Catherine Magnus, Per Reichborn-Kjennerud, Ted Schjolberg, Synnve Suren, Pal Susser, Ezra Svendsen, Britt Kveim von Tetzchner, Stephen Oyen, Anne-Siri Stoltenberg, Camilla TI Identifying Children with Autism Spectrum Disorder at 18 Months in a General Population Sample SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE Norwegian Mother and Child Cohort Study; early identification; Autism Birth Cohort Study; longitudinal studies; M-CHAT; autism spectrum disorders ID PERVASIVE DEVELOPMENTAL DISORDERS; MODIFIED CHECKLIST; SCREENING INSTRUMENT; EARLY RECOGNITION; TODDLERS; AGE; DIAGNOSIS; COHORT; 1ST; SIGNS AB Background Previous research on clinical and high-risk samples suggests that signs of autism spectrum disorder (ASD) can be detected between 1 and 2 years of age. We investigated signs of ASD at 18 months in a population-based sample and the association with later ASD diagnosis. Methods The study sample includes 52 026 children born 2003 through 2008 and is a subset of children that participated in the Norwegian Mother and Child Cohort (MoBa), a population-based longitudinal study, and the Autism Birth Cohort (ABC), a sub-study on ASD. Parents completed all 23 items from the Modified Checklist for Autism in Toddlers (M-CHAT) at 18 months. Results The M-CHAT 6-critical-item criterion and the 23-item criterion had a specificity of 97.9% and 92.7% and a sensitivity of 20.8% and 34.1%, respectively. In the 173 children diagnosed with ASD to date, 60 children (34.7%) scored above the cut-off on either of the screening criteria. The items with the highest likelihood ratios were 'interest in other children', 'show objects to others' and 'response to name'. Conclusion Even though one-third of the children who later received an ASD diagnosis were identified through M-CHAT items, the majority scored below cut-off on the screening criteria at 18 months. The results imply that it might not be possible to detect all children with ASD at this age. C1 [Stenberg, Nina; Gunnes, Nina; Lie, Kari Kveim; Magnus, Per; Reichborn-Kjennerud, Ted; Schjolberg, Synnve; Suren, Pal; Oyen, Anne-Siri; Stoltenberg, Camilla] Norwegian Inst Publ Hlth, N-0403 Oslo, Norway. [Bresnahan, Michaeline; Hornig, Mady; Lipkin, W. Ian; Susser, Ezra] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [von Tetzchner, Stephen] Univ Oslo, Inst Psychol, Oslo, Norway. [Susser, Ezra] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Hornig, Mady; Lipkin, W. Ian] Columbia Univ, Ctr Infect & Immun, New York, NY USA. [Svendsen, Britt Kveim; Oyen, Anne-Siri] Lovisenberg Hosp, Nic Waals Inst, Oslo, Norway. [Hirtz, Deborah] NINDS, NIH, Bethesda, MD 20892 USA. [Lord, Catherine] New York Presbyterian Hosp, Weill Cornell Med Coll, Inst Brain Dev, New York, NY USA. [Lord, Catherine] Columbia Univ, Med Ctr, New York, NY USA. [Stoltenberg, Camilla] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. [Reichborn-Kjennerud, Ted] Univ Oslo, Inst Psychiat, Oslo, Norway. RP Stenberg, N (reprint author), Norwegian Inst Publ Hlth, POB 4404 Nydalen, N-0403 Oslo, Norway. EM nist@fhi.no FU Norwegian Ministry of Health and Care Services; Norwegian Ministry of Education and Research; Research Council of Norway/FUGE [151918]; National Institute of Neurological Disorders and Stroke (NIH/NINDS), Bethesda, MD, USA [NS47537]; National Institute of Environmental Health Sciences (NIH/NIEHS), Research Triangle Park, NC, USA [NO-ES-75558]; National Institute of Neurological Disorders and Stroke, (NIH/NINDS), Bethesda, MD, USA [NS47537]; Norwegian Research Council [196452] FX The authors would like to acknowledge and thank all participating families. The Norwegian Mother and Child Cohort Study is funded by the Norwegian Ministry of Health and Care Services, the Norwegian Ministry of Education and Research, the Research Council of Norway/FUGE (grant no. 151918), the National Institute of Neurological Disorders and Stroke (NIH/NINDS), Bethesda, MD, USA (grant no. NS47537) and the National Institute of Environmental Health Sciences (NIH/NIEHS), Research Triangle Park, NC, USA (contract no. NO-ES-75558). The Autism Birth Cohort study is funded by the National Institute of Neurological Disorders and Stroke, (NIH/NINDS), Bethesda, MD, USA (grant no. NS47537). The present study was supported by a grant from the Norwegian Research Council (grant no. 196452). NR 42 TC 16 Z9 16 U1 4 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 EI 1365-3016 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAY PY 2014 VL 28 IS 3 BP 255 EP 262 DI 10.1111/ppe.12114 PG 8 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA AE2KH UT WOS:000333801300009 PM 24547686 ER PT J AU Schisterman, EF AF Schisterman, Enrique F. CA EAGeR Team TI A randomised trial to evaluate the effects of low-dose aspirin in gestation and reproduction: Design and baseline characteristics (vol 27, pg 598, 2013) SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Correction C1 [Schisterman, Enrique F.; EAGeR Team] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD 20854 USA. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,7B03, Rockville, MD 20854 USA. EM schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 EI 1365-3016 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAY PY 2014 VL 28 IS 3 BP 275 EP 275 DI 10.1111/ppe.12122 PG 1 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA AE2KH UT WOS:000333801300012 ER PT J AU Saleem, KS Miller, B Price, JL AF Saleem, Kadharbatcha S. Miller, Brad Price, Joseph L. TI Subdivisions and Connectional Networks of the Lateral Prefrontal Cortex in the Macaque Monkey SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE LPFC; VLPFC; DPFC; CLPFC; OMPFC; OPFC; MPFC; superior temporal gyrus; parietal cortex; inferior temporal cortex; superior temporal sulcus; insula; connections ID SUPERIOR TEMPORAL SULCUS; FRONTAL EYE FIELD; COMPARATIVE CYTOARCHITECTONIC ANALYSIS; EFFERENT ASSOCIATION PATHWAYS; PRIMATE ORBITOFRONTAL CORTEX; MOTION-SENSITIVE CELLS; DEEP BRAIN-STIMULATION; REWARD-GUIDED BEHAVIOR; RHESUS-MONKEY; CORTICAL PROJECTIONS AB Neuroanatomical studies have long indicated that corticocortical connections are organized in networks that relate distinct sets of areas. Such networks have been emphasized by development of functional imaging methods for correlating activity across the cortex. Previously, two networks were recognized in the orbitomedial prefrontal cortex, the orbital and medial networks (OPFC and MPFC, respectively). In this study, three additional networks are proposed for the lateral prefrontal cortex: 1) a ventrolateral network (VLPFC) in and ventral to the principal sulcus; 2) a dorsal network (DPFC) in and dorsal to the principal sulcus and in the frontal pole; 3) a caudolateral network (CLPFC) in and rostral to the arcuate sulcus and the caudal principal sulcus. The connections of the first two networks are described here. Areas in each network are connected primarily with other areas in the same network, with overlaps around the principal sulcus. The VLPFC and DPFC are also connected with the OPFC and MPFC, respectively. Outside the prefrontal cortex, the VLPFC connects with specific areas related to somatic/visceral sensation and vision, in the frontoparietal operculum, insula, ventral bank/fundus of the superior temporal sulcus, inferior temporal gyrus, and inferior parietal cortex. In contrast, the DPFC connects with the rostral superior temporal gyrus, dorsal bank of the superior temporal sulcus, parahippocampal cortex, and posterior cingulate and retrosplenial cortex. Area 45a, in caudal VLPFC, is unique, having connections with all the networks. Its extrinsic connections resemble those of the DPFC. In addition, it has connections with both auditory belt/parabelt areas, and visual related areas. J. Comp. Neurol. 522:1641-1690, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Saleem, Kadharbatcha S.; Miller, Brad; Price, Joseph L.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Saleem, Kadharbatcha S.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Saleem, KS (reprint author), NIMH, Neuropsychol Lab, 49 Convent Dr,Bldg 49,1B80 MSc 4415, Bethesda, MD 20892 USA. EM saleemks@mail.nih.gov OI Saleem, Kadharbatcha S/0000-0002-4450-9234 FU National Institutes of Health [MH70941]; McDonnell Center for Higher Brain Function; National Institute of Mental Health Intramural Research Program FX Grant sponsor: National Institutes of Health; Grant number: MH70941; Grant sponsor: McDonnell Center for Higher Brain Function; Grant sponsor: National Institute of Mental Health Intramural Research Program. NR 155 TC 29 Z9 29 U1 5 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 1 PY 2014 VL 522 IS 7 BP 1641 EP 1690 DI 10.1002/cne.23498 PG 50 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA AD0HY UT WOS:000332916300010 PM 24214159 ER PT J AU Dauter, Z Wlodawer, A Minor, W Jaskolski, M Rupp, B AF Dauter, Zbigniew Wlodawer, Alexander Minor, Wladek Jaskolski, Mariusz Rupp, Bernhard TI Avoidable errors in deposited macromolecular structures: an impediment to efficient data mining SO IUCRJ LA English DT Article DE macromolecular crystallography; model validation; Protein Data Bank ID PROTEIN DATA-BANK; VALIDATION TASK-FORCE; CRYSTAL-STRUCTURE; CRYSTALLOGRAPHIC ANALYSIS; POWDER DIFFRACTION; DATA QUALITY; UNIT-CELL; Z-DNA; RESOLUTION; BINDING AB Whereas the vast majority of the more than 85 000 crystal structures of macromolecules currently deposited in the Protein Data Bank are of high quality, some suffer from a variety of imperfections. Although this fact has been pointed out in the past, it is still worth periodic updates so that the metadata obtained by global analysis of the available crystal structures, as well as the utilization of the individual structures for tasks such as drug design, should be based on only the most reliable data. Here, selected abnormal deposited structures have been analysed based on the Bayesian reasoning that the correctness of a model must be judged against both the primary evidence as well as prior knowledge. These structures, as well as information gained from the corresponding publications (if available), have emphasized some of the most prevalent types of common problems. The errors are often perfect illustrations of the nature of human cognition, which is frequently influenced by preconceptions that may lead to fanciful results in the absence of proper validation. Common errors can be traced to negligence and a lack of rigorous verification of the models against electron density, creation of non-parsimonious models, generation of improbable numbers, application of incorrect symmetry, illogical presentation of the results, or violation of the rules of chemistry and physics. Paying more attention to such problems, not only in the final validation stages but during the structure-determination process as well, is necessary not only in order to maintain the highest possible quality of the structural repositories and databases but most of all to provide a solid basis for subsequent studies, including large-scale data-mining projects. For many scientists PDB deposition is a rather infrequent event, so the need for proper training and supervision is emphasized, as well as the need for constant alertness of reason and critical judgment as absolutely necessary safeguarding measures against such problems. Ways of identifying more problematic structures are suggested so that their users may be properly alerted to their possible shortcomings. C1 [Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne Natl Lab, Argonne, IL 60439 USA. [Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. [Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. [Minor, Wladek] Midwest Ctr Struct Genom, Argonne, IL USA. [Minor, Wladek] New York Struct Genom Consortium, New York, NY USA. [Minor, Wladek] Ctr Struct Genom Infect Dis, Seattle, WA USA. [Minor, Wladek] Enzyme Funct Initiat, Urbana, IL USA. [Jaskolski, Mariusz] Adam Mickiewicz Univ, Fac Chem, Dept Crystallog, Poznan, Poland. [Jaskolski, Mariusz] Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, Poznan, Poland. [Rupp, Bernhard] KK Hofkristallamt, Vista, CA 92084 USA. [Rupp, Bernhard] Med Univ Innsbruck, Dept Genet Epidemiol, A-6020 Innsbruck, Austria. RP Dauter, Z (reprint author), NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne Natl Lab, Argonne, IL 60439 USA. EM dauter@anl.gov OI Minor, Wladek/0000-0001-7075-7090 FU NIH, National Cancer Institute, Center for Cancer Research; European Union [PIIF-GA-2011-300025]; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272201200026C]; NIH [GM094662, GM093342, GM053163, GM094585] FX The authors wish to thank Szymon Krzywda, Mirek Gilski, Ivan Shabalin and Marcin Cymborowski for help in the preparation of some of the data used as examples. This work was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (ZD and AW). BR acknowledges support from the European Union under a FP7 Marie Curie People Action, grant PIIF-GA-2011-300025 (SAXCESS). WM was supported by federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under Contract No. HHSN272201200026C and by NIH grants GM094662, GM093342, GM053163 and GM094585. NR 84 TC 29 Z9 29 U1 2 U2 12 PU INT UNION CRYSTALLOGRAPHY PI CHESTER PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND SN 2052-2525 J9 IUCRJ JI IUCrJ PD MAY PY 2014 VL 1 BP 179 EP 193 DI 10.1107/S2052252514005442 PN 3 PG 15 WC Chemistry, Multidisciplinary; Crystallography; Materials Science, Multidisciplinary SC Chemistry; Crystallography; Materials Science GA CL3QA UT WOS:000356864000007 PM 25075337 ER PT J AU Ehsani, JP Bingham, CR Ionides, E Childers, D AF Ehsani, Johnathon P. Bingham, C. Raymond Ionides, Edward Childers, David TI The Impact of Michigan's Text Messaging Restriction on Motor Vehicle Crashes SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Motor vehicle crashes; Texting; Restriction; Law; Distraction; Adolescent driver AB Purpose: The purpose of this study was to determine the effects of Michigan's universal text messaging restriction (effective July 2010) across different age groups of drivers and crash severities. Methods: Changes in monthly crash rates and crash trends per 10,000 licensed drivers aged 16, 17, 18, 19, 20-24, and 25-50 years were estimated using time series analysis for three levels of crash severity: (1) fatal/disabling injury; (2) nondisabling injury; and (3) possible injury/property damage only (PDO) crashes for the period 2005-2012. Analyses were adjusted for crash rates of drivers' aged 65-99 years, Michigan's unemployment rate, and gasoline prices. Results: After the introduction of the texting restriction, significant increases were observed in crash rates and monthly trends in fatal/disabling injury crashes and nondisabling injury crashes, and significant decreases in possible injury/PDO crashes. The magnitude of the effects where significant changes were observed was small. Conclusions: The introduction of the texting restriction was not associated with a reduction in crash rates or trends in severe crash types. On the contrary, small increases in the most severe crash types (fatal/disabling and nondisabling injury) and small decreases in the least severe crash types (possible injury/PDO) were observed. These findings extend the literature on the effects of cell phone restrictions by examining the effects of the restriction on newly licensed adolescent drivers and adult drivers separately by crash severity. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine. C1 [Ehsani, Johnathon P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA. [Bingham, C. Raymond] Univ Michigan, Transportat Res Inst, Young Driver Behav & Injury Prevent Grp, Ann Arbor, MI 48109 USA. [Bingham, C. Raymond] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Ionides, Edward] Univ Michigan, Dept Stat, Coll Literature Sci & Arts, Ann Arbor, MI 48109 USA. [Childers, David] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. RP Ehsani, JP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. EM johnathon.ehsani@nih.gov FU University of Michigan Injury Center; National Center for Injury Prevention and Control of the Centers for Disease Control and Prevention FX The University of Michigan Injury Center and the National Center for Injury Prevention and Control of the Centers for Disease Control and Prevention provided support for this research. NR 42 TC 11 Z9 11 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD MAY PY 2014 VL 54 IS 5 SU S BP S68 EP S74 DI 10.1016/j.jadohealth.2014.01.003 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA V43TA UT WOS:000209702500010 PM 24759444 ER PT J AU Falk, EB Cascio, CN O'Donnell, MB Carp, J Tinney, FJ Bingham, CR Shope, JT Ouimet, MC Pradhan, AK Simons-Morton, BG AF Falk, Emily B. Cascio, Christopher N. O'Donnell, Matthew Brook Carp, Joshua Tinney, Francis J., Jr. Bingham, C. Raymond Shope, Jean T. Ouimet, Marie Claude Pradhan, Anuj K. Simons-Morton, Bruce G. TI Neural Responses to Exclusion Predict Susceptibility to Social Influence SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Adolescent behavior; Risk taking; Driving; Social exclusion; Social influence; Peer influence; Social pain; Mentalizing; fMRI; Neuroimaging AB Purpose: Social influence is prominent across the lifespan, but sensitivity to influence is especially high during adolescence and is often associated with increased risk taking. Such risk taking can have dire consequences. For example, in American adolescents, traffic-related crashes are leading causes of nonfatal injury and death. Neural measures may be especially useful in understanding the basic mechanisms of adolescents' vulnerability to peer influence. Methods: We examined neural responses to social exclusion as potential predictors of risk taking in the presence of peers in recently licensed adolescent drivers. Risk taking was assessed in a driving simulator session occurring approximately 1 week after the neuroimaging session. Results: Increased activity in neural systems associated with the distress of social exclusion and mentalizing during an exclusion episode predicted increased risk taking in the presence of a peer (controlling for solo risk behavior) during a driving simulator session outside the neuroimaging laboratory 1 week later. These neural measures predicted risky driving behavior above and beyond self-reports of susceptibility to peer pressure and distress during exclusion. Conclusions: These results address the neural bases of social influence and risk taking; contribute to our understanding of social and emotional function in the adolescent brain; and link neural activity in specific, hypothesized, regions to risk-relevant outcomes beyond the neuroimaging laboratory. Results of this investigation are discussed in terms of the mechanisms underlying risk taking in adolescents and the public health implications for adolescent driving. (C) 2014 Society for Adolescent Health and Medicine. C1 [Falk, Emily B.; Cascio, Christopher N.; O'Donnell, Matthew Brook] Univ Penn, Annenberg Sch Commun, 3620 Walnut St, Philadelphia, PA 19104 USA. [Carp, Joshua] Univ Michigan, Dept Psychol, Ann Arbor, MI USA. [Tinney, Francis J., Jr.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Bingham, C. Raymond; Shope, Jean T.; Pradhan, Anuj K.] Univ Michigan, UMTRI, Ann Arbor, MI 48109 USA. [Ouimet, Marie Claude] Univ Sherbrooke, Fac Med & Hlth Sci, Longueuil, PQ, Canada. [Simons-Morton, Bruce G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Bethesda, MD USA. RP Falk, EB (reprint author), Univ Penn, Annenberg Sch Commun, 3620 Walnut St, Philadelphia, PA 19104 USA. EM falk@asc.upenn.edu OI Pradhan, Anuj/0000-0002-7612-4208; Simons-Morton, Bruce/0000-0003-1099-6617 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN275201000007 C]; University of Michigan Injury Center Pilot Grant FX The research was supported by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development contract # HHSN275201000007 C (PI: Bingham) and the University of Michigan Injury Center Pilot Grant (PI: Falk). NR 71 TC 12 Z9 12 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD MAY PY 2014 VL 54 IS 5 SU S BP S22 EP S31 DI 10.1016/j.jadohealth.2013.12.035 PG 10 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA V43TA UT WOS:000209702500005 PM 24759437 ER PT J AU Pradhan, AK Li, KG Bingham, CR Simons-Morton, BG Ouimet, MC Shope, JT AF Pradhan, Anuj K. Li, Kaigang Bingham, C. Raymond Simons-Morton, Bruce G. Ouimet, Marie Claude Shope, Jean T. TI Peer Passenger Influences on Male Adolescent Drivers' Visual Scanning Behavior During Simulated Driving SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Adolescent driver; Peer passenger; Driving simulation; Eye tracking; Distraction AB Purpose: There is a higher likelihood of crashes and fatalities when an adolescent drives with peer passengers, especially for male drivers and male passengers. Simulated driving of male adolescent drivers with male peer passengers was studied to examine passenger influences on distraction and inattention. Methods: Male adolescents drove in a high-fidelity driving simulator with a male confederate who posed either as a risk-accepting passenger or as a risk-averse passenger. Drivers' eye movements were recorded. The visual scanning behavior of the drivers was compared when driving alone with when driving with a passenger and when driving with a risk-accepting passenger with a risk-averse passenger. Results: The visual scanning of a driver significantly narrowed horizontally and vertically when driving with a peer passenger. There were no significant differences in the times the drivers' eyes were off the forward roadway when driving with a passenger versus when driving alone. Some significant correlations were found between personality characteristics and the outcome measures. Conclusions: The presence of a male peer passenger was associated with a reduction in the visual scanning range of male adolescent drivers. This reduction could be a result of potential cognitive load imposed on the driver due to the presence of a passenger and the real or perceived normative influences or expectations from the passenger. (C) 2014 Society for Adolescent Health and Medicine. C1 [Pradhan, Anuj K.; Bingham, C. Raymond; Shope, Jean T.] Univ Michigan, Transportat Res Inst, 2901 Baxter Rd, Ann Arbor, MI 48109 USA. [Li, Kaigang; Simons-Morton, Bruce G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD USA. [Ouimet, Marie Claude] Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. RP Pradhan, AK (reprint author), Univ Michigan, Transportat Res Inst, 2901 Baxter Rd, Ann Arbor, MI 48109 USA. EM anujkp@umich.edu OI Pradhan, Anuj/0000-0002-7612-4208; Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN275201000007C] FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract # HHSN275201000007C. NR 43 TC 10 Z9 10 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD MAY PY 2014 VL 54 IS 5 SU S BP S42 EP S49 DI 10.1016/j.jadohealth.2014.01.004 PG 8 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA V43TA UT WOS:000209702500007 PM 24759440 ER PT J AU Simons-Morton, BG Guo, F Klauer, SG Ehsani, JP Pradhan, AK AF Simons-Morton, Bruce G. Guo, Feng Klauer, Sheila G. Ehsani, Johnathon P. Pradhan, Anuj K. TI Keep Your Eyes on the Road: Young Driver Crash Risk Increases According to Duration of Distraction SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Adolescents; Risk taking; Cell phone use; Secondary task; Teenage driver; Naturalistic driving methods AB Purpose: Secondary task engagement that distracts the driver is a contributing factor to motor vehicle crashes among adults. However, the association between eye glance duration and crash risk with novice teenage drivers has not been determined. Methods: Vehicles of 42 newly licensed teenage drivers were instrumented with cameras, accelerometers, Global Positioning System(s) (GPS), and other devices. Data were collected continuously for 18 months. Crashes and near crashes (CNCs) were identified by examining highly elevated gravitational force events. Video footage of the 6 seconds prior to each CNC and randomly sampled non-CNC road segments were coded for the duration of eye glances off the forward roadway and the presence of secondary task engagement. The likelihood (odds ratios) of CNC due to eye glance behavior was calculated by comparing the prevalence of secondary task engagement and duration of eyes off road prior to CNC with the prevalence and duration of eyes off road during non-CNC road segments. Results: Crash risk increased with the duration of single longest glance during all secondary tasks (OR = 3.8 for > 2 s) and wireless secondary task engagement (OR = 5.5 for > 2 s). Single longest glance provided a more consistent estimate of crash risk than total time eyes off the forward roadway. Conclusions: Those eye glances away from the forward roadway involving secondary tasks increased the likelihood of CNC. The longer the duration of eye glance away from the road the greater the risk, regardless of type of secondary task. Education and policy discouraging secondary task engagement, particularly for prolonged periods, is warranted. (C) 2014 Society for Adolescent Health and Medicine. C1 [Simons-Morton, Bruce G.; Ehsani, Johnathon P.; Pradhan, Anuj K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA. [Guo, Feng; Klauer, Sheila G.] Virginia Tech Univ, Virginia Tech Transportat Inst, Blacksburg, VA USA. RP Simons-Morton, BG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B13M, Bethesda, MD 20892 USA. EM mortonb@mail.nih.gov OI Pradhan, Anuj/0000-0002-7612-4208 FU Foundation for Advancing Alcohol Responsibility FX Publication of this article was supported by the Foundation for Advancing Alcohol Responsibility. The opinions or views expressed in this paper are those of the authors and do not necessarily represent the official position of the Foundation for Advancing Alcohol Responsibility. NR 29 TC 15 Z9 16 U1 4 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD MAY PY 2014 VL 54 IS 5 SU S BP S61 EP S67 DI 10.1016/j.jadohealth.2013.11.021 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA V43TA UT WOS:000209702500009 PM 24759443 ER PT J AU Adkins, E Wang, XL Sproule, T Christianson, G Park, GJ Carter, G Morse, H Roopenian, D AF Adkins, Elisabeth Wang, Xulong Sproule, Thomas Christianson, Gregory Park, Giljun Carter, Gregory Morse, Herbert Roopenian, Derry TI A novel population of interleukin 21-producing pre-follicular T helper cells develop spontaneously in young naive mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Adkins, Elisabeth; Wang, Xulong; Sproule, Thomas; Christianson, Gregory; Park, Giljun; Carter, Gregory; Roopenian, Derry] Jackson Lab, Bar Harbor, ME 04609 USA. [Adkins, Elisabeth; Roopenian, Derry] Tufts Univ, Sackler Sch Grad Biomed Sci, Genet, Boston, MA 02111 USA. [Morse, Herbert] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM3P.743 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000124 ER PT J AU Azzam, K Madenspacher, J Lai, LH Gowdy, K Clayton, N Cunningham, W Janardhan, K Taylor, G Fessler, M AF Azzam, Kathleen Madenspacher, Jennifer Lai, Lihua Gowdy, Kymberly Clayton, Natasha Cunningham, Willie Janardhan, Kyathanahalli Taylor, Gregory Fessler, Michael TI Irgm1 regulates the pulmonary innate immune response SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Azzam, Kathleen; Madenspacher, Jennifer; Lai, Lihua; Gowdy, Kymberly; Fessler, Michael] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. [Clayton, Natasha; Cunningham, Willie; Janardhan, Kyathanahalli] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Taylor, Gregory] Durham VA Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA MUC5P.864 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005045 ER PT J AU Baseler, W O'Connor, G McVicar, D AF Baseler, Walter O'Connor, Geraldine McVicar, Daniel TI Mitochondrial-mediated inflammasome activation controls production of Hepatoma-derived IL-1 beta SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Baseler, Walter; O'Connor, Geraldine; McVicar, Daniel] NCI, Canc Inflammat Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA TUM7P.942 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000160 ER PT J AU Basu, S Bowen, B Sheyach, E AF Basu, Samik Bowen, Britany Sheyach, Ethan TI Foxp3-mediated inhibition of Akt inhibits Glut1 expression in human T regulatory cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Basu, Samik; Bowen, Britany; Sheyach, Ethan] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA14P.203 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005190 ER PT J AU Berkower, I Virnik, K Hockenbury, M Rosati, M Alicea, C Valentin, A Pavlakis, G Felber, B AF Berkower, Ira Virnik, Konstantin Hockenbury, Max Rosati, Margherita Alicea, Candido Valentin, Antonio Pavlakis, George Felber, Barbara TI Live attenuated rubella vectors express HIV Env and SIV Gag antigens in the context of an acute infection and elicit high antibody titers, memory B cells, and Gag specific CD8+T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Berkower, Ira; Virnik, Konstantin; Hockenbury, Max] US FDA, Ctr Biol, Bethesda, MD 20014 USA. [Rosati, Margherita; Alicea, Candido; Valentin, Antonio; Pavlakis, George; Felber, Barbara] NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VIR5P.1033 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005023 ER PT J AU Biragyn, A Bodogai, M Lee-Chang, C AF Biragyn, Arya Bodogai, Monica Lee-Chang, Catalina TI The central role of tumor-evoked Bregs in breast cancer metastasis as inducers of metastasis-promoting Tregs and myeloid-derived suppressive cells. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Biragyn, Arya; Bodogai, Monica; Lee-Chang, Catalina] NIA, Baltimore, MD 21224 USA. RI Lee-Chang, Catalina/A-5580-2015 OI Lee-Chang, Catalina/0000-0002-7675-2124 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA TUM4P.903 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004043 ER PT J AU Boelte, K Sen, S Priel, DL Lau, K Cardone, M Yoshimura, T Barb, J Joehanes, R Accame, D Teer, J Singh, L Adams, L Zhang, XQ Chowdhury, S Johnson, A Green, E Mullikin, J Kolodgie, F Virmani, R O'Donnell, C Munson, P Trinchieri, G Kuhns, D Biesecker, L McVicar, D AF Boelte, Kimberly Sen, Shurjo Priel, Debra Long Lau, Karen Cardone, Marco Yoshimura, Teizo Barb, Jennifer Joehanes, Roby Accame, David Teer, Jamie Singh, Larry Adams, Lila Zhang, XiaoQing Chowdhury, Soma Johnson, Andrew Green, Eric Mullikin, James Kolodgie, Frank Virmani, Renu O'Donnell, Christopher Munson, Peter Trinchieri, Giorgio Kuhns, Douglas Biesecker, Leslie McVicar, Daniel TI TREML4 expression by myeloid cells may play a role in coronary artery disease SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Boelte, Kimberly; Cardone, Marco; Yoshimura, Teizo; Trinchieri, Giorgio; McVicar, Daniel] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Sen, Shurjo; Accame, David; Singh, Larry; Green, Eric; Mullikin, James; Biesecker, Leslie] NHGRI, NIH, Bethesda, MD 20892 USA. [Johnson, Andrew; O'Donnell, Christopher] NHLBI, NIH, Bethesda, MD 20892 USA. [Chowdhury, Soma] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Adams, Lila; Zhang, XiaoQing; Kolodgie, Frank; Virmani, Renu] CVPath Inst, Gaithersburg, MD USA. [Teer, Jamie] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Barb, Jennifer; Joehanes, Roby; Munson, Peter] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. [Priel, Debra Long; Lau, Karen; Kuhns, Douglas] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HUM1P.308 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000235 ER PT J AU Bolanos, RB Sharma, A Sultana, D Chen, QH Heller, N Sen, J AF Bolanos, Rosa Berga Sharma, Archna Sultana, Dil Chen, Qinghua Heller, Nicola Sen, Jyoti TI T Cell Factor-1 and beta-catenin specifically and critically control the generation and function of T helper 2-type natural killer T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Bolanos, Rosa Berga; Sharma, Archna; Sultana, Dil; Chen, Qinghua; Sen, Jyoti] NIA, Immune Cells & Inflammat Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Heller, Nicola] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. RI Sharma, Archna/R-9377-2016 OI Sharma, Archna/0000-0003-4745-0220 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM7P.725 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005222 ER PT J AU Bowen, S Sharrow, S Hodes, R AF Bowen, Steven Sharrow, Susan Hodes, Richard TI Hybrid V gamma-C beta TCR chains support T cell development and an immunocompetent T cell repertoire SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Bowen, Steven; Sharrow, Susan; Hodes, Richard] NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM7P.713 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005230 ER PT J AU Chang, CL Bodogai, M Moritoh, K Croft, M Gress, R Ferrucci, L Hakim, F Biragyn, A AF Chang, Catalina Lee Bodogai, Monica Moritoh, Kanako Croft, Michael Gress, Ronald Ferrucci, Luigi Hakim, Fran Biragyn, Arya TI A novel aging-associate B-cell subset controls antitumor CD8+T-cell response SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chang, Catalina Lee; Bodogai, Monica; Moritoh, Kanako; Biragyn, Arya] NIH, Immunoregulat Sect, Lab Mol Biol & Immunol, Baltimore, MD USA. [Croft, Michael] La Jolla Inst Allergy & Immunol, Div Immune Regulat, La Jolla, CA USA. [Gress, Ronald] NCI, Translat Surg Pathol, NIH, Bethesda, MD 20892 USA. [Ferrucci, Luigi] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Hakim, Fran] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRC3P.469 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004167 ER PT J AU Chen, GB Solokina, A Li, HF Truong, T Oelke, M Wersto, R Schneck, J Leng, S Weng, NP AF Chen, Guobing Solokina, Arina Li, Huifen Truong, Thai Oelke, Mathias Wersto, Robert Schneck, Jonathan Leng, Sean Weng, Nan-ping TI Different competency of CMV-pp65 or Flu-M1 specific CD8+T cells in naive and central memory population in healthy human adults SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chen, Guobing; Solokina, Arina; Truong, Thai; Wersto, Robert; Weng, Nan-ping] NIA, Baltimore, MD 21224 USA. [Li, Huifen; Oelke, Mathias; Schneck, Jonathan; Leng, Sean] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RI Chen, Guobing/D-9572-2012 OI Chen, Guobing/0000-0002-2401-6168 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA TRAN3P.885 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765006145 ER PT J AU Chen, J Feigenbaum, L Awasthi, P Butcher, D Anver, M Golubeva, Y Bamford, R Zhang, XJ St Claire, M Thomas, C Discepolo, V Jabri, B Waldmann, T AF Chen, Jing Feigenbaum, Lionel Awasthi, Parirokh Butcher, Donna Anver, Miriam Golubeva, Yelena Bamford, Richard Zhang, XiaoJie St Claire, Mark Thomas, Craig Discepolo, Valentina Jabri, Bana Waldmann, Thomas TI Increased expression of IL-15 and IL-15Ra in the islets of patients with T1D SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chen, Jing; Waldmann, Thomas] NCI, Metab Branch, Bethesda, MD 20892 USA. [Feigenbaum, Lionel; Awasthi, Parirokh; Butcher, Donna; Anver, Miriam; Golubeva, Yelena] SAIC, Lab Anim Sci Program, Frederick, MD USA. [Bamford, Richard] Transponics, Jacobus, PA USA. [Zhang, XiaoJie; St Claire, Mark] NIDDK, Lab Anim Sci Sect, Bethesda, MD 20892 USA. [Thomas, Craig] NHGRI, NIHchem Genom Ctr, Rockville, MD USA. [Discepolo, Valentina; Jabri, Bana] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CCR3P.217 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001158 ER PT J AU Chen, X Xiao, HT Howard, OMZ Oppenheim, J AF Chen, Xin Xiao, Haitao Howard, O. M. Zack Oppenheim, Joost TI TNFR2 expression by CD4 effector T cells is required to induce full-fledged experimental colitis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chen, Xin] Leidos Biomed Resaerch Inc, Basic Sci Program, Frederick, MD USA. [Chen, Xin; Xiao, Haitao; Howard, O. M. Zack; Oppenheim, Joost] NCI, Lab Mol Immunoregulat, Frederick, MD 21701 USA. [Xiao, Haitao] Hong Kong Baptist Univ, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CCR3P.204 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001147 ER PT J AU Chiang, YP Hodes, R AF Chiang, Yungping Hodes, Richard TI Lck is essential in the non-canonical T cell receptor CR signaling pathway regulated pressed by Cbl during T cell development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chiang, Yungping; Hodes, Richard] NCI, EIB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM7P.727 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005229 ER PT J AU Chong, WP Chen, J Silver, P Caspi, R AF Chong, Wai Po Chen, Jun Silver, Phyllis Caspi, Rachel TI Reciprocal interaction between NK cells and DCs regulates the Th17 response by controlling the innate IFN-gamma/IL-27 axis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chong, Wai Po; Chen, Jun; Silver, Phyllis; Caspi, Rachel] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA13P.124 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005169 ER PT J AU Coligan, J Tian, LJ Margulies, D Krzewski, K Murakami, Y AF Coligan, John Tian, Linjie Margulies, David Krzewski, Konrad Murakami, Yousuke TI Mouse CD300b (CLM-7) regulates the phagocytosis of apoptotic cells via phosphatidylserine recognition. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Coligan, John; Tian, Linjie; Krzewski, Konrad; Murakami, Yousuke] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Margulies, David] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA4P.215 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002199 ER PT J AU Cruse, G Music, S Bradding, P Beaven, M Metcalfe, D AF Cruse, Glenn Music, Stephen Bradding, Peter Beaven, Michael Metcalfe, Dean TI MS4A4 regulates KIT receptor trafficking, signaling and function in mast cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Cruse, Glenn; Music, Stephen; Metcalfe, Dean] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Bradding, Peter] Univ Leicester, Infect Immun & Inflammat, Leicester, Leics, England. [Beaven, Michael] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HYP3P.343 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003122 ER PT J AU Cruz, A Ramaswamy, M Sengupta, P Lippincott-Schwartz, J Siegel, R AF Cruz, Anthony Ramaswamy, Madhu Sengupta, Prabhudda Lippincott-Schwartz, Jennifer Siegel, Richard TI Palmitoylation is required for Fas receptor clustering and cell death in CD4(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Cruz, Anthony; Ramaswamy, Madhu; Siegel, Richard] NIAMS, NIH, Bethesda, MD USA. [Sengupta, Prabhudda; Lippincott-Schwartz, Jennifer] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM7P.722 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005236 ER PT J AU Dambuza, I Yu, CR Wang, RX Kim, SY Mahdi, R Dolinska, M Sergeev, Y Wingfield, P Egwuagu, C AF Dambuza, Ivy Yu, Cheng-Rong Wang, Ren-Xi Kim, Sung-Ye Mahdi, Rashid Dolinska, Monika Sergeev, Yuri Wingfield, Paul Egwuagu, Charles TI IL-12p35 single chain subunit antagonizes IL-6 mediated STAT1 and STAT3 activation and prevents expansion of Th17 cells in experimental autoimmune uveitis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Dambuza, Ivy; Yu, Cheng-Rong; Wang, Ren-Xi; Kim, Sung-Ye; Mahdi, Rashid; Dolinska, Monika; Sergeev, Yuri; Egwuagu, Charles] NEI, Bethesda, MD 20892 USA. [Wingfield, Paul] NIAMS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CCR1P.246 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003014 ER PT J AU Edwards, J Thornton, A Shevach, E AF Edwards, Justin Thornton, Angela Shevach, Ethan TI Integrin beta 8 is a marker of mouse regulatory T-cells (Treg) and is required for processing of latent TGF-beta 1 from the GARP/latent TGF-beta 1 complex SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Edwards, Justin; Thornton, Angela; Shevach, Ethan] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRC4P.483 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005039 ER PT J AU Ferdinand, J Meylan, F Siegel, R Al-Shamkhani, A AF Ferdinand, John Meylan, Francoise Siegel, Richard Al-Shamkhani, Aymen TI The biological function of membrane versus soluble TL1A SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ferdinand, John; Al-Shamkhani, Aymen] Univ Southampton, Canc Sci Div, Fac Med, Southampton, Hants, England. [Ferdinand, John; Meylan, Francoise; Siegel, Richard] NIAMS, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CCR3P.205 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001154 ER PT J AU Filardy, A He, JP Silyeira, D Kelsall, B AF Filardy, Alessandra He, JianPing Silyeira, Danielle Kelsall, Brian TI Poor expression and activation of the NLRP3 inflammasome in resident but not inflammatory colonic monocytes/macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Filardy, Alessandra; He, JianPing; Silyeira, Danielle; Kelsall, Brian] NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA MUC2P.831 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001187 ER PT J AU Frey, B Sui, YJ Wang, YC Hogg, A Yu, B Berman, P Berzofsky, J AF Frey, Blake Sui, Yongjun Wang, Yichuan Hogg, Alison Yu, Bin Berman, Phillip Berzofsky, Jay TI Modulating cathepsin cleavage sites in HIV gp 120 envelope protein alters the cellular immune response. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Frey, Blake; Sui, Yongjun; Wang, Yichuan; Hogg, Alison; Berzofsky, Jay] NCI, Bethesda, MD 20892 USA. [Yu, Bin; Berman, Phillip] Univ Calif Santa Cruz, Biomol Engn, Santa Cruz, CA 95064 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC7P.989 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002054 ER PT J AU Fujihara, C Williams, J Jeon, H Hodes, R AF Fujihara, Chiharu Williams, Joy Jeon, Hyein Hodes, Richard TI Cognate CD40-CD40L interaction is important for maintenance of thymic B cells. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Fujihara, Chiharu; Williams, Joy; Jeon, Hyein; Hodes, Richard] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRM8P.705 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003240 ER PT J AU Ghosh, A De, S Bell, J Weber, B Wood, W Becker, K Sen, J Bhandoola, A Sen, R AF Ghosh, Amalendu De, Supriyo Bell, Jeremiah Weber, Brittany Wood, William Becker, Kevin Sen, Jyoti Bhandoola, Avinash Sen, Ranjan TI Generation and resolution of bivalent chromatin during hematopoiesis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ghosh, Amalendu; De, Supriyo; Wood, William; Becker, Kevin; Sen, Jyoti; Sen, Ranjan] NIA, LMBI, Baltimore, MD 21224 USA. [Bell, Jeremiah; Weber, Brittany; Bhandoola, Avinash] Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HEM2P.259 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001086 ER PT J AU Hart, G Wei, CW Chida, A Crompton, P Sanz, I Pierce, S AF Hart, Geoffrey Wei, Chungwen Chida, Asiya Crompton, Peter Sanz, Ignacio Pierce, Susan TI A B cell riddle: a new tool to study the link between malaria and Burkitt's Lymphoma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hart, Geoffrey; Crompton, Peter; Pierce, Susan] NIAID, NIH, Rockville, MD USA. [Wei, Chungwen; Chida, Asiya; Sanz, Ignacio] Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA TUM5P.935 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003073 ER PT J AU Hataye, J Casazza, J Ambrozak, D Boritz, E Yamamoto, T Douek, D Koup, R AF Hataye, Jason Casazza, Joseph Ambrozak, David Boritz, Eli Yamamoto, Takuya Douek, Daniel Koup, Richard TI A scalable RNA RT-PCR based assay to quantify latency disruption in HIV-1 infected cells from patients on antiretroviral therapy SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hataye, Jason; Casazza, Joseph; Ambrozak, David; Boritz, Eli; Yamamoto, Takuya; Douek, Daniel; Koup, Richard] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VIR1P.1001 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005006 ER PT J AU Hathcock, K Padilia-Nash, H Camps, J Triner, D Shin, DM Maul, R Gearhart, P Morse, H Ried, T Hodes, R AF Hathcock, Karen Padilia-Nash, Hesed Camps, Jordi Triner, Daniel Shin, Dong-Mi Maul, Robert Gearhart, Patricia Morse, Herbert Ried, Thomas Hodes, Richard TI ATM-deficiency in the absence of T cells promotes the development of B cell lymphomas with dependence on NF-kappa B SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hathcock, Karen; Padilia-Nash, Hesed; Camps, Jordi; Triner, Daniel; Shin, Dong-Mi; Maul, Robert; Gearhart, Patricia; Morse, Herbert; Ried, Thomas; Hodes, Richard] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA TUM7P.927 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000153 ER PT J AU Hayashi, T Hu, YQ Furukawa, K Ohishi, W Geyer, S Weng, NP Hayashi, I Yoshida, K Kajimura, J Kyoizumi, S Kusunoki, Y Nakachi, K AF Hayashi, Tomonori Hu, Yiqun Furukawa, Kyoji Ohishi, Waka Geyer, Susan Weng, Nan-ping Hayashi, Ikue Yoshida, Kengo Kajimura, Junko Kyoizumi, Seishi Kusunoki, Yoichiro Nakachi, Kei TI The association of ROS levels in blood cells with age, past radiation exposure, and IL6R gene polymorphisms SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hayashi, Tomonori; Hu, Yiqun; Hayashi, Ikue; Yoshida, Kengo; Kajimura, Junko; Kyoizumi, Seishi; Kusunoki, Yoichiro; Nakachi, Kei] Radiat Effects Res Fdn, Dept Radiobiol Mol Epidemiol, Hiroshima, Japan. [Furukawa, Kyoji] Radiat Effects Res Fdn, Dept Stat, Hiroshima, Japan. [Ohishi, Waka] Radiat Effects Res Fdn, Dept Clin Studies, Hiroshima, Japan. [Geyer, Susan] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Weng, Nan-ping] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Hayashi, Ikue] Hiroshima Univ, Fac Dent, Hiroshima, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CCR3P.211 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001164 ER PT J AU Herz, J McGavern, D AF Herz, Jasmin McGavern, Dorian TI Therapeutic clearance of the virally infected nervous system via noncytopathic T cell interactions with resident myeloid cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Herz, Jasmin; McGavern, Dorian] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC6P.945 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000071 ER PT J AU Highfill, S Smith, J Long, A Cui, YZ Orentas, R Mackail, C AF Highfill, Steven Smith, Jillian Long, Adrienne Cui, Yongzhi Orentas, Rimas Mackail, Crystal TI Neutralization of murine myeloid suppressor cells enhances the efficacy of GD2-specific CAR T cells directed against human sarcoma in a xenograft model SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Highfill, Steven; Smith, Jillian; Long, Adrienne; Cui, Yongzhi; Orentas, Rimas; Mackail, Crystal] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC11P1010 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000083 ER PT J AU Hodge, D Berthet, C Coppola, V Kastenmuller, W Buschman, M Shirota, H Schaughency, P Anver, M Della Reynolds, Sanford, M Kaldis, P Young, H AF Hodge, Deborah Berthet, Cyril Coppola, Vincenzo Kastenmueller, Wolfgang Buschman, Matthew Shirota, Hidekazu Schaughency, Paul Anver, Miriam Reynolds, Della Sanford, Michael Kaldis, Philipp Young, Howard TI Autoimmunity in interferon-gamma AU-rich element deleted-mice is associated with loss of marginal zone B cells and macrophages. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hodge, Deborah; Reynolds, Della; Sanford, Michael; Young, Howard] NCI, Frederick, MD 21701 USA. [Berthet, Cyril] Oncodesign, Dijon, France. [Coppola, Vincenzo] Ohio State Univ, Immunol & Med Genet, Columbus, OH 43210 USA. [Buschman, Matthew] Univ Calif San Diego, San Diego, CA 92103 USA. [Anver, Miriam] Leidos Biomed Res, Frederick, MD USA. [Kaldis, Philipp] Agcy Sci Technol & Res, Singapore, Singapore. [Kastenmueller, Wolfgang] Univ Bonn, Bonn, Germany. [Shirota, Hidekazu] Tohoku Univ Hosp, Sendai, Miyagi, Japan. [Schaughency, Paul] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA15P.217 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002247 ER PT J AU Indramohan, M Break, T Witter, A Berg, R AF Indramohan, Mohanalaxmi Break, Timothy Witter, Alexandra Berg, Rance TI The role of IL-23 in regulating the function of phagocytic cells during Listeria monocytogenes infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Indramohan, Mohanalaxmi; Witter, Alexandra; Berg, Rance] Univ North Texas, Hlth Sci Ctr, Cell Biol & Immunol, Ft Worth, TX USA. [Break, Timothy] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA MPF3P.822 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002174 ER PT J AU Jain, S Adkins, E McPhee, C Christianson, G Sproule, T Shin, DM Roopenian, D Morse, H AF Jain, Shweta Adkins, Elisabeth McPhee, Caroline Christianson, Gregory Sproule, Thomas Shin, Dong-Mi Roopenian, Derry Morse, Herbert TI Intricate interplay of cytokines determine the progression of SLE-like disease in BXSB.Yaa mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Jain, Shweta; Shin, Dong-Mi; Morse, Herbert] NIAID, Lab Immunogenet, NIH, Rockville, MD USA. [Adkins, Elisabeth; McPhee, Caroline; Christianson, Gregory; Sproule, Thomas; Roopenian, Derry] Jackson Labs, Bar Harbor, ME USA. [Shin, Dong-Mi] Seoul Natl Univ, Dept Food & Nutr, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA12P.104 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002142 ER PT J AU Janelsins, B Datta, S AF Janelsins, Brian Datta, Sandip TI Altered inactivation of commensal LPS due to acyloxyacyl hydrolase deficiency in colonic dendritic cells impairs mucosal Th17 immunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Janelsins, Brian; Datta, Sandip] NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA MUC4P.825 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003206 ER PT J AU Jeon, H Williams, J Hodes, R AF Jeon, Hyein Williams, Joy Hodes, Richard TI Cell types important for fostering normal thymic medullary epithelial cell development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Jeon, Hyein; Williams, Joy; Hodes, Richard] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HEM4P.242 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005113 ER PT J AU Jones, J Brandmaier, A Umetsu, S Bu, X Umetsu, D DeKruyff, R Freeman, G AF Jones, Jennifer Brandmaier, Andrew Umetsu, Sarah Bu, Xia Umetsu, Dale DeKruyff, Rosemarie Freeman, Gordon TI Evolutionary origins and structural analysis of phosphatidylserine binding by the TIM gene family SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Jones, Jennifer; Brandmaier, Andrew] NCI, NIH, Bethesda, MD 20892 USA. [Bu, Xia; Freeman, Gordon] DFCI, Boston, MA USA. [Umetsu, Sarah] UCSF, San Francisco, CA USA. [Umetsu, Dale; DeKruyff, Rosemarie] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CAM5P.244 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002110 ER PT J AU Kamiyama, R Yoshimi, R Tsukahara, T Ueda, A Takeno, M Ozato, K Ishigatsubo, Y AF Kamiyama, Reikou Yoshimi, Ryusuke Tsukahara, Toshinori Ueda, Atsuhisa Takeno, Mitsuhiro Ozato, Keiko Ishigatsubo, Yoshiyuki TI The dysfunction of the E3 ubiquitin ligase TRIM21 in systemic lupus erythematosus SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kamiyama, Reikou; Yoshimi, Ryusuke; Tsukahara, Toshinori; Ueda, Atsuhisa; Takeno, Mitsuhiro; Ishigatsubo, Yoshiyuki] Yokohama City Univ, Grad Sch Med, Dept Internal Med & Clin Immunol, Yokohama, Kanagawa, Japan. [Ozato, Keiko] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HUM7P.301 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000209 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 IMMUNOLOGY LA English DT Meeting Abstract C1 [Kapnick, Senta; Schwartzberg, Pamela] NHGRI, GDRB, NIH, Bethesda, MD 20892 USA. [Kapnick, Senta] Johns Hopkins Univ, CMDB, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HUM8P.343 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002019 ER PT J AU Kato, S Terabe, M Berzofsky, J AF Kato, Shingo Terabe, Masaki Berzofsky, Jay TI Liver sulfatide-reactive type II NKT cells recognize endogenous phospholipids SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kato, Shingo; Terabe, Masaki; Berzofsky, Jay] NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA INC9P.445 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003045 ER PT J AU Kim, JW Subedi, K Wersto, R Zhao, KJ Peng, WQ Weng, NP AF Kim, Jiewan Subedi, Kalpana Wersto, Robert Zhao, Keji Peng, Weiqun Weng, Nan-ping TI The role of genes with bivalent chromatin in memory CD8 T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kim, Jiewan; Subedi, Kalpana; Wersto, Robert; Weng, Nan-ping] NIA, LMBI, NIH, Baltimore, MD 21224 USA. [Zhao, Keji] NHLBI, Lab Epigenome Biol, NIH, Bethesda, MD 20892 USA. [Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRM4P.496 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004017 ER PT J AU Kines, R Cuburu, N Kobayashi, H MacDougall, J de los Pinos, E Schiller, J AF Kines, Rhonda Cuburu, Nicolas Kobayashi, Hisataka MacDougall, John de los Pinos, Elisabet Schiller, John TI HPV based photodynamic therapy: a new approach for anti-cancer therapy SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kines, Rhonda; MacDougall, John; de los Pinos, Elisabet] Aura Biosci, Cambridge, MA USA. [Kines, Rhonda; Cuburu, Nicolas; Schiller, John] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Kobayashi, Hisataka] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC12P1019 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002012 ER PT J AU Kovacs, S Sheikh, V Rupert, A Thompson, W Estes, J Sandler, N Roby, G Freeman, A Sereti, I AF Kovacs, Stephen Sheikh, Virginia Rupert, Adam Thompson, William Estes, Jacob Sandler, Netanya Roby, Gregg Freeman, Alexandra Sereti, Irini TI Evidence of T cell lymphopenia in the colonic mucosa in idiopathic CD4 lymphocytopenia patients SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kovacs, Stephen] Leidos Biomed Res Inc, Lab Immunoregulat, Frederick Natl Lab Canc Res, Frederick, MD USA. [Sheikh, Virginia; Thompson, William; Roby, Gregg; Freeman, Alexandra; Sereti, Irini] NIAID, NIH, Bethesda, MD 20892 USA. [Rupert, Adam] Leidos Biomed Res Inc, AIDS Monitoring Lab, Frederick Natl Lab Canc Res, Frederick, MD USA. [Estes, Jacob] Leidos Biomed Res Inc, Retroviral Immunopathol Sect, Frederick Natl Lab Canc Res, Frederick, MD USA. [Sandler, Netanya] Univ Texas Med Branch, Infect Dis Sect, Galveston, TX 77555 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HEM4P.250 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003021 ER PT J AU Kwong, B McGavern, D Lazarevic, V AF Kwong, Brandon McGavern, Dorian Lazarevic, Vanja TI Pathogenicity of autoreactive Th17 cells is dependent on T-bet expression in non-T-helper cells in experimental autoimmune encephalomyelitis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kwong, Brandon; Lazarevic, Vanja] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [McGavern, Dorian] NINDS, Viral Immunol & Intravital Imaging Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA13P.117 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005162 ER PT J AU Lazarevic, V Wang, Y Godec, J Ben-Aissa, K Cui, K Zhao, K Pucsek, A Weaver, C Yagi, R AF Lazarevic, Vanja Wang, Yan Godec, Jernej Ben-Aissa, Khadija Cui, Kairong Zhao, Keji Pucsek, Alexandra Weaver, Casey Yagi, Ryoji TI T-bet and Runx transcription factors are required for the ontogeny of pathogenic IFN gamma-producing Th17 cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lazarevic, Vanja; Wang, Yan; Ben-Aissa, Khadija] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Godec, Jernej] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA USA. [Cui, Kairong; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Pucsek, Alexandra] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Weaver, Casey] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Yagi, Ryoji] Chiba Univ, Dept Immunol, Chiba, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM3P.729 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000122 ER PT J AU Le Saout, C Hasley, R Imamichi, H Tcheung, L Hu, Z Luckey, M Park, JH Durum, S Smith, M Rupert, A Sneller, M Lane, HC Catalfamo, M AF Le Saout, Cecile Hasley, Rebecca Imamichi, Hiromi Tcheung, Lueng Hu, Zonghui Luckey, Megan Park, Jung-Hyun Durum, Scott Smith, Mindy Rupert, Adam Sneller, Michael Lane, H. Clifford Catalfamo, Marta TI IL-7/Lymphopenia enhanced Type-I IFN response by modulating STAT-1 levels: its impact in CD4 T cell homeostasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Le Saout, Cecile; Hasley, Rebecca; Imamichi, Hiromi; Tcheung, Lueng; Smith, Mindy; Sneller, Michael; Lane, H. Clifford; Catalfamo, Marta] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Hu, Zonghui] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Luckey, Megan; Park, Jung-Hyun] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Durum, Scott] NCI, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. [Rupert, Adam] SAIC, AIDS Monitoring Labs, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HUM8P.338 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002045 ER PT J AU Leger, AS Karauzum, H Datta, S Caspi, R AF Leger, Anthony St. Karauzum, Hatice Datta, Sandip Caspi, Rachel TI A new model to study mucosal immunity at the ocular surface SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Leger, Anthony St.; Caspi, Rachel] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Karauzum, Hatice; Datta, Sandip] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA MUC7P.758 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004147 ER PT J AU Lerman, Y Sarangi, P Hyun, YM Lim, K Falkner, K Pietropaoli, A Kim, M AF Lerman, Yelena Sarangi, Pranita Hyun, Young-Min Lim, Kihong Falkner, Kathleen Pietropaoli, Anthony Kim, Minsoo TI Exacerbated tissue homing of neutrophils during sepsis and TLR2-induced cytokine production are regulated by integrin alpha 3 beta 1. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lerman, Yelena; Sarangi, Pranita; Hyun, Young-Min; Lim, Kihong; Falkner, Kathleen; Pietropaoli, Anthony; Kim, Minsoo] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Sarangi, Pranita] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CAM5P.230 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002114 ER PT J AU Li, WQ Xiao, Z Ravichandran, S Luke, B Collins, J Durum, S AF Li, Wenqing Xiao, Zhen Ravichandran, Sarangan Luke, Brian Collins, Jack Durum, Scott TI Role of lysine dimethylation in Bcl-2 function and T cell activation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Li, Wenqing; Durum, Scott] NCI, Canc & Inflammat Program, CCR, NIH, Frederick, MD 21701 USA. [Xiao, Zhen] NCI, Lab Prote & Alalyt Technol, SAIC Frederick Inc, NIH, Frederick, MD 21701 USA. [Ravichandran, Sarangan; Luke, Brian; Collins, Jack] NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick Inc,NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM4P.744 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005136 ER PT J AU Ligons, D Sato, N Park, JH AF Ligons, Davinna Sato, Noriko Park, Jung-Hyun TI CD103 downregulation marks memory-phenotype CD8 T cells and excludes them from the gut SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ligons, Davinna; Park, Jung-Hyun] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Sato, Noriko] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CAM1P.231 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003098 ER PT J AU Lin, B Fraser, L AF Lin, Bin Fraser, Lain TI Investigating the mechanism of TLR signaling crosstalk in mouse macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lin, Bin; Fraser, Lain] NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRM5P.702 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004228 ER PT J AU Liu, Q Li, ZZ Gao, JL Wan, WZ McDermott, D Murphy, P AF Liu, Qian Li, Zhanzhuo Gao, Ji-Liang Wan, Wuzhou McDermott, David Murphy, Philip TI CXCR4 antagonist AMD3100 mobilizes leukocytes from bone marrow and thymus to blood in mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Liu, Qian; Li, Zhanzhuo; Gao, Ji-Liang; Wan, Wuzhou; McDermott, David; Murphy, Philip] NIAID, Lab Mol Immunol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HEM2P.265 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001088 ER PT J AU Liu, Y Biancotto, A Huang, Y Gadina, M McCoy, JP Goldbach-Mansky, R AF Liu, Yin Biancotto, Angelique Huang, Yan Gadina, Massimo McCoy, John Philip Goldbach-Mansky, Rapheala TI Proteasome defects in candle patients' cells lead to IFN production in both hemopoietic and non-hemopoietic cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Liu, Yin; Huang, Yan; Goldbach-Mansky, Rapheala] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA. [Biancotto, Angelique; McCoy, John Philip] NHLBI, NIH, Bethesda, MD 20892 USA. [Gadina, Massimo] NIAMS, Off Sci & Technol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA INM6P.416 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002090 ER PT J AU Lu, YC Yao, X Crystal, J Li, Y El-Gamil, M Gross, C Davis, L Dudley, M Yang, J Samuels, Y Rosenberg, S Robbins, P AF Lu, Yong-Chen Yao, Xin Crystal, Jessica Li, Yong El-Gamil, Mona Gross, Colin Davis, Lindy Dudley, Mark Yang, James Samuels, Yardena Rosenberg, Steven Robbins, Paul TI Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lu, Yong-Chen; Yao, Xin; Crystal, Jessica; Li, Yong; El-Gamil, Mona; Gross, Colin; Davis, Lindy; Dudley, Mark; Yang, James; Rosenberg, Steven; Robbins, Paul] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Samuels, Yardena] Weizmann Inst Sci, Mol Cell Biol, Rehovot, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA TUM2P.878 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001226 ER PT J AU Lucas, C Lenardo, M AF Lucas, Carrie Lenardo, Michael TI Activating mutations in p110 delta cause human immunodeficiency and reveal important roles of PI3K in T cell senescence and homeostatic cell death SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lucas, Carrie; Lenardo, Michael] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Lucas, Carrie] NIGMS, Postdoctoral Res Associate PRAT Program, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HUM2P.334 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001073 ER PT J AU Malhotra, D Linehan, J Jenkins, M AF Malhotra, Deepali Linehan, Jon Jenkins, Marc TI Self-tolerance in the polyclonal CD4+T cell repertoire SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Malhotra, Deepali; Jenkins, Marc] Univ Minnesota, Ctr Immunol, Microbiol, Minneapolis, MN USA. [Linehan, Jon] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA8P.132 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005177 ER PT J AU McBerry, C Sakai, S Kauffman, K Barber, D AF McBerry, Cortez Sakai, Shunsuke Kauffman, Keith Barber, Daniel TI inhibits Th1 responses during cryptococcus neoformans infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [McBerry, Cortez; Sakai, Shunsuke; Kauffman, Keith; Barber, Daniel] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRC2P.452 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002239 ER PT J AU McVicar, D Howard, OMZ Sublesk, J Quigley, L Yang, YF Rayman, P Rini, B Linehan, WM Sayers, T Finke, J Stappenbeck, T Ford, J AF McVicar, Daniel Howard, O. M. Zack Sublesk, Jeff Quigley, Laura Yang, Youfeng Rayman, Patricia Rini, Brian Linehan, W. Marston Sayers, Thomas Finke, James Stappenbeck, Thaddeus Ford, Jill TI The myeloid receptor TREM2 exacerbates DSS-induced colitis and promotes colitis-associated cancer SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [McVicar, Daniel; Howard, O. M. Zack; Sublesk, Jeff; Quigley, Laura; Ford, Jill] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. [Yang, Youfeng; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Rayman, Patricia] Cleveland Clin, Dept Immunol, Cleveland, OH 44106 USA. [Rini, Brian] Cleveland Clin, Dept Solid Tumor Oncol, Cleveland, OH 44106 USA. [Stappenbeck, Thaddeus] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA TUM4P.916 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004047 ER PT J AU Metidji, A Shevach, E AF Metidji, Amina Shevach, Ethan TI Type I IFNs modulate T effector (Teff) and T regulatory (Treg) cell function during experimental autoimmune encephalomyelitis (EAE) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Metidji, Amina; Shevach, Ethan] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRC4P.485 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005042 ER PT J AU Mistry, P Laird, M Schwarz, R Greene, S Dyson, T Jabre, S Snyder, G Deredge, D Chauhan, J Wintrode, P Xiao, T Sundberg, E Fletcher, S Toshchakov, V MacKerell, A Vogel, S AF Mistry, Pragnesh Laird, Michelle Schwarz, Ryan Greene, Shannon Dyson, Tristan Jabre, Sandra Snyder, Greg Deredge, Daniel Chauhan, Jamal Wintrode, Patrick Xiao, Tsan Sundberg, Eric Fletcher, Steven Toshchakov, Vladimir MacKerell, Alexander Vogel, Stefanie TI Inhibition of TLR2 signaling by small molecule inhibitors targeting a novel putative pocket within the TLR2 TIR domain SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mistry, Pragnesh; Laird, Michelle; Schwarz, Ryan; Dyson, Tristan; Jabre, Sandra; Snyder, Greg; Sundberg, Eric; Toshchakov, Vladimir; Vogel, Stefanie] Univ Maryland, Microbiol & Immunol, Baltimore, MD 21201 USA. [Greene, Shannon; Deredge, Daniel; Chauhan, Jamal; Wintrode, Patrick; Fletcher, Steven; MacKerell, Alexander] Univ Maryland, Pharmaceut Sci, Baltimore, MD 21201 USA. [Xiao, Tsan] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA INM9P.448 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765006104 ER PT J AU Morozov, G Zhao, HY Mage, M Boyd, L Schuck, P Natarajan, K Margulies, D AF Morozov, Giora Zhao, Huaying Mage, Michael Boyd, Lisa Schuck, Peter Natarajan, Kannan Margulies, David TI Tapasin-related protein TAPBPR interacts directly with peptide-free MHC-I/beta 2-microgolbulin complexes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Morozov, Giora; Mage, Michael; Boyd, Lisa; Natarajan, Kannan; Margulies, David] NIAID, Lab Immunol, NIH, Bethesda, MD 20892 USA. [Zhao, Huaying; Schuck, Peter] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA APP3P.101 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000014 ER PT J AU Moseman, E Heydari, S Zinselmeyer, B McGavern, D AF Moseman, E. Heydari, Sara Zinselmeyer, Bernd McGavern, Dorian TI Adoptive B cell immunotherapy accelerates control of chronic viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Moseman, E.; Heydari, Sara; Zinselmeyer, Bernd; McGavern, Dorian] NINDS, Viral Immunol & Intravital Imaging Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC6P.947 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000057 ER PT J AU Nakano, H Moran, T Bortner, C Cook, D AF Nakano, Hideki Moran, Timothy Bortner, Carl Cook, Donald TI Responsiveness to anaphylatoxin C5a delineates hematopoietic lineage of pulmonary dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Nakano, Hideki; Moran, Timothy; Cook, Donald] NIEHS, Resp Biol, Res Triangle Pk, NC 27709 USA. [Bortner, Carl] NIEHS, Signal Transduct, Res Triangle Pk, NC 27709 USA. [Moran, Timothy] Duke Univ, Med Ctr, Pediat, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HYP6P.257 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002212 ER PT J AU Nundel, K Mande, P Shaffer, A Sindhava, V Cancro, M Marshak-Rothstein, A AF Nundel, Kerstin Mande, Purvi Shaffer, Art Sindhava, Vishal Cancro, Michael Marshak-Rothstein, Ann TI Distinct roles for TLR7 and TLR9 in regulation of B cell signal strength and differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Nundel, Kerstin; Mande, Purvi; Marshak-Rothstein, Ann] UMass Med Sch, Worcester, MA USA. [Shaffer, Art] NIH, Bethesda, MD 20892 USA. [Sindhava, Vishal; Cancro, Michael] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM6P.766 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000086 ER PT J AU Pandiyan, P Zheng, LX Bhaskaran, N Weinberg, A AF Pandiyan, Pushpa Zheng, Lixin Bhaskaran, Natarajan Weinberg, Aaron TI Differential effects of TLR-2 ligands on CD4+CD25+Foxp3+regulatory cells depending on inflammatory cytokine milieu SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pandiyan, Pushpa; Bhaskaran, Natarajan; Weinberg, Aaron] Case Western Reserve Univ, Dept Biol Sci, Cleveland, OH 44106 USA. [Zheng, Lixin] NIAID, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRC4P.489 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005032 ER PT J AU Park, JY Keller, H Sato, N Park, JH AF Park, Joo-Young Keller, Hilary Sato, Noriko Park, Jung-Hyun TI NKT cells require IL-7, not IL-15, for survival and homeostasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Park, Joo-Young; Keller, Hilary; Sato, Noriko; Park, Jung-Hyun] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM4P.761 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005128 ER PT J AU Park, JH Feigenbaum, L Luckey, M AF Park, Jung-Hyun Feigenbaum, Lionel Luckey, Megan TI Overexpression of suppressor of cytokine signaling-4 impairs T cell development and homeostasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Park, Jung-Hyun; Luckey, Megan] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] NCI, Lab Anim Sci Program, Frederick CRDC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM7P.723 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005227 ER PT J AU Penaloza-MacMaster, P Barber, D Wherry, J Provine, N Teigler, J Blackmore, S Borducchi, E Bronson, R Barouch, D AF Penaloza-MacMaster, Pablo Barber, Daniel Wherry, John Provine, Nicholas Teigler, Jeffrey Blackmore, Steven Borducchi, Erica Bronson, Roderick Barouch, Dan TI Vaccine induced immunopathology mediated by memory CD4 T cells following chronic viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Penaloza-MacMaster, Pablo; Provine, Nicholas; Teigler, Jeffrey; Blackmore, Steven; Borducchi, Erica; Barouch, Dan] Harvard Univ, BIDMC, Boston, MA 02115 USA. [Barber, Daniel] NIAID, Lab Parasit Dis, Bethesda, MD 20892 USA. [Wherry, John] Univ Penn, Dept Microbiol 3, Philadelphia, PA 19104 USA. [Wherry, John] Univ Penn, Inst Immunol, Philadelphia, PA 19104 USA. [Bronson, Roderick] Harvard Med Sch, Mouse Histopathol Core, Boston, MA USA. [Barouch, Dan] Ragon Inst MGH MIT & Harvard, MGH MIT & Harvard, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VIR7P.1054 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000021 ER PT J AU Perez-Diez, A Liu, XD Sheikh, V Sereti, I AF Perez-Diez, Ainhoa Liu, Xiangdong Sheikh, Virginia Sereti, Irini TI Use of humanized mouse models for the study of idiopathic CD4 lymphocytopenia SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Perez-Diez, Ainhoa; Liu, Xiangdong; Sheikh, Virginia; Sereti, Irini] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HUM7P.313 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000183 ER PT J AU Petrovas, C Paris, R Koup, R AF Petrovas, Constantinos Paris, Robert Koup, Richard TI Activated PD-1highCD127highCD27highCD45RAlowCD4 T cell phenotype is associated with increased susceptibility to HIV infection rather than exhaustion. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Petrovas, Constantinos; Paris, Robert; Koup, Richard] NIAID, VRC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HUM8P.339 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002034 ER PT J AU Richard, A Tan, CY Hawley, E Gomez-Rodriguez, J Goswami, R Yang, XP Cruz, A Penumetcha, P Hayes, E Pelletier, M Gabay, O Walsh, M Ferdinand, J Keane-Myers, A Choi, Y O'Shea, J Al-Shamkhani, A Kaplan, M Gery, I Siegel, R Meylan, F AF Richard, Arianne Tan, Cuiyan Hawley, Eric Gomez-Rodriguez, Julio Goswami, Ritobrata Yang, Xiangping Cruz, Anthony Penumetcha, Pallavi Hayes, Erika Pelletier, Martin Gabay, Odile Walsh, Matthew Ferdinand, John Keane-Myers, Andrea Choi, Yongwon O'Shea, John Al-Shamkhani, Aymen Kaplan, Mark Gery, Igal Siegel, Richard Meylan, Francoise TI The TNF family member TL1A promotes Th9 differentiation and Th9-mediated immunopathology SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Richard, Arianne; Hawley, Eric; Cruz, Anthony; Penumetcha, Pallavi; Hayes, Erika; Pelletier, Martin; Gabay, Odile; Ferdinand, John; Siegel, Richard; Meylan, Francoise] NIAMS, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD USA. [Tan, Cuiyan; Gery, Igal] NEI, Expt Immunol Sect, NIH, Bethesda, MD 20892 USA. [Gomez-Rodriguez, Julio] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Goswami, Ritobrata; Kaplan, Mark] Indiana Univ Sch Med, Dept Pediat & Microbiol & Immunol, Indianapolis, IN 46202 USA. [Yang, Xiangping; O'Shea, John] NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD USA. [Walsh, Matthew; Choi, Yongwon] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Ferdinand, John; Al-Shamkhani, Aymen] Univ Southampton, Fac Med, Canc Sci Div, Southampton, Hants, England. [Keane-Myers, Andrea] Naval Med Res Ctr, Biol Def Res Directorate, Ft Detrick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM3P.733 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000127 ER PT J AU Robertson, F Lu, XJ Terabe, M Berzofsky, J AF Robertson, Faith Lu, Xiuju Terabe, Masaki Berzofsky, Jay TI Type II NKT cells play a role in the regulation of CD4 T cell subsets SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Robertson, Faith; Lu, Xiuju; Terabe, Masaki; Berzofsky, Jay] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM8P.730 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003050 ER PT J AU Robins, H Muraro, P Malhotra, S Howell, M Phippard, D Desmarais, C Sousa, ADA Griffith, L Lim, N Nash, R Turka, L AF Robins, Harlan Muraro, Paolo Malhotra, Sachin Howell, Michael Phippard, Deborah Desmarais, Cindy Sousa, Alessandra de Paula Alves Griffith, Linda Lim, Noha Nash, Richard Turka, Laurence TI T cell repertoire renewal following autologous stem cell transplantation for multiple sclerosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Robins, Harlan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Muraro, Paolo; Sousa, Alessandra de Paula Alves] Imperial Coll, Div Brain Sci, Dept Med, London, England. [Malhotra, Sachin; Howell, Michael; Phippard, Deborah; Lim, Noha; Turka, Laurence] Immune Tolerance Network, Bethesda, MD USA. [Griffith, Linda] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Nash, Richard] PSL, Colorado Blood Ctr Inst, Denver, CO USA. [Turka, Laurence] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Turka, Laurence] Harvard Med Sch, Boston, MA USA. [Robins, Harlan; Desmarais, Cindy] Adapt Biotechnol, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA THER3P.879 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001242 ER PT J AU Rus, V Tegla, C Nguyen, V Cudrici, C Badea, T Rus, H AF Rus, Violeta Tegla, Cosmin Vinh Nguyen Cudrici, Cornelia Badea, Tudor Rus, Horea TI RGC-32 is essential for TGF-beta mediated Th17 cell differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Rus, Violeta; Vinh Nguyen] Univ Maryland, Med, Baltimore, MD 21201 USA. [Tegla, Cosmin; Rus, Horea] Univ Maryland, Neurol, Baltimore, MD 21201 USA. [Rus, Violeta; Tegla, Cosmin; Vinh Nguyen; Rus, Horea] VAMHCS, Res Serv, Baltimore, MD USA. [Badea, Tudor] NEI, Retinal Circuit Dev & Genet Unit, NIH, Bethesda, MD 20892 USA. [Cudrici, Cornelia] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM3P.728 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000121 ER PT J AU Sadegh-Nasseri, S Kim, A Hartman, I Cuidad, MT Song, NB Boronina, T Caspi, R Jaraquemada, D AF Sadegh-Nasseri, Scheherazade Kim, AeRyon Hartman, Isamu Teresa Cuidad, M. Song, Nianbin Boronina, Tatiana Caspi, Rachel Jaraquemada, Dolores TI Multiple paths to immunodominance: dominant epitopes are captured by MHC II prior, or post antigen proteolysis, and are enriched by HLA-DM SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Sadegh-Nasseri, Scheherazade; Kim, AeRyon; Hartman, Isamu; Song, Nianbin] Johns Hopkins Univ, Pathol, Baltimore, MD USA. [Boronina, Tatiana] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD USA. [Teresa Cuidad, M.; Jaraquemada, Dolores] Univ Autonoma Barcelona, Cell Biol Physiol & Immunol, Barcelona, Spain. [Caspi, Rachel] NIH, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA APP2P.103 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001145 ER PT J AU Sagar, D Masih, S Schell, T Jacobson, S Wigdahi, B Khan, Z Jain, P AF Sagar, Divya Masih, Shet Schell, Todd Jacobson, Steven Wigdahi, Brian Khan, Zafar Jain, Pooja TI In vivo immunogenicity of Tax 11-19 epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Sagar, Divya; Masih, Shet; Wigdahi, Brian; Khan, Zafar; Jain, Pooja] Drexel Univ, Coll Med, Microbiol & Immunol, Doylestown, PA USA. [Schell, Todd] Penn State Univ, Microbiol & Immunol, Hershey, PA USA. [Jacobson, Steven] NIH, Viral Immunol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC12P1020 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002008 ER PT J AU Sckisel, G Bouchlaka, M Mirsoian, A Sungur, C Soulika, A Wiltrout, R Blazar, B Murphy, W AF Sckisel, Gail Bouchlaka, Myriam Mirsoian, Annie Sungur, Can Soulika, Athena Wiltrout, Robert Blazar, Bruce Murphy, William TI Cytokine-based cancer immunotherapy impairs primary T cell immunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Sckisel, Gail; Mirsoian, Annie; Sungur, Can; Murphy, William] Univ Calif Davis, Sch Med, Dermatol, Sacramento, CA 95817 USA. [Bouchlaka, Myriam] Univ Nevada, Microbiol & Immunol, Reno, NV 89557 USA. [Soulika, Athena] Shriners Hosp Children Northern Calif, Inst Pediat Regenerat Med, Sacramento, CA USA. [Wiltrout, Robert] NCI, Canc & Inflammat Program, Bethesda, MD 20892 USA. [Blazar, Bruce] Univ Minnesota, Pediat, Minneapolis, MN USA. [Murphy, William] Univ Calif Davis, Internal Med, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC3P.942 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004192 ER PT J AU Serti, E Werner, J Chattergoon, M Cox, A Lohmann, V Rehermann, B AF Serti, Elisavet Werner, Jens Chattergoon, Michael Cox, Andrea Lohmann, Volker Rehermann, Barbara TI Monocytes sense hepatitis C virus-replicating cells and induce natural killer cell antiviral activity in an IL-18-mediated manner SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Serti, Elisavet; Werner, Jens; Rehermann, Barbara] NIDDK, Immunl Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA. [Chattergoon, Michael; Cox, Andrea] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. [Lohmann, Volker] Heidelberg Univ, Dept Infect Dis, Mol Virol, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA INC8P.437 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001029 ER PT J AU Sgourakis, N Natarajan, K Margulies, D Bax, A AF Sgourakis, Nikolaos Natarajan, Kannan Margulies, David Bax, Ad TI A structural approach to the study of viral immune evasion mechanisms SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Sgourakis, Nikolaos; Bax, Ad] NIDDK, NIH, Bethesda, MD 20892 USA. [Natarajan, Kannan; Margulies, David] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA TECH1P.850 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765006008 ER PT J AU Siebeniist, U Claudio, E Ha, HL AF Siebeniist, Ulrich Claudio, Estefania Ha, Hye-Lin TI Critical target cell-specific roles for IL-17 family cytokines/CIKS-mediated signaling in mouse models of skin and lung inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Siebeniist, Ulrich; Claudio, Estefania; Ha, Hye-Lin] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CCR6P.276 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765006056 ER PT J AU Singh, A Zhang, YQ Wood, W Becker, K Sen, R AF Singh, Amit Zhang, Yongqing Wood, William Becker, Kevin Sen, Ranjan TI First mitotic division programs naive B cell for successive cell divisions SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Singh, Amit; Sen, Ranjan] NIA, LMBI, NIH, Baltimore, MD 21224 USA. [Zhang, Yongqing; Wood, William; Becker, Kevin] NIA, Lab Genet, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM6P.778 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000097 ER PT J AU Singh, S Zhang, H Tsang, H Gardina, P Myers, T Farber, J AF Singh, Satya Zhang, Howard Tsang, Hsinyi Gardina, Paul Myers, Timothy Farber, Joshua TI PLZF supports the acquisition and maintenance of the Th17 phenotype in human cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Singh, Satya; Zhang, Howard; Tsang, Hsinyi; Farber, Joshua] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Gardina, Paul; Myers, Timothy] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CCR5P.250 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003186 ER PT J AU Singh, TP Zhang, H Farber, J AF Singh, Tej Pratap Zhang, Howard Farber, Joshua TI Blood monocytes expressing CCR6 and monocyte-derived dendritic cells in dermis and epidermis are critical for IL-23-induced psoriasis-like inflammation in mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Singh, Tej Pratap; Zhang, Howard; Farber, Joshua] NIAID, Inflammat Biol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CAM5P.238 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002104 ER PT J AU Skarzynski, M Vire, B Thomas, J Nelson, C David, A Aue, G Burke, T Rader, C Wiestner, A AF Skarzynski, Martin Vire, Berengere Thomas, Joshua Nelson, Christopher David, Alexandre Aue, Georg Burke, Terrence Rader, Christoph Wiestner, Adrian TI Novel IgM-derived antibody-drug conjugate selectively kills chronic lymphocytic leukemia cells through binding of Fc mu-receptor leading to rapid internalization and intracellular cytotoxic payload delivery SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Skarzynski, Martin; Vire, Berengere; Aue, Georg; Wiestner, Adrian] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Thomas, Joshua; Nelson, Christopher; Burke, Terrence] NCI, Chem Biol Lab, Mol Discovery Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [David, Alexandre] NIAID, Lab Viral Dis, Bethesda, MD 20892 USA. [Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Rader, Christoph] Scripps Florida, Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA. [Rader, Christoph] Scripps Florida, Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC3P.953 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004199 ER PT J AU Slota, C Weng, NP AF Slota, Christina Weng, Nan-ping TI The effect of norepinephrine on CD8 T cell subsets in healthy human adults SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Slota, Christina; Weng, Nan-ping] NIA IRP, Lab Mol Biol & Immunol, Baltimore, MD USA. [Slota, Christina] Univ Penn, Nursing, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CCR3P.215 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001166 ER PT J AU Smith, C Vivekanandan-Giri, A Pennathur, S Kaplan, M AF Smith, Carolyne Vivekanandan-Giri, Anuradha Pennathur, Subramaniam Kaplan, Mariana TI Neutrophil extracellular traps as a source of high density lipoprotein oxidation in lupus related cardiovascular disease. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Smith, Carolyne; Kaplan, Mariana] NIAMSD, NIH, Bethesda, MD 20892 USA. [Vivekanandan-Giri, Anuradha; Pennathur, Subramaniam] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HUM1P.312 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000225 ER PT J AU Snyder, G Deredge, D Waldhuber, A Fresquez, T Smith, P Duerr, S Cirl, C Jiang, J Jennings, W Luchetti, T Snyder, N Sundberg, E Wintrode, P Miethke, T Xiao, T AF Snyder, Greg Deredge, Daniel Waldhuber, Anna Fresquez, Theresa Smith, Patrick Duerr, Suri Cirl, Christine Jiang, Jiansheng Jennings, William Luchetti, Timothy Snyder, Nathaniel Sundberg, Eric Wintrode, Patrick Miethke, Thomas Xiao, Tsan TI Development of microbial-derived inhibitory peptides using structural studies of microbial TIR proteins TcpB, TcpC and host adapters TIRAP and MyD88. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Snyder, Greg; Sundberg, Eric] Univ Maryland, Sch Med, Dept Med, Inst Human Virol, Baltimore, MD 21201 USA. [Snyder, Greg; Fresquez, Theresa; Smith, Patrick; Jiang, Jiansheng; Jennings, William; Luchetti, Timothy; Snyder, Nathaniel; Xiao, Tsan] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Deredge, Daniel; Wintrode, Patrick] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Waldhuber, Anna; Duerr, Suri; Cirl, Christine; Miethke, Thomas] Heidelberg Univ, Med Fac Mannheim, Inst Med Microbiol & Hyg, Mannheim, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA INM9P.449 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765006108 ER PT J AU Sommers, C Rouquette-Jazdanian, A Li, WM Nguyen, P Kortum, R Samelson, L AF Sommers, Connie Rouquette-Jazdanian, Alexandre Li, WenMei Nguyen, Phan Kortum, Robert Samelson, Lawrence TI miR-155 regulates lymphocyte homeostasis in LAT mutant mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Sommers, Connie; Rouquette-Jazdanian, Alexandre; Li, WenMei; Nguyen, Phan; Kortum, Robert; Samelson, Lawrence] NCI, LCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM4P.749 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005125 ER PT J AU Song, W Seeley-Fallen, M Onabajo, O Tan, TH Upadhyaya, A AF Song, Wenxia Seeley-Fallen, Margaret Onabajo, Olusegun Tan, Tse-Hua Upadhyaya, Arpita TI Actin-binding protein 1 links B-cell receptor to negative signaling pathways SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Song, Wenxia; Seeley-Fallen, Margaret] Univ Maryland, Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Onabajo, Olusegun] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Tan, Tse-Hua] Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA. [Upadhyaya, Arpita] Univ Maryland, Dept Phys, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRC3P.462 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004166 ER PT J AU Stagliano, K Zhu, ZQ Hurwitz, A AF Stagliano, Katherine Zhu, Ziqiang Hurwitz, Arthur TI Very low avidity endogenous memory CD8+T cells control tumor growth SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Stagliano, Katherine; Zhu, Ziqiang; Hurwitz, Arthur] NCI, Canc Inflammat Program, Frederick, MD 21701 USA. [Stagliano, Katherine; Hurwitz, Arthur] George Washington Univ, Inst Biomed Sci, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA TUM2P.893 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001210 ER PT J AU Swanson, P McGavern, D AF Swanson, Phillip McGavern, Dorian TI CNS stromal cells modulate antiviral CD8 T cell immunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Swanson, Phillip; McGavern, Dorian] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VIR4P.1009 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001059 ER PT J AU Tarbell, K Price, J Rahir, G Beauchamp, N Zhao, YG Doog, M AF Tarbell, Kristin Price, Jeffrey Rahir, Gwendoline Beauchamp, Nicole Zhao, Yongge Doog, Matthew TI In autoimmune-prone NOD mice, altered DC subsets induce aberrant activation of CD4 T cells, yet DCIR2+DCs can still induce tolerance. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tarbell, Kristin; Price, Jeffrey; Rahir, Gwendoline; Beauchamp, Nicole; Zhao, Yongge; Doog, Matthew] NIDDK, Immune Tolerance Sect, DEOB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA15P.218 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002243 ER PT J AU Taylor, K Woods, T Peterson, K AF Taylor, Katherine Woods, Tyson Peterson, Karin TI Innate immune-induced neuronal cell apoptosis via a SARM1 mediated mechanism in the absence of viral replication. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Taylor, Katherine; Woods, Tyson; Peterson, Karin] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA INM9P.451 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765006102 ER PT J AU Terabe, M Robertson, F Mizra, A Berzofsky, J AF Terabe, Masaki Robertson, Faith Mizra, Amer Berzofsky, Jay TI Effect of blocking different TGF-beta isoforms on tumor immunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Terabe, Masaki; Robertson, Faith; Berzofsky, Jay] NCI, NIH, Bethesda, MD 20892 USA. [Mizra, Amer] Xoma US LLC, Barkeley, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA TUM5P.937 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003076 ER PT J AU Thomas, L Long, E AF Thomas, Louis Long, Eric TI Actin confinement of activating receptors does not dictate natural killer cell licensing SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Thomas, Louis; Long, Eric] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA INM2P.431 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765006124 ER PT J AU Tian, LJ Choi, SC Murakami, Y Allen, J Morse, H Qi, CF Krzewski, K Coligan, J AF Tian, Linjie Choi, Seung-Chul Murakami, Yousuke Allen, Joselyn Morse, Herbert Qi, Chen-Feng Krzewski, Konrad Coligan, John TI p85a recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tian, Linjie; Choi, Seung-Chul; Murakami, Yousuke; Allen, Joselyn; Morse, Herbert; Qi, Chen-Feng; Krzewski, Konrad; Coligan, John] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA4P.222 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002203 ER PT J AU Tilahun, M Revilleza, MJ Mans, J Natarajan, K Margulies, D AF Tilahun, Mulualem Revilleza, Maria Jamela Mans, Janet Natarajan, Kannan Margulies, David TI Mouse cytomegalovirus glycoprotein m153 binds a dendritic cell-surface ligand SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tilahun, Mulualem; Revilleza, Maria Jamela; Natarajan, Kannan; Margulies, David] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Mans, Janet] Univ Pretoria, Dept Med Virol, Pretoria, South Africa. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VIR5P.1026 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005024 ER PT J AU Ujiie, H Shevach, E AF Ujiie, Hideyuki Shevach, Ethan TI gamma delta T cells protect TCR alpha deficient mice from the autoimmunity induced by scurfy lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ujiie, Hideyuki; Shevach, Ethan] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA13P.118 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005164 ER PT J AU van Panhuys, N Klauschen, F Germain, R AF van Panhuys, Nicholas Klauschen, Frederick Germain, Ronald TI TCR strength of signal is upstream of and dominates over cytokine effects in controlling CD4+T cell polarization in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [van Panhuys, Nicholas; Germain, Ronald] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Klauschen, Frederick] Charlie Univ Hosp, Inst Pathol, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRC2P.449 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002233 ER PT J AU Wang, JM Xiang, Y Huang, JQ Gong, WH Yoshimura, T Tessarollo, L Li, YY Chen, KQ AF Wang, Ji Ming Xiang, Yi Huang, Jiaqiang Gong, Wanghua Yoshimura, Teizo Tessarollo, Lino Li, Yingying Chen, Keqiang TI Fpr2 and its endogenous ligand CRAMP promote dendritic cell maturation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wang, Ji Ming; Xiang, Yi; Huang, Jiaqiang; Yoshimura, Teizo; Tessarollo, Lino; Chen, Keqiang] NCI, Lab Mol Immunoregulat, Frederick, MD 21701 USA. [Gong, Wanghua] Leidos, Lab Mol Immunoregulat, Frederick, MD USA. [Li, Yingying] Chinese Acad Sci, Shanghai, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRC5P.461 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004092 ER PT J AU Wang, ZY Sun, G Faucette, A Unger, B Hong, P Yao, FY Guterman, J Mathiarasu, A Deng, J Tang, XN Bluth, M Armant, D Lum, L Siddiqui, M Chen, K AF Wang, Zhao-Yuan Sun, Guang Faucette, Azure Unger, Benjamin Hong, Peng Yao, Fayi Guterman, Jacqueline Mathiarasu, Aditya Deng, Jie Tang, Xiangna Bluth, Martin Armant, D. Lum, Lawrence Siddiqui, Maq Chen, Kang TI A HEXIM1-AIRE transcriptional counterbalance in trophoblasts regulates maternal-fetal mucosal immunity in pregnancy SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wang, Zhao-Yuan; Faucette, Azure; Unger, Benjamin; Yao, Fayi; Guterman, Jacqueline; Mathiarasu, Aditya; Deng, Jie; Tang, Xiangna; Armant, D.; Chen, Kang] Wayne State Univ, Obstet & Gynecol, Detroit, MI USA. [Wang, Zhao-Yuan; Faucette, Azure; Unger, Benjamin; Yao, Fayi; Mathiarasu, Aditya; Tang, Xiangna; Chen, Kang] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Detroit, MI USA. [Sun, Guang] Republ Polytech, Sch Appl Sci, Singapore, Singapore. [Hong, Peng; Siddiqui, Maq] Suny Downstate Med Ctr, Cell Biol, Brooklyn, NY USA. [Hong, Peng; Siddiqui, Maq] VA New York Harbor Healthcare Syst, New York, NY USA. [Bluth, Martin] Wayne State Univ, Pathol, Detroit, MI USA. [Bluth, Martin; Lum, Lawrence; Chen, Kang] Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Armant, D.] Wayne State Univ, Anat & Cell Biol, Detroit, MI USA. [Armant, D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Lum, Lawrence] Wayne State Univ, Med, Detroit, MI USA. [Lum, Lawrence; Chen, Kang] Wayne State Univ, Immunol & Microbiol, Detroit, MI USA. [Chen, Kang] NIAID, MIST, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004161 ER PT J AU Watanabe, M Moon, KD Vacchio, M Hathcock, K Hodes, R AF Watanabe, Masashi Moon, Kyung Duk Vacchio, Melanie Hathcock, Karen Hodes, Richard TI Down-modulation of tumor suppressor p53 by T cell receptor signaling is critical for antigen-specific T cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Watanabe, Masashi; Moon, Kyung Duk; Vacchio, Melanie; Hathcock, Karen; Hodes, Richard] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRM10P.737 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005082 ER PT J AU Weindel, C Richey, L Bolland, S Huber, B AF Weindel, Chi Richey, Lauren Bolland, Silvia Huber, Brigitte TI B cell autophagy mediates TLR7-dependent SLE and controls extramedullary hematopoiesis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Weindel, Chi; Huber, Brigitte] Tufts Univ, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. [Richey, Lauren] Tufts Univ, Div Lab Anim Med, Boston, MA 02111 USA. [Bolland, Silvia] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Huber, Brigitte] Tufts Univ, Sch Med, Dept Integrat Physiol & Pathobiol, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA4P.217 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002196 ER PT J AU Weiskopf, D Angelo, M Bangs, D Sidney, J de Silva, A Lindow, J Durbin, A Whitehead, S Kirkpatrick, B Sette, A AF Weiskopf, Daniela Angelo, Michael Bangs, Derek Sidney, John de Silva, Aruna Lindow, Janet Durbin, Anna Whitehead, Stephen Kirkpatrick, Beth Sette, Alessandro TI HLA restricted CD8+T cell responses following vaccination with monovalent and tetravalent dengue live attenuated vaccines SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Weiskopf, Daniela; Sette, Alessandro] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USA. [Weiskopf, Daniela] Genetech Res Inst, Colombo, Sri Lanka. [Lindow, Janet; Kirkpatrick, Beth] Univ Vermont, Coll Med, Burlington, VT USA. [Durbin, Anna] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Whitehead, Stephen] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC7P.983 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002051 ER PT J AU Weng, NP Shi, A Li, HM Hiroi, T Zhang, YQ Chen, GB Metter, J Ferrucci, L AF Weng, Nan-ping Shi, Alvin Li, Hoi-Ming Hiroi, Toyoko Zhang, Yongqing Chen, Guobing Metter, Jeffrey Ferrucci, Luigi TI Analysis of human TCR beta repertoire by a RARE-sequencing method reveals distinct features of TCR beta diversity and distribution and their alterations with age SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Weng, Nan-ping; Shi, Alvin; Li, Hoi-Ming; Hiroi, Toyoko; Chen, Guobing] NIA, LMBI, NIH, Baltimore, MD 21224 USA. [Zhang, Yongqing] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA. [Metter, Jeffrey; Ferrucci, Luigi] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. RI Chen, Guobing/D-9572-2012 OI Chen, Guobing/0000-0002-2401-6168 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRM10P.758 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005099 ER PT J AU Wessel, A Hsu, A Goldbach-Mansky, R Zilberman-Rudenko, J Siegel, R Hanson, E AF Wessel, Alex Hsu, Amy Goldbach-Mansky, Rapheala Zilberman-Rudenko, Jevgenia Siegel, Richard Hanson, Eric TI Inflammatory disease due to selectively impaired NF-kB activation and type I interferon response resulting from a de novo human NEMO hypomorphic mutation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wessel, Alex; Goldbach-Mansky, Rapheala; Zilberman-Rudenko, Jevgenia; Siegel, Richard; Hanson, Eric] NIAMSD, NIH, Bethesda, MD 20892 USA. [Zilberman-Rudenko, Jevgenia] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Hsu, Amy] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HUM2P.333 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765001072 ER PT J AU Whibley, N Mamo, A Conti, H Traggiai, E Kolbinger, F Vogel, B Kammueller, M Siebenlist, U Iwakura, Y Gaffen, S AF Whibley, Natasha Mamo, Anna Conti, Heather Traggiai, Elisabetta Kolbinger, Frank Vogel, Beate Kammueller, Michael Siebenlist, Ulrich Iwakura, Yoichiro Gaffen, Sarah TI Differential requirements of IL-17 family cytokines in host defense against oral candidiasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Whibley, Natasha; Mamo, Anna; Conti, Heather; Gaffen, Sarah] Univ Pittsburgh, Rheumatol & Clin Immunol, Pittsburgh, PA USA. [Traggiai, Elisabetta; Kolbinger, Frank; Vogel, Beate; Kammueller, Michael] Novartis Inst Biomed Res, Basel, Switzerland. [Siebenlist, Ulrich] NIAID, NIH, Bethesda, MD 20892 USA. [Iwakura, Yoichiro] Tokyo Univ Sci, Chiba, Japan. RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA CCR6P.272 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765006046 ER PT J AU Xiao, T Jin, TC Chuenchor, W Ravilious, G Jiang, JS Smith, P AF Xiao, Tsan Jin, Tengchuan Chuenchor, Watchalee Ravilious, Geoffrey Jiang, Jiansheng Smith, Patrick TI DNA sensing by innate immune receptors SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Xiao, Tsan; Jin, Tengchuan; Chuenchor, Watchalee; Ravilious, Geoffrey; Jiang, Jiansheng; Smith, Patrick] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA INM6P.408 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002086 ER PT J AU Yang, G Liu, MF Wiehe, K Nicely, N Haynes, B Mascola, J Bjorkman, P Kelsoe, G AF Yang, Guang Liu, Mengfei Wiehe, Kevin Nicely, Nathan Haynes, Barton Mascola, John Bjorkman, Pamela Kelsoe, Garnett TI HIV broadly neutrizing antibodies and immunological tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yang, Guang; Liu, Mengfei; Haynes, Barton; Kelsoe, Garnett] Duke Univ, Immunol, Durham, NC USA. [Wiehe, Kevin; Nicely, Nathan; Haynes, Barton; Kelsoe, Garnett] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA. [Mascola, John] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Bjorkman, Pamela] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Bjorkman, Pamela] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC7P.988 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002078 ER PT J AU Yang, YJ Gordon, S Doster, M Liyanage, N Chang, J Williams, C Agy, M Mclain, R Agricola, B Law, L Franchini, G Palermo, R Katze, M AF Yang, Yajie Gordon, Shari Doster, Melvin Liyanage, Namal Chang, Jean Williams, Chris Agy, Michael Mclain, Randy Agricola, Brian Law, Lynn Franchini, Genoveffa Palermo, Robert Katze, Michael TI A systems biology approach revealed distinct host responses between ALVAC-SIV and NYVAC-SIV vaccines during an evaluation of immunogenicity in rheusus macaques SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yang, Yajie; Chang, Jean; Williams, Chris; Law, Lynn; Palermo, Robert; Katze, Michael] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Gordon, Shari; Doster, Melvin; Liyanage, Namal; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccine Sect, Bethesda, MD 20892 USA. [Agy, Michael; Mclain, Randy; Agricola, Brian; Palermo, Robert; Katze, Michael] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC7P.992 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002062 ER PT J AU Yin, ZJ Gildersleeve, J Finn, MG Huang, XF AF Yin, Zhaojun Gildersleeve, Jeffrey Finn, M. G. Huang, Xuefei TI Developing bacteriophage Q beta as versatile carrier for anti-carbohydrate cancer vaccine: influence of antigen design on antibody responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yin, Zhaojun; Huang, Xuefei] Michigan State Univ, Chem, E Lansing, MI 48824 USA. [Finn, M. G.] Georgia Inst Technol, Chem & Biochem, Atlanta, GA 30332 USA. [Gildersleeve, Jeffrey] NCI, Biol Chem Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC8P.998 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003079 ER PT J AU Yoon, JH Wang, HS Morse, H AF Yoon, Jeong Heon Wang, Hongsheng Morse, Herbert TI ENPP1-positive B cells and activation in human peripheral blood SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yoon, Jeong Heon; Wang, Hongsheng; Morse, Herbert] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA LYM6P.772 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000088 ER PT J AU Zanotti, K Gearhart, P AF Zanotti, Kimberly Gearhart, Patricia TI ATAD5 deficiency decreases B cell division and Igh recombination SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zanotti, Kimberly; Gearhart, Patricia] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRM8P.700 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003247 ER PT J AU Zarate-Blades, C Horai, R Chen, J Silver, P Dillenburg-Pilla, P Yamane, H Chan, CC Honda, K Caspi, R AF Zarate-Blades, Carlos Horai, Reiko Chen, Jun Silver, Phyllis Dillenburg-Pilla, Patricia Yamane, Hidehiro Chan, Chi-Chao Honda, Kenya Caspi, Rachel TI Activation of autoreactive T cells by endogenous microflora induces spontaneous autoimmunity in the immunologically privileged retina SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zarate-Blades, Carlos; Horai, Reiko; Chen, Jun; Silver, Phyllis; Chan, Chi-Chao; Caspi, Rachel] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Dillenburg-Pilla, Patricia] NIH, OPCB, Bethesda, MD 20892 USA. [Yamane, Hidehiro] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Honda, Kenya] RIKEN IMS RCAI, Yokohama, Kanagawa, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA8P.130 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005175 ER PT J AU Ahlman, M Dave, J Sadek, A Mehta, N Bluemke, D AF Ahlman, Mark Dave, Jenny Sadek, Ahmed Mehta, Nehal Bluemke, David TI Vascular uptake of F-18-fluorodeoxyglucose (FDG) correlates with blood, liver, splenic, and myocardial uptake SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Ahlman, Mark; Bluemke, David] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Dave, Jenny; Sadek, Ahmed; Mehta, Nehal] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1748 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438102414 ER PT J AU Bagci, U Xu, ZY Mollura, D AF Bagci, Ulas Xu, Ziyue Mollura, Daniel TI Recent advances in PET, PET-CT, and MRI-PET image segmentation techniques SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Bagci, Ulas; Xu, Ziyue; Mollura, Daniel] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1280 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438101444 ER PT J AU Bhatt, G Wu, XY Li, XF Rai, S Civelek, AC AF Bhatt, Geetika Wu, Xiaoyong Li, Xiao-Feng Rai, Shesh Civelek, A. Cahid TI Three hour solid gastric emptying accurately predicts the 4-h result: Is 4-h measurement necessary? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Bhatt, Geetika; Wu, Xiaoyong; Li, Xiao-Feng; Rai, Shesh] Univ Louisville, Louisville, KY 40292 USA. [Civelek, A. Cahid] NIH, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1962 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438104123 ER PT J AU Bhatt, G Wu, XY Li, XF Rai, S Civelek, AC AF Bhatt, Geetika Wu, Xiaoyong Li, Xiao-Feng Rai, Shesh Civelek, A. Cahid TI Three hour solid gastric emptying accurately predicts the 4-h result: Is 4-h measurement necessary? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Bhatt, Geetika; Wu, Xiaoyong; Li, Xiao-Feng; Rai, Shesh] Univ Louisville, Louisville, KY 40292 USA. [Civelek, A. Cahid] NIH, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1962 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438103133 ER PT J AU Bhatt, G Li, XF Civelek, AC AF Bhatt, Geetika Li, Xiao-Feng Civelek, A. Cahid TI 131I Thyroid cancer therapy in chronically bedridden & dialysis patients with severe renal failure: Challenges and solutions for determining the optimum therapy dose and how to minimize radiation dose to caregivers SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Civelek, A. Cahid] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Bhatt, Geetika; Li, Xiao-Feng] Univ Louisville, Louisville, KY 40292 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1365 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438102031 ER PT J AU Crandall, J Shankar, L Wahl, R AF Crandall, John Shankar, Lalitha Wahl, Richard TI Phase II single-arm trial comparing the use of FLT PET/CT to standard computed tomography to assess the treatment response of neoadjuvant docetaxel and cisplatin in stage IB-IIIA resectable non-small cell lung cancer SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Crandall, John; Wahl, Richard] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Shankar, Lalitha] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1609 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438102275 ER PT J AU Dickstein, L Zanotti-Fregonara, P Dustin, I Hong, J Liow, JS Pike, V Zoghbi, S Rallis-Frutos, D Innis, R Theodore, W AF Dickstein, Leah Zanotti-Fregonara, Paolo Dustin, Irene Hong, Jinsoo Liow, Jeih-San Pike, Victor Zoghbi, Sami Rallis-Frutos, Denise Innis, Robert Theodore, William TI Comparison of [11C]DPA-713 and [11C]PBR28 to measure translocator protein in epilepsy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Dickstein, Leah; Zanotti-Fregonara, Paolo; Dustin, Irene; Hong, Jinsoo; Liow, Jeih-San; Pike, Victor; Zoghbi, Sami; Rallis-Frutos, Denise; Innis, Robert; Theodore, William] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 417 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100418 ER PT J AU Dormish, P Chen, C Maass-Moreno, R AF Dormish, Phil Chen, Clara Maass-Moreno, Roberto TI Validation of a SUV-based correction for internal exposure dosimetry using Monte Carlo simulations SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Chen, Clara; Maass-Moreno, Roberto] NIH, Radiol, Bethesda, MD 20892 USA. [Dormish, Phil] Univ Virginia, Biomed Engn, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 99 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100100 ER PT J AU Feng, T Ahlman, M Tsui, B Guo, LH Guttman, M McVeigh, E Bluemke, D AF Feng, Tao Ahlman, Mark Tsui, Benjamin Guo, Liheng Guttman, Mike McVeigh, Elliot Bluemke, David TI Hybrid MR-guided and PET-guided motion correction of PET images in simultaneous PET/MR SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Feng, Tao; Tsui, Benjamin; Guo, Liheng; Guttman, Mike; McVeigh, Elliot] Johns Hopkins Univ, Baltimore, MD USA. [Ahlman, Mark; Bluemke, David] NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 646 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438101141 ER PT J AU Fujita, M Hines, C Zoghbi, S Rallis-Frutos, D Xu, R Pike, V Drevets, W Zarate, C Innis, R AF Fujita, Masahiro Hines, Christina Zoghbi, Sami Rallis-Frutos, Denise Xu, Rong Pike, Victor Drevets, Wayne Zarate, Carlos Innis, Robert TI Cyclic AMP cascade in major depressive disorder imaged with C-11-(R)-rolipram - Downregulation in unmedicated patients and normalization by antidepressant treatment SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Fujita, Masahiro; Hines, Christina; Zoghbi, Sami; Rallis-Frutos, Denise; Xu, Rong; Pike, Victor; Innis, Robert] NIMH, Mol Imaging Br, Bethesda, MD 20892 USA. [Zarate, Carlos] NIMH, Exp Therap & Pathophysiol, Bethesda, MD 20892 USA. [Drevets, Wayne] Johnson & Johnson, New Brunswick, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 81 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100082 ER PT J AU Guo, LH Ahlman, M Feng, T Guttman, M McVeigh, E Bluemke, D Tsui, B Herzka, D AF Guo, Liheng Ahlman, Mark Feng, Tao Guttman, Michael McVeigh, Elliot Bluemke, David Tsui, Benjamin Herzka, Daniel TI Real-time 3D MR respiratory motion acquisition for simultaneous PET/MR imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Guo, Liheng; McVeigh, Elliot; Herzka, Daniel] Johns Hopkins Univ, Biomed Engn, Baltimore, MD USA. [Feng, Tao; Tsui, Benjamin] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Ahlman, Mark; Bluemke, David] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Guttman, Michael] Johns Hopkins Univ, Sch Med, Cardiol, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 644 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438101139 ER PT J AU Hirvonen, J Zanotti-Fregonara, P Gorelick, D Rallis-Frutos, D Morse, C Zoghbi, S Pike, V Huestis, M Innis, R AF Hirvonen, Jussi Zanotti-Fregonara, Paolo Gorelick, David Rallis-Frutos, Denise Morse, Cheryl Zoghbi, Sami Pike, Victor Huestis, Marilyn Innis, Robert TI Decreased brain cannabinoid CB1 receptor binding in tobacco smokers examined with positron emission tomography SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Hirvonen, Jussi; Zanotti-Fregonara, Paolo; Rallis-Frutos, Denise; Morse, Cheryl; Zoghbi, Sami; Pike, Victor; Innis, Robert] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Gorelick, David; Huestis, Marilyn] NIDA, Chem & Drug Metab Sect, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 84 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100085 ER PT J AU Hurtle, B Cai, LS Qu, BX Diaz-Arrastia, R Innis, R Pike, V AF Hurtle, Bryan Cai, Lisheng Qu, Bao-Xi Diaz-Arrastia, Ramon Innis, Robert Pike, Victor TI Ligand-based virtual screening identifies novel leads for candidate PET radioligands for neurofibrillary tangles and amyloid plaques SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Hurtle, Bryan; Cai, Lisheng; Innis, Robert; Pike, Victor] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Qu, Bao-Xi; Diaz-Arrastia, Ramon] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 551 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438101046 ER PT J AU Ikawa, M Lyoo, CH Jenko, K Morse, C Zoghbi, S Pike, V McMahon, F Turner, R Innis, R Kreisl, W AF Ikawa, Masamichi Lyoo, Chul Hyoung Jenko, Kimberly Morse, Cheryl Zoghbi, Sami Pike, Victor McMahon, Francis Turner, Raymond Innis, Robert Kreisl, William TI Ratio measure of C-11-PBR28 binding allows noninvasive quantification of neuroinflammation in Alzheimer's disease SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Ikawa, Masamichi; Lyoo, Chul Hyoung; Jenko, Kimberly; Morse, Cheryl; Zoghbi, Sami; Pike, Victor; McMahon, Francis; Innis, Robert; Kreisl, William] NIMH, Bethesda, MD 20892 USA. [Turner, Raymond] Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1826 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438102492 ER PT J AU Kim, JS Kim, I Lee, SJ Kim, H Davies-Venn, C Won, S Niu, G Chen, XY Paik, C Bluemke, D AF Kim, Jin Su Kim, Insook Lee, Sung-Jin Kim, Heejung Davies-Venn, Cynthia Won, Samuel Niu, Gang Chen, Xiaoyuan Paik, Chang Bluemke, David TI Longitudinal analysis of PET imaging with Cu-64-labeled collagen specific peptides for the detection of collagen in myocardial fibrosis in rats SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Kim, Jin Su; Lee, Sung-Jin; Kim, Heejung; Paik, Chang] NIH, NMD, RAD&IS, CC, Bethesda, MD 20892 USA. [Kim, Insook] Leidos Inc, ADRD, Frederick, MD USA. [Davies-Venn, Cynthia; Won, Samuel; Bluemke, David] NIH, RAD&IS, CC, Bethesda, MD 20892 USA. [Niu, Gang; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 408 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100409 ER PT J AU Kobayashi, M Zanotti-Fregonara, P Dickstein, L Zoghbi, S Lohith, T Rallis-Frutos, D Telu, S Pike, V Fujita, M Innis, R AF Kobayashi, Masato Zanotti-Fregonara, Paolo Dickstein, Leah Zoghbi, Sami Lohith, Talakad Rallis-Frutos, Denise Telu, Sanjay Pike, Victor Fujita, Masahiro Innis, Robert TI Influence of polymorphism rs6971 on [C-11]DPA-713 imaging in human brain SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Kobayashi, Masato; Zanotti-Fregonara, Paolo; Dickstein, Leah; Zoghbi, Sami; Lohith, Talakad; Rallis-Frutos, Denise; Telu, Sanjay; Pike, Victor; Fujita, Masahiro; Innis, Robert] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 322 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100323 ER PT J AU Kreisl, W Bhatia, R Morse, C Zoghbi, S Shetty, HU Liow, JS Pike, V Innis, R AF Kreisl, William Bhatia, Ritwik Morse, Cheryl Zoghbi, Sami Shetty, H. Umesha Liow, Jeih-San Pike, Victor Innis, Robert TI Increased P-gp inhibition at the human blood brain barrier can be safely achieved and reliably measured by performing PET during peak plasma concentrations of tariquidar SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Kreisl, William; Bhatia, Ritwik; Morse, Cheryl; Zoghbi, Sami; Shetty, H. Umesha; Liow, Jeih-San; Pike, Victor; Innis, Robert] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1801 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438102467 ER PT J AU Lee, D Thada, S Guo, J Hall, K Barker, W Hammoud, D AF Lee, Dianne Thada, Shanthalaxmi Guo, Juen Hall, Kevin Barker, William Hammoud, Dima TI Quantitative comparison of motion correction methods in HRRT brain imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Lee, Dianne; Hammoud, Dima] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Thada, Shanthalaxmi; Barker, William] NIH, PET Dept, Bethesda, MD 20892 USA. [Guo, Juen; Hall, Kevin] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 2111 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438104272 ER PT J AU Lee, D Thada, S Guo, JE Hall, K Barker, W Hammoud, D AF Lee, Dianne Thada, Shanthalaxmi Guo, Juen Hall, Kevin Barker, William Hammoud, Dima TI Quantitative comparison of motion correction methods in HRRT brain imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Lee, Dianne; Hammoud, Dima] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Thada, Shanthalaxmi; Barker, William] NIH, PET Dept, Bethesda, MD 20892 USA. [Guo, Juen; Hall, Kevin] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 2111 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438103282 ER PT J AU Lee, D Reid, W Ibrahim, W Peterson, K Lentz, M Jagoda, E Hammoud, D AF Lee, Dianne Reid, William Ibrahim, Wael Peterson, Kristin Lentz, Margaret Jagoda, Elaine Hammoud, Dima TI Decreased striatal D2/3 receptors in HIV-1 transgenic rat seen with [18F]Fallypride-PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Lee, Dianne; Reid, William; Ibrahim, Wael; Peterson, Kristin; Lentz, Margaret; Hammoud, Dima] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Jagoda, Elaine] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 29 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100030 ER PT J AU Lee, SJ Kim, JS Kim, I Yao, ZS Lee, JH Pastan, I Paik, C AF Lee, Sung-Jin Kim, Jin Su Kim, Insook Yao, Zhengsheng Lee, Jae-Ho Pastan, Ira Paik, Chang TI Serial fractional doses of mAb B3 and paclitaxel improve accumulation and penetration of B3 due to apoptosis of tumor cells SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Lee, Sung-Jin; Kim, Jin Su; Yao, Zhengsheng; Lee, Jae-Ho; Paik, Chang] NIH, NMD, RAD&IS, CC, Bethesda, MD 20892 USA. [Kim, Insook] Leidos Inc, ADRD, Frederick, MD USA. [Pastan, Ira] NCI, LMB, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1376 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438102042 ER PT J AU Lindenberg, L Adler, S Thomas, A Maltzman, J Wallin, B Mena, E Kurdziel, K Paik, C Choyke, P Hassan, R AF Lindenberg, Liza Adler, Stephen Thomas, Anish Maltzman, Julia Wallin, Bruce Mena, Esther Kurdziel, Karen Paik, Chang Choyke, Peter Hassan, Raffit TI Initial clinical experience of 111In radiolabelled amatuximab in patients with mesothelin-expressing cancers SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Lindenberg, Liza; Mena, Esther; Kurdziel, Karen; Choyke, Peter] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Maltzman, Julia; Wallin, Bruce] Morphotek Inc, Exton, PA USA. [Thomas, Anish; Hassan, Raffit] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Adler, Stephen] NCI, Mol Imaging Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Paik, Chang] NIH, Radiopharmaceut Lab, Div Nucl Med, Dept Radiol & Imaging Sci,Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1138 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438101302 ER PT J AU Lohith, T Tsujikawa, T Zoghbi, S Jaaro-Peled, H Kimura, Y Morse, C Pike, V Sawa, A Innis, R Fujita, M AF Lohith, Talakad Tsujikawa, Tetsuya Zoghbi, Sami Jaaro-Peled, Hanna Kimura, Yasuyuki Morse, Cheryl Pike, Victor Sawa, Akira Innis, Robert Fujita, Masahiro TI PET imaging of increased C-11-(R)-rolipram binding in Disc1 transgenic mouse brain suggesting regulation of cAMP cascade by DISC1 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Lohith, Talakad; Tsujikawa, Tetsuya; Zoghbi, Sami; Kimura, Yasuyuki; Morse, Cheryl; Pike, Victor; Innis, Robert; Fujita, Masahiro] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Jaaro-Peled, Hanna; Sawa, Akira] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 469 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100470 ER PT J AU Lohith, T Fabrice, S Zoghbi, S Morse, C Pike, V Innis, R Fujita, M AF Lohith, Talakad Fabrice, Simeon Zoghbi, Sami Morse, Cheryl Pike, Victor Innis, Robert Fujita, Masahiro TI Potential utility of C-11-FPEB as a PET ligand for imaging metabotropic glutamate receptor 5 (mGluR5) in human brain SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Lohith, Talakad; Fabrice, Simeon; Zoghbi, Sami; Morse, Cheryl; Pike, Victor; Innis, Robert; Fujita, Masahiro] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 360 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100361 ER PT J AU Mansoor, A Bagci, U Mollura, D AF Mansoor, Awais Bagci, Ulas Mollura, Daniel TI Noise adaptive multi-resolution technique to accurately denoise PET, MRI-PET, and PET-CT images SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Mansoor, Awais; Bagci, Ulas; Mollura, Daniel] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 2050 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438104211 ER PT J AU Mansoor, A Bagci, U Mollura, D AF Mansoor, Awais Bagci, Ulas Mollura, Daniel TI Noise adaptive multi-resolution technique to accurately denoise PET, MRI-PET, and PET-CT images SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Mansoor, Awais; Bagci, Ulas; Mollura, Daniel] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 2050 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438103221 ER PT J AU Reynolds, J Maass-Moreno, R AF Reynolds, James Maass-Moreno, Roberto TI Comparison of SULmax and PERCIST SULpeak across patients and scanners SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Reynolds, James; Maass-Moreno, Roberto] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 2069 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438104230 ER PT J AU Reynolds, J Maass-Moreno, R AF Reynolds, James Maass-Moreno, Roberto TI Comparison of SULmax and PERCIST SULpeak across patients and scanners SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Reynolds, James; Maass-Moreno, Roberto] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 2069 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438103240 ER PT J AU Sadek, A Ahlman, M Dave, J Hasan, J Krishnamoorthy, P Rose, S Weiner, E Herscovitch, P Bluemke, D Mehta, N AF Sadek, Ahmed Ahlman, Mark Dave, Jenny Hasan, Josh Krishnamoorthy, Parasuram Rose, Shawn Weiner, Elizabeth Herscovitch, Peter Bluemke, David Mehta, Nehal TI Detection of vascular inflammation by PET/MRI as compared to PET/CT SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Sadek, Ahmed; Dave, Jenny; Hasan, Josh; Rose, Shawn; Weiner, Elizabeth; Mehta, Nehal] NHLBI, NIH, Bethesda, MD 20892 USA. [Krishnamoorthy, Parasuram] Englewood Hosp, Englewood, NJ USA. [Herscovitch, Peter] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Ahlman, Mark; Bluemke, David] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1778 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438102444 ER PT J AU Sail, D Matsumoto, S Vasalatiy, O Cherukuri, M Mitchell, J AF Sail, Deepak Matsumoto, Shingo Vasalatiy, Olga Cherukuri, Murali Mitchell, James TI Synthesis of novel fully deuterated 13C labeled 5,5-dimethyl pyrroline-N-oxide as spin trap agent SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Sail, Deepak; Vasalatiy, Olga] NIH, Imaging Probe Dev Ctr, Rockville, MD USA. [Matsumoto, Shingo; Cherukuri, Murali; Mitchell, James] NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1205 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438101369 ER PT J AU Sato, N Wu, HT Griffiths, G Choyke, P AF Sato, Noriko Wu, Haitao Griffiths, Gary Choyke, Peter TI Generation and use of long-lasting cell labeling agent for positron emission tomography (PET) imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Sato, Noriko; Griffiths, Gary; Choyke, Peter] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Wu, Haitao] NHLBI, Imaging Probe Dev Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 273 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100274 ER PT J AU Satz, S Baum, R Kulkarni, H Narasimhan, D Mueller, D Brechbiel, M Kim, YS AF Satz, Stanley Baum, Richard Kulkarni, Harshad Narasimhan, Danthi Mueller, Dirk Brechbiel, Martin Kim, Young-Seung TI First clinical application of a non-cyclic peptidomimetic theranostic SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Satz, Stanley] Adv Imaging Projects Inc, Lake Worth, FL USA. [Baum, Richard; Kulkarni, Harshad; Mueller, Dirk] Bad Berka Clin, Nucl Med, Bad Berka, Germany. [Narasimhan, Danthi; Brechbiel, Martin; Kim, Young-Seung] NCI, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1193 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438101357 ER PT J AU Singh, P Cai, LS Morse, C Gladding, R Fujita, M Innis, R Pike, V AF Singh, Prachi Cai, Lisheng Morse, Cheryl Gladding, Robert Fujita, Masahiro Innis, Robert Pike, Victor TI Radiosynthesis of [11C]sotrastaurin and evaluation as a PET radioligand for imaging brain PKC in monkey SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Singh, Prachi; Cai, Lisheng; Morse, Cheryl; Gladding, Robert; Fujita, Masahiro; Innis, Robert; Pike, Victor] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1114 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438101278 ER PT J AU Suzuki, A Leland, P Kobayashi, H Choyke, P Jagoda, E Inoue, T Joshi, B Puri, R AF Suzuki, Akiko Leland, Pamela Kobayashi, Hisataka Choyke, Peter Jagoda, Elaine Inoue, Tomio Joshi, Bharat Puri, Raj TI Evaluation of intracranial distribution of interleukin-13 receptor directed immunotoxin after convection enhanced delivery by SPECT/CT in a human brain tumor mouse model SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Suzuki, Akiko; Leland, Pamela; Joshi, Bharat; Puri, Raj] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Kobayashi, Hisataka; Choyke, Peter; Jagoda, Elaine] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Inoue, Tomio] Yokohama City Univ, Radiol, Yokohama, Kanagawa 232, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1027 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438101191 ER PT J AU Talbott, S Bhatt, G Li, XF Civelek, AC AF Talbott, Sabrina Bhatt, Geetika Li, Xiao-Feng Civelek, A. Cahid TI Dose related decreased image quality of CT doesn't degrade the diagnostic quality of PET-CT SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Civelek, A. Cahid] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Talbott, Sabrina; Bhatt, Geetika; Li, Xiao-Feng] Univ Louisville, Radiol & Med, Louisville, KY 40292 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 423 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100424 ER PT J AU Wang, Y Yue, XY Kiesewetter, D Lu, J Teng, GJ Niu, G Chen, XY AF Wang, Yu Yue, Xuyi Kiesewetter, Dale Lu, Jie Teng, Gaojun Niu, Gang Chen, Xiaoyuan TI Reduced TSPO expression after AMD3100 treatment in mouse stroke model: A PET study with [18F]DPA-714 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Wang, Yu; Yue, Xuyi; Kiesewetter, Dale; Lu, Jie; Niu, Gang; Chen, Xiaoyuan] NIBIB, NIH, Bethesda, MD USA. [Teng, Gaojun] SEU, Dept Radiol, Nanjing, Jiangsu, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1799 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438102465 ER PT J AU Wang, Z Wang, Y Niu, G Chen, XY AF Wang, Zhe Wang, Yu Niu, Gang Chen, Xiaoyuan TI Spatiotemporal molecular imaging of dynamic differentiation of transplanted neural stem cells in traumatic brain injury SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Wang, Zhe; Wang, Yu; Niu, Gang; Chen, Xiaoyuan] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 472 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100473 ER PT J AU Xu, ZY Bagci, U Mollura, D AF Xu, Ziyue Bagci, Ulas Mollura, Daniel TI Diffusion based enhancement of PET images for improved diagnostic measurements in clinical nuclear medicine SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Xu, Ziyue; Bagci, Ulas; Mollura, Daniel] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 2051 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438104212 ER PT J AU Xu, ZY Bagci, U Mollura, D AF Xu, Ziyue Bagci, Ulas Mollura, Daniel TI Diffusion based enhancement of PET images for improved diagnostic measurements in clinical nuclear medicine SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Xu, Ziyue; Bagci, Ulas; Mollura, Daniel] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 2051 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438103222 ER PT J AU Zanotti-Fregonara, P Zoghbi, S Liow, JS Xu, R Rallis-Frutos, D Pike, V Innis, R AF Zanotti-Fregonara, Paolo Zoghbi, Sami Liow, Jeih-San Xu, Rong Rallis-Frutos, Denise Pike, Victor Innis, Robert TI [18F]FIMX is a promising tracer to quantify metabotropic glutamate receptor 1 (mGluR1) in human brain SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Zanotti-Fregonara, Paolo; Zoghbi, Sami; Liow, Jeih-San; Xu, Rong; Rallis-Frutos, Denise; Pike, Victor; Innis, Robert] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 359 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100360 ER PT J AU Zanotti-Fregonara, P Lyoo, CH Zoghbi, S Liow, JS Xu, R Pike, V Zarate, C Fujita, M Innis, R AF Zanotti-Fregonara, Paolo Lyoo, Chul Hyoung Zoghbi, Sami Liow, Jeih-San Xu, Rong Pike, Victor Zarate, Carlos Fujita, Masahiro Innis, Robert TI Image-derived input function derived from a supervised clustering algorithm: Methodology and validation in a clinical protocol using [11C](R)-rolipram SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Zanotti-Fregonara, Paolo; Lyoo, Chul Hyoung; Zoghbi, Sami; Liow, Jeih-San; Xu, Rong; Pike, Victor; Zarate, Carlos; Fujita, Masahiro; Innis, Robert] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 316 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438100317 ER PT J AU Massey, PR Cowen, EW Okman, JS Wilkerson, J AF Massey, Paul R. Cowen, Edward W. Okman, Jonathan S. Wilkerson, Julia TI VEGF inhibitors have distinct cutaneous and systemic toxicity profiles: A metaanalysis and review of the literature SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Academy-of-Dermatology CY MAR 21-25, 2014 CL Denver, CO SP Amer Acad Dermatol C1 [Massey, Paul R.; Okman, Jonathan S.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cowen, Edward W.; Wilkerson, Julia] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2014 VL 70 IS 5 SU 1 MA P8285 BP AB120 EP AB120 PG 1 WC Dermatology SC Dermatology GA CQ4OI UT WOS:000360583900473 ER PT J AU Hou, Y Ghosh, P Wan, RQ Ouyang, X Cheng, HP Mattson, MP Cheng, AW AF Hou, Yan Ghosh, Paritosh Wan, Ruiqian Ouyang, Xin Cheng, Heping Mattson, Mark P. Cheng, Aiwu TI Permeability transition pore-mediated mitochondrial superoxide flashes mediate an early inhibitory effect of amyloid beta1-42 on neural progenitor cell proliferation SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Amyloid beta-peptide; ERK; Mitochondrial permeability transition pore; Neurogenesis; SOD ID ADULT HIPPOCAMPAL NEUROGENESIS; FAMILIAL ALZHEIMERS-DISEASE; TRANSGENIC MOUSE MODEL; ISCHEMIC BRAIN-INJURY; PRECURSOR PROTEIN; OXIDATIVE STRESS; A-BETA; STEM-CELLS; ENVIRONMENTAL ENRICHMENT; IMPAIRED NEUROGENESIS AB Cellular damage by reactive oxygen species and altered neurogenesis are implicated in the etiology of AD and the pathogenic actions of amyloid beta-peptide (A beta); the underlying mechanisms and the early oxidative intracellular events triggered by A beta are not established. In the present study, we found that mouse embryonic cortical neural progenitor cells exhibit intermittent spontaneous mitochondrial superoxide (SO) flashes that require transient opening of mitochondrial permeability transition pores (mPTPs). The incidence of mitochondria SO flash activity in neural progenitor cells (NPCs) increased during the first 6-24 hours of exposure to aggregating amyloid beta-peptide (A beta 1-42), indicating an increase in transient mPTP opening. Subsequently, the SO flash frequency progressively decreased and ceased between 48 and 72 hours of exposure to A beta 1-42, during which time global cellular reactive oxygen species increased, mitochondrial membrane potential decreased, cytochrome C was released from mitochondria and the cells degenerated. Inhibition of mPTPs and selective reduction in mitochondrial SO flashes significantly ameliorated the negative effects of A beta 1-42 on NPC proliferation and survival. Our findings suggest that mPTP-mediated bursts of mitochondrial SO production is a relatively early and pivotal event in the adverse effects of A beta 1-42 on NPCs. If a beta inhibits NPC proliferation in the brains of AD patients by a similar mechanism, then interventions that inhibit mPTP-mediated superoxide flashes would be expected to protect NPCs against the adverse effects of A beta. Published by Elsevier Inc. C1 [Hou, Yan; Wan, Ruiqian; Ouyang, Xin; Mattson, Mark P.; Cheng, Aiwu] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Ghosh, Paritosh] NIA, Immunol Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Cheng, Heping] Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. [Cheng, Heping] Peking Univ, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov; chengai@mail.nih.gov FU Intramural Research Program of the National Institute on Aging; Glenn Foundation for Medical Research; National Natural Science Foundation; National Basic Research Program of China [2011CB809100] FX This work was supported by the Intramural Research Program of the National Institute on Aging, by the Glenn Foundation for Medical Research, and by the National Natural Science Foundation and National Basic Research Program of China (2011CB809100). NR 89 TC 16 Z9 16 U1 0 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY PY 2014 VL 35 IS 5 BP 975 EP 989 DI 10.1016/j.neurobiolaging.2013.11.002 PG 15 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AC2DO UT WOS:000332308300004 PM 24325797 ER PT J AU Rothman, SM Griffioen, KJ Fishbein, KW Spencer, RG Makrogiannis, S Cong, WN Martin, B Mattson, MP AF Rothman, Sarah M. Griffioen, Kathleen J. Fishbein, Kenneth W. Spencer, Richard G. Makrogiannis, Sokratis Cong, Wei-na Martin, Bronwen Mattson, Mark P. TI Metabolic abnormalities and hypoleptinemia in alpha-synuclein A53T mutant mice SO NEUROBIOLOGY OF AGING LA English DT Article DE Parkinson's disease; Energy metabolism; Leptin; Insulin; Body fat ID PARKINSONS-DISEASE PATIENTS; IMPAIRED GLUCOSE-TOLERANCE; WEIGHT-LOSS; SLEEP DISTURBANCES; JAPANESE-AMERICANS; VISCERAL ADIPOSITY; INSULIN-RESISTANCE; ENERGY-EXPENDITURE; LEPTIN RECEPTOR; PLASMA LEPTIN AB Parkinson's disease (PD) patients frequently display loss of body fat mass and increased energy expenditure, and several studies have outlined a relationship between these metabolic abnormalities and disease severity, yet energy metabolism is largely unstudied in mouse models of PD. Here we characterize metabolic and physiologic responses to a high calorie diet (HCD) in mice expressing in neurons a mutant form of human a-synuclein (A53T) that causes dominantly inherited familial forms of the disease. A53T (SNCA) and wild type (WT) littermate mice were placed on a HCD for 12 weeks and evaluated for weight gain, food intake, body fat, blood plasma leptin, hunger, glucose tolerance, and energy expenditure. Results were compared with both SNCA and WT mice on a control diet. Despite consuming similar amounts of food, WT mice gained up to 66% of their original body weight on a HCD, whereas SNCA mice gained only 17%. Further, after 12 weeks on a HCD, magnetic resonance imaging analysis revealed that WT mice had significantly greater total and visceral body fat compared with SNCA mice (p < 0.007). At the age of 24 weeks SNCA mice displayed significantly increased hunger compared with WT (p < 0.03). At the age of 36 weeks, SNCA mice displayed significant hypoleptinemia compared with WT, both on a normal diet and a HCD (p < 0.03). The HCD induced insulin insensitivity in WT, but not SNCA mice, as indicated by an oral glucose tolerance test. Finally, SNCA mice displayed greater energy expenditure compared with WT, as measured in a Comprehensive Laboratory Animal Monitoring System, after 12 weeks on a HCD. Thus, SNCA mice are resistant to HCD-induced obesity and insulin resistance and display reduced body fat, increased hunger, hypoleptinemia and increased energy expenditure. Our findings reveal a profile of metabolic dysfunction in a mouse model of PD that is similar to that of human PD patients, thus providing evidence that alpha-synuclein pathology is sufficient to drive such metabolic abnormalities and providing an animal model for discovery of the underlying mechanisms and potential therapeutic interventions. Published by Elsevier Inc. C1 [Rothman, Sarah M.; Griffioen, Kathleen J.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Fishbein, Kenneth W.; Spencer, Richard G.] NIA, Magnet Resonance Imaging & Spect Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Makrogiannis, Sokratis] NIA, Longitudinal Studies Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Cong, Wei-na; Martin, Bronwen] NIA, Lab Clin Invest, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM mark.mattson@nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. The authors thank Catherine Crews and Charles Reitz for assistance with management of the mouse colonies. NR 43 TC 3 Z9 3 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY PY 2014 VL 35 IS 5 BP 1153 EP 1161 DI 10.1016/j.neurobiolaging.2013.10.088 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AC2DO UT WOS:000332308300022 PM 24239384 ER PT J AU Periwal, V Gaillard, JR Needleman, L Doria, C AF Periwal, V. Gaillard, J. R. Needleman, L. Doria, C. TI Mathematical Model of Liver Regeneration in Human Live Donors SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID LIVING-DONOR; TRANSPLANTATION; RAT AB Liver regeneration after injury occurs in many mammals. Rat liver regenerates after partial hepatectomy over a period of 2 weeks while human liver regeneration takes several months. Notwithstanding this enormous difference in time-scales, with new data from five human live liver transplant donors, we show that a mathematical model of rat liver regeneration can be transferred to human, with all biochemical interactions and signaling unchanged. Only six phenomenological parameters need change, and three of these parameter changes are rescalings of rate constants by the ratio of human lifespan to rat lifespan. Data from three donor subjects with approximately equal resections were used to fit the three parameters and the data from the other two donor subjects was used to independently verify the fit. J. Cell. Physiol. 229: 599-606, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Periwal, V.; Gaillard, J. R.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20814 USA. [Needleman, L.; Doria, C.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. RP Periwal, V (reprint author), NIDDK, Math Cell Modeling Sect, NIH, Bldg 12A,Room 4007,12 S Dr, Bethesda, MD 20814 USA. EM vipulp@mail.nih.gov FU National Institutes of Health, NIDDK FX Contract grant sponsor: National Institutes of Health, NIDDK. NR 16 TC 6 Z9 6 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 2014 VL 229 IS 5 BP 599 EP 606 DI 10.1002/jcp.24482 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA AA4JX UT WOS:000331063000009 PM 24446196 ER PT J AU Lee, KS Park, JE Kang, YH Kim, TS Bang, JK AF Lee, Kyung S. Park, Jung-Eun Kang, Young Hwi Kim, Tae-Sung Bang, Jeong K. TI Mechanisms Underlying Plk1 Polo-Box Domain-Mediated Biological Processes and Their Physiological Significance SO MOLECULES AND CELLS LA English DT Review DE non-self-priming; self-priming; Plk1; polo-box domain ID KINASE 1; PROTEIN-KINASE; SUBCELLULAR-LOCALIZATION; SPINDLE CHECKPOINT; MITOTIC FUNCTIONS; STRUCTURAL BASIS; CANCER-THERAPY; PHOSPHORYLATION; POLO-LIKE-KINASE-1; CYTOKINESIS AB Mammalian polo-like kinase 1 (Plk1) has been studied intensively as a key regulator of various cell cycle events that are critical for proper M-phase progression. The polo-box domain (PBD) present in Plk1's C-terminal noncatalytic region has been shown to play a central role in targeting the N-terminal kinase domain of Plk1 to specific subcellular locations. Subsequent studies reveal that PBD binds to a phosphorylated motif generated by one of the two mechanisms - self-priming by Plk1 itself or non-self-priming by a Pro-directed kinase, such as Cdc2. Here, we comparatively review the differences in the biochemical steps of these mechanisms and discuss their physiological significance. Considering the diverse functions of Plk1 during the cell cycle, a better understanding of how the catalytic activity of Plk1 functions in concert with its cis-acting PBD and how this coordinated process is intricately regulated to promote Plk1 functions will be important for providing new insights into different mechanisms underlying various Plk1-mediated biological events that occur at the multiple stages of the cell cycle. C1 [Lee, Kyung S.; Park, Jung-Eun; Kim, Tae-Sung] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Kang, Young Hwi] Ewha Womans Univ, Dept Life Sci, Immune & Vasc Cell Network Res Ctr, Seoul 120750, South Korea. [Kang, Young Hwi] Ewha Womans Univ, Program GT5, Seoul 120750, South Korea. [Bang, Jeong K.] Korea Basic Sci Inst, Div Magnet Resonance, Ochang 363883, South Korea. RP Lee, KS (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM kyunglee@mail.nih.gov FU National Cancer Institute; Korea Basic Science Institute [T33418] FX We are grateful to all the past and present members of the Lee laboratory for stimulating discussions about self-priming and non-self-priming mechanisms for PBD binding. This work was supported in part by a National Cancer Institute intramural grant (K.S.L.) and Korea Basic Science Institute's research grant T33418 (J.K.B). NR 50 TC 4 Z9 4 U1 0 U2 4 PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY PI SEOUL PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 EI 0219-1032 J9 MOL CELLS JI Mol. Cells PD APR 30 PY 2014 VL 37 IS 4 BP 286 EP 294 DI 10.14348/molcells.2014.0002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AQ1RZ UT WOS:000342560000002 PM 24722413 ER PT J AU Schrack, JA Zipunnikov, V Goldsmith, J Bandeen-Roche, K Crainiceanu, CM Ferrucci, L AF Schrack, Jennifer A. Zipunnikov, Vadim Goldsmith, Jeff Bandeen-Roche, Karen Crainiceanu, Ciprian M. Ferrucci, Luigi TI Estimating Energy Expenditure from Heart Rate in Older Adults: A Case for Calibration SO PLOS ONE LA English DT Article ID DOUBLY LABELED WATER; PHYSICAL-ACTIVITY QUESTIONNAIRES; ACCELEROMETRY; FITNESS AB Background: Accurate measurement of free-living energy expenditure is vital to understanding changes in energy metabolism with aging. The efficacy of heart rate as a surrogate for energy expenditure is rooted in the assumption of a linear function between heart rate and energy expenditure, but its validity and reliability in older adults remains unclear. Objective: To assess the validity and reliability of the linear function between heart rate and energy expenditure in older adults using different levels of calibration. Design: Heart rate and energy expenditure were assessed across five levels of exertion in 290 adults participating in the Baltimore Longitudinal Study of Aging. Correlation and random effects regression analyses assessed the linearity of the relationship between heart rate and energy expenditure and cross-validation models assessed predictive performance. Results: Heart rate and energy expenditure were highly correlated (r = 0.98) and linear regardless of age or sex. Intra-person variability was low but inter-person variability was high, with substantial heterogeneity of the random intercept (s.d. = 0.372) despite similar slopes. Cross-validation models indicated individual calibration data substantially improves accuracy predictions of energy expenditure from heart rate, reducing the potential for considerable measurement bias. Although using five calibration measures provided the greatest reduction in the standard deviation of prediction errors (1.08 kcals/min), substantial improvement was also noted with two (0.75 kcals/min). Conclusion: These findings indicate standard regression equations may be used to make population-level inferences when estimating energy expenditure from heart rate in older adults but caution should be exercised when making inferences at the individual level without proper calibration. C1 [Schrack, Jennifer A.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Schrack, Jennifer A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Zipunnikov, Vadim; Goldsmith, Jeff; Bandeen-Roche, Karen; Crainiceanu, Ciprian M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Schrack, Jennifer A.; Bandeen-Roche, Karen] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. RP Schrack, JA (reprint author), NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. EM jschrack@jhsph.edu FU National Institutes of Health, National Institute on Aging FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. Data for these analyses were obtained from the Baltimore Longitudinal Study of Aging, a study performed by the National Institute on Aging. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 5 Z9 5 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 30 PY 2014 VL 9 IS 4 AR e93520 DI 10.1371/journal.pone.0093520 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AL1WP UT WOS:000338917300004 PM 24787146 ER PT J AU Tomasi, D Volkow, ND AF Tomasi, Dardo Volkow, Nora D. TI Mapping Small-World Properties through Development in the Human Brain: Disruption in Schizophrenia SO PLOS ONE LA English DT Article ID FUNCTIONAL CONNECTIVITY MRI; HUMAN CEREBRAL-CORTEX; RESTING-STATE; 1ST-DEGREE RELATIVES; ALZHEIMERS-DISEASE; DEFAULT NETWORK; CORTICAL HUBS; LOW-FREQUENCY; TEST-RETEST; ORGANIZATION AB Evidence from imaging studies suggests that the human brain has a small-world network topology that might be disrupted in certain brain disorders. However, current methodology is based on global graph theory measures, such as clustering, C, characteristic path length, L, and small-worldness, S, that lack spatial specificity and are insufficient to identify regional brain abnormalities. Here we propose novel ultra-fast methodology for mapping local properties of brain network topology such as local C, L and S (lC, lL and lS) in the human brain at 3-mm isotropic resolution from 'resting-state' magnetic resonance imaging data. Test-retest datasets from 40 healthy children/adolescents were used to demonstrate the overall good reliability of the measures across sessions and computational parameters (intraclass correlation >0.5 for lC and lL) and their low variability across subjects (< 29%). Whereas regions with high local functional connectivity density (lFCD; local degree) in posterior parietal and occipital cortices demonstrated high lC and short lL, subcortical regions (globus pallidus, thalamus, hippocampus and amygdala), cerebellum (lobes and vermis), cingulum and temporal cortex also had high, lS, demonstrating stronger small-world topology than other hubs. Children/adolescents had stronger lFCD, higher lC and longer lL in most cortical regions and thalamus than 74 healthy adults, consistent with pruning of functional connectivity during maturation. In contrast, lFCD, lC and lL were weaker in thalamus and midbrain, and lL was shorter in frontal cortical regions and cerebellum for 69 schizophrenia patients than for 74 healthy controls, suggesting exaggerated pruning of connectivity in schizophrenia. Follow up correlation analyses for seeds in thalamus and midbrain uncovered lower positive connectivity of these regions in thalamus, putamen, cerebellum and frontal cortex (cingulum, orbitofrontal, inferior frontal) and lower negative connectivity in auditory, visual, motor, premotor and somatosensory cortices for schizophrenia patients than for controls, consistent with prior findings of thalamic disconnection in schizophrenia. C1 [Tomasi, Dardo; Volkow, Nora D.] NIAAA, Bethesda, MD 20892 USA. [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. RP Tomasi, D (reprint author), NIAAA, Bethesda, MD 20892 USA. EM tomasidg@mail.nih.gov RI Tomasi, Dardo/J-2127-2015 FU National Institutes of Alcohol Abuse and Alcoholism [2RO1AA09481] FX This work was accomplished with support from the National Institutes of Alcohol Abuse and Alcoholism (2RO1AA09481). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 74 TC 11 Z9 13 U1 6 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 30 PY 2014 VL 9 IS 4 AR e96176 DI 10.1371/journal.pone.0096176 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AL1WP UT WOS:000338917300030 PM 24788815 ER PT J AU Johnen, VM Buch, ER Neubert, FX AF Johnen, Vanessa M. Buch, Ethan R. Neubert, Franz-Xaver TI Can Cortical Stimulation of Inferior Frontal Cortex Enhance Proactive Control? SO JOURNAL OF NEUROSCIENCE LA English DT Editorial Material ID PLASTICITY; BRAIN C1 [Johnen, Vanessa M.; Neubert, Franz-Xaver] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [Johnen, Vanessa M.; Neubert, Franz-Xaver] Univ Oxford, John Radcliffe Hosp, Ctr Funct Magnet Resonance Imaging Brain, Oxford OX3 9DU, England. [Buch, Ethan R.] NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bethesda, MD 20814 USA. [Buch, Ethan R.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. RP Johnen, VM (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England. EM vanessa.johnen@psy.ox.ac.uk NR 11 TC 0 Z9 0 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 30 PY 2014 VL 34 IS 18 BP 6125 EP 6127 DI 10.1523/JNEUROSCI.0590-14.2014 PG 3 WC Neurosciences SC Neurosciences & Neurology GA AH2AA UT WOS:000335921900001 PM 24790182 ER PT J AU Mehta, B Ke, JB Zhang, L Baden, AD Markowitz, AL Nayak, S Briggman, KL Zenisek, D Singer, JH AF Mehta, Bhupesh Ke, Jiang-Bin Zhang, Lei Baden, Alexander D. Markowitz, Alexander L. Nayak, Subhashree Briggman, Kevin L. Zenisek, David Singer, Joshua H. TI Global Ca2+ Signaling Drives Ribbon-Independent Synaptic Transmission at Rod Bipolar Cell Synapses SO JOURNAL OF NEUROSCIENCE LA English DT Article DE exocytosis; retina; ribbon; vesicle ID INNER PLEXIFORM LAYER; AII AMACRINE CELLS; NEUROTRANSMITTER RELEASE; MOUSE RETINA; TRANSMITTER RELEASE; RABBIT RETINA; HAIR-CELLS; PRESYNAPTIC CALCIUM; GLUTAMATE RELEASE; MULTIVESICULAR RELEASE AB Ribbon-type presynaptic active zones are a hallmark of excitatory retinal synapses, and the ribbon organelle is thought to serve as the organizing point of the presynaptic active zone. Imaging of exocytosis from isolated retinal neurons, however, has revealed ectopic release (i.e., release away from ribbons) in significant quantities. Here, we demonstrate in an in vitro mouse retinal slice preparation that ribbon-independent release from rod bipolar cells activates postsynaptic AMPARs on AII amacrine cells. This form of release appears to draw on a unique, ribbon-independent, vesicle pool. Experimental, anatomical, and computational analyses indicate that it is elicited by a significant, global elevation of intraterminal [Ca2+] arising following local buffer saturation. Our observations support the conclusion that ribbon-independent release provides a read-out of the average behavior of all of the active zones in a rod bipolar cell's terminal. C1 [Mehta, Bhupesh; Zenisek, David] Yale Univ, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. [Mehta, Bhupesh; Zenisek, David] Yale Univ, Dept Ophthalmol & Visual Sci, New Haven, CT 06520 USA. [Ke, Jiang-Bin; Zhang, Lei; Baden, Alexander D.; Markowitz, Alexander L.; Nayak, Subhashree; Singer, Joshua H.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA. [Briggman, Kevin L.] NINDS, Circuit Dynam & Connect Unit, NIH, Bethesda, MD 20892 USA. RP Zenisek, D (reprint author), Dept Cellular & Mol Physiol, POB 208026,333 Cedar St, New Haven, CT 06520 USA. EM david.zenisek@yale.edu; jhsinger@umd.edu FU Intramural Research Program of the National Institutes of Health; National Institute of Neurological Disorders and Stroke; Howard Hughes Medical Institute through the Precollege and Undergraduate Science Education Program; [EY017836]; [014990] FX We thank J. Jiang for technical support; S. Ali, A. Ayala, P. Ghorbani, C. Hahn, J. Masison, A. Merrihew, N. Park, K. Sistani, and M. Yi for assistance with EM reconstruction; Victor Matveev for his help with CalC; and Greg Sullivan for access to the computing resources of the UMD Particle Astrophysics group. Supported by EY017836 to J.H.S.; by 014990 to D.Z.; and by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke (K.L.B.). S.N. received support from a grant to the University of Maryland from the Howard Hughes Medical Institute through the Precollege and Undergraduate Science Education Program. NR 93 TC 9 Z9 9 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 30 PY 2014 VL 34 IS 18 BP 6233 EP 6244 DI 10.1523/JNEUROSCI.5324-13.2014 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AH2AA UT WOS:000335921900013 PM 24790194 ER PT J AU Kamhawi, S Oliveira, F Valenzuela, JG AF Kamhawi, Shaden Oliveira, Fabiano Valenzuela, Jesus G. TI Using Humans to Make a Human Leishmaniasis Vaccine SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material ID VISCERAL LEISHMANIASIS; MODEL AB The cellular immune response to peptide pools from conserved Leishmania antigens in leishmaniasis-immune individuals identified epitopes for a human DNA vaccine (Das et al., this issue). C1 [Kamhawi, Shaden; Oliveira, Fabiano; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM jvalenzuela@niaid.nih.gov RI Oliveira, Fabiano/B-4251-2009 OI Oliveira, Fabiano/0000-0002-7924-8038 NR 10 TC 4 Z9 4 U1 1 U2 4 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 30 PY 2014 VL 6 IS 234 AR 234fs18 DI 10.1126/scitranslmed.3009118 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AG6GC UT WOS:000335516100008 PM 24786322 ER PT J AU Gill, J Lee, H Barr, T Baxter, T Heinzelmann, M Rak, H Mysliwiec, V AF Gill, Jessica Lee, Hyunhwa Barr, Taura Baxter, Tristin Heinzelmann, Morgan Rak, Hannah Mysliwiec, Vincent TI Lower health related quality of life in US military personnel is associated with service-related disorders and inflammation SO PSYCHIATRY RESEARCH LA English DT Article DE IL-6; Post-traumatic stress disorder; Depression; Traumatic brain injury ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; SELF-RATED HEALTH; MENTAL-HEALTH; CARDIOVASCULAR EVENTS; PTSD; DEPRESSION; MORTALITY; VETERANS; DEPLOYMENT AB Military personnel who have combat exposures are at increased risk for the service-related disorders of post-traumatic stress disorder (PTSD), depression, sleep disturbances and decreased health related quality of life (HRQOL). Those with a traumatic brain injury (TBI) are at even greater risk. Inflammation is associated with these disorders and may underlie the risk for health declines. We evaluated 110 recently deployed, military personnel presenting with sleep disturbances for service-related disorders (TBI, PTSD, and depression) as well as HRQOL. ANOVA models were used to examine differences among military personnel with two or more service-related disorders (high comorbid group), or one or no disorders (low comorbid group). Logistic regression models were used to determine associations among interleukin-6 (IL-6) to HRQOL and service-related disorders. Approximately one-third of the sample had two or more service-related disorders. HRQOL was lower and IL-6 concentrations were higher in military personnel with PTSD or depression, with the most profound differences in those with more service-related disorders, regardless of sleep disorder. Having symptoms of depression and PTSD resulted in a 3.5-fold risk to be in the lower quartile of HRQOL and the highest quartile of IL-6. In a linear regression model, 41% of the relationship between HRQOL and IL-6 concentrations was mediated by PTSD and depression. Military personnel with PTSD and depression are at high risk for lower HRQOL, and higher IL-6 concentrations. Comprehensive treatment is required to address co-occurring service-related disorders in military personnel to promote health and well-being. (C) 2014 Published by Elsevier Ireland Ltd. C1 [Gill, Jessica; Lee, Hyunhwa; Heinzelmann, Morgan; Rak, Hannah] NINR, NIH, Bethesda, MD 20892 USA. [Barr, Taura] W Virginia Univ, Morgantown, WV 26506 USA. [Baxter, Tristin; Mysliwiec, Vincent] Madigan Army Med Ctr, Tacoma, WA 98431 USA. RP Gill, J (reprint author), NINR, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM gillj@mail.nih.gov FU Center for Neuroscience and Regenerative Medicine [60855] FX This study was funded, in part, by the Center for Neuroscience and Regenerative Medicine (Grant 60855). The opinions and assertions in this manuscript are those of the authors and do not necessarily represent those of the Department of the Army, Department of Defense, U.S. Government, or the Center for Neuroscience and Regenerative Medicine. NR 53 TC 10 Z9 10 U1 7 U2 17 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 30 PY 2014 VL 216 IS 1 BP 116 EP 122 DI 10.1016/j.psychres.2014.01.046 PG 7 WC Psychiatry SC Psychiatry GA AE6XL UT WOS:000334141200018 PM 24559851 ER PT J AU Nagy, Z Kovacs, I Torol, M Toth, D Vereb, G Buzas, K Juhasz, I Blumberg, PM Biro, T Czifra, G AF Nagy, Zsuzsanna Kovacs, Ilona Toeroel, Miklos Toth, Dezso Vereb, Gyoergy Buzas, Krisztina Juhasz, Istvan Blumberg, Peter M. Biro, Tamas Czifra, Gabriella TI Function of RasGRP3 in the formation and progression of human breast cancer SO MOLECULAR CANCER LA English DT Article DE Ras activator; RasGRP3; Human breast cancer; Chemotherapeutic resistance; Tamoxifen; Trastuzumab; Tumorigenesis; EGF; IGF-I; Signaling pathways ID GROWTH-FACTOR-I; ACTIVATED PROTEIN-KINASE; NUCLEOTIDE EXCHANGE FACTOR; ESTROGEN-RECEPTOR; DYNEIN LIGHT-CHAIN-1; TRASTUZUMAB HERCEPTIN; ENDOCRINE RESISTANCE; SIGNAL-TRANSDUCTION; PHORBOL ESTERS; RAS ACTIVATION AB Introduction: Ras guanine nucleotide exchange factors (RasGEFs) mediate the activation of the Ras signaling pathway that is over activated in many human cancers. The RasGRP3, an activator of H-Ras and R-Ras protein exerts oncogenic effects and the overexpression of the protein is observed in numerous malignant cancer types. Here, we investigated the putative alteration of expression and potential function of RasGRP3 in the formation and progression of human breast cancer. Methods: The RasGRP3 and phosphoRasGRP3 expressions were examined in human invasive ductal adenocarcinoma derived samples and cell lines (BT-474, JIMT-1, MCF7, SK-BR-3, MDA-MB-453, T-47D) both in mRNA (Q-PCR) and protein (Western blot; immunohistochemistry) levels. To explore the biological function of the protein, RasGRP3 knockdown cultures were established. To assess the role of RasGRP3 in the viability of cells, annexin-V/PI staining and MitoProbe (TM) DilC1 (5) assay were performed. To clarify the function of the protein in cell proliferation and in the development of chemotherapeutic resistance, CyQuant assay was performed. To observe the RasGRP3 function in tumor formation, the Severe combined immunodeficiency (SCID) mouse model was used. To investigate the role of the protein in Ras-related signaling Q-PCR and Western blot experiments were performed. Results: RasGRP3 expression was elevated in human breast tumor tissue samples as well as in multiple human breast cancer cell lines. Down-regulation of RasGRP3 expression in breast cancer cells decreased cell proliferation, induced apoptosis in MCF7 cells, and sensitized T-47D cells to the action of drugs Tamoxifen and trastuzumab (Herceptin). Gene silencing of RasGRP3 reduced tumor formation in mouse xenografts as well. Inhibition of RasGRP3 expression also reduced Akt, ERK1/2 and estrogen receptor alpha phosphorylation downstream from IGF-I insulin like growth factor-I (IGF-I) or epidermal growth factor (EGF) stimulation confirming the functional role of RasGRP3 in the altered behavior of these cells. Conclusions: Taken together, our results suggest that the Ras activator RasGRP3 may have a role in the pathological behavior of breast cancer cells and may constitute a therapeutic target for human breast cancer. C1 [Nagy, Zsuzsanna; Biro, Tamas; Czifra, Gabriella] Univ Debrecen, DE MTA Lendulet Cellular Physiol Res Grp, Dept Physiol, Res Ctr Mol Med,Med & Hlth Sci Ctr, H-4032 Debrecen, Hungary. [Kovacs, Ilona; Toeroel, Miklos] Gyula Kenezy Hosp, Dept Pathol, Debrecen, Hungary. [Toth, Dezso] Gyula Kenazy Hosp, Dept Surg, Debrecen, Hungary. [Vereb, Gyoergy] Univ Debrecen, Med & Hlth Sci Ctr, Fac Med, Dept Biophys & Cell Biol, H-4032 Debrecen, Hungary. [Buzas, Krisztina] Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, H-6701 Szeged, Hungary. [Juhasz, Istvan] Univ Debrecen, Med & Hlth Sci Ctr, Dept Dermatol, H-4032 Debrecen, Hungary. [Blumberg, Peter M.] NCI, Canc Biol Lab, Bethesda, MD 20892 USA. [Blumberg, Peter M.] NCI, Genet Ctr Canc Res, Bethesda, MD 20892 USA. RP Czifra, G (reprint author), Univ Debrecen, DE MTA Lendulet Cellular Physiol Res Grp, Dept Physiol, Res Ctr Mol Med,Med & Hlth Sci Ctr, Nagyerdei Krt 98,POB 22, H-4032 Debrecen, Hungary. EM czifrag@gmail.com RI Vereb, Gyorgy/A-4241-2008 OI Vereb, Gyorgy/0000-0003-2157-3265 FU Hungarian research grants [TAMOP-4.2.2.A-11/1/KONV-2012-0025, "Lendulet" LP003/2011]; University of Debrecen [RH/885/2013]; [TAMOP-4.2.2./B-10/1-2010-0024] FX The authors thank Dr. Peter Nagy (University of Debrecen) for providing human breast cancer cell lines; Laboratory of Cancer Biology and Genetics (Center for Cancer Research, National Cancer Institute) for providing human prostate cancer cell line PC-3, Dr. Laszlo Simon (University of Debrecen) for assistance with SCID mice experiment. This study was supported by Hungarian research grants TAMOP-4.2.2.A-11/1/KONV-2012-0025. and "Lendulet" LP003/2011 and by the University of Debrecen (RH/885/2013). Zs. Nagy is a recipient of the TAMOP-4.2.2./B-10/1-2010-0024. Predoctoral Research Scholarship. NR 73 TC 1 Z9 1 U1 5 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD APR 29 PY 2014 VL 13 AR 96 DI 10.1186/1476-4598-13-96 PG 17 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA AK2IV UT WOS:000338243600001 PM 24779681 ER PT J AU Krupovic, M Bamford, DH Koonin, EV AF Krupovic, Mart Bamford, Dennis H. Koonin, Eugene V. TI Conservation of major and minor jelly-roll capsid proteins in Polinton (Maverick) transposons suggests that they are bona fide viruses SO BIOLOGY DIRECT LA English DT Article DE Polintons; Mavericks; Transposable elements; Double jelly-roll fold; Capsid proteins; Virus evolution ID STRANDED-DNA VIRUSES; GENETIC ELEMENTS; EVOLUTION; EUKARYOTES; VIROPHAGE; GENOMICS; RECONSTRUCTION; TRANSPOVIRONS; ADENOVIRUS; MECHANISM AB Polintons (also known as Mavericks) and Tlr elements of Tetrahymena thermophila represent two families of large DNA transposons widespread in eukaryotes. Here, we show that both Polintons and Tlr elements encode two key virion proteins, the major capsid protein with the double jelly-roll fold and the minor capsid protein, known as the penton, with the single jelly-roll topology. This observation along with the previously noted conservation of the genes for viral genome packaging ATPase and adenovirus-like protease strongly suggests that Polintons and Tlr elements combine features of bona fide viruses and transposons. We propose the name ` Polintoviruses' to denote these putative viruses that could have played a central role in the evolution of several groups of DNA viruses of eukaryotes. C1 [Krupovic, Mart] Inst Pasteur, Dept Microbiol, Unite Biol Mol Gene Chez Extremophiles, F-75015 Paris, France. [Bamford, Dennis H.] Univ Helsinki, Dept Biosci, Viikki Bioctr 2, FIN-00014 Helsinki, Finland. [Bamford, Dennis H.] Univ Helsinki, Inst Biotechnol, Viikki Bioctr 2, FIN-00014 Helsinki, Finland. [Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Krupovic, M (reprint author), Inst Pasteur, Dept Microbiol, Unite Biol Mol Gene Chez Extremophiles, F-75015 Paris, France. EM krupovic@pasteur.fr; koonin@ncbi.nlm.nih.gov RI Krupovic, Mart/I-4209-2012; OI Krupovic, Mart/0000-0001-5486-0098; Bamford, Dennis/0000-0002-6438-8118 FU European Molecular Biology Organization [ASTF 82-2014]; Academy of Finland [271413, 272853, 255342, 256518]; University of Helsinki; EU ESFRI Instruct Centre; US Department of Health and Human Services FX MK was partly supported by the European Molecular Biology Organization (ASTF 82-2014).; DHB is supported by the Academy of Finland (grants 271413 and 272853 as well as Academy Professor funding grants 255342 and 256518). DHB is also grateful to the University of Helsinki for the support to EU ESFRI Instruct Centre. EVK is supported by intramural funds of the US Department of Health and Human Services (to the National Library of Medicine). NR 40 TC 23 Z9 24 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD APR 29 PY 2014 VL 9 AR 6 DI 10.1186/1745-6150-9-6 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AI3LF UT WOS:000336762200001 PM 24773695 ER PT J AU Chen, J Miller, BF Furano, AV AF Chen, Jia Miller, Brendan F. Furano, Anthony V. TI Repair of naturally occurring mismatches can induce mutations in flanking DNA SO ELIFE LA English DT Article ID BASE EXCISION-REPAIR; SHUTTLE VECTOR PLASMID; MAMMALIAN-CELLS; SOMATIC HYPERMUTATION; HUMAN CANCERS; POSTREPLICATION REPAIR; POLYMERASE-ETA; BREAST-CANCER; MUTL-ALPHA; STRAND AB 'Normal' genomic DNA contains hundreds of mismatches that are generated daily by the spontaneous deamination of C (U/G) and methyl-C (T/G). Thus, a mutagenic effect of their repair could constitute a serious genetic burden. We show here that while mismatches introduced into human cells on an SV40-based episome were invariably repaired, this process induced mutations in flanking DNA at a significantly higher rate than no mismatch controls. Most mutations involved the C of TpC, the substrate of some single strand-specific APOBEC cytidine deaminases, similar to the mutations that can typify the 'mutator phenotype' of numerous tumors. siRNA knockdowns and chromatin immunoprecipitation showed that TpC preferring APOBECs mediate the mutagenesis, and siRNA knockdowns showed that both the base excision and mismatch repair pathways are involved. That naturally occurring mispairs can be converted to mutators, represents an heretofore unsuspected source of genetic changes that could underlie disease, aging, and evolutionary change. C1 [Chen, Jia; Miller, Brendan F.; Furano, Anthony V.] NIDDK, Sect Genom Struct & Funct, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Furano, AV (reprint author), NIDDK, Sect Genom Struct & Funct, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. EM avf@helix.nih.gov FU Intramural Research Program of the NIH FX Intramural Research Program of the NIH Anthony V Furano NR 73 TC 14 Z9 14 U1 0 U2 11 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 29 PY 2014 VL 3 AR e02001 DI 10.7554/eLife.02001 PG 27 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AH1UP UT WOS:000335907000003 PM 24843013 ER PT J AU Nyante, SJ Gierach, GL Dallal, CM Freedman, ND Park, Y Danforth, KN Hollenbeck, AR Brinton, LA AF Nyante, S. J. Gierach, G. L. Dallal, C. M. Freedman, N. D. Park, Y. Danforth, K. N. Hollenbeck, A. R. Brinton, L. A. TI Cigarette smoking and postmenopausal breast cancer risk in a prospective cohort SO BRITISH JOURNAL OF CANCER LA English DT Article DE smoking; menarche; family history of breast cancer; breast cancer risk; cohort study ID NIH-AARP DIET; ALCOHOL-CONSUMPTION; HORMONE-RECEPTOR; PASSIVE SMOKING; ACTIVE SMOKING; DNA-ADDUCTS; FOLLOW-UP; WOMEN; HEALTH; ASSOCIATION AB Background: The relationship between cigarette smoking and breast cancer risk has been inconsistent, potentially due to modification by other factors or confounding. Methods: We examined smoking and breast cancer risk in a prospective cohort of 186 150 female AARP (formerly American Association of Retired Persons) members, ages 50-71 years, who joined the study in 1995-96 by responding to a questionnaire. Through 2006, 7481 breast cancers were diagnosed. Multivariable-adjusted hazard ratios (HRs) were estimated, overall and stratified by breast cancer risk factors, using Cox proportional hazards regression. Multiplicative interactions were evaluated using the likelihood ratio test. Results: Increased breast cancer risk was associated with current (HR 1.19, 95% confidence interval (CI) 1.10-1.28) and former (HR 1.07, CI 1.01-1.13) smoking. The current smoking association was stronger among women without (HR 1.24, CI 1.15-1.35) as compared to those with a family history of breast cancer (HR 0.94, CI 0.78-1.13) (P-interaction=0.03). The current smoking association was also stronger among those with later (>= 15 years: HR 1.52, CI 1.20-1.94) as compared with earlier (<= 12 years: HR 1.14, CI 1.03-1.27; 13-14 years: HR 1.18, CI 1.05-1.32) ages at menarche (P-interaction=0.03). Conclusions: Risk was elevated in smokers, particularly in those without a family history or late menarche. Research into smoking's effects on the genome and breast development may clarify these relationships. C1 [Nyante, S. J.; Gierach, G. L.; Freedman, N. D.; Park, Y.; Brinton, L. A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Dallal, C. M.] Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, College Pk, MD 20742 USA. [Danforth, K. N.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Hollenbeck, A. R.] AARP Res Ctr, Strateg Issues Res, Washington, DC 20049 USA. RP Nyante, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM sarah.nyante@nih.gov RI Brinton, Louise/G-7486-2015; Freedman, Neal/B-9741-2015; Gierach, Gretchen/E-1817-2016; OI Brinton, Louise/0000-0003-3853-8562; Freedman, Neal/0000-0003-0074-1098; Gierach, Gretchen/0000-0002-0165-5522; Park, Yikyung/0000-0002-6281-489X FU Intramural Research Program of the National Cancer Institute at the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health. Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected by the California Department of Health Services, Cancer Surveillance Section. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (FCDC) under contract with the Florida Department of Health (FDOH). Cancer incidence data from Louisiana were collected by the Louisiana Tumour Registry, Louisiana State University Medical Center in New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. Cancer incidence data from Arizona were collected by the Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services. We are indebted to the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation. We also thank Sigurd Hermansen and Kerry Grace Morrissey from Westat for study outcomes ascertainment and management and Leslie Carroll at Information Management Services for data support and analysis. NR 45 TC 11 Z9 11 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 29 PY 2014 VL 110 IS 9 BP 2339 EP 2347 DI 10.1038/bjc.2014.132 PG 9 WC Oncology SC Oncology GA AG6XQ UT WOS:000335562800022 PM 24642621 ER PT J AU Petrick, JL Wyss, AB Butler, AM Cummings, C Sun, X Poole, C Smith, JS Olshan, AF AF Petrick, J. L. Wyss, A. B. Butler, A. M. Cummings, C. Sun, X. Poole, C. Smith, J. S. Olshan, A. F. TI Prevalence of human papillomavirus among oesophageal squamous cell carcinoma cases: systematic review and meta-analysis SO BRITISH JOURNAL OF CANCER LA English DT Review ID POLYMERASE-CHAIN-REACTION; GENITAL HUMAN PAPILLOMAVIRUSES; RISK HUMAN-PAPILLOMAVIRUS; REPUBLIC-OF-CHINA; ENVIRONMENTAL SURFACES; CANCER INCIDENCE; VIRAL LOAD; INFECTION; HPV; DNA AB Background: Oncogenic human papillomavirus (HPV) has been hypothesised as a risk factor for oesophageal squamous cell carcinoma (OSCC), but aetiological research has been limited by the varying methodology used for establishing HPV prevalence. The aims of this systematic review and meta-analysis were to estimate the prevalence of HPV DNA detected in OSCC tumours and the influence of study characteristics. Methods: Study-level estimates of overall and type-specific HPV prevalence were meta-analysed to obtain random-effects summary estimates. Results: This analysis included 124 studies with a total of 13 832 OSCC cases. The average HPV prevalence (95% confidence interval) among OSCC cases was 0.277 (0.234, 0.320) by polymerase chain reaction; 0.243 (0.159, 0.326) by in situ hybridisation; 0.304 (0.185, 0.423) by immunohistochemistry; 0.322 (0.154, 0.490) by L1 serology; and 0.176 (0.061, 0.292) by Southern/slot/dot blot. The highest HPV prevalence was found in Africa and Asia, notably among Chinese studies from provinces with high OSCC incidence rates. Conclusions: Future research should focus on quantifying HPV in OSCC cases using strict quality control measures, as well as determining the association between HPV and OSCC incidence by conducting large, population-based case-control studies. Such studies will provide a richer understanding of the role of HPV in OSCC aetiology. C1 [Petrick, J. L.; Wyss, A. B.; Butler, A. M.; Cummings, C.; Sun, X.; Poole, C.; Smith, J. S.; Olshan, A. F.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Wyss, A. B.] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Smith, J. S.; Olshan, A. F.] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Olshan, A. F.] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. RP Petrick, JL (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. EM jessica.petrick@unc.edu FU National Institutes of Health (NIH); National Cancer Institute [T32CA009330-25]; National Institutes of Environmental Health and Susceptibility [T32ES007018]; Intramural Research Programme of the NIH, National Institute of Environmental Health Sciences FX We are grateful to Anne Rositch for her advice on meta-analytic methods and Hazel Nichols for her feedback on the manuscript. Additionally, we are grateful to Hilda Razzaghi and Csaba Marosvari for their help in translating a Persian and Hungarian article, respectively. We would also like to acknowledge the efforts of the contacted study authors for providing additional data to this meta-analysis. This was supported by the National Institutes of Health (NIH), National Cancer Institute (T32CA009330-25) and the National Institutes of Environmental Health and Susceptibility (T32ES007018), as well as in part by the Intramural Research Programme of the NIH, National Institute of Environmental Health Sciences. NR 77 TC 11 Z9 12 U1 0 U2 7 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 29 PY 2014 VL 110 IS 9 BP 2369 EP 2377 DI 10.1038/bjc.2014.96 PG 9 WC Oncology SC Oncology GA AG6XQ UT WOS:000335562800026 PM 24619077 ER PT J AU Ardeljan, D Wang, Y Park, S Shen, D Chu, XK Yu, CR Abu-Asab, M Tuo, J Eberhart, CG Olsen, TW Mullins, RF White, G Wadsworth, S Scaria, A Chan, CC AF Ardeljan, Daniel Wang, Yujuan Park, Stanley Shen, Defen Chu, Xi Kathy Yu, Cheng-Rong Abu-Asab, Mones Tuo, Jingsheng Eberhart, Charles G. Olsen, Timothy W. Mullins, Robert F. White, Gary Wadsworth, Sam Scaria, Abraham Chan, Chi-Chao TI Interleukin-17 Retinotoxicity Is Prevented by Gene Transfer of a Soluble Interleukin-17 Receptor Acting as a Cytokine Blocker: Implications for Age-Related Macular Degeneration SO PLOS ONE LA English DT Article ID NLRP3 INFLAMMASOME; PIGMENT EPITHELIUM; THERAPEUTIC LEVELS; MICE; IL-17; CELLS; NEOVASCULARIZATION; COMPLEMENT; ACTIVATION; EXPRESSION AB Age-related macular degeneration (AMD) is a common yet complex retinal degeneration that causes irreversible central blindness in the elderly. Pathology is widely believed to follow loss of retinal pigment epithelium (RPE) and photoreceptor degeneration. Here we report aberrant expression of interleukin-17A (IL17A) and the receptor IL17RC in the macula of AMD patients. In vitro, IL17A induces RPE cell death characterized by the accumulation of cytoplasmic lipids and autophagosomes with subsequent activation of pro-apoptotic Caspase-3 and Caspase-9. This pathology is reduced by siRNA knockdown of IL17RC. IL17-dependent retinal degeneration in a mouse model of focal retinal degeneration can be prevented by gene therapy with adeno-associated virus vector encoding soluble IL17 receptor. This intervention rescues RPE and photoreceptors in a MAPK-dependent process. The IL17 pathway plays a key role in RPE and photoreceptor degeneration and could hold therapeutic potential in AMD. C1 [Ardeljan, Daniel; Wang, Yujuan; Park, Stanley; Shen, Defen; Chu, Xi Kathy; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Ardeljan, Daniel] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Wang, Yujuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China. [Park, Stanley] Howard Hughes Med Inst, Chevy Chase, MD USA. [Yu, Cheng-Rong] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD USA. [Abu-Asab, Mones] NEI, Histol Core, Immunol Lab, NIH, Bethesda, MD USA. [Eberhart, Charles G.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Olsen, Timothy W.] Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA. [Mullins, Robert F.] Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA USA. [White, Gary; Wadsworth, Sam; Scaria, Abraham] Genzyme Corp, Framingham, MA 01701 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov RI wang, yujuan/C-8428-2016 FU National Eye Institute Intramural Research Program; Genzyme FX The National Eye Institute Intramural Research Program & Genzyme funded the work. The funder Genzyme provided support in the form of salaries for authors GW, SW, and AS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 17 Z9 17 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 29 PY 2014 VL 9 IS 4 AR e95900 DI 10.1371/journal.pone.0095900 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6CA UT WOS:000335504900011 PM 24780906 ER PT J AU Sweeney, EM Vogelstein, JT Cuzzocreo, JL Calabresi, PA Reich, DS Crainiceanu, CM Shinohara, RT AF Sweeney, Elizabeth M. Vogelstein, Joshua T. Cuzzocreo, Jennifer L. Calabresi, Peter A. Reich, Daniel S. Crainiceanu, Ciprian M. Shinohara, Russell T. TI A Comparison of Supervised Machine Learning Algorithms and Feature Vectors for MS Lesion Segmentation Using Multimodal Structural MRI SO PLOS ONE LA English DT Article ID MULTIPLE-SCLEROSIS LESIONS; WHITE-MATTER LESIONS; OF-THE-ART; BRAIN MRI; IMAGES; CLASSIFICATION; SCIENCE AB Machine learning is a popular method for mining and analyzing large collections of medical data. We focus on a particular problem from medical research, supervised multiple sclerosis (MS) lesion segmentation in structural magnetic resonance imaging (MRI). We examine the extent to which the choice of machine learning or classification algorithm and feature extraction function impacts the performance of lesion segmentation methods. As quantitative measures derived from structural MRI are important clinical tools for research into the pathophysiology and natural history of MS, the development of automated lesion segmentation methods is an active research field. Yet, little is known about what drives performance of these methods. We evaluate the performance of automated MS lesion segmentation methods, which consist of a supervised classification algorithm composed with a feature extraction function. These feature extraction functions act on the observed T1-weighted (T1-w), T2-weighted (T2-w) and fluid-attenuated inversion recovery (FLAIR) MRI voxel intensities. Each MRI study has a manual lesion segmentation that we use to train and validate the supervised classification algorithms. Our main finding is that the differences in predictive performance are due more to differences in the feature vectors, rather than the machine learning or classification algorithms. Features that incorporate information from neighboring voxels in the brain were found to increase performance substantially. For lesion segmentation, we conclude that it is better to use simple, interpretable, and fast algorithms, such as logistic regression, linear discriminant analysis, and quadratic discriminant analysis, and to develop the features to improve performance. C1 [Sweeney, Elizabeth M.; Reich, Daniel S.; Crainiceanu, Ciprian M.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Sweeney, Elizabeth M.; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, Bethesda, MD USA. [Vogelstein, Joshua T.] Duke Univ, Dept Stat Sci, Durham, NC USA. [Vogelstein, Joshua T.] Child Mind Inst, Ctr Developing Brain, New York, NY USA. [Cuzzocreo, Jennifer L.; Reich, Daniel S.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Calabresi, Peter A.; Reich, Daniel S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Shinohara, Russell T.] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Sweeney, EM (reprint author), Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. EM emsweene@jhsph.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU NINDS [R01 NS070906, RO1 NS08521] FX This research was partially supported by the Intramural Research Program of NINDS and NINDS R01 NS070906 and NINDS RO1 NS08521. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 3 Z9 3 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 29 PY 2014 VL 9 IS 4 AR e95753 DI 10.1371/journal.pone.0095753 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6CA UT WOS:000335504900009 PM 24781953 ER PT J AU Kellis, M Wold, B Snyder, MP Bernstein, BE Kundaje, A Marinov, GK Ward, LD Birney, E Crawford, GE Dekker, J Dunham, I Elnitski, LL Farnham, PJ Feingold, EA Gerstein, M Giddings, MC Gilbert, DM Gingeras, TR Green, ED Guigo, R Hubbard, T Kent, J Lieb, JD Myers, RM Pazin, MJ Ren, B Stamatoyannopoulos, JA Weng, ZP White, KP Hardison, RC AF Kellis, Manolis Wold, Barbara Snyder, Michael P. Bernstein, Bradley E. Kundaje, Anshul Marinov, Georgi K. Ward, Lucas D. Birney, Ewan Crawford, Gregory E. Dekker, Job Dunham, Ian Elnitski, Laura L. Farnham, Peggy J. Feingold, Elise A. Gerstein, Mark Giddings, Morgan C. Gilbert, David M. Gingeras, Thomas R. Green, Eric D. Guigo, Roderic Hubbard, Tim Kent, Jim Lieb, Jason D. Myers, Richard M. Pazin, Michael J. Ren, Bing Stamatoyannopoulos, John A. Weng, Zhiping White, Kevin P. Hardison, Ross C. TI Defining functional DNA elements in the human genome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PARALLEL REPORTER ASSAY; GENE-EXPRESSION; CHROMATIN IMMUNOPRECIPITATION; REGULATORY ELEMENTS; HUMAN-CELLS; JUNK DNA; SYSTEMATIC DISSECTION; PURIFYING SELECTION; ADAPTIVE EVOLUTION; MAMMALIAN GENOME AB With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease. C1 [Kellis, Manolis; Kundaje, Anshul; Ward, Lucas D.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Kellis, Manolis; Bernstein, Bradley E.; Kundaje, Anshul; Ward, Lucas D.] Broad Inst, Cambridge, MA 02139 USA. [Wold, Barbara; Marinov, Georgi K.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA. [Snyder, Michael P.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Birney, Ewan; Dunham, Ian] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England. [Crawford, Gregory E.] Duke Univ, Durham, NC 27708 USA. [Dekker, Job; Weng, Zhiping] Univ Massachusetts, Sch Med, Program Syst Biol, Worcester, MA 01605 USA. [Ward, Lucas D.; Elnitski, Laura L.; Feingold, Elise A.; Green, Eric D.; Pazin, Michael J.] NHGRI, NIH, Bethesda, MD 20892 USA. [Farnham, Peggy J.] Univ So Calif, Los Angeles, CA 90089 USA. [Gerstein, Mark] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Giddings, Morgan C.] Mkt Your Sci LLC, Boise, ID 83702 USA. [Gilbert, David M.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. [Gingeras, Thomas R.] Cold Spring Harbor Lab, Funct Genom Grp, Cold Spring Harbor, NY 11724 USA. [Guigo, Roderic] Ctr Genome Regulat, Bioinformat & Genom Program, E-08003 Barcelona, Catalonia, Spain. [Hubbard, Tim] Kings Coll London, Cambridge CB10 1SD, England. [Hubbard, Tim] Wellcome Trust Sanger Inst, Cambridge CB10 1SD, England. [Kent, Jim] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. [Lieb, Jason D.] Princeton Univ, Lewis Sigler Inst, Princeton, NJ 08544 USA. [Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Ren, Bing] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Stamatoyannopoulos, John A.] Univ Washington, Seattle, WA 98195 USA. [White, Kevin P.] Univ Chicago, Chicago, IL 60637 USA. [Hardison, Ross C.] Penn State Univ, University Pk, PA 16802 USA. RP Kellis, M (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM manoli@mit.edu; rch8@psu.edu RI Guigo, Roderic/D-1303-2010; Hubbard, Tim/C-2567-2008; OI Guigo, Roderic/0000-0002-5738-4477; Hubbard, Tim/0000-0002-1767-9318; Gingeras, Thomas/0000-0001-9106-3573; Farnham, Peggy/0000-0003-4469-7914; Dunham, Ian/0000-0003-2525-5598; Birney, Ewan/0000-0001-8314-8497; Pazin, Michael/0000-0002-7561-3640 FU NCI NIH HHS [P30 CA008748, P30 CA045508]; NHGRI NIH HHS [R01 HG003143, R01 HG004037, U41 HG007234, U54 HG006996, U54 HG006997]; NIA NIH HHS [R01 AG016379]; NIGMS NIH HHS [R01 GM083337] NR 117 TC 164 Z9 167 U1 30 U2 124 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 29 PY 2014 VL 111 IS 17 BP 6131 EP 6138 DI 10.1073/pnas.1318948111 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG1TL UT WOS:000335199000025 PM 24753594 ER PT J AU Heinecke, JL Ridnour, LA Cheng, RYS Switzer, CH Lizardo, MM Khanna, C Glynn, SA Hussain, SP Young, HA Ambs, S Wink, DA AF Heinecke, Julie L. Ridnour, Lisa A. Cheng, Robert Y. S. Switzer, Christopher H. Lizardo, Michael M. Khanna, Chand Glynn, Sharon A. Hussain, S. Perwez Young, Howard A. Ambs, Stefan Wink, David A. TI Tumor microenvironment-based feed-forward regulation of NOS2 in breast cancer progression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NITRIC-OXIDE SYNTHASE; PREDICTS POOR SURVIVAL; MELANOMA PATIENTS; CELL-LINE; HYPOXIA; EXPRESSION; INDUCTION; ESTROGEN; GENE; RESISTANCE AB Inflammation is widely recognized as an inducer of cancer progression. The inflammation-associated enzyme, inducible nitric oxide synthase (NOS2), has emerged as a candidate oncogene in estrogen receptor (ER)-negative breast cancer, and its increased expression is associated with disease aggressiveness and poor survival. Although these observations implicate NOS2 as an attractive therapeutic target, the mechanisms of both NOS2 induction in tumors and nitric oxide (NO)-driven cancer progression are not fully understood. To enhance ourmechanistic understanding of NOS2 induction in tumors and its role in tumor biology, we used stimulants of NOS2 expression in ER-and ER+ breast cancer cells and examined downstream NO-dependent effects. Herein, we show that up-regulation of NOS2 occurs in response to hypoxia, serum withdrawal, IFN-gamma, and exogenous NO, consistent with a feed-forward regulation of NO production by the tumor microenvironment in breast cancer biology. Moreover, we found that key indicators of an aggressive cancer phenotype including increased S100 calcium binding protein A8, IL-6, IL-8, and tissue inhibitor matrix metalloproteinase- 1 are up-regulated by these NOS2 stimulants, whereas inhibition of NOS2 in MDA-MB-231 breast cancer cells suppressed these markers. Moreover, NO altered cellular migration and chemoresistance of MDA-MB-231 cells to Taxol. Most notably, MDA-MB231 tumor xenographs and cell metastases from the fat pad to the brainwere significantly suppressed by NOS2 inhibition in nude mice. In summary, these results link elevated NOS2 to signals from the tumor microenvironment that arise with cancer progression and show that NO production regulates chemoresistance and metastasis of breast cancer cells. C1 [Heinecke, Julie L.; Ridnour, Lisa A.; Cheng, Robert Y. S.; Switzer, Christopher H.; Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Lizardo, Michael M.; Khanna, Chand] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Hussain, S. Perwez; Ambs, Stefan] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Glynn, Sharon A.] Natl Univ Ireland, Prostate Canc Inst, Galway, Ireland. [Young, Howard A.] NCI, Expt Immunol Lab, NIH, Frederick, MD 21702 USA. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. EM wink@mail.nih.gov RI Glynn, Sharon/D-7136-2013 OI Glynn, Sharon/0000-0003-1459-2580 FU Intramural Research Program of the US National Institutes of Health; National Cancer Institute; Center for Cancer Research FX The work was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, and Center for Cancer Research. NR 37 TC 32 Z9 32 U1 2 U2 17 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 29 PY 2014 VL 111 IS 17 BP 6323 EP 6328 DI 10.1073/pnas.1401799111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG1TL UT WOS:000335199000057 PM 24733928 ER PT J AU Dmitrieva, NI Burg, MB AF Dmitrieva, Natalia I. Burg, Maurice B. TI Secretion of von Willebrand factor by endothelial cells links sodium to hypercoagulability and thrombosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE blood clotting; HUVEC; osmotic stress ID DEEP-VEIN THROMBOSIS; PLASMA SODIUM; HYPERNATREMIC DEHYDRATION; ATHEROSCLEROSIS RISK; DISEASE; ABNORMALITIES; COMMUNITIES; VASOPRESSIN; HEMOSTASIS; THERAPY AB Hypercoagulability increases risk of thrombi that cause cardiovascular events. Here we identify plasma sodium concentration as a factor that modulates blood coagulability by affecting the production of von Willebrand factor (vWF), a key initiator of the clotting cascade. We find that elevation of salt over a range from the lower end of what is normal in blood to the level of severe hypernatremia reversibly increases vWF mRNA in endothelial cells in culture and the rate of vWF secretion from them. The high NaCl increases expression of tonicity-regulated transcription factor NFAT5 and its binding to promoter of vWF gene, suggesting involvement of hypertonic signaling in vWF up-regulation. To elevate NaCl in vivo, we modeled mild dehydration, subjecting mice to water restriction (WR) by feeding them with gel food containing 30% water. Such WR elevates blood sodium from 145.1 +/- 0.5 to 150.2 +/- 1.3 mmol/L and activates hypertonic signaling, evidenced from increased expression of NFAT5 in tissues. WR increases vWF mRNA in liver and lung and raises vWF protein in blood. Immunostaining of liver revealed increased production of vWF protein by endothelium and increased number of microthrombi inside capillaries. WR also increases blood level of D-dimer, indicative of ongoing coagulation and thrombolysis. Multivariate regression analysis of clinical data from the Atherosclerosis Risk in Communities Study demonstrated that serum sodium significantly contributes to prediction of plasma vWF and risk of stroke. The results indicate that elevation of extracellular sodium within the physiological range raises vWF sufficiently to increase coagulability and risk of thrombosis. C1 [Dmitrieva, Natalia I.; Burg, Maurice B.] NHLBI, Renal Cellular & Mol Biol Sect, NIH, Bethesda, MD 20892 USA. RP Dmitrieva, NI (reprint author), NHLBI, Renal Cellular & Mol Biol Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dmitrien@nhlbi.nih.gov; maurice_burg@nih.gov RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 FU Intramural Program of NHLBI FX We thank Daniil A. Kitchaev for writing Python script for CMYK yellow channel extraction from immunohistochemistry images, Daniela Malide and Christian Combs at the National Heart, Lung, and Blood Institute (NHLBI) Light Microscopy Core facility for help with microscopy, Leigh Samsel at NHLBI Flow Cytometry Core Facility for help with Luminex analysis, and Eric S. Leifer at the NHLBI Office of Biostatistics Research for expert advice on the clinical data analysis. This manuscript was prepared using Atherosclerosis Risk in Communities research materials obtained from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center. The study was supported by the Intramural Program of NHLBI. NR 50 TC 10 Z9 10 U1 0 U2 7 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 29 PY 2014 VL 111 IS 17 BP 6485 EP 6490 DI 10.1073/pnas.1404809111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG1TL UT WOS:000335199000084 PM 24733925 ER PT J AU Campbell, CT Gulley, JL Oyelaran, O Hodge, JW Schlom, J Gildersleeve, JC AF Campbell, Christopher T. Gulley, James L. Oyelaran, Oyindasola Hodge, James W. Schlom, Jeffrey Gildersleeve, Jeffrey C. TI Humoral response to a viral glycan correlates with survival on PROSTVAC-VF SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glycan array; Forssman antigen ID RESISTANT PROSTATE-CANCER; MELANOMA-CELL VACCINE; BLOOD-GROUP; SERUM ANTIBODIES; FORSSMAN ANTIGEN; CLINICAL-TRIALS; DENDRITIC CELLS; IMMUNOTHERAPY; MICROARRAY; MITOXANTRONE AB Therapeutic cancer vaccines can be effective for treating patients, but clinical responses vary considerably from patient to patient. Early indicators of a favorable response are crucial for making individualized treatment decisions and advancing vaccine design, but no validated biomarkers are currently available. In this study, we used glycan microarrays to profile antiglycan antibody responses induced by PROSTVAC-VF, a poxvirus-based cancer vaccine currently in phase III clinical trials. Although the vaccine is designed to induce T-cell responses to prostate-specific antigen, we demonstrate that this vaccine also induces humoral responses to a carbohydrate on the poxvirus, the Forssman disaccharide (GalNAc alpha 1-3GalNAc beta). These responses had a statistically significant correlation with overall survival in two independent sample sets (P = 0.015 and 0.008) comprising more than 100 patients. Additionally, anti-Forssman humoral responses correlated with clinical outcome in a separate study of PROSTVAC-VF combined with a radiopharmaceutical (Quadramet). Studies on control subjects demonstrated that the survival correlation was specific to the vaccine. The results provide evidence that antiglycan antibody responses may serve as early biomarkers of a favorable response to PROSTVAC-VF and offer unique insights for improving vaccine design. C1 [Campbell, Christopher T.; Oyelaran, Oyindasola; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA. [Gulley, James L.; Hodge, James W.; Schlom, Jeffrey] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA. EM gildersj@mail.nih.gov RI Gildersleeve, Jeffrey/N-3392-2014; Hodge, James/D-5518-2015; Gulley, James/K-4139-2016 OI Hodge, James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute; Pharmacology Research Associate Program of the National Institute of General Medical Sciences FX We thank Kevin Camphausen for providing sera from nonvaccinated patients with prostate cancer and Professor Tom Tolbert (University of Kansas), Professor Lai-Xi Wang (University of Maryland), and Dr. Joseph Barchi (National Cancer Institute) for contributing glycans for the array. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. C.T.C. received fellowship funding from the Pharmacology Research Associate Program of the National Institute of General Medical Sciences. NR 63 TC 18 Z9 18 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 29 PY 2014 VL 111 IS 17 BP E1749 EP E1758 DI 10.1073/pnas.1314722111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG1TL UT WOS:000335199000013 PM 24733910 ER PT J AU Chapman, S McDermott, DH Shen, K Jang, MK McBride, AA AF Chapman, Sandra McDermott, David H. Shen, Kui Jang, Moon Kyoo McBride, Alison A. TI The effect of Rho kinase inhibition on long-term keratinocyte proliferation is rapid and conditional SO STEM CELL RESEARCH & THERAPY LA English DT Article ID REPROGRAMMED CELLS; EPITHELIAL-CELLS; STEM-CELLS; GROWTH; DIFFERENTIATION; MULTIPLICATION; Y-27632 AB Introduction: We previously demonstrated that the lifespan of primary human keratinocytes could be extended indefinitely by culture in the presence of the Rho kinase (ROCK) inhibitor Y-27632. This technique has proven to be very useful in diverse areas of basic and clinical research. Methods: In this follow-up study we determine whether the continual presence of Y-27632 is required for sustained proliferation. We also test whether different ROCK inhibitors can be used for this technique and whether it can also promote indefinite proliferation of animal keratinocytes. We measure keratinocyte gene expression, proliferation, behaviour and lifespan in the presence and absence of Y-27632. Results: We demonstrate that the extension of lifespan observed by culture of keratinocytes in the presence of fibroblast feeders and a ROCK inhibitor is reversible and that cells senesce gradually when the inhibitor is removed from the medium. Conversely, keratinocytes that are close to the end of their replicative life span can be revived by ROCK inhibition. We demonstrate that different inhibitors of ROCK can also efficiently extend the lifespan of human keratinocytes and that ROCK inhibition extends the lifespan of animal keratinocytes derived from mouse and bovine epithelia. Gene expression analysis of human epidermal keratinocytes cells grown in the presence of Y-27632 demonstrates that ROCK inhibition primarily inhibits keratinocyte differentiation. Live-imaging of keratinocytes cultured with ROCK inhibitors show that the effect of ROCK inhibition on cellular proliferation is immediate and ROCK inhibited cells proliferate rapidly without differentiation or stratification. Conclusions: ROCK inhibition rapidly and conditionally induces indefinite proliferation of keratinocytes. This method has far-reaching applications for basic research, as well as for regenerative and personalized medicine. C1 [Chapman, Sandra; Jang, Moon Kyoo; McBride, Alison A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [McDermott, David H.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Shen, Kui] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA. RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM amcbride@nih.gov RI Shen, Kui/E-2764-2015; OI McDermott, David/0000-0001-6978-0867; McBride, Alison/0000-0001-5607-5157 FU NIAID, NIH FX We thank Wendy Weinberg for mouse keratinocytes and Wesley Stepp for human foreskin keratinocytes. This work was funded by the Intramural Research Program of the NIAID, NIH. The opinions expressed herein are solely those of the authors, and use of trade or product names does not imply endorsement of the United States Government. NR 28 TC 9 Z9 9 U1 0 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1757-6512 J9 STEM CELL RES THER JI Stem Cell Res. Ther. PD APR 28 PY 2014 VL 5 AR 60 DI 10.1186/scrt449 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AI9KK UT WOS:000337251300001 PM 24774536 ER PT J AU Reece, KM Richardson, ED Cook, KM Campbell, TJ Pisle, ST Holly, AJ Venzon, DJ Liewehr, DJ Chau, CH Price, DK Figg, WD AF Reece, Kelie M. Richardson, Emily D. Cook, Kristina M. Campbell, Tessa J. Pisle, Stephen T. Holly, Alesia J. Venzon, David J. Liewehr, David J. Chau, Cindy H. Price, Douglas K. Figg, William D. TI Epidithiodiketopiperazines (ETPs) exhibit in vitro antiangiogenic and in vivo antitumor activity by disrupting the HIF-1 alpha/p300 complex in a preclinical model of prostate cancer SO MOLECULAR CANCER LA English DT Article DE Hypoxia; HIF-1 alpha; p300; ETPs; Angiogenesis; VEGF ID HYPOXIA-INDUCIBLE FACTOR-1; TRANSCRIPTIONAL REGULATION; ANGIOGENESIS INHIBITORS; THERAPY; GROWTH; GENE; FARNESYLTRANSFERASE; GLIOTOXIN; TARGET; HIF-1 AB The downstream targets of hypoxia inducible factor-1 alpha (HIF-1 alpha) play an important role in tumor progression and angiogenesis. Therefore, inhibition of HIF-mediated transcription has potential in the treatment of cancer. One attractive strategy for inhibiting HIF activity is the disruption of the HIF-1 alpha/p300 complex, as p300 is a crucial coactivator of hypoxia-inducible transcription. Several members of the epidithiodiketopiperazine (ETP) family of natural products have been shown to disrupt the HIF-1 alpha/p300 complex in vitro; namely, gliotoxin, chaetocin, and chetomin. Here, we further characterized the molecular mechanisms underlying the antiangiogenic and antitumor effects of these ETPs using a preclinical model of prostate cancer. In the rat aortic ring angiogenesis assay, gliotoxin, chaetocin, and chetomin significantly inhibited microvessel outgrowth at a GI(50) of 151, 8, and 20 nM, respectively. In vitro co-immunoprecipitation studies in prostate cancer cell extracts demonstrated that these compounds disrupted the HIF-1 alpha/p300 complex. The downstream effects of inhibiting the HIF-1 alpha/p300 interaction were evaluated by determining HIF-1 alpha target gene expression at the mRNA and protein levels. Dose-dependent decreases in levels of secreted VEGF were detected by ELISA in the culture media of treated cells, and the subsequent downregulation of VEGFA, LDHA, and ENO1 HIF-1 alpha target genes were confirmed by semi-quantitative real-time PCR. Finally, treatment with ETPs in mice bearing prostate tumor xenografts resulted in significant inhibition of tumor growth. These results suggest that directly targeting the HIF-1 alpha/p300 complex with ETPs may be an effective approach for inhibiting angiogenesis and tumor growth. C1 [Reece, Kelie M.; Richardson, Emily D.; Cook, Kristina M.; Campbell, Tessa J.; Chau, Cindy H.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Holly, Alesia J.; Figg, William D.] NCI, Clin Pharmacol Core, Ctr Canc Res, Bethesda, MD 20892 USA. [Venzon, David J.; Liewehr, David J.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Pisle, Stephen T.] SAIC Frederick, Frederick Natl Lab Canc Res, Clin Pharmacol Program, Ft Detrick, MD 21702 USA. [Figg, William D.] NIH, NCI, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Ctr Canc Res, Bethesda, MD 20892 USA. EM figgw@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, MD, USA; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, MD, USA. 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 (STP). NR 36 TC 19 Z9 19 U1 2 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD APR 28 PY 2014 VL 13 AR 91 DI 10.1186/1476-4598-13-91 PG 12 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA AH3ZR UT WOS:000336065500001 PM 24775564 ER PT J AU Moreland, RT Nguyen, AD Ryan, JF Schnitzler, CE Koch, BJ Siewert, K Wolfsberg, TG Baxevanis, AD AF Moreland, R. Travis Nguyen, Anh-Dao Ryan, Joseph F. Schnitzler, Christine E. Koch, Bernard J. Siewert, Katherine Wolfsberg, Tyra G. Baxevanis, Andreas D. TI A customized Web portal for the genome of the ctenophore Mnemiopsis leidyi SO BMC GENOMICS LA English DT Article DE Mnemiopsis leidyi; Genome browser; Customized Web portal; Gene wiki ID DATABASE; SIMILARITY; EVOLUTION; SERVER; GENES; SCALE; TOOL AB Background: Mnemiopsis leidyi is a ctenophore native to the coastal waters of the western Atlantic Ocean. A number of studies on Mnemiopsis have led to a better understanding of many key biological processes, and these studies have contributed to the emergence of Mnemiopsis as an important model for evolutionary and developmental studies. Recently, we sequenced, assembled, annotated, and performed a preliminary analysis on the 150-megabase genome of the ctenophore, Mnemiopsis. This sequencing effort has produced the first set of whole-genome sequencing data on any ctenophore species and is amongst the first wave of projects to sequence an animal genome de novo solely using next-generation sequencing technologies. Description: The Mnemiopsis Genome Project Portal (http://research.nhgri.nih.gov/mnemiopsis/) is intended both as a resource for obtaining genomic information on Mnemiopsis through an intuitive and easy-to-use interface and as a model for developing customized Web portals that enable access to genomic data. The scope of data available through this Portal goes well beyond the sequence data available through GenBank, providing key biological information not available elsewhere, such as pathway and protein domain analyses; it also features a customized genome browser for data visualization. Conclusions: We expect that the availability of these data will allow investigators to advance their own research projects aimed at understanding phylogenetic diversity and the evolution of proteins that play a fundamental role in metazoan development. The overall approach taken in the development of this Web site can serve as a viable model for disseminating data from whole-genome sequencing projects, framed in a way that best-serves the specific needs of the scientific community. C1 [Moreland, R. Travis; Nguyen, Anh-Dao; Ryan, Joseph F.; Schnitzler, Christine E.; Koch, Bernard J.; Siewert, Katherine; Wolfsberg, Tyra G.; Baxevanis, Andreas D.] NHGRI, Genome Technol Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Ryan, Joseph F.] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32080 USA. RP Baxevanis, AD (reprint author), NHGRI, Genome Technol Branch, Div Intramural Res, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM andy@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. We would like to thank Steven Bond, Mark Fredriksen, Derek Gildea, and Evan Maxwell for their thoughtful, constructive comments during the development of the Portal. We also thank Steven Bond, Derek Gildea, and Evan Maxwell for their critical reading of the manuscript. NR 28 TC 2 Z9 2 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD APR 28 PY 2014 VL 15 AR 316 DI 10.1186/1471-2164-15-316 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AH1EY UT WOS:000335863800001 PM 24773765 ER PT J AU Hales, CM Seyfried, NT Dammer, EB Duong, D Yi, H Gearing, M Troncoso, JC Mufson, EJ Thambisetty, M Levey, AI Lah, JJ AF Hales, Chadwick M. Seyfried, Nicholas T. Dammer, Eric B. Duong, Duc Yi, Hong Gearing, Marla Troncoso, Juan C. Mufson, Elliott J. Thambisetty, Madhav Levey, Allan I. Lah, James J. TI U1 small nuclear ribonucleoproteins (snRNPs) aggregate in Alzheimer's disease due to autosomal dominant genetic mutations and trisomy 21 SO MOLECULAR NEURODEGENERATION LA English DT Article DE Spliceosome; snRNP; Alzheimer's disease; Down syndrome; U1-70k; SmD; Presenilin; Amyloid precursor protein ID PAIRED HELICAL FILAMENTS; ELECTRON-MICROSCOPY; SPLICEOSOME; CORTEX AB Background: We recently identified U1 small nuclear ribonucleoprotein (snRNP) tangle-like aggregates and RNA splicing abnormalities in sporadic Alzheimer's disease (AD). However little is known about snRNP biology in early onset AD due to autosomal dominant genetic mutations or trisomy 21 in Down syndrome. Therefore we investigated snRNP biochemical and pathologic features in these disorders. Findings: We performed quantitative proteomics and immunohistochemistry in postmortem brain from genetic AD cases. Electron microscopy was used to characterize ultrastructural features of pathologic aggregates. U1-70k and other snRNPs were biochemically enriched in the insoluble fraction of human brain from subjects with presenilin 1 (PS1) mutations. Aggregates of U1 snRNP-immunoreactivity formed cytoplasmic tangle-like structures in cortex of AD subjects with PS1 and amyloid precursor protein (APP) mutations as well as trisomy 21. Ultrastructural analysis with electron microscopy in an APP mutation case demonstrated snRNP immunogold labeling of paired helical filaments (PHF). Conclusions: These studies identify U1 snRNP pathologic changes in brain of early onset genetic forms of AD. Since dominant genetic mutations and trisomy 21 result in dysfunctional amyloid processing, the findings suggest that aberrant beta-amyloid processing may influence U1 snRNP aggregate formation. C1 [Hales, Chadwick M.; Levey, Allan I.; Lah, James J.] Emory Univ, Dept Neurol, Sch Med, Atlanta, GA 30322 USA. [Hales, Chadwick M.; Seyfried, Nicholas T.; Dammer, Eric B.; Duong, Duc; Levey, Allan I.; Lah, James J.] Emory Univ, Ctr Neurodegenerat Dis, Atlanta, GA 30322 USA. [Seyfried, Nicholas T.; Dammer, Eric B.] Emory Univ, Dept Biochem, Sch Med, Atlanta, GA 30322 USA. [Yi, Hong] Emory Univ, Robert P Apkarian Integrated Electron Microscopy, Atlanta, GA 30322 USA. [Gearing, Marla] Emory Univ, Dept Pathol, Sch Med, Atlanta, GA 30322 USA. [Troncoso, Juan C.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Troncoso, Juan C.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Mufson, Elliott J.] Rush Univ, Dept Neurol Sci, Chicago, IL 60612 USA. [Thambisetty, Madhav] NIA, NIH, Bethesda, MD 20892 USA. RP Lah, JJ (reprint author), Emory Univ, Dept Neurol, Sch Med, Atlanta, GA 30322 USA. EM jlah@emory.edu OI Dammer, Eric/0000-0003-2947-7606 FU Robert P. Apkarian Integrated Electron Microscopy Core of Emory University; Clinical Research Training Fellowship from the American Brain Foundation; Emory Alzheimer's Disease Research Center [NIA-AG025688, NIAP01AG14449]; Emory Neuroscience NINDS Core Facility [P30NS055077]; University of Washington ADRC [NIA-P50-AG05136]; Alzheimer's Association New Investigator Research Award [NIRG-12-242297]; NIA intramural Research Program of the National Institutes of Health FX This research project was supported in part by the Robert P. Apkarian Integrated Electron Microscopy Core of Emory University. Clinical Research Training Fellowship from the American Brain Foundation (CMH). Emory Alzheimer's Disease Research Center-NIA-AG025688 (AIL), NIAP01AG14449 (JJL, EJM), Emory Neuroscience NINDS Core Facility-P30NS055077, University of Washington ADRC-NIA-P50-AG05136 and an Alzheimer's Association New Investigator Research Award (NIRG-12-242297) to NTS. This work was supported in part by the NIA intramural Research Program of the National Institutes of Health. We are grateful for pathological specimens provided by MG, JCT and Thomas Montine M.D, Ph.D. NR 25 TC 4 Z9 4 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PD APR 28 PY 2014 VL 9 AR 15 DI 10.1186/1750-1326-9-15 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AG7MT UT WOS:000335602900001 PM 24773620 ER PT J AU Wang, ZQ Fan, M Candas, D Zhang, TQ Qin, LL Eldridge, A Wachsmann-Hogiu, S Ahmed, KM Chromy, BA Nantajit, D Duru, N He, FC Chen, M Finkel, T Weinstein, LS Li, JJ AF Wang, Zhaoqing Fan, Ming Candas, Demet Zhang, Tie-Qiao Qin, Lili Eldridge, Angela Wachsmann-Hogiu, Sebastian Ahmed, Kazi M. Chromy, Brett A. Nantajit, Danupon Duru, Nadire He, Fuchu Chen, Min Finkel, Toren Weinstein, Lee S. Li, Jian Jian TI Cyclin B1/Cdk1 Coordinates Mitochondrial Respiration for Cell-Cycle G2/M Progression SO DEVELOPMENTAL CELL LA English DT Article ID LEUKEMIC HL-60 CELLS; COMPLEX-I; MITOTIC PHOSPHORYLATION; S-PHASE; PROTEIN; CDC2; B1; MECHANISMS; CHECKPOINT; MITOSIS AB A substantial amount of mitochondrial energy is required for cell-cycle progression. The mechanisms underlying the coordination of the mitochondrial respiration with cell-cycle progression, especially the G2/M transition, remain to be elucidated. Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function. Mitochondria-targeted cyclin B1/Cdk1 increases mitochondrial respiration with enhanced oxygen consumption and ATP generation, which provides cells with efficient bioenergy for G2/M transition and shortens overall cell-cycle time. Thus, cyclin B1/Cdk1-mediated phosphorylation of mitochondrial substrates allows cells to sense and respond to increased energy demand for G2/M transition and, subsequently, to upregulate mitochondrial respiration for successful cell-cycle progression. C1 [Wang, Zhaoqing; Fan, Ming; Candas, Demet; Qin, Lili; Nantajit, Danupon; Duru, Nadire; Li, Jian Jian] Univ Calif Davis, Dept Radiat Oncol, Sacramento, CA 95817 USA. [Zhang, Tie-Qiao; Wachsmann-Hogiu, Sebastian] Univ Calif Davis, Ctr Biophoton Sci & Technol, Sacramento, CA 95817 USA. [Ahmed, Kazi M.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Dept Canc & DNA Damage Response, Life Sci Div, Berkeley, CA 94720 USA. [Eldridge, Angela; Chromy, Brett A.] Univ Calif Davis, Dept Pathol & Lab Med, Sacramento, CA 95817 USA. [He, Fuchu] Beijing Prote Res Ctr, State Key Lab Prote, Beijing 102206, Peoples R China. [Chen, Min; Weinstein, Lee S.] NIDDK, Signal Transduct Sect, NIH, Bethesda, MD 20892 USA. [Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. [Li, Jian Jian] Univ Calif Davis, Sch Med, NCI Designated Comprehens Canc Ctr, Sacramento, CA 95817 USA. RP Li, JJ (reprint author), Univ Calif Davis, Dept Radiat Oncol, Sacramento, CA 95817 USA. EM jijli@ucdavis.edu FU NIH [CA133402, CA152313]; Department of Energy Office of Science [DE-SC0001271]; NIH Intramural Research Program of NIDDK FX We thank Grate Adamson at Electron Microscopy Laboratory, University of California Davis School of Medicine, for technical assistance in mitochondrial analysis and Haiying Hang at Institute of Biophysics, Chinese Academy of Sciences, for analysis of cell-cycle data. This work was supported by NIH grants CA133402 and CA152313 and Department of Energy Office of Science DE-SC0001271 (to J.L.) and the NIH Intramural Research Program of NIDDK (to L.S.W. and T.F.). NR 47 TC 35 Z9 37 U1 7 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD APR 28 PY 2014 VL 29 IS 2 BP 217 EP 232 DI 10.1016/j.devcel.2014.03.012 PG 16 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA AG4XA UT WOS:000335422500011 PM 24746669 ER PT J AU Kane, LA Lazarou, M Fogel, AI Li, Y Yamano, K Sarraf, SA Banerjee, S Youle, RJ AF Kane, Lesley A. Lazarou, Michael Fogel, Adam I. Li, Yan Yamano, Koji Sarraf, Shireen A. Banerjee, Soojay Youle, Richard J. TI PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MITOCHONDRIAL DEPOLARIZATION; DAMAGED MITOCHONDRIA; SIGNALING NETWORKS; MITOPHAGY; RECRUITMENT; PROTEASOME; MEMBRANE; BINDING; PHOSPHOPEPTIDES; TRANSLOCATION AB PINK1 kinase activates the E3 ubiquitin ligase Parkin to induce selective autophagy of damaged mitochondria. However, it has been unclear how PINK1 activates and recruits Parkin to mitochondria. Although PINK1 phosphorylates Parkin, other PINK1 substrates appear to activate Parkin, as the mutation of all serine and threonine residues conserved between Drosophila and human, including Parkin 565, did not wholly impair Parkin translocation to mitochondria. Using mass spectrometry, we discovered that endogenous PINK1 phosphorylated ubiquitin at serine 65, homologous to the site phosphorylated by PINK1 in Parkin's ubiquitin-like domain. Recombinant TcPINK1 directly phosphorylated ubiquitin and phosphoubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. In cells, the phosphomimetic ubiquitin mutant S65D bound and activated Parkin. Furthermore, expression of ubiquitin S65A, a mutant that cannot be phosphorylated by PINK1, inhibited Parkin translocation to damaged mitochondria. These results explain a feed-forward mechanism of PINK1-mediated initiation of Parkin E3 ligase activity. C1 [Kane, Lesley A.; Lazarou, Michael; Fogel, Adam I.; Yamano, Koji; Sarraf, Shireen A.; Banerjee, Soojay; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20824 USA. [Li, Yan] NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20824 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20824 USA. EM youler@ninds.nih.gov OI Lazarou, Michael/0000-0003-2150-5545 FU National Institute of Neurological Disorders and Stroke intramural program FX This work was supported by the National Institute of Neurological Disorders and Stroke intramural program. NR 42 TC 214 Z9 222 U1 4 U2 37 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD APR 28 PY 2014 VL 205 IS 2 BP 143 EP 153 DI 10.1083/jcb.201402104 PG 11 WC Cell Biology SC Cell Biology GA AG3DT UT WOS:000335296700004 PM 24751536 ER PT J AU Watanabe, J Hattori, M Berriman, M Lehane, MJ Hall, N Solano, P Aksoy, S Hide, W Toure, Y Attardo, GM Darby, AC Toyoda, A Hertz-Fowler, C Larkin, DM Cotton, JA Watanabe, J Sanders, MJ Swain, MT Hattori, M Berriman, M Quail, MA Inoue, N Ravel, S Taylor, TD Srivastava, TP Sharma, V Warren, W Wilson, RK Suzuki, Y Lawson, D Hughes, DST Megy, K Masiga, DK Mireji, PO Attardo, GM Hansen, IA Van den Abbeele, J Benoit, JB Bourtzis, K Lehane, MJ Aksoy, S Masiga, DK Obiero, GFO Robertson, HM Jones, JW Zhou, JJ Field, LM Friedrich, M Mireji, PO Nyanjom, SRG Telleria, EL Caljon, G Van den Abbeele, J Ribeiro, JMC Acosta-Serrano, A Benoit, JB Ooi, CP Rose, C Price, DP Haines, LR Lehane, MJ Christoffels, A Sim, C Pham, DQD Denlinger, DL Geiser, DL Omedo, IA Benoit, JB Winzerling, JJ Peyton, JT Marucha, KK Jonas, M Meuti, ME Rawlings, ND Mireji, PO Zhang, QR Macharia, RW Michalkova, V Dashti, ZJS Baumann, AA Gade, G Marco, HG Hansen, IA Caers, J Schoofs, L Riehle, MA Hu, WQ Tu, ZJ Tarone, AM Malacrida, AR Kibet, CK Benoit, JB Scolari, F Attardo, GM Koekemoer, JJO Willis, J Gomulski, LM Falchetto, M Scott, MJ Fu, SH Sze, SH Luiz, T Weiss, B Walshe, DP Wang, JW Benoit, JB Attardo, GM Wamalwa, M Mwangi, S Aksoy, S Ramphul, UN Snyder, AK Brelsfoard, CL Thomas, GH Tsiamis, G Bourtzis, K Arensburger, P Rio, RVM Macdonald, SJ Panji, S Kruger, A Christoffels, A Benkahla, A Balyeidhusa, ASP Msangi, A Ooi, CP Okoro, CK Masiga, DK Stephens, D Walshe, DP Stanley, EJ Mpondo, F Wamwiri, F Mramba, F Attardo, GM Siwo, G Obiero, GFO Githinji, G Harkins, G Murilla, G Lehvaslaiho, H Malele, I Koekemoer, JJO Auma, JE Kinyua, JK Ouma, J Watanabe, J Megy, K Okedi, L Manga, L Jonas, M Wamalwa, M Aslett, M Koffi, M Berriman, M Lehane, MJ Gaunt, MW Makgamathe, M Hall, N Mulder, N Manangwa, O Abila, PP Wincker, P Mireji, PO Gregory, R Rio, RVM Bateta, R Sakate, R Aksoy, S Ommeh, S Lehane, S Nyanjom, SRG Imanishi, T Taylor, TD Osamor, VC Sharma, V Hide, W Kawahara, Y Benoit, JB AF Watanabe, Junichi Hattori, Masahira Berriman, Matthew Lehane, Michael J. Hall, Neil Solano, Philippe Aksoy, Serap Hide, Winston Toure, Yeya Attardo, Geoffrey M. Darby, Alistair C. Toyoda, Atsushi Hertz-Fowler, Christiane Larkin, Denis M. Cotton, James A. Watanabe, Junichi Sanders, Mandy J. Swain, Martin T. Hattori, Masahira Berriman, Matthew Quail, Michael A. Inoue, Noboru Ravel, Sophie Taylor, Todd D. Srivastava, Tulika P. Sharma, Vineet Warren, Wesley Wilson, Richard K. Suzuki, Yutaka Lawson, Daniel Hughes, Daniel S. T. Megy, Karyn Masiga, Daniel K. Mireji, Paul O. Attardo, Geoffrey M. Hansen, Imma A. Van den Abbeele, Jan Benoit, Joshua B. Bourtzis, Kostas Lehane, Michael J. Aksoy, Serap Masiga, Daniel K. Obiero, George F. O. Robertson, Hugh M. Jones, Jeffery W. Zhou, Jing-Jiang Field, Linda M. Friedrich, Markus Mireji, Paul O. Nyanjom, Steven R. G. Telleria, Erich L. Caljon, Guy Van den Abbeele, Jan Ribeiro, Jose M. C. Acosta-Serrano, Alvaro Benoit, Joshua B. Ooi, Cher-Pheng Rose, Clair Price, David P. Haines, Lee R. Lehane, Michael J. Christoffels, Alan Sim, Cheolho Pham, Daphne Q. D. Denlinger, David L. Geiser, Dawn L. Omedo, Irene A. Benoit, Joshua B. Winzerling, Joy J. Peyton, Justin T. Marucha, Kevin K. Jonas, Mario Meuti, Megan E. Rawlings, Neil D. Mireji, Paul O. Zhang, Qirui Macharia, Rosaline W. Michalkova, Veronika Dashti, Zahra Jalali Sefid Baumann, Aaron A. Gaede, Gerd Marco, Heather G. Hansen, Immo A. Caers, Jelle Schoofs, Liliane Riehle, Michael A. Hu, Wanqi Tu, Zhijian Tarone, Aaron M. Malacrida, Anna R. Kibet, Caleb K. Benoit, Joshua B. Scolari, Francesca Attardo, Geoffrey M. Koekemoer, Jacobus J. O. Willis, Judith Gomulski, Ludvik M. Falchetto, Marco Scott, Maxwell J. Fu, Shuhua Sze, Sing-Hoi Luiz, Thiago Weiss, Brian Walshe, Deirdre P. Wang, Jingwen Benoit, Joshua B. Attardo, Geoffrey M. Wamalwa, Mark Mwangi, Sarah Aksoy, Serap Ramphul, Urvashi N. Snyder, Anna K. Brelsfoard, Corey L. Thomas, Gavin H. Tsiamis, George Bourtzis, Kostas Arensburger, Peter Rio, Rita V. M. Macdonald, Sandy J. Panji, Sumir Kruger, Adele Christoffels, Alan Benkahla, Alia Balyeidhusa, Apollo S. P. Msangi, Atway Ooi, Cher-Pheng Okoro, Chinyere K. Masiga, Daniel K. Stephens, Dawn Walshe, Deirdre P. Stanley, Eleanor J. Mpondo, Feziwe Wamwiri, Florence Mramba, Furaha Attardo, Geoffrey M. Siwo, Geoffrey Obiero, George F. O. Githinji, George Harkins, Gordon Murilla, Grace Lehvaeslaiho, Heikki Malele, Imna Koekemoer, Jacobus J. O. Auma, Joanna E. Kinyua, Johnson K. Ouma, Johnson Watanabe, Junichi Megy, Karyn Okedi, Loyce Manga, Lucien Jonas, Mario Wamalwa, Mark Aslett, Martin Koffi, Mathurin Berriman, Matthew Lehane, Michael J. Gaunt, Michael W. Makgamathe, Mmule Hall, Neil Mulder, Nicola Manangwa, Oliver Abila, Patrick P. Wincker, Patrick Mireji, Paul O. Gregory, Richard Rio, Rita V. M. Bateta, Rosemary Sakate, Ryuichi Aksoy, Serap Ommeh, Sheila Lehane, Stella Nyanjom, Steven R. G. Imanishi, Tadashi Taylor, Todd D. Osamor, Victor C. Sharma, Vineet Hide, Winston Kawahara, Yoshihiro Benoit, Joshua B. CA IGGI TI Genome Sequence of the Tsetse Fly (Glossina morsitans): Vector of African Trypanosomiasis SO SCIENCE LA English DT Article ID PERITROPHIC MATRIX; IMMUNE-RESPONSES; AQUAPORINS; PROTEINS; DIPTERA; FLIES AB Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein-encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/ chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology. C1 [Lehvaeslaiho, Heikki] KAUST, Thuwal 239556900, Saudi Arabia. [Arensburger, Peter] Calif State Polytech Univ Pomona, Dept Biol Sci, Pomona, CA 91768 USA. [Bourtzis, Kostas] Alexander Fleming Biomed Sci Res Ctr, Biomed Sci Res Ctr, Vari 16672, Greece. [Wincker, Patrick] CEA, F-91507 Evry, France. [Macharia, Rosaline W.] Univ Nairobi, Ctr Biotechnol & Bioinformat, Nairobi 00100, Kenya. [Suzuki, Yutaka] Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol, Ctr Om & Bioinformat, Kashiwa, Chiba 2778561, Japan. [Toyoda, Atsushi] Natl Inst Genet, Comparat Genom Lab, Mishima, Shizuoka 4118540, Japan. [Panji, Sumir; Mulder, Nicola] Univ Cape Town, Fac Hlth Sci, IIDMM, Computat Biol Grp, ZA-7925 Cape Town, South Africa. [Fu, Shuhua] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA. [Marucha, Kevin K.; Bateta, Rosemary] Egerton Univ, Dept Biochem & Mol Biol, Njoro, Kenya. [Kinyua, Johnson K.] JKUAT, Dept Biochem, Nairobi, Kenya. [Hu, Wanqi; Tu, Zhijian] Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA. [Zhou, Jing-Jiang; Field, Linda M.] Rothamsted Res, Dept Biol Chem & Crop Protect, Harpenden AL5 2JQ, Herts, England. [Benoit, Joshua B.] Univ Cincinnati, McMicken Coll Arts & Sci, Dept Biol Sci, Cincinnati, OH 45221 USA. [Gaede, Gerd; Marco, Heather G.] Univ Cape Town, Dept Biol Sci, ZA-7700 Rondebosch, South Africa. [Pham, Daphne Q. D.] Univ Wisconsin Parkside, Dept Biol Sci, Kenosha, WI 53144 USA. [Jones, Jeffery W.; Friedrich, Markus] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. [Malacrida, Anna R.; Scolari, Francesca; Gomulski, Ludvik M.; Falchetto, Marco] Univ Pavia, Dept Biol & Biotechnol, I-27100 Pavia, Italy. [Sim, Cheolho] Baylor Univ, Dept Biol, Waco, TX 76798 USA. [Caers, Jelle; Schoofs, Liliane] Katholieke Univ Leuven, Dept Biol, B-3000 Louvain, Belgium. [Hansen, Imma A.; Price, David P.; Hansen, Immo A.] New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA. [Thomas, Gavin H.; Macdonald, Sandy J.] Univ York, Dept Biol, York Y010 5DD, N Yorkshire, England. [Snyder, Anna K.; Rio, Rita V. M.] W Virginia Univ, Dept Biol, Morgantown, WV 26506 USA. [Van den Abbeele, Jan; Caljon, Guy] Inst Trop Med Antwerp, Dept Biomed Sci, B-2000 Antwerp, Belgium. [Willis, Judith] Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA. [Omedo, Irene A.] CGMRC, KEMRI Wellcome Trust Programme, Dept Clin Res, Kilifi, Kenya. [Osamor, Victor C.] Covenant Univ, Coll Sci & Technol, Dept Comp & Informat Sci, Ota, Ogun State, Nigeria. [Sze, Sing-Hoi] Texas A&M Univ, Dept Biochem & Biophys, Dept Comp Sci & Engn, College Stn, TX 77843 USA. [Scott, Maxwell J.] N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA. [Tarone, Aaron M.] Texas A&M Univ, Dept Entomol, College Stn, TX 77843 USA. [Denlinger, David L.; Zhang, Qirui] Ohio State Univ, Dept Entomol, Aronoff Lab 400, Columbus, OH 43210 USA. [Riehle, Michael A.] Univ Arizona, Dept Entomol, Tucson, AZ 85721 USA. [Robertson, Hugh M.] Univ Illinois, Dept Entomol, Urbana, IL 61801 USA. Joint FAO IAEA Programme Nucl Tech Food & Agr, Insect Pest Control Lab, A-1220 Vienna, Austria. [Tsiamis, George] Univ Patras, Dept Environm & Nat Resources Management, Agrinion 30100, Greece. [Telleria, Erich L.; Michalkova, Veronika; Luiz, Thiago; Weiss, Brian; Wang, Jingwen] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA. [Peyton, Justin T.] Ohio State Univ, Dept Ecol Evolut & Organismal Biol, Aronoff Lab 300, Columbus, OH 43210 USA. [Brelsfoard, Corey L.] St Catharine Coll, Dept Nat Sci, St Catharine, KY 40061 USA. [Winzerling, Joy J.] Univ Arizona, Coll Agr & Life Sci, Dept Nutr Sci, Career Serv, Tucson, AZ 85721 USA. [Winzerling, Joy J.] Univ Arizona, Coll Agr & Life Sci, Dept Nutr Sci, Acad Serv, Tucson, AZ 85721 USA. [Geiser, Dawn L.] Univ Arizona, Dept Nutr Sci, Tucson, AZ 85721 USA. [Gaunt, Michael W.] Univ London London Sch Hyg & Trop Med, Dept Pathogen Mol Biol, London WC1E 7HT, England. [Acosta-Serrano, Alvaro; Rose, Clair] Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England. [Acosta-Serrano, Alvaro; Haines, Lee R.; Walshe, Deirdre P.; Ramphul, Urvashi N.; Lehane, Stella] Univ Liverpool, Liverpool Sch Trop Med, Dept Vector Biol, Liverpool L3 5QA, Merseyside, England. [Koekemoer, Jacobus J. O.] Onderstepoort Vet Inst, Entomol Sect, ZA-110 Onderstepoort, South Africa. [Siwo, Geoffrey] Univ Notre Dame, Dept Biol Sci, Eck Inst Global Hlth, Notre Dame, IN 46556 USA. Univ Pretoria, Dept Vet Trop Dis, ZA-110 Onderstepoort, South Africa. [Lawson, Daniel; Hughes, Daniel S. T.; Stanley, Eleanor J.] European Bioinformat Inst EMBL EBI, European Mol Biol Labs, Cambridge CB10 1SA, Cambs, England. [Benkahla, Alia] Inst Pasteur Tunis, Lab Med Parasitol Biotechnol & Biomol, Grp Bioinformat & Modeling, Tunis 1002, Tunisia. [Solano, Philippe; Koffi, Mathurin] CIRDES Bobo Dioulasso, UMR IRD CIRAD INTERTRYP 177, IRD, Bobo Dioulasso, Burkina Faso. [Ravel, Sophie] LRCT Campus Int Baillarguet, UMR IRD CIRAD INTERTRYP 177, IRD, Montpellier, France. [Larkin, Denis M.; Swain, Martin T.] Aberystwyth Univ, Inst Biol Environm & Rural Sci, Aberystwyth SY23 3FG, Ceredigion, Wales. [Ommeh, Sheila] JKUAT, Biotechnol Res Inst, Nairobi, Kenya. [Darby, Alistair C.; Gregory, Richard] Univ Liverpool, Inst Integrat Biol, Liverpool L69 7ZB, Merseyside, England. [Michalkova, Veronika] Slovak Acad Sci, Inst Zool, Bratislava 84506, Slovakia. [Sakate, Ryuichi; Imanishi, Tadashi; Kawahara, Yoshihiro] Natl Inst Adv Ind Sci & Technol, Biol Informat Res Ctr, Integrated Database Team, Koto Ku, Tokyo 1350064, Japan. [Wamwiri, Florence; Murilla, Grace; Auma, Joanna E.; Ouma, Johnson] Kenya Agr Res Inst, Trypanosomiasis Res Ctr, Kikuyu 902, Kenya. [Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA. [Stephens, Dawn; Makgamathe, Mmule] Technol Innovat Agcy, Natl Genom Platform, ZA-4058 Durban, South Africa. [Balyeidhusa, Apollo S. P.] Makerere Univ, Dept Biochem & Sports Sci, Kampala, Uganda. [Rawlings, Neil D.] EMBL European Bioinformat Inst, Wellcome Trust Sanger Inst, Bateman Grp, Cambridge CB10 1SA, Cambs, England. [Obiero, George F. O.; Kibet, Caleb K.] Int Ctr Insect Physiol & Ecol, Mol Biol & Bioinformat Unit, Nairobi, Kenya. [Okedi, Loyce; Abila, Patrick P.] Natl Livestock Resources Res Inst NaLIRRI, Tororo, Uganda. [Inoue, Noboru] Obihiro Univ Agr & Vet Med, Natl Res Ctr Protozoan Dis, Obihiro, Hokkaido 0808555, Japan. [Hertz-Fowler, Christiane; Cotton, James A.; Sanders, Mandy J.; Quail, Michael A.; Aslett, Martin] Wellcome Trust Sanger Inst, Parasite Genom Grp, Cambridge CB10 1SA, Cambs, England. [Baumann, Aaron A.] Howard Hughes Med Inst, Riddiford Lab, Ashburn, VA 20147 USA. [Srivastava, Tulika P.; Sharma, Vineet; Sharma, Vineet] RIKEN Ctr Integrat Med Sci, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. [Christoffels, Alan; Macharia, Rosaline W.; Dashti, Zahra Jalali Sefid; Wamalwa, Mark; Mwangi, Sarah; Panji, Sumir; Kruger, Adele; Mpondo, Feziwe; Harkins, Gordon] Univ Western Cape, South African MRC Bioinformat Unit, South African Natl Bioinformat Inst, ZA-7530 Bellville, South Africa. [Toure, Yeya] WHO, Special Programme Res & Training Trop Dis TDR, CH-1211 Geneva 27, Switzerland. [Warren, Wesley; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USA. [Msangi, Atway; Mramba, Furaha; Malele, Imna; Manangwa, Oliver] TTRI, Tanga, Tanzania. [Ouma, Johnson] Vector Hlth Int, Arusha, Tanzania. [Okoro, Chinyere K.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, Cambs, England. [Manga, Lucien] WHO, WHO Reg Off Africa, Brazzaville, Congo. [Srivastava, Tulika P.] Indian Inst Technol, Sch Basic Sci, Mandi 175001, Himachal Prades, India. [Githinji, George] CGMRC, KEMRI Wellcome Trust Programme, Dept Parasite Vector & Human Biol, Kilifi, Kenya. [Watanabe, Junichi] Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan. Kenyatta Univ, Dept Biochem & Biotechnol, Nairobi, Kenya. [Sharma, Vineet; Sharma, Vineet] Indian Inst Sci Educ & Res, Dept Biol Sci, Bhopal 462066, Madhya Pradesh, India. King Abdulaziz Univ, Fac Sci, Jeddah 21589, Saudi Arabia. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02461 USA. [Kawahara, Yoshihiro] Natl Inst Agrobiol Sci, Agrogen Res Ctr, Bioinformat Res Unit, Tsukuba, Ibaraki 3058602, Japan. RP Aksoy, S (reprint author), Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, 60 Coll St, New Haven, CT 06520 USA. EM geoffrey.attardo@yale.edu; mb4@sanger.ac.uk; serap.aksoy@yale.edu RI Rawlings, Neil/M-5566-2013; Darby, Alistair/I-6485-2012; Zhang, Qirui/C-6579-2011; Cotton, James/B-8806-2008; Telleria, Erich/F-1580-2015; Thomas, Gavin/E-5753-2011; Taylor, Todd/A-7121-2009; Ribeiro, Jose/J-7011-2015; Acosta-Serrano, Alvaro/L-5503-2015; scolari, francesca/L-9233-2015; Hattori, Masahira/C-6958-2016; Silva, Thiago/L-7699-2016; Caljon, Guy/E-1310-2017; Faculty of, Sciences, KAU/E-7305-2017; OI solano, philippe/0000-0002-4351-3506; Macdonald, Sandy/0000-0002-4112-0987; Lawson, Daniel/0000-0001-7765-983X; Rawlings, Neil/0000-0001-5557-7665; Masiga, Daniel/0000-0001-7513-0887; christoffels, alan/0000-0002-0420-2916; Baumann, Aaron/0000-0002-7410-8482; Darby, Alistair/0000-0002-3786-6209; Zhang, Qirui/0000-0002-2749-9740; Cotton, James/0000-0001-5475-3583; Thomas, Gavin/0000-0002-9763-1313; Taylor, Todd/0000-0003-4247-6253; Acosta-Serrano, Alvaro/0000-0002-2576-7959; scolari, francesca/0000-0003-3085-9038; Hattori, Masahira/0000-0001-9467-0344; Silva, Thiago/0000-0002-8520-5405; Caljon, Guy/0000-0002-4870-3202; Hide, Winston/0000-0002-8621-3271; Tarone, Aaron/0000-0003-0965-7634; Hall, Neil/0000-0003-2808-0009; Geiser, Dawn/0000-0002-6004-8407; Aksoy, Serap/0000-0001-9941-143X; Ribeiro, Jose/0000-0002-9107-0818; Scott, Maxwell/0000-0001-6536-4735 FU Wellcome Trust [085775/Z/08/Z, 098051]; World Health Organization (WHO) Special Programme for Research and Training in Tropical Diseases (TDR) [A90088]; Ambrose Monell Foundation; Food and Agriculture Organization/International Atomic Energy Agency Coordinated Research Program "Improving SIT for Tsetse Flies through Research on their Symbionts"; European Union Cooperation in Science and Technology (COST) Action [FA0701]; Ministry of Education, Culture, Sports, Science, and Technology of Japan FX The public release and future updates of the genome sequence and associated information are hosted at VectorBase (www.vectorbase.org). The genome sequence can also be found at GenBank under the accession no. CCAG010000000. The Glossina morsitans genome project was funded by the Wellcome Trust (grants 085775/Z/08/Z and 098051) and World Health Organization (WHO) Special Programme for Research and Training in Tropical Diseases (TDR) (project no. A90088) and the Ambrose Monell Foundation. Authors also acknowledge support by the Food and Agriculture Organization/International Atomic Energy Agency Coordinated Research Program "Improving SIT for Tsetse Flies through Research on their Symbionts," the European Union Cooperation in Science and Technology (COST) Action FA0701 "Arthropod Symbiosis: From Fundamental Studies to Pest and Disease Management," and a grant-in-aid for Scientific Research on Priority Areas "Comprehensive Genomics" from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to M. H.). BAC libraries were generated through National Institute of Allergy and Infectious Diseases resources, and sequencing was supported by RIKEN Japan. We thank the staff in the library construction, sequence production, and informatics support groups at the Wellcome Trust Sanger Institute. NR 38 TC 64 Z9 64 U1 9 U2 72 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 25 PY 2014 VL 344 IS 6182 BP 380 EP 386 DI 10.1126/science.1249656 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF7BG UT WOS:000334867800033 ER PT J AU Habicht, KL Singh, NS Khadeer, MA Shimmo, R Wainer, IW Moaddel, R AF Habicht, K-L. Singh, N. S. Khadeer, M. A. Shimmo, R. Wainer, I. W. Moaddel, R. TI Characterization of a multiple endogenously expressed adenosine triphosphate-binding cassette transporters using nuclear and cellular membrane affinity chromatography columns SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 20th International Symposium on Electro- and Liquid Phase-Separation Techniques (ITP) CY OCT 06-09, 2013 CL Puerto de la Cruz, SPAIN DE Breast cancer resistant protein; Bioaffinity chromatography; Frontal chromatography; Glioblastoma ID STATIONARY-PHASE; PROTEINS; CELLS AB Glioblastoma multiforme is an aggressive form of human astrocytoma, with poor prognosis due to multidrug resistance to a number of anticancer drugs. The observed multi-drug resistance is primarily due to the efflux activity of ATP-Binding Cassette (ABC) efflux transporters such as Pgp, MRP1 and BCRP. The expression of these transporters has been demonstrated in nuclear and cellular membranes of the LN-229 human glioblastoma cell line. Nuclear membrane and cellular membrane fragments from LN-229 cells were immobilized on the IAM stationary phase to create nuclear and cellular membrane affinity chromatography columns, (NMAC(LN-229)) and (CMAC(LN-229)), respectively. Pgp, MRP1 and BCRP transporters co-immobilized on both columns were characterized and compared by establishing the binding affinities for estrone-3-sulfate (3.8 vs. 3.7 mu M), verapamil (0.6 vs. 0.7 mu M) and prazosin (0.099 vs. 0.03311 mu M) on each column and no significant differences were observed. Since the marker ligands had overlapping selectivities, the selective characterization of each transporter was carried out by saturation of the binding sites of the non-targeted transporters. The addition of verapamil (Pgp and MRP1 substrate) to the mobile phase allowed the comparative screening of eight compounds at the nuclear and cellular BCRP using etoposide as the marker ligand. AZT increased the retention of etoposide (+15%), a positive allosteric interaction, on the CMAC(LN-229) column and decreased it (-5%) on the NMAC(LN-229), while the opposite effect was produced by rhodamine. The results indicate that there are differences between the cellular and nuclear membrane expressed BCRP and that NMAC and CMAC columns can be used to probe these differences. Published by Elsevier B.V. C1 [Habicht, K-L.; Singh, N. S.; Khadeer, M. A.; Wainer, I. W.; Moaddel, R.] NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. [Habicht, K-L.; Shimmo, R.] Tallinn Univ, Inst Math & Nat Sci, Dept Nat Sci, EE-10120 Tallinn, Estonia. RP Moaddel, R (reprint author), NIA, Bioanalyt & Drug Discovery Unit, Clin Invest Lab, NIH, Suite 100,8B131 Biomed Res Ctr,251 Bayview Boul, Baltimore, MD 21224 USA. EM moaddelru@grc.nia.nih.gov RI Singh, Nagendra/K-8966-2015 FU Intramural NIH HHS [Z99 AG999999] NR 15 TC 6 Z9 6 U1 4 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 EI 1873-3778 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 25 PY 2014 VL 1339 BP 80 EP 85 DI 10.1016/j.chroma.2014.02.076 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AG1UG UT WOS:000335201100010 PM 24642394 ER PT J AU Szu, SC Klugman, KP Hunt, S AF Szu, Shousun C. Klugman, Keith P. Hunt, Steven TI Re-examination of immune response and estimation of anti-Vi IgG protective threshold against typhoid fever-based on the efficacy trial of Vi conjugate in young children SO VACCINE LA English DT Article DE Vi antibody protective threshold against typhoid fever Vi conjugate efficacy trial ID CAPSULAR POLYSACCHARIDE VACCINE; SALMONELLA-TYPHI; IMMUNIZATION; IMMUNOGENICITY; PERSISTENCE; ANTIBODIES AB Background: The capsular polysaccharide of Salmonella enterica serovar Typhi, Vi antigen, is an essential virulence factor and a protective antigen. Similar to other polysaccharide vaccines, the protective action of Vi, both to the polysaccharide alone or when presented as a conjugate, is mediated by serum IgG Vi antibodies. The evaluation of Vi capsular polysaccharide based vaccines to prevent typhoid fever would be significantly facilitated by the identification of a "protective level" of serum antibodies to Vi antigen. Methods: The protective level of anti-Vi IgG against typhoid fever was derived from the protective efficacy and immune response of a Vi-rEPA conjugate vaccine efficacy trial. The estimation was derived by two methods: correlation of the percent efficacy and the antibody distribution profile in the vaccine group at a given period of observation, and use of the relative ratio of anti-Vi IgG levels between the vaccine and placebo groups greater or equal to the Relative Risk of typhoid fever used in the efficacy determination. Results: Both methods predicted a similar range of a minimum protective level of anti-Vi IgG between 1.4 and 2.0 mu g/ml (short term threshold). When applying a protective threshold of 10 mu g/ml at 6 months post immunization, an IgG level in excess of 1.4 mu g/ml was achieved by 90% of children at 46 months post immunization, consistent with an 89% level of protection over the duration of the study. We thus suggest that the proportion of children with Vi IgG > 10 mu g/ml (long term threshold) 6 months after immunization may reflect the proportion protected over at least a 4 year period. Conclusion: The current assignment of an anti-Vi IgG protective level may be of value when evaluating vaccine performance of future Vi conjugate vaccines. Published by Elsevier Ltd. C1 [Szu, Shousun C.; Hunt, Steven] NICHHD, NIH, Bethesda, MD 20892 USA. [Klugman, Keith P.] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA. RP Szu, SC (reprint author), NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM szus@mail.nih.gov OI Hunt, Steven/0000-0003-3533-0627 FU Intramural Research Program; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Bill and Melinda Gates Foundation FX This work was supported by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health and a grant from the Bill and Melinda Gates Foundation. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the National Institutes of Health or the Bill and Melinda Gates Foundation. NR 25 TC 5 Z9 5 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD APR 25 PY 2014 VL 32 IS 20 BP 2359 EP 2363 DI 10.1016/j.vaccine.2014.02.050 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AG0JA UT WOS:000335100600015 PM 24630869 ER PT J AU Tao-Cheng, JH Thein, S Yang, Y Reese, TS Gallant, PE AF Tao-Cheng, J. -H. Thein, S. Yang, Y. Reese, T. S. Gallant, P. E. TI HOMER IS CONCENTRATED AT THE POSTSYNAPTIC DENSITY AND DOES NOT REDISTRIBUTE AFTER ACUTE SYNAPTIC STIMULATION SO NEUROSCIENCE LA English DT Article DE synapse; shanks; CaMKII; electron microscopy; PSD; mGluR. ID METABOTROPIC GLUTAMATE RECEPTORS; CEREBELLAR GRANULE CELLS; HIPPOCAMPAL-NEURONS; SUBTHALAMIC NUCLEUS; FAMILY PROTEINS; MOUSE-BRAIN; SYNAPSES; LOCALIZATION; MECHANISMS; EXPRESSION AB Homer is a postsynaptic density (PSD) scaffold protein that is involved in synaptic plasticity, calcium signaling and neurological disorders. Here, we use pre-embedding immunogold electron microscopy to illustrate the differential localization of three Homer gene products (Homer 1, 2, and 3) in different regions of the mouse brain. In cross-sectioned PSDs, Homer occupies a layer similar to 30-100 nm from the postsynaptic membrane lying just beyond the dense material that defines the PSD core (similar to 30-nm-thick). Homer is evenly distributed within the PSD area along the lateral axis, but not at the peri-PSD locations within 60 nm from the edge of the PSD, where type I-metabotropic glutamate receptors (mGluR1 and 5) are concentrated. This distribution of Homer matches that of Shank, another major PSD scaffold protein, but differs from those of other two major binding partners of Homer, type I mGluR and IP3 receptors. Many PSD proteins rapidly redistribute upon acute (2 min) stimulation. To determine whether Homer distribution is affected by acute stimulation, we examined its distribution in dissociated hippocampal cultures under different conditions. Both the pattern and density of label for Homer 1, the isoform that is ubiquitous in hippocampus, remained unchanged under high K+ depolarization (90 mM for 2-5 min), N-methyl-D-asparic acid (NMDA) treatment (50 mu M for 2 min), and calcium-free conditions (EGTA at 1 mM for 2 min). In contrast, Shank and calcium/calmodulin-dependent kinase II (CaMKII) accumulate at the PSD upon NMDA treatment, and CaMKII is excluded from the PSD complex under low calcium conditions. (C) 2014 Published by Elsevier Ltd. on behalf of IBRO. C1 [Tao-Cheng, J. -H.] NINDS, EM Facil, NIH, Bethesda, MD 20892 USA. [Thein, S.; Yang, Y.; Reese, T. S.; Gallant, P. E.] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Tao-Cheng, JH (reprint author), 49 Convent Dr,Room 3A50, Bethesda, MD 20892 USA. EM chengs@ninds.nih.gov FU NIH, NINDS FX We thank Christine A. Winters for hippocampal neuronal cultures, Virginia Crocker and Rita Azzam for expert EM technical support, Dr. Ayse Dosemeci for helpful discussions and critical reading of the manuscript. Supported by the Intramural Research Program of the NIH, NINDS. NR 42 TC 6 Z9 6 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD APR 25 PY 2014 VL 266 BP 80 EP 90 DI 10.1016/j.neuroscience.2014.01.066 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AE8VO UT WOS:000334281200008 PM 24530450 ER PT J AU Sadat, MA Moir, S Chun, TW Lusso, P Kaplan, G Wolfe, L Memoli, MJ He, M Vega, H Kim, LJY Huang, Y Hussein, N Nievas, E Mitchell, R Garofalo, M Louie, A Ireland, DC Grunes, C Cimbro, R Patel, V Holzapfel, G Salahuddin, D Bristol, T Adams, D Marciano, BE Hegde, M Li, YX Calvo, KR Stoddard, J Justement, JS Jacques, J Priel, DAL Murray, D Sun, P Kuhns, DB Boerkoel, CF Chiorini, JA Di Pasquale, G Verthelyi, D Rosenzweig, SD AF Sadat, Mohammed A. Moir, Susan Chun, Tae-Wook Lusso, Paolo Kaplan, Gerardo Wolfe, Lynne Memoli, Matthew J. He, Miao Vega, Hugo Kim, Leo J. Y. Huang, Yan Hussein, Nadia Nievas, Elma Mitchell, Raquel Garofalo, Mary Louie, Aaron Ireland, Derek C. Grunes, Claire Cimbro, Raffaello Patel, Vyomesh Holzapfel, Genevieve Salahuddin, Daniel Bristol, Tyler Adams, David Marciano, Beatriz E. Hegde, Madhuri Li, Yuxing Calvo, Katherine R. Stoddard, Jennifer Justement, J. Shawn Jacques, Jerome Priel, Debra A. Long Murray, Danielle Sun, Peter Kuhns, Douglas B. Boerkoel, Cornelius F. Chiorini, John A. Di Pasquale, Giovanni Verthelyi, Daniela Rosenzweig, Sergio D. TI Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANTIRETROVIRAL THERAPY; OTITIS-MEDIA; HIV; BIOSYNTHESIS; RESERVOIR; CHILDREN; EFFICACY; ENTRY; CD4 AB Genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase (the first enzyme in the processing pathway of N-linked oligosaccharide), cause the rare congenital disorder of glycosylation type IIb (CDG-IIb), also known as MOGS-CDG. MOGS is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans. We evaluated two siblings with CDG-IIb who presented with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemia but limited clinical evidence of an infectious diathesis. A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia. Impaired viral replication and cellular entry may explain a decreased susceptibility to infections. C1 [Sadat, Mohammed A.; Hussein, Nadia; Nievas, Elma; Mitchell, Raquel; Garofalo, Mary; Rosenzweig, Sergio D.] NIAID, Infect Dis Susceptibil Unit, Lab Host Def, NIH, Bethesda, MD 20892 USA. [Moir, Susan; Chun, Tae-Wook; Lusso, Paolo; Kim, Leo J. Y.; Louie, Aaron; Cimbro, Raffaello; Justement, J. Shawn; Murray, Danielle] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Memoli, Matthew J.; Bristol, Tyler] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Marciano, Beatriz E.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Holzapfel, Genevieve; Salahuddin, Daniel; Sun, Peter] NIAID, Lab Immunogenet, NIH, Bethesda, MD 20892 USA. [Rosenzweig, Sergio D.] NIAID, Primary Immunodeficiency Clin, NIH, Bethesda, MD 20892 USA. [Wolfe, Lynne; Vega, Hugo; Huang, Yan; Adams, David; Boerkoel, Cornelius F.] Natl Human Res Genome Inst, Undiagnosed Dis Program, NIH, Bethesda, MD USA. [Calvo, Katherine R.; Stoddard, Jennifer] Natl Inst Dent & Craniofacial Res, Dept Lab Med, Clin Ctr, NIH, Bethesda, MD USA. [Patel, Vyomesh] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Chiorini, John A.; Di Pasquale, Giovanni] Natl Inst Dent & Craniofacial Res, Adeno Associated Virus Biol Sect, NIH, Bethesda, MD USA. [Kaplan, Gerardo; Jacques, Jerome] Ctr Biol Evaluat & Res, Silver Spring, MD USA. [Ireland, Derek C.; Grunes, Claire; Verthelyi, Daniela] Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Priel, Debra A. Long; Kuhns, Douglas B.] US FDA, Clin Serv Program, Silver Spring, MD USA. [Priel, Debra A. Long; Kuhns, Douglas B.] Frederick Natl Lab Canc Res, SAIC Frederick, Frederick, MD USA. [He, Miao; Hegde, Madhuri] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Li, Yuxing] Ctr Neutralizing Antibodies TSRI, IAVI Int AIDS Vaccine Initiat, La Jolla, CA USA. [Li, Yuxing] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA USA. RP Rosenzweig, SD (reprint author), CC, Serv Immunol, DLM, 10 Ctr Dr,Bldg 10 2C410F, Bethesda, MD 20892 USA. EM srosenzweig@cc.nih.gov OI Calvo, Katherine/0000-0002-0771-4191; Cimbro, Raffaello/0000-0002-6251-5160 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute [HHSN261200800001E] FX Supported by the Intramural Research Program of the National Institutes of Health and by a grant from the National Cancer Institute (HHSN261200800001E). NR 22 TC 21 Z9 21 U1 1 U2 7 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 24 PY 2014 VL 370 IS 17 BP 1615 EP 1625 DI 10.1056/NEJMoa1302846 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AH4TG UT WOS:000336120500008 PM 24716661 ER PT J AU Brzezniak, C Szabo, E AF Brzezniak, Christina Szabo, Eva TI Sunitinib-Associated Hair Depigmentation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Brzezniak, Christina] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA. [Szabo, Eva] NIH, Bethesda, MD 20892 USA. RP Brzezniak, C (reprint author), Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA. EM christina.e.brzezniak.mil@health.mil NR 0 TC 4 Z9 4 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 24 PY 2014 VL 370 IS 17 BP E27 EP E27 DI 10.1056/NEJMicm1309906 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AH4TG UT WOS:000336120500001 PM 24758639 ER PT J AU Schnitzler, CE Simmons, DK Pang, K Martindale, MQ Baxevanis, AD AF Schnitzler, Christine E. Simmons, David K. Pang, Kevin Martindale, Mark Q. Baxevanis, Andreas D. TI Expression of multiple Sox genes through embryonic development in the ctenophore Mnemiopsis leidyi is spatially restricted to zones of cell proliferation SO EVODEVO LA English DT Article DE Sox; Ctenophore; Lobate; Mnemiopsis leidyi; Cell proliferation; Stem cell ID MIXED MODELS; STEM-CELLS; FAMILY; MECHANISMS; EVOLUTION; METAZOAN; PROTEINS; MCCRADYI; SPECIFICATION; REGULATORS AB Background: The Sox genes, a family of transcription factors characterized by the presence of a high mobility group (HMG) box domain, are among the central groups of developmental regulators in the animal kingdom. They are indispensable in progenitor cell fate determination, and various Sox family members are involved in managing the critical balance between stem cells and differentiating cells. There are 20 mammalian Sox genes that are divided into five major groups (B, C, D, E, and F). True Sox genes have been identified in all animal lineages but not outside Metazoa, indicating that this gene family arose at the origin of the animals. Whole-genome sequencing of the lobate ctenophore Mnemiopsis leidyi allowed us to examine the full complement and expression of the Sox gene family in this early-branching animal lineage. Results: Our phylogenetic analyses of the Sox gene family were generally in agreement with previous studies and placed five of the six Mnemiopsis Sox genes into one of the major Sox groups: SoxB (MleSox1), SoxC (MleSox2), SoxE (MleSox3, MleSox4), and SoxF (MleSox5), with one unclassified gene (MleSox6). We investigated the expression of five out of six Mnemiopsis Sox genes during early development. Expression patterns determined through in situ hybridization generally revealed spatially restricted Sox expression patterns in somatic cells within zones of cell proliferation, as determined by EdU staining. These zones were located in the apical sense organ, upper tentacle bulbs, and developing comb rows in Mnemiopsis, and coincide with similar zones identified in the cydippid ctenophore Pleurobrachia. Conclusions: Our results are consistent with the established role of multiple Sox genes in the maintenance of stem cell pools. Both similarities and differences in juvenile cydippid stage expression patterns between Mnemiopsis Sox genes and their orthologs from Pleurobrachia highlight the importance of using multiple species to characterize the evolution of development within a given phylum. In light of recent phylogenetic evidence that Ctenophora is the earliest-branching animal lineage, our results are consistent with the hypothesis that the ancient primary function of Sox family genes was to regulate the maintenance of stem cells and function in cell fate determination. C1 [Schnitzler, Christine E.; Baxevanis, Andreas D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Simmons, David K.; Martindale, Mark Q.] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL USA. [Pang, Kevin] Univ Bergen, Sars Int Ctr Marine Mol Biol, Bergen, Norway. RP Baxevanis, AD (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM andy@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health; NSF; NASA FX This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. This work was also supported by grants from NSF and NASA to MQM. The authors would like to thank Joe Ryan and Adam Reitzel for their helpful comments on the manuscript. We also thank two anonymous reviewers for their comments, which improved the manuscript. NR 56 TC 14 Z9 14 U1 0 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2041-9139 J9 EVODEVO JI EvoDevo PD APR 24 PY 2014 VL 5 AR 15 DI 10.1186/2041-9139-5-15 PG 17 WC Evolutionary Biology; Developmental Biology SC Evolutionary Biology; Developmental Biology GA AG6MF UT WOS:000335532000001 PM 24834317 ER PT J AU Turtzo, LC Lescher, J Janes, L Dean, DD Budde, MD Frank, JA AF Turtzo, L. Christine Lescher, Jacob Janes, Lindsay Dean, Dana D. Budde, Matthew D. Frank, Joseph A. TI Macrophagic and microglial responses after focal traumatic brain injury in the female rat SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Controlled cortical impact; Inflammation; Macrophage; Microglia; MRI; Rat; Traumatic brain injury ID TUMOR-ASSOCIATED MACROPHAGES; SPINAL-CORD-INJURY; CYTOKINE EXPRESSION; NERVOUS-SYSTEM; ESTROUS-CYCLE; PROGESTERONE; ACTIVATION; RECOVERY; NEUROINFLAMMATION; POLARIZATION AB Background: After central nervous system injury, inflammatory macrophages (M1) predominate over anti-inflammatory macrophages (M2). The temporal profile of M1/M2 phenotypes in macrophages and microglia after traumatic brain injury (TBI) in rats is unknown. We subjected female rats to severe controlled cortical impact (CCI) and examined the postinjury M1/M2 time course in their brains. Methods: The motor cortex (2.5 mm left laterally and 1.0 mm anteriorly from the bregma) of anesthetized female Wistar rats (ages 8 to 10 weeks; N = 72) underwent histologically moderate to severe CCI with a 5-mm impactor tip. Separate cohorts of rats had their brains dissociated into cells for flow cytometry, perfusion-fixed for immunohistochemistry (IHC) and ex vivo magnetic resonance imaging or flash-frozen for RNA and protein analysis. For each analytical method used, separate postinjury times were included for 24 hours; 3 or 5 days; or 1, 2, 4 or 8 weeks. Results: By IHC, we found that the macrophagic and microglial responses peaked at 5 to 7 days post-TBI with characteristics of mixed populations of M1 and M2 phenotypes. Upon flow cytometry examination of immunological cells isolated from brain tissue, we observed that peak M2-associated staining occurred at 5 days post-TBI. Chemokine analysis by multiplex assay showed statistically significant increases in macrophage inflammatory protein 1 alpha and keratinocyte chemoattractant/growth-related oncogene on the ipsilateral side within the first 24 hours after injury relative to controls and to the contralateral side. Quantitative RT-PCR analysis demonstrated expression of both M1- and M2-associated markers, which peaked at 5 days post-TBI. Conclusions: The responses of macrophagic and microglial cells to histologically severe CCI in the female rat are maximal between days 3 and 7 postinjury. The response to injury is a mixture of M1 and M2 phenotypes. C1 [Turtzo, L. Christine; Lescher, Jacob; Janes, Lindsay; Frank, Joseph A.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Turtzo, L. Christine; Lescher, Jacob; Janes, Lindsay; Dean, Dana D.; Budde, Matthew D.; Frank, Joseph A.] NIH, Frank Lab, Bethesda, MD 20814 USA. [Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20814 USA. [Dean, Dana D.] Baylor Univ, Dept Environm Sci, Waco, TX 76798 USA. [Budde, Matthew D.] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA. RP Turtzo, LC (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM turtzolc@mail.nih.gov FU US Department of Defense Center for Neuroscience and Regenerative Medicine under Henry M. Jackson Foundation for the Advancement of Military Medicine award [300604-13.01-60855]; National Institutes of Health Intramural Research Program FX These studies were supported by the US Department of Defense Center for Neuroscience and Regenerative Medicine under Henry M. Jackson Foundation for the Advancement of Military Medicine award 300604-13.01-60855 and by the National Institutes of Health Intramural Research Program. We would also like to thank Aneeka Chaudhry, Tiziana Coppola and Eric Gold for their invaluable technical assistance with these studies. NR 57 TC 36 Z9 36 U1 2 U2 16 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 24 PY 2014 VL 11 AR 82 DI 10.1186/1742-2094-11-82 PG 14 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA AG6IW UT WOS:000335523300001 PM 24761998 ER PT J AU Rogatsky, I Adelman, K AF Rogatsky, Inez Adelman, Karen TI Preparing the First Responders: Building the Inflammatory Transcriptome from the Ground Up SO MOLECULAR CELL LA English DT Review ID RNA-POLYMERASE-II; NF-KAPPA-B; BROMODOMAIN PROTEIN BRD4; P-TEFB; GENE-EXPRESSION; PROINFLAMMATORY GENES; ELONGATION-FACTORS; BINDING MOTIFS; CPG ISLANDS; IN-VITRO AB In cells of the immune system, inflammatory stimuli trigger highly coordinated cascades of gene activation that are precisely calibrated to the nature and strength of the stimulus. Herein, we describe the forces that control inflammatory gene transcription and highlight that many critical determinants of responsiveness are established prior to challenge. We discuss key steps in the transcription cycle that are regulated during gene activation and the importance of the underlying enhancer landscape. Further, we illustrate how the diversity in regulatory strategies employed at inflammatory genes provides novel opportunities for therapeutic intervention. C1 [Rogatsky, Inez] Hosp Special Surg, Div Res, New York, NY 10021 USA. [Rogatsky, Inez] David Rosensweig Genom Ctr, New York, NY 10021 USA. [Rogatsky, Inez] Weill Cornell Grad Sch Med Sci, Grad Program Immunol & Microbial Pathogenesis, New York, NY 10021 USA. [Adelman, Karen] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Adelman, K (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. EM adelmank@niehs.nih.gov FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01 ES101987]; NIH NIAID; HSS David Rosensweig Genomics Center FX We thank L. Ivashkiv (HSS), C. Glass (UCSD), and S. Smale (UCLA) for comments on the manuscript and Y. Chinenov (HSS) for help with figures. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences to K.A. (Z01 ES101987), and grants from the NIH NIAID and the HSS David Rosensweig Genomics Center to I.R. NR 83 TC 11 Z9 12 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD APR 24 PY 2014 VL 54 IS 2 BP 245 EP 254 DI 10.1016/j.molcel.2014.03.038 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AF8TA UT WOS:000334987300008 PM 24766888 ER PT J AU Costi, R Metifiot, M Chung, S Crucitti, GC Maddali, K Pescatori, L Messore, A Madia, VN Pupo, G Scipione, L Tortorella, S Di Leva, FS Cosconati, S Marinelli, L Novellino, E Le Grice, SFJ Corona, A Pommier, Y Marchand, C Di Santo, R AF Costi, Roberta Metifiot, Mathieu Chung, Suhman Crucitti, Giuliana Cuzzucoli Maddali, Kasthuraiah Pescatori, Luca Messore, Antonella Madia, Valentina Noemi Pupo, Giovanni Scipione, Luigi Tortorella, Silvano Di Leva, Francesco Saverio Cosconati, Sandro Marinelli, Luciana Novellino, Ettore Le Grice, Stuart F. J. Corona, Angela Pommier, Yves Marchand, Christophe Di Santo, Roberto TI Basic Quinolinonyl Diketo Acid Derivatives as Inhibitors of HIV Integrase and their Activity against RNase H Function of Reverse Transcriptase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID VIRUS TYPE-1 INTEGRASE; DUAL INHIBITORS; RIBONUCLEASE-H; CRYSTAL-STRUCTURES; CATALYTIC DOMAIN; STRUCTURAL BASIS; BIOLOGICAL-ACTIVITIES; STRAND TRANSFER; RNA/DNA HYBRID; BINDING-SITE AB A series of antiviral basic quinolinonyl diketo acid derivatives were developed as inhibitors of HIV-1 IN. Compounds 12d,f,i inhibited HIV-1 IN with IC50 values below 100 nM for strand transfer and showed a 2 order of magnitude selectivity over 3'-processing. These strand transfer selective inhibitors also inhibited HIV-1 RNase H with low micromolar potencies. Molecular modeling studies based on both the HIV-1 IN and RNase H catalytic core domains provided new structural insights for the future development of these compounds as dual HIV-1 IN and RNase H inhibitors. C1 [Costi, Roberta; Crucitti, Giuliana Cuzzucoli; Pescatori, Luca; Messore, Antonella; Madia, Valentina Noemi; Pupo, Giovanni; Scipione, Luigi; Tortorella, Silvano; Di Santo, Roberto] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur Fdn Cenci Bolognetti, I-00185 Rome, Italy. [Metifiot, Mathieu; Maddali, Kasthuraiah; Pommier, Yves; Marchand, Christophe] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chung, Suhman; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Di Leva, Francesco Saverio; Marinelli, Luciana; Novellino, Ettore] Univ Naples Federico II, Dipartimento Farm, I-80131 Naples, Italy. [Cosconati, Sandro] Univ Naples 2, DiSTABiF, I-81100 Caserta, Italy. [Corona, Angela] Univ Cagliari, Dept Life & Environm Sci, I-09124 Cagliari, Italy. RP Costi, R (reprint author), Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur Fdn Cenci Bolognetti, Ple Aldo Moro 5, I-00185 Rome, Italy. EM roberta.costi@uniroma1.it; marchand@nih.gov RI Corona, Angela/G-7327-2014; Pescatori, Luca/H-5917-2016; OI Corona, Angela/0000-0002-6630-8636; Pescatori, Luca/0000-0003-4734-7856; TORTORELLA, Silvano/0000-0002-3279-9182; COSTI, Roberta/0000-0002-1314-9029; Marinelli, Luciana/0000-0002-4084-8044; Di Santo, Roberto/0000-0002-4279-7666; Cosconati, Sandro/0000-0002-8900-0968; scipione, luigi/0000-0002-2006-7005; Madia, Valentina Noemi/0000-0002-5724-612X FU Italian MIUR [ISS 40H4, PAIN (2010W2KM5L_002)]; FP7 CHAARM project; NIH Intramural Research Program, Center for Cancer Research, National Cancer Institute; NIH grants from the AIDS Intramural Targeted Program (IATAP) FX We thank the Italian MIUR for financial support, ISS 40H4, PAIN 2010-2011 (2010W2KM5L_002). R. Di Santo and R. Costi thank the FP7 CHAARM project for support. This work was also supported by the NIH Intramural Research Program, Center for Cancer Research, National Cancer Institute, and by NIH grants from the AIDS Intramural Targeted Program (IATAP). NR 79 TC 14 Z9 15 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD APR 24 PY 2014 VL 57 IS 8 BP 3223 EP 3234 DI 10.1021/jm5001503 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AG0OD UT WOS:000335113900005 PM 24684270 ER PT J AU Xiao, JB Free, RB Barnaeva, E Conroy, JL Doyle, T Miller, B Bryant-Genevier, M Taylor, MK Hu, X Dulcey, AE Southall, N Ferrer, M Titus, S Zheng, W Sibley, DR Marugan, JJ AF Xiao, Jingbo Free, R. Benjamin Barnaeva, Elena Conroy, Jennie L. Doyle, Trevor Miller, Brittney Bryant-Genevier, Marthe Taylor, Mercedes K. Hu, Xin Dulcey, Andres E. Southall, Noel Ferrer, Marc Titus, Steve Zheng, Wei Sibley, David R. Marugan, Juan J. TI Discovery, Optimization, and Characterization of Novel D-2 Dopamine Receptor Selective Antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID INDUCED WEIGHT-GAIN; D3 RECEPTOR; HIGH-AFFINITY; BINDING; SCHIZOPHRENIA; PHARMACOLOGY; ANALOGS; BIOLOGY; POTENT AB The D2 dopamine receptor (D2 DAR) is one of the most validated drug targets for neuropsychiatric and endocrine disorders. However, clinically approved drugs targeting 02 DAR display poor selectivity between the D2 and other receptors, especially the D3 DAR This lack of selectivity may lead to undesirable side effects. Here we describe the chemical and pharmacological characterization of a novel 02 DAR antagonist series with excellent D2 versus D1, D3, D4, and D5 receptor selectivity. The final probe 65 was obtained through a quantitative high-throughput screening campaign, followed by medicinal chemistry optimization, to yield a selective molecule with good in vitro physical properties, metabolic stability, and in vivo pharmacokinetics. The optimized molecule may be a useful in vivo probe for studying D2 DAR signal modulation and could also serve as a lead compound for the development of D2 DAR-selective druglike molecules for the treatment of multiple neuropsychiatric and endocrine disorders. C1 [Xiao, Jingbo; Barnaeva, Elena; Bryant-Genevier, Marthe; Taylor, Mercedes K.; Hu, Xin; Dulcey, Andres E.; Southall, Noel; Ferrer, Marc; Titus, Steve; Zheng, Wei; Marugan, Juan J.] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Free, R. Benjamin; Conroy, Jennie L.; Doyle, Trevor; Miller, Brittney; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Marugan, JJ (reprint author), NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM maruganj@mail.nih.gov RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014 OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757 FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research [U54MH084681, R21NS064831]; Intramural Research Program of the National Center for Advancing Translational Sciences; National Institute of Neurological Disorders and Stroke, National Institutes of Health FX We thank Paul Shinn, Danielle van Leer, William Leister, Chris LeClair, and Heather Baker for assistance with compound purification, HRMS analysis, and compound management. We also thank Drs. Arnold L. Rheingold and Curtis Moore at the University of California, San Diego for the X-ray analysis of compounds (R)-59 and 65. This research was supported by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research (Grants U54MH084681 and R21NS064831 to D.R.S.) and the Intramural Research Program of the National Center for Advancing Translational Sciences and National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 29 TC 6 Z9 6 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD APR 24 PY 2014 VL 57 IS 8 BP 3450 EP 3463 DI 10.1021/jm500126s PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AG0OD UT WOS:000335113900021 PM 24666157 ER PT J AU MacArthur, DG Manolio, TA Dimmock, DP Rehm, HL Shendure, J Abecasis, GR Adams, DR Altman, RB Antonarakis, SE Ashley, EA Barrett, JC Biesecker, LG Conrad, DF Cooper, GM Cox, NJ Daly, MJ Gerstein, MB Goldstein, DB Hirschhorn, JN Leal, SM Pennacchio, LA Stamatoyannopoulos, JA Sunyaev, SR Valle, D Voight, BF Winckler, W Gunter, C AF MacArthur, D. G. Manolio, T. A. Dimmock, D. P. Rehm, H. L. Shendure, J. Abecasis, G. R. Adams, D. R. Altman, R. B. Antonarakis, S. E. Ashley, E. A. Barrett, J. C. Biesecker, L. G. Conrad, D. F. Cooper, G. M. Cox, N. J. Daly, M. J. Gerstein, M. B. Goldstein, D. B. Hirschhorn, J. N. Leal, S. M. Pennacchio, L. A. Stamatoyannopoulos, J. A. Sunyaev, S. R. Valle, D. Voight, B. F. Winckler, W. Gunter, C. TI Guidelines for investigating causality of sequence variants in human disease SO NATURE LA English DT Article ID DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; PROTEIN-CODING GENES; HUMAN GENOME; INTELLECTUAL DISABILITY; COMPLEX TRAITS; RARE VARIANTS; ASSOCIATION; POPULATION; PHENOTYPE AB The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development. C1 [MacArthur, D. G.; Daly, M. J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [MacArthur, D. G.; Daly, M. J.; Hirschhorn, J. N.; Winckler, W.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Manolio, T. A.] NHGRI, Div Genom Med, Bethesda, MD 20892 USA. [Dimmock, D. P.] Med Coll Wisconsin, Dept Pediat, Div Genet, Milwaukee, WI 53226 USA. [Rehm, H. L.] Partners Healthcare Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA 02139 USA. [Rehm, H. L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Shendure, J.] Univ Washington, Dept Genome Sci, Seattle, WA 98115 USA. [Abecasis, G. R.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Adams, D. R.] NIH, NIH Undiagnosed Dis Program, Off Rare Dis Res, Bethesda, MD 20892 USA. [Adams, D. R.] NHGRI, Bethesda, MD 20892 USA. [Adams, D. R.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Altman, R. B.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Altman, R. B.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Antonarakis, S. E.] Univ Geneva, Sch Med, Dept Med Genet, CH-1211 Geneva, Switzerland. [Antonarakis, S. E.] iGE3 Inst Genet & Genom Geneva, CH-1211 Geneva, Switzerland. [Ashley, E. A.] Stanford Univ, Sch Med, Ctr Inherited Cardiovasc Dis, Stanford, CA 94305 USA. [Barrett, J. C.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. [Biesecker, L. G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Conrad, D. F.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Conrad, D. F.] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. [Conrad, D. F.] Washington Univ, Sch Med, Dept Immunol, St Louis, MO 63110 USA. [Cooper, G. M.; Gunter, C.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Cox, N. J.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. [Gerstein, M. B.] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Gerstein, M. B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. [Gerstein, M. B.] Yale Univ, Dept Mol Biophys, New Haven, CT 06520 USA. [Gerstein, M. B.] Yale Univ, Dept Biochem, New Haven, CT 06520 USA. [Goldstein, D. B.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA. [Hirschhorn, J. N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Hirschhorn, J. N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Leal, S. M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Pennacchio, L. A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA. [Pennacchio, L. A.] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA. [Stamatoyannopoulos, J. A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Sunyaev, S. R.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Sunyaev, S. R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Valle, D.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA. [Voight, B. F.] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. [Voight, B. F.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA. RP MacArthur, DG (reprint author), Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. EM macarthur@atgu.mgh.harvard.edu; drchrisgunter@gmail.com RI Antonarakis, Stylianos/N-8866-2014; Dimmock, David/I-7913-2015; OI Antonarakis, Stylianos/0000-0001-8907-5823; Dimmock, David/0000-0001-6690-2523; Gunter, Chris/0000-0001-9369-7537; Barrett, Jeffrey/0000-0002-1152-370X; Shendure, Jay/0000-0002-1516-1865 FU NHGRI NIH HHS [R01 HG007022, U54 HG006997]; NHLBI NIH HHS [R01 HL117626]; NIDDK NIH HHS [P30 DK020595]; NIMH NIH HHS [R01 MH101810] NR 60 TC 324 Z9 329 U1 8 U2 80 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 24 PY 2014 VL 508 IS 7497 BP 469 EP 476 DI 10.1038/nature13127 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF5GI UT WOS:000334741600026 PM 24759409 ER PT J AU Zhang, YE Li, H Zhao, G Sun, AJ Zong, NC Li, ZF Zhu, HM Zou, YZ Yang, XD Ge, JB AF Zhang, Youen Li, Hua Zhao, Gang Sun, Aijun Zong, Nobel C. Li, Zhaofeng Zhu, Hongming Zou, Yunzeng Yang, Xiangdong Ge, Junbo TI Hydrogen Sulfide Attenuates the Recruitment of CD11b(+)Gr-1(+) Myeloid Cells and Regulates Bax/Bcl-2 Signaling in Myocardial Ischemia Injury SO SCIENTIFIC REPORTS LA English DT Article ID CYSTATHIONINE GAMMA-LYASE; REPERFUSION INJURY; SUPPRESSOR-CELLS; HEART-FAILURE; ISCHEMIA/REPERFUSION INJURY; INFLAMMATORY RESPONSE; DENDRITIC CELLS; INFARCTION; MICE; INFILTRATION AB Hydrogen sulfide, an endogenous signaling molecule, plays an important role in the physiology and pathophysiology of the cardiovascular system. Using a mouse model of myocardial infarction, we investigated the anti-inflammatory and anti-apoptotic effects of the H2S donor sodium hydrosulfide (NaHS). The results demonstrated that the administration of NaHS improved survival, preserved left ventricular function, limited infarct size, and improved H2S levels in cardiac tissue to attenuate the recruitment of CD11b(+)Gr-1(+) myeloid cells and to regulate the Bax/Bcl-2 pathway. Furthermore, the cardioprotective effects of NaHS were enhanced by inhibiting the migration of CD11b(+)Gr-1(+) myeloid cells from the spleen into the blood and by attenuating post-infarction inflammation. These observations suggest that the novel mechanism underlying the cardioprotective function of H2S is secondary to a combination of attenuation the recruitment of CD11b(+)Gr-1(+) myeloid cells and regulation of the Bax/Bcl-2 apoptotic signaling. C1 [Zhang, Youen; Li, Hua; Zhao, Gang; Sun, Aijun; Li, Zhaofeng; Zou, Yunzeng; Yang, Xiangdong; Ge, Junbo] Fudan Univ, Zhongshan Hosp, Shanghai Inst Cardiovasc Dis, Shanghai 200032, Peoples R China. [Li, Hua; Zong, Nobel C.; Zhu, Hongming] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Li, Hua; Zong, Nobel C.; Zhu, Hongming] Univ Calif Los Angeles, Sch Med, Dept Med CVRL, Los Angeles, CA 90095 USA. [Sun, Aijun; Zou, Yunzeng; Ge, Junbo] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China. [Zong, Nobel C.] Univ Calif Los Angeles, Sch Med, NHLBI Prote Ctr, NHLBI Prote Program, Los Angeles, CA 90095 USA. RP Yang, XD (reprint author), Fudan Univ, Zhongshan Hosp, Shanghai Inst Cardiovasc Dis, Shanghai 200032, Peoples R China. EM yang.xiangdong@zs-hospital.sh.cn; ge.junbo@zs-hospital.sh.cn FU State Key Development Program for Basic Research of China [2011CB503905]; National Key Technology Support Program [2011BAI11B10]; Major Program of the National Natural Science Foundation of China [81230007]; Shanghai Pujiang Program [12PJ1401700] FX This study was supported by the State Key Development Program for Basic Research of China (No. 2011CB503905), the National Key Technology Support Program (No.2011BAI11B10), the Major Program of the National Natural Science Foundation of China (No.81230007), and the Shanghai Pujiang Program (12PJ1401700). NR 35 TC 7 Z9 8 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD APR 24 PY 2014 VL 4 AR 4774 DI 10.1038/srep04774 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF6RC UT WOS:000334841300007 PM 24758901 ER PT J AU Minakshi, R Padhan, K AF Minakshi, Rinki Padhan, Kartika TI The YXXempty set motif within the severe acute respiratory syndrome coronavirus (SARS-CoV) 3a protein is crucial for its intracellular transport SO VIROLOGY JOURNAL LA English DT Article ID LIPID DROPLETS; ENDOPLASMIC-RETICULUM; TRANSMEMBRANE PROTEINS; STRUCTURAL PROTEIN; PLASMA-MEMBRANE; HONG-KONG; CAVEOLIN; CELLS; EXPORT; IDENTIFICATION AB Background: The SARS coronavirus (SARS-CoV) 3a protein functions as an ion channel, induces apoptosis and is important for viral pathogenesis. It is expressed on the cell surface and contains a tyrosine-based sorting motif and a di-acidic motif, which may be crucial for its intracellular trafficking. However the role of these motifs is not fully understood in the case of 3a protein. Methods: The subcellular distribution of the 3a protein was studied by immunofluorescence staining of cells transfected with wild type and mutant constructs along with markers for different intracellular compartments. Semi-quantitative RT-PCR was performed to estimate the mRNA where as western blotting was carried out to detect protein levels of wild type and mutant 3a proteins. In vitro transcription-translation was performed to estimate cell free protein synthesis. Results: While the wild type 3a protein is efficiently transported to the plasma membrane, the protein with mutations in the tyrosine and valine residues within the YXXV motif (Delta YXXempty set) accumulated in the Golgi compartment. However the 3a protein with mutations within the EXD di-acidic motif (Delta EXD) showed an intracellular distribution similar to the wild type protein. Increased retention of the Delta YXXempty set protein in the Golgi compartment also increased its association with lipid droplets. The Delta YXXempty set protein also expressed at significantly lower levels compared to the wild type 3a protein, which was reversed with Brefeldin A and Aprotinin. Conclusions: The data suggest that the YXXempty set motif of the SARS-CoV 3a protein is necessary for Golgi to plasma membrane transport, in the absence of which the protein is targeted to lysosomal degradation compartment via lipid droplets. C1 [Minakshi, Rinki; Padhan, Kartika] Int Ctr Genet Engn & Biotechnol, New Delhi, India. [Padhan, Kartika] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. RP Padhan, K (reprint author), Int Ctr Genet Engn & Biotechnol, New Delhi, India. EM kartikpadhan@gmail.com FU CSIR (India) FX We thank Dr. Shahid Jameel for generously providing us lab space and reagents to conduct the experiments. We also thank Dr. Manjula Kalia and Charu Tanwar for their help with confocal microscopy. A Senior Research Fellowship to K. P. from CSIR (India) is gratefully acknowledged. NR 44 TC 1 Z9 1 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD APR 24 PY 2014 VL 11 AR 75 DI 10.1186/1743-422X-11-75 PG 10 WC Virology SC Virology GA AG1NJ UT WOS:000335182000001 PM 24762043 ER PT J AU Erdem, AL Jaszczur, M Bertram, JG Woodgate, R Cox, MM Goodman, MF AF Erdem, Aysen L. Jaszczur, Malgorzata Bertram, Jeffrey G. Woodgate, Roger Cox, Michael M. Goodman, Myron F. TI DNA polymerase V activity is autoregulated by a novel intrinsic DNA-dependent ATPase SO ELIFE LA English DT Article ID UMUD MUTAGENESIS PROTEIN; SINGLE-STRANDED-DNA; ESCHERICHIA-COLI; RECA PROTEIN; IN-VITRO; BIOCHEMICAL BASIS; SOS MUTAGENESIS; BINDING PROTEIN; PURIFICATION; CLEAVAGE AB Escherichia coli DNA polymerase V (pol V), a heterotrimeric complex composed of UmuD'C-2, is marginally active. ATP and RecA play essential roles in the activation of pol V for DNA synthesis including translesion synthesis (TLS). We have established three features of the roles of ATP and RecA. 1) RecA-activated DNA polymerase V (pol V Mut), is a DNA-dependent ATPase; 2) bound ATP is required for DNA synthesis; 3) pol V Mut function is regulated by ATP, with ATP required to bind primer/template (p/t) DNA and ATP hydrolysis triggering dissociation from the DNA. Pol V Mut formed with an ATPase-deficient RecA E38K/K72R mutant hydrolyzes ATP rapidly, establishing the DNA-dependent ATPase as an intrinsic property of pol V Mut distinct from the ATP hydrolytic activity of RecA when bound to single-stranded (ss) DNA as a nucleoprotein filament (RecA*). No similar ATPase activity or autoregulatory mechanism has previously been found for a DNA polymerase. C1 [Erdem, Aysen L.; Jaszczur, Malgorzata; Bertram, Jeffrey G.; Goodman, Myron F.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. [Erdem, Aysen L.; Jaszczur, Malgorzata; Bertram, Jeffrey G.; Goodman, Myron F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. [Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. [Cox, Michael M.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. RP Erdem, AL (reprint author), Univ So Calif, Dept Biol Sci, Univ Pk, Los Angeles, CA 90089 USA. FU NIEHS NIH HHS [ES012259, R01 ES012259]; NIGMS NIH HHS [R01 GM032335, GM32335, GM21422] NR 32 TC 7 Z9 7 U1 3 U2 3 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD APR 24 PY 2014 VL 3 AR e02384 DI 10.7554/eLife.02384 PG 29 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AF7VO UT WOS:000334923200008 PM 24843026 ER PT J AU Fritsch, B Reis, J Gasior, M Kaminski, RM Rogawski, MA AF Fritsch, Brita Reis, Janine Gasior, Maciej Kaminski, Rafal M. Rogawski, Michael A. TI Role of GluK1 Kainate Receptors in Seizures, Epileptic Discharges, and Epileptogenesis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ATPA; BLA; epilepsy; kainate receptor; kindling; seizure ID MEDIATED SYNAPTIC-TRANSMISSION; BASOLATERAL AMYGDALA; PHARMACOLOGICAL CHARACTERIZATION; HIPPOCAMPAL INTERNEURONS; ELECTRICAL-STIMULATION; TONIC INHIBITION; GRANULE CELLS; IN-VITRO; GLUR5; EXPRESSION AB Kainate receptors containing the GluK1 subunit have an impact on excitatory and inhibitory neurotransmission in brain regions, such as the amygdala and hippocampus, which are relevant to seizures and epilepsy. Here we used 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a potent and selective agonist of kainate receptors that include the GluK1 subunit, in conjunction with mice deficient in GluK1 and GluK2 kainate receptor subunits to assess the role of GluK1 kainate receptors in provoking seizures and in kindling epileptogenesis. We found that systemic ATPA, acting specifically via GluK1 kainate receptors, causes locomotor arrest and forelimb extension (a unique behavioral characteristic of GluK1 activation) and induces myoclonic behavioral seizures and electrographic seizure discharges in the BLA and hippocampus. In contrast, the proconvulsant activity of systemic AMPA, kainate, and pentylenetetrazol is not mediated by GluK1 kainate receptors, and deletion of these receptors does not elevate the threshold for seizures in the 6 Hz model. ATPA also specifically activates epileptiform discharges in BLA slices in vitro via GluK1 kainate receptors. Olfactory bulb kindling developed similarly in wild-type, GluK1, and GluK2 knock-out mice, demonstrating that GluK1 kainate receptors are not required for epileptogenesis or seizure expression in this model. We conclude that selective activation of kainate receptors containing the GluK1 subunit can trigger seizures, but these receptors are not necessary for seizure generation in models commonly used to identify therapeutic agents for the treatment of epilepsy. C1 [Fritsch, Brita; Reis, Janine; Gasior, Maciej; Kaminski, Rafal M.; Rogawski, Michael A.] NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. [Fritsch, Brita; Reis, Janine] Univ Hosp, Dept Neurol, D-79106 Freiburg, Germany. [Rogawski, Michael A.] Univ Calif Davis, Sch Med, Dept Neurol, Sacramento, CA 95817 USA. [Rogawski, Michael A.] Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA. RP Rogawski, MA (reprint author), Univ Calif Davis, Dept Neurol, 4860 Y St,Suite 3700, Sacramento, CA 95817 USA. EM rogawski@ucdavis.edu RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health [NS072094, NS079292]; NINDS Intramural Research Program FX This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NS072094, NS079292) and by the NINDS Intramural Research Program. B.F. was a fellow of the NINDS Intramural Research Program. We thank Wayne D. Yonekawa and Megan Lyle Desai for assistance with experiments, and David Ide and Danny Trang for technical support. NR 45 TC 6 Z9 6 U1 1 U2 13 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 23 PY 2014 VL 34 IS 17 BP 5765 EP 5775 DI 10.1523/JNEUROSCI.5307-13.2014 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AF7XP UT WOS:000334929100005 PM 24760837 ER PT J AU Pecina, M Martinez-Jauand, M Love, T Heffernan, J Montoya, P Hodgkinson, C Stohler, CS Goldman, D Zubieta, JK AF Pecina, Marta Martinez-Jauand, Mercedes Love, Tiffany Heffernan, Joseph Montoya, Pedro Hodgkinson, Colin Stohler, Christian S. Goldman, David Zubieta, Jon-Kar TI Valence-Specific Effects of BDNF Val(66)Met Polymorphism on Dopaminergic Stress and Reward Processing in Humans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BDNF Val66Met; dopamine; nucleus accumbens; pain; reward; stress ID ACTIVITY-DEPENDENT SECRETION; NEUROTROPHIC FACTOR; IN-VIVO; INDIVIDUAL-DIFFERENCES; PSYCHOLOGICAL STRESS; CONTINUOUS-INFUSION; CORTICAL-NEURONS; MOOD DISORDERS; SOCIAL DEFEAT; WILD-TYPE AB Brain-derived neurotrophic factor (BDNF) levels in dopaminergic (DA) cells within the ventral tegmental area (VTA)/nucleus accumbens (NAc) circuitry appear to be a candidate mechanism for the neuroadaptive changes that follow stress and reward responses in animal models. However, the role of the BDNF gene variants in responses to salient cues through DA neurotransmission in humans remains unexplored. Here, we studied the effect of the common functional BDNF Val(66)Met (rs6265) polymorphism on rewarding experiences in the striatum and DA-mediated responses to stress. Seventy-two healthy controls were genotyped for the BDNF Val(66)Met polymorphism and underwent the monetary incentive delay task during an functional magnetic resonance imaging (fMRI) session. Forty-nine of them also underwent a sustained pain challenge with and without placebo administration with potential analgesic properties during PET measures of DA D-2/3-receptor-mediated neurotransmission. Neuroimaging results revealed a significant effect of BDNF (Met(66) carriers > Val/Val) on brain responses during the anticipation of monetary losses, baseline D-2/3 receptor availability, and pain-stress-induced DA release in the NAc. Conversely, BDNF Met(66) carriers showed no activation in response to monetary gains and a blunted DA response to the analgesic placebo in the NAc. These results provide initial human evidence regarding the effect of the BDNF Val(66)Met polymorphism on DA-mediated responses to stress, its cognitive regulation by positive expectations, and the anticipatory responses to monetary gains and losses in the VTA-NAc pathway. Our results are of relevance to the neurobiology of stress and reward interactions and the pathophysiology of stress-related disorders. C1 [Pecina, Marta; Love, Tiffany; Zubieta, Jon-Kar] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Pecina, Marta; Love, Tiffany; Heffernan, Joseph; Zubieta, Jon-Kar] Univ Michigan, Mol & Behav Neurosci Inst, Dept Radiol, Ann Arbor, MI 48109 USA. [Martinez-Jauand, Mercedes; Montoya, Pedro] Inst Univ Invest Ciencies Salut IUNICS, Res Inst Hlth Sci, Palma de Mallorca 07122, Spain. [Stohler, Christian S.] Columbia Univ, Coll Dent Med, New York, NY 10032 USA. [Hodgkinson, Colin; Goldman, David] NIAAA, Rockville, MD 20852 USA. RP Zubieta, JK (reprint author), Univ Michigan, Mol & Behav Neurosci Inst, 205 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM Zubieta@umich.edu RI Goldman, David/F-9772-2010; Montoya, Pedro/A-4666-2009; OI Goldman, David/0000-0002-1724-5405; Montoya, Pedro/0000-0001-8652-948X; Love, Tiffany/0000-0001-9299-3190 FU National Institutes of Health-National Institute of Drug Abuse [R01 DA 022520, R01 DA 027494]; Phil F. Jenkins Foundation; Spanish Ministry of Education [AP2008-03742]; Spanish Ministry of Science and Innovation and European (Regional Development Fund) [PSI2010-19372] FX This work was supported by The National Institutes of Health-National Institute of Drug Abuse (Grants R01 DA 022520 and R01 DA 027494 to J.K.Z.), the Phil F. Jenkins Foundation, the Spanish Ministry of Education (Grant AP2008-03742 to M.M.-J.), and the Spanish Ministry of Science and Innovation and European (Regional Development Fund Grant PSI2010-19372 to P. M.). We thank the technologists of the PET Center and the fMRI laboratory at the University of Michigan. NR 69 TC 26 Z9 26 U1 2 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 23 PY 2014 VL 34 IS 17 BP 5874 EP 5881 DI 10.1523/JNEUROSCI.2152-13.2014 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AF7XP UT WOS:000334929100015 PM 24760847 ER PT J AU Yu, T Calvo, L Anta, B Lopez-Benito, S Lopez-Bellido, R Vicente-Garcia, C Tessarollo, L Rodriguez, RE Arevalo, JC AF Yu, Tao Calvo, Laura Anta, Begona Lopez-Benito, Saray Lopez-Bellido, Roger Vicente-Garcia, Cristina Tessarollo, Lino Rodriguez, Raquel E. Arevalo, Juan C. TI In Vivo Regulation of NGF-Mediated Functions by Nedd4-2 Ubiquitination of TrkA SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neurotrophins; pain; TrkA neurotrophin receptor; ubiquitination ID NERVE GROWTH-FACTOR; ADULT SENSORY NEURONS; CONGENITAL INSENSITIVITY; NEUROTROPHIN RECEPTORS; TYROSINE KINASE; PAIN; PROTOONCOGENE; ANHIDROSIS; MUTATIONS; PROTEIN AB Trk neurotrophin receptor ubiquitination in response to ligand activation regulates signaling, trafficking, and degradation of the receptors. However, the in vivo consequences of Trk ubiquitination remain to be addressed. We have developed a mouse model with a mutation in the TrkA neurotrophin receptor (P782S) that results in reduced ubiquitination due to a lack of binding to the E3 ubiquitin ligase, Nedd4-2. In vivo analyses of TrkAP782S indicate that defective ubiquitination of the TrkA mutant results in an altered trafficking and degradation of the receptor that affects the survival of sensory neurons. The dorsal root ganglia from the TrkAP782S knock-in mice display an increased number of neurons expressing CGRP and substance P. Moreover, the mutant mice show enhanced sensitivity to thermal and inflammatory pain. Our results indicate that the ubiquitination of the TrkA neurotrophin receptor plays a critical role in NGF-mediated functions, such as neuronal survival and sensitivity to pain. C1 [Yu, Tao; Calvo, Laura; Anta, Begona; Lopez-Benito, Saray; Vicente-Garcia, Cristina; Arevalo, Juan C.] Univ Salamanca, Inst Neurociencias Castilla & Leon INCyL, Dept Cell Biol & Pathol, Salamanca 37007, Spain. [Lopez-Bellido, Roger; Rodriguez, Raquel E.] Univ Salamanca, Inst Neurociencias Castilla & Leon INCyL, Dept Biochem & Mol Biol, Salamanca 37007, Spain. [Tessarollo, Lino] NCI, Neural Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Yu, Tao; Calvo, Laura; Anta, Begona; Lopez-Benito, Saray; Lopez-Bellido, Roger; Vicente-Garcia, Cristina; Rodriguez, Raquel E.; Arevalo, Juan C.] Inst Biomed Res Salamanca, Salamanca 37007, Spain. RP Arevalo, JC (reprint author), Univ Salamanca, INCyL, C Pintor Fernando Gallego 1, Salamanca 37007, Spain. EM arevalojc@usal.es RI ArAvalo, Juan Carlos/J-8154-2014; OI ArAvalo, Juan Carlos/0000-0003-1994-3095; Rodriguez Rodriguez, Raquel/0000-0003-1805-3066 FU Ministerio de Ciencia e Innovacion [BFU2008-00162]; Ministerio de Economia y Competitividad [BFU2011-22898]; Marie Curie International Reintegration Grant within the VII European Community Framework Programme by Conserjeria de Educacion [SA074A08]; Conserjeria de Sanidad de Junta Castilla y Leon; Intramural Research Program of the NCI, Center for Cancer Research, NIH; NARSAD FX This work was supported by Ministerio de Ciencia e Innovacion Grant BFU2008-00162, by Ministerio de Economia y Competitividad (BFU2011-22898), by a Marie Curie International Reintegration Grant within the VII European Community Framework Programme by Conserjeria de Educacion (SA074A08), and Conserjeria de Sanidad de Junta Castilla y Leon (J.C.A.). J.C.A. was a "Ramon y Cajal" Investigator from the University of Salamanca and NARSAD 2009 Young Investigator Awardee. L.T. was supported by the Intramural Research Program of the NCI, Center for Cancer Research, NIH. We thank Dionisio Martin-Zanca, Louis Reichardt, and Moses Chao for the anti-203 Trk, RTA, and p75 antibodies, respectively; Moses Chao and Francis Lee for critical review of the paper and helpful discussions; Lino Tessarollo for sharing unpublished results; and Synphen Wu and Nicholas Skinner for corrections to the paper. NR 37 TC 12 Z9 12 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 23 PY 2014 VL 34 IS 17 BP 6098 EP 6106 DI 10.1523/JNEUROSCI.4271-13.2014 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AF7XP UT WOS:000334929100037 PM 24760869 ER PT J AU Mire, CE Geisbert, JB Agans, KN Satterfield, BA Versteeg, KM Fritz, EA Feldmann, H Hensley, LE Geisbert, TW AF Mire, Chad E. Geisbert, Joan B. Agans, Krystle N. Satterfield, Benjamin A. Versteeg, Krista M. Fritz, Elizabeth A. Feldmann, Heinz Hensley, Lisa E. Geisbert, Thomas W. TI Durability of a Vesicular Stomatitis Virus-Based Marburg Virus Vaccine in Nonhuman Primates SO PLOS ONE LA English DT Article ID ATTENUATED RECOMBINANT VACCINE; EBOLA-VIRUS; HEMORRHAGIC-FEVER; IMMUNE-RESPONSES; IMMUNIZATION; PROTECTION; CHALLENGE; VECTORS; LIVE; GLYCOPROTEINS AB The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines. C1 [Mire, Chad E.; Geisbert, Joan B.; Agans, Krystle N.; Satterfield, Benjamin A.; Versteeg, Krista M.; Fritz, Elizabeth A.; Geisbert, Thomas W.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Mire, Chad E.; Geisbert, Joan B.; Agans, Krystle N.; Satterfield, Benjamin A.; Versteeg, Krista M.; Fritz, Elizabeth A.; Geisbert, Thomas W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA. [Hensley, Lisa E.] NIAID, Integrated Res Facil Ft Detrick, Div Clin Res, NIH, Frederick, MD USA. RP Geisbert, TW (reprint author), Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. EM twgeisbe@utmb.edu OI Satterfield, Benjamin/0000-0002-7798-0938 FU US Army Medical Research Acquisition Activity [WX81XWH-10-2-0050]; Department of Health and Human Services, NIH [AI098817] FX This work was supported by an award from the US Army Medical Research Acquisition Activity to TG (award number WX81XWH-10-2-0050). Some non-animal portions of the work were also supported by the Department of Health and Human Services, NIH, grant AI098817 to Dr. John Eldridge and TWG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 19 Z9 21 U1 1 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 23 PY 2014 VL 9 IS 4 AR e94355 DI 10.1371/journal.pone.0094355 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG3EI UT WOS:000335298200015 PM 24759889 ER PT J AU Wall, M McDermott, MP Kieburtz, KD Corbett, JJ Feldon, SE Friedman, DI Katz, DM Keltner, JL Schron, EB Kupersmith, MJ AF Wall, Michael McDermott, Michael P. Kieburtz, Karl D. Corbett, James J. Feldon, Steven E. Friedman, Deborah I. Katz, David M. Keltner, John L. Schron, Eleanor B. Kupersmith, Mark J. CA NORDIC Idiopathic Intracranial TI Effect of Acetazolamide on Visual Function in Patients With Idiopathic Intracranial Hypertension and Mild Visual Loss The Idiopathic Intracranial Hypertension Treatment Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PSEUDOTUMOR CEREBRI; PRESSURE; VALIDATION; DIAGNOSIS; SHUNT AB IMPORTANCE Acetazolamide is commonly used to treat idiopathic intracranial hypertension (IIH), but there is insufficient information to establish an evidence base for its use. OBJECTIVE To determine whether acetazolamide is beneficial in improving vision when added to a low-sodium weight reduction diet in patients with IIH and mild visual loss. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-masked, placebo-controlled study of acetazolamide in 165 participants with IIH and mild visual loss who received a low-sodium weight-reduction diet. Participants were enrolled at 38 academic and private practice sites in North America from March 2010 to November 2012 and followed up for 6 months (last visit in June 2013). All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation (PMD) between -2 dB and -7 dB. The mean age was 29 years and all but 4 participants were women. INTERVENTIONS Low-sodium weight-reduction diet plus the maximally tolerated dosage of acetazolamide (up to 4 g/d) or matching placebo for 6 months. MAIN OUTCOMES AND MEASURES The planned primary outcome variable was the change in PMD from baseline to month 6 in the most affected eye, as measured by Humphrey Field Analyzer. Perimetric mean deviation is a measure of global visual field loss (mean deviation from age-corrected normal values), with a range of 2 to -32 dB; larger negative values indicate greater vision loss. Secondary outcome variables included changes in papilledema grade, quality of life (Visual Function Questionnaire 25 [VFQ-25] and 36-Item Short Form Health Survey), headache disability, and weight at month 6. RESULTS The mean improvement in PMD was greater with acetazolamide (1.43 dB, from -3.53 dB at baseline to -2.10dB at month 6; n = 86) than with placebo (0.71 dB, from -3.53 dB to -2.82 dB; n = 79); the difference was 0.71 dB (95% CI, 0to 1.43 dB; P = .050). Mean improvements in papilledema grade (acetazolamide: -1.31, from 2.76 to 1.45; placebo: -0.61, from 2.76 to 2.15; treatment effect, -0.70; 95% CI, -0.99 to -0.41; P < .001) and vision-related quality of life as measured by the National Eye Institute VFQ-25 (acetazolamide: 8.33, from 82.97 to 91.30; placebo: 1.98, from 82.97 to 84.95; treatment effect, 6.35; 95% CI, 2.22 to 10.47; P = .003) and its 10-item neuro-ophthalmic supplement (acetazolamide: 9.82, from 75.45 to 85.27; placebo: 1.59, from 75.45 to 77.04; treatment effect, 8.23; 95% CI, 3.89 to 12.56; P < .001) were also observed with acetazolamide. Participants assigned to acetazolamide also experienced a reduction in weight (acetazolamide: -7.50 kg, from 107.72 kg to 100.22 kg; placebo: -3.45 kg, from 107.72 kg to 104.27 kg; treatment effect, -4.05 kg, 95% CI, -6.27 to -1.83 kg; P < .001). CONCLUSIONS AND RELEVANCE In patients with IIH and mild visual loss, the use of acetazolamide with a low-sodium weight-reduction diet compared with diet alone resulted in modest improvement in visual field function. The clinical importance of this improvement remains to be determined. C1 [Wall, Michael] Univ Iowa, Iowa City, IA USA. [McDermott, Michael P.; Kieburtz, Karl D.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Corbett, James J.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Feldon, Steven E.] Univ Rochester, Inst Eye, Rochester, NY USA. [Friedman, Deborah I.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Katz, David M.] Bethesda Neurol LLC, Bethesda, MD USA. [Keltner, John L.] Univ Calif Davis, Med Ctr, Davis, CA USA. [Schron, Eleanor B.] NEI, Bethesda, MD 20892 USA. [Kupersmith, Mark J.] St Lukes Roosevelt Hosp, New York, NY 10025 USA. RP Wall, M (reprint author), Univ Iowa Hosp & Clin, Dept Neurol, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM michael-wall@uiowa.edu OI Bruce, Beau/0000-0003-3003-2962; Subramanian, Prem/0000-0001-5824-8322 FU National Eye Institute (NEI) [1U10EY017281-01A1, 1U10EY017387-01A1, 3U10EY017281-01A1S1, 1U10EY017387-01A1S1] FX This work was supported by National Eye Institute (NEI) grants 1U10EY017281-01A1, DCBC 1U10EY017387-01A1, ARRA for NORDIC 3U10EY017281-01A1S1, and DCBC 1U10EY017387-01A1S1, and supplements for NORDIC 3U10EY017281-01A1S2. NR 25 TC 60 Z9 61 U1 0 U2 12 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 23 PY 2014 VL 311 IS 16 BP 1641 EP 1651 DI 10.1001/jama.2014.3312 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AF4OU UT WOS:000334693900024 ER PT J AU Bachran, C Gupta, PK Bachran, S Leysath, CE Hoover, B Fattah, RJ Leppla, SH AF Bachran, Christopher Gupta, Pradeep K. Bachran, Silke Leysath, Clinton E. Hoover, Benjamin Fattah, Rasem J. Leppla, Stephen H. TI Reductive Methylation and Mutation of an Anthrax Toxin Fusion Protein Modulates its Stability and Cytotoxicity SO SCIENTIFIC REPORTS LA English DT Article ID LETHAL FACTOR; DIPHTHERIA-TOXIN; PROTECTIVE ANTIGEN; LYSINE RESIDUES; TRANSLOCATION; TUMOR; IMMUNOTOXIN; POTENCY; DOMAINS; BINDING AB We characterized an anti-cancer fusion protein consisting of anthrax lethal factor (LF) and the catalytic domain of Pseudomonas exotoxin A by (i) mutating the N-terminal amino acids and by (ii) reductive methylation to dimethylate all lysines. Dimethylation of lysines was achieved quantitatively and specifically without affecting binding of the fusion protein to PA or decreasing the enzymatic activity of the catalytic moiety. Ubiquitination in vitro was drastically decreased for both the N-terminally mutated and dimethylated variants, and both appeared to be slightly more stable in the cytosol of treated cells. The dimethylated variant showed greatly reduced neutralization by antibodies to LF. The two described modifications offer unique advantages such as increased cytotoxic activity and diminished antibody recognition, and thus may be applicable to other therapeutic proteins that act in the cytosol of cells. C1 [Bachran, Christopher; Gupta, Pradeep K.; Bachran, Silke; Leysath, Clinton E.; Hoover, Benjamin; Fattah, Rasem J.; Leppla, Stephen H.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov FU Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA FX This research was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA. The authors thank J. Eric Anderson for mass spectrometric analysis of the proteins described here. NR 34 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 2045-2322 J9 SCI REP-UK JI Sci Rep PD APR 23 PY 2014 VL 4 AR 4754 DI 10.1038/srep04754 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF6PH UT WOS:000334836500001 PM 24755540 ER PT J AU Hackett, TA de la Mothe, LA Camalier, CR Falchier, A Lakatos, P Kajikawa, Y Schroeder, CE AF Hackett, Troy A. de la Mothe, Lisa A. Camalier, Corrie R. Falchier, Arnaud Lakatos, Peter Kajikawa, Yoshinao Schroeder, Charles E. TI Feedforward and feedback projections of caudal belt and parabelt areas of auditory cortex: refining the hierarchical model SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE connections; brain; monkey; functional organization; laminar; architecture; anatomy; laminar ID SUPERIOR TEMPORAL SULCUS; CORTICO-CORTICAL CONNECTIONS; OLD-WORLD MONKEYS; RHESUS-MONKEY; MACAQUE MONKEY; MULTISENSORY CONVERGENCE; ASSOCIATION CORTEX; PREFRONTAL CORTEX; MARMOSET MONKEYS; VISUAL AREAS AB Our working model of the primate auditory cortex recognizes three major regions (core, belt, parabelt), subdivided into thirteen areas. The connections between areas are topographically ordered in a manner consistent with information flow along two major anatomical axes: core-belt-parabelt and caudal-rostral. Remarkably, most of the connections supporting this model were revealed using retrograde tracing techniques. Little is known about laminar circuitry, as anterograde tracing of axon terminations has rarely been used. The purpose of the present study was to examine the laminar projections of three areas of auditory cortex, pursuant to analysis of all areas. The selected areas were: middle lateral belt (MU; caudomedial belt (CM); and caudal parabelt (CPB). Injections of anterograde tracers yielded data consistent with major features of our model, and also new findings that compel modifications. Results supporting the model were: (1) feedforward projection from ML and CM terminated in CPB; (2) feedforward projections from ML and CPB terminated in rostral areas of the belt and parabelt; and (3) feedback projections typified inputs to the core region from belt and parabelt. At odds with the model was the convergence of feedforward inputs into rostral medial belt from ML and CPB. This was unexpected since CPB is at a higher stage of the processing hierarchy, with mainly feedback projections to all other belt areas. Lastly, extending the model, feedforward projections from CM, ML, and CPB overlapped in the temporal parietal occipital area (TPO) in the superior temporal sulcus, indicating significant auditory influence on sensory processing in this region. The combined results refine our working model and highlight the need to complete studies of the laminar inputs to all areas of auditory cortex. Their documentation is essential for developing informed hypotheses about the neurophysiological influences of inputs to each layer and area. C1 [Hackett, Troy A.; Camalier, Corrie R.] Vanderbilt Univ, Sch Med, Dept Hearing & Speech Sci, Nashville, TN 37232 USA. [de la Mothe, Lisa A.] Tennessee State Univ, Dept Psychol, Nashville, TN 37203 USA. [Camalier, Corrie R.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. [Falchier, Arnaud; Lakatos, Peter; Kajikawa, Yoshinao; Schroeder, Charles E.] Nathan S Kline Inst Psychiat Res, Cognit Neurosci & Schizophrenia Program, Orangeburg, NY 10962 USA. [Falchier, Arnaud; Lakatos, Peter; Kajikawa, Yoshinao; Schroeder, Charles E.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Hackett, TA (reprint author), Vanderbilt Univ, Sch Med, Dept Hearing & Speech Sci, 465 21st Ave South MRB-3 Suite 7110, Nashville, TN 37232 USA. EM troy.a.hackett@vanderbilt.edu FU NIH [R01DC04318, R01DC011490]; [R21DC012918] FX The authors gratefully acknowledge the support of NIH grants R01DC04318 to Troy A. Hackett, R01DC011490 to Charles E. Schroeder, and R21DC012918 to Yoshinao Kajikawa. NR 91 TC 9 Z9 9 U1 2 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD APR 22 PY 2014 VL 8 AR UNSP 72 DI 10.3389/fnins.2014.00072 PG 21 WC Neurosciences SC Neurosciences & Neurology GA AW7UD UT WOS:000346468800001 PM 24795550 ER PT J AU Adomas, AB Grimm, SA Malone, C Takaku, M Sims, JK Wade, PA AF Adomas, Aleksandra B. Grimm, Sara A. Malone, Christine Takaku, Motoki Sims, Jennifer K. Wade, Paul A. TI Breast tumor specific mutation in GATA3 affects physiological mechanisms regulating transcription factor turnover SO BMC CANCER LA English DT Article DE Breast cancer; ChIP-seq; GATA3; Mutation; Transcription factor ID ESTROGEN-RECEPTOR; GENE-EXPRESSION; CANCER METASTASIS; ALPHA EXPRESSION; MAMMARY-GLAND; HDR SYNDROME; ER-ALPHA; DIFFERENTIATION; BINDING; GENOME AB Background: The transcription factor GATA3 is a favorable prognostic indicator in estrogen receptor-a (ERa)-positive breast tumors in which it participates with ERa and FOXA1 in a complex transcriptional regulatory program driving tumor growth. GATA3 mutations are frequent in breast cancer and have been classified as driver mutations. To elucidate the contribution(s) of GATA3 alterations to cancer, we studied two breast cancer cell lines, MCF7, which carries a heterozygous frameshift mutation in the second zinc finger of GATA3, and T47D, wild-type at this locus. Methods: Immunofluorescence staining and subcellular fractionation were employed to verify cellular localization of GATA3 in T47D and MCF7 cells. To test protein stability, cells were treated with translation inhibitor, cycloheximide or proteasome inhibitor, MG132, and GATA3 abundance was measured over time using immunoblot. GATA3 turn-over in response to hormone was determined by treating the cells with estradiol or ERa agonist, ICI 182,780. DNA binding ability of recombinant GATA3 was evaluated using electrophoretic mobility shift assay and heparin chromatography. Genomic location of GATA3 in MCF7 and T47D cells was assessed by chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq). Results: GATA3 localized in the nucleus in T47D and MCF7 cells, regardless of the mutation status. The truncated protein in MCF7 had impaired interaction with chromatin and was easily released from the nucleus. Recombinant mutant GATA3 was able to bind DNA to a lesser degree than the wild-type protein. Heterozygosity for the truncating mutation conferred protection from regulated turnover of GATA3, ERa and FOXA1 following estrogen stimulation in MCF7 cells. Thus, mutant GATA3 uncoupled protein-level regulation of master regulatory transcription factors from hormone action. Consistent with increased protein stability, ChIP-seq profiling identified greater genome-wide accumulation of GATA3 in MCF7 cells bearing the mutation, albeit with a similar distribution across the genome, comparing to T47D cells. Conclusions: We propose that this specific, cancer-derived mutation in GATA3 deregulates physiologic protein turnover, stabilizes GATA3 binding across the genome and modulates the response of breast cancer cells to estrogen signaling. C1 [Adomas, Aleksandra B.; Malone, Christine; Takaku, Motoki; Sims, Jennifer K.; Wade, Paul A.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Grimm, Sara A.] NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. RP Wade, PA (reprint author), NIEHS, Mol Carcinogenesis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM wadep2@niehs.nih.gov FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 41 TC 12 Z9 12 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD APR 22 PY 2014 VL 14 AR 278 DI 10.1186/1471-2407-14-278 PG 14 WC Oncology SC Oncology GA AG2QD UT WOS:000335260300004 PM 24758297 ER PT J AU Makarev, E Gorivodsky, M AF Makarev, Evgeny Gorivodsky, Marat TI Islet1 and Its Co-Factor Ldb1 Are Expressed in Quiescent Cells of Mouse Intestinal Epithelium SO PLOS ONE LA English DT Article ID LIM-HOMEODOMAIN PROTEINS; STEM-CELL; PROGENITOR CELLS; HOMEOBOX GENES; DIFFERENTIATION; LGR5; MARKERS; ISL1; IDENTIFICATION; REQUIREMENT AB Islet1 belongs to Lim homeobox (Lhx) gene family which encodes transcription factors that have been conserved in evolution. They form complexes with other transcriptional regulators, among them obligatory co-factors encoded by Ldb genes. Isl1 (Islet1), Lhx and Ldb1 genes play a crucial role in organ patterning, cell fate determination and cell differentiation in both embryonic and adult tissues. In this study we analyzed expression pattern of Isl1 and its co-factor Ldb1 in small intestine. We also studied the biological role of Ldb1 in gut endoderm. Quantitative PCR analysis revealed a relatively high level of expression of Lhx1, Isl1, Isl2, Lmx1a, Ldb1 and Ldb2 mRNAs in the gut tissue as compared to the level of less abundant detectable Lmx1b mRNA. Immunohistochemical studies demonstrated a unique pattern of Ldb1 and Islet1 proteins in the crypt compartment. Ldb1 is produced at a low level in majority of crypt cells; but, its abundant expression was demonstrated for some single cells. Islet1 is also expressed in single cells of the crypt. Double staining experiments with Ldb1 and Isl1 antibodies showed that both genes are co-expressed in certain cells of the crypt. Further analysis revealed the Ldb1-expressing cells in the gut are both of endodermal and mesodermal origin. Proliferation studies using antibodies to phospho-histone H3 and Ki-67 antigens, as well as long-term BrdU labeling, showed that cells prominently expressing Ldb1/Islet1 are quiescent but do not belong to any known terminally differentiated cell lineages. They may represent a group of stem-like cells in the crypt. Further experiments by cell lineage tracing should be performed to better characterize this cell population. Functional studies of mice with Ldb1 gene ablated in gut endoderm revealed no specific role of Ldb1 in that tissue. C1 [Makarev, Evgeny; Gorivodsky, Marat] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mammalian Mol Genet, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. RP Gorivodsky, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mammalian Mol Genet, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. EM lvmarat@yahoo.com FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 2 Z9 2 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 22 PY 2014 VL 9 IS 4 AR e95256 DI 10.1371/journal.pone.0095256 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2IS UT WOS:000335240300034 PM 24755910 ER PT J AU Le Pichon, CE Chesler, AT AF Le Pichon, Claire E. Chesler, Alexander T. TI The functional and anatomical dissection of somatosensory subpopulations using mouse genetics SO FRONTIERS IN NEUROANATOMY LA English DT Review DE somatosensation; pain; nociception; TRP channel; touch; thermodetection; itch; sensory neuron ID NOCICEPTIVE SENSORY NEURONS; LONG-TERM DEPRESSION; CAPSAICIN RECEPTOR; VESICULAR GLUTAMATE; MOLECULAR-MECHANISMS; BEHAVIORAL-RESPONSES; TRANSGENIC MICE; ITCH SENSATION; CUTANEOUS WARM; COLD SENSATION AB The word somatosensation comes from joining the Greek word for body (soma) with a word for perception (sensation). Somatosensory neurons comprise the largest sensory system in mammals and have nerve endings coursing throughout the skin, viscera, muscle, and bone. Their cell bodies reside in a chain of ganglia adjacent to the dorsal spinal cord (the dorsal root ganglia) and at the base of the skull (the trigeminal ganglia). While the neuronal cell bodies are intermingled within the ganglia, the somatosensory system is in reality composed of numerous sub-systems, each specialized to detect distinct stimuli, such as temperature and touch. Historically, somatosensory neurons have been classified using a diverse host of anatomical and physiological parameters, such as the size of the cell body, degree of myelination, histological labeling with markers, specialization of the nerve endings, projection patterns in the spinal cord and brainstem, receptive tuning, and conduction velocity of their action potentials. While useful, the picture that emerged was one of heterogeneity, with many markers at least partially overlapping. More recently, by capitalizing on advances in molecular techniques, researchers have identified specific ion channels and sensory receptors expressed in subsets of sensory neurons. These studies have proved invaluable as they allow genetic access to small subsets of neurons for further molecular dissection. Data being generated from transgenic mice favor a model whereby an array of dedicated neurons is responsible for selectively encoding different modalities. Here we review the current knowledge of the different sensory neuron subtypes in the mouse, the markers used to study them, and the neurogenetic strategies used to define their anatomical projections and functional roles. C1 [Le Pichon, Claire E.] NINDS, NIH, Bethesda, MD 20892 USA. [Chesler, Alexander T.] NIH, Intramural Pain Program, Sect Sensory Cells & Circuits, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Chesler, AT (reprint author), NIH, Intramural Pain Program, Sect Sensory Cells & Circuits, Natl Ctr Complementary & Alternat Med, Bldg 35A,1E450,35 Convent Dr, Bethesda, MD 20892 USA. EM alexander.chesler@nih.gov FU NIH Intramural program for Pain in NCCAM; NIH/NINDS FX We would like to thank Catherine Bushnell (NIH/NCCAM), Mark Pitcher (NIH/NCCAM), Mark Hoon (NIH/NIDCR), Alexander Jackson (University of Connecticut), and Anna-Lisa Lucido (The Jackson Laboratory) for their helpful comments on our manuscript. We are particular grateful to Mark Hoon (NIH/NIDCR), Danial Cavanaugh (University of Pennsylvania), Allan Basbaum (UCSF), and Gregory Scherrer (Stanford University) for generously sharing their data and providing images. This work was funded by the NIH Intramural program for Pain in NCCAM as well as NIH/NINDS. NR 92 TC 23 Z9 23 U1 1 U2 18 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5129 J9 FRONT NEUROANAT JI Front. Neuroanat. PD APR 22 PY 2014 VL 8 AR 21 DI 10.3389/fnana.2014.00021 PG 18 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA AF8VQ UT WOS:000334994100001 PM 24795573 ER PT J AU Li, X Marchant, NJ Shaham, Y AF Li, Xuan Marchant, Nathan J. Shaham, Yavin TI Opposing roles of cotransmission of dynorphin and hypocretin on reward and motivation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID OREXIN; NEURONS; NEUROPEPTIDES; RECEPTORS; PEPTIDES; BEHAVIOR; SYSTEMS; STRESS C1 [Li, Xuan; Marchant, Nathan J.; Shaham, Yavin] Natl Inst Drug Abuse, Behav Neurosci Res Branch, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. RP Li, X (reprint author), Natl Inst Drug Abuse, Behav Neurosci Res Branch, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. EM anna.li@nih.gov; yshaham@intra.nida.nih.gov RI shaham, yavin/G-1306-2014; OI Marchant, Nathan/0000-0001-8269-0532 FU Intramural NIH HHS NR 17 TC 5 Z9 5 U1 0 U2 1 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 22 PY 2014 VL 111 IS 16 BP 5765 EP 5766 DI 10.1073/pnas.1403603111 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF4OV UT WOS:000334694000022 PM 24706899 ER PT J AU Alberts, B Kirschner, MW Tilghman, S Varmus, H AF Alberts, Bruce Kirschner, Marc W. Tilghman, Shirley Varmus, Harold TI Rescuing US biomedical research from its systemic flaws SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE graduate education; postdoctoral education; federal funding; peer review AB The long-held but erroneous assumption of never-ending rapid growth in biomedical science has created an unsustainable hypercompetitive system that is discouraging even the most outstanding prospective students from entering our profession-and making it difficult for seasoned investigators to produce their best work. This is a recipe for long-term decline, and the problems cannot be solved with simplistic approaches. Instead, it is time to confront the dangers at hand and rethink some fundamental features of the US biomedical research ecosystem. C1 [Alberts, Bruce] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA. [Kirschner, Marc W.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Tilghman, Shirley] Princeton Univ, Dept Mol Biol, Princeton, NJ 08540 USA. [Varmus, Harold] NCI, Bethesda, MD 20892 USA. RP Tilghman, S (reprint author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08540 USA. EM smt@princeton.edu NR 20 TC 163 Z9 164 U1 4 U2 49 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 22 PY 2014 VL 111 IS 16 BP 5773 EP 5777 DI 10.1073/pnas.1404402111 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF4OV UT WOS:000334694000025 PM 24733905 ER PT J AU Yu, WS Briones, V Lister, R McIntosh, C Han, YX Lee, EY Ren, JK Terashima, M Leighty, RM Ecker, JR Muegge, K AF Yu, Weishi Briones, Victorino Lister, Ryan McIntosh, Carl Han, Yixing Lee, Eunice Y. Ren, Jianke Terashima, Minoru Leighty, Robert M. Ecker, Joseph R. Muegge, Kathrin TI CG hypomethylation in Lsh(-/-) mouse embryonic fibroblasts is associated with de novo H3K4me1 formation and altered cellular plasticity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA METHYLATION; STEM-CELLS; HISTONE METHYLTRANSFERASE; CYTOSINE METHYLATION; TRANSCRIPTION FACTOR; CPG METHYLATION; FAMILY-MEMBER; BINDING-SITE; GENE; LSH AB DNA methylation patterns are established in early embryogenesis and are critical for cellular differentiation. To investigate the role of CG methylation in potential enhancer formation, we assessed H3K4me1 modification in murine embryonic fibroblasts (MEFs) derived from the DNA methylation mutant Lsh(-/-) mice. We report here de novo formation of putative enhancer elements at CG hypomethylated sites that can be dynamically altered. We found a subset of differentially enriched H3K4me1 regions clustered at neuronal lineage genes and overlapping with known cis-regulatory elements present in brain tissue. Reprogramming of Lsh(-/-) MEFs into induced pluripotent stem (iPS) cells leads to increased neuronal lineage gene expression of premarked genes and enhanced differentiation potential of Lsh(-/-) iPS cells toward the neuronal lineage pathway compared with WT iPS cells in vitro and in vivo. The state of CG hypomethylation and H3K4me1 enrichment is partially maintained in Lsh(-/-) iPS cells. The acquisition of H3K27ac and activity of sub-cloned fragments in an enhancer reporter assay indicate functional activity of several of de novo H3K4me1-marked sequences. Our results suggest a functional link of H3K4me1 enrichment at CG hypomethylated sites, enhancer formation, and cellular plasticity. C1 [Yu, Weishi; Briones, Victorino; Han, Yixing; Lee, Eunice Y.; Ren, Jianke; Terashima, Minoru; Muegge, Kathrin] NCI, Mouse Canc & Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Lister, Ryan; Ecker, Joseph R.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA. [Lister, Ryan; Ecker, Joseph R.] Salk Inst Biol Studies, Genome Anal Lab, La Jolla, CA 92037 USA. [McIntosh, Carl] NCI, Basic Sci Program, Ctr Canc Res Genet Core, Frederick, MD 21702 USA. [Leighty, Robert M.] NCI, Data Management Serv Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Muegge, Kathrin] Frederick Natl Lab, Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21702 USA. RP Muegge, K (reprint author), NCI, Mouse Canc & Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. EM Kathrin.Muegge@nih.gov RI Lister, Ryan/B-5168-2012; Ecker, Joseph/B-9144-2008 OI Lister, Ryan/0000-0001-6637-7239; Ecker, Joseph/0000-0001-5799-5895 FU National Cancer Institute, National Institutes of Health [HHSN26120080001E]; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank Dr. Lino Tessarolo and Dr. Michael Bustin for helpful suggestions on the manuscript. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health (Contract HHSN26120080001E). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 40 TC 7 Z9 7 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 22 PY 2014 VL 111 IS 16 BP 5890 EP 5895 DI 10.1073/pnas.1320945111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF4OV UT WOS:000334694000045 PM 24711395 ER PT J AU Park, JS Rhau, B Hermann, A McNally, KA Zhou, C Gong, D Weiner, OD Conklin, BR Onuffer, J Lim, WA AF Park, Jason S. Rhau, Benjamin Hermann, Aynur McNally, Krista A. Zhou, Carmen Gong, Delquin Weiner, Orion D. Conklin, Bruce R. Onuffer, James Lim, Wendell A. TI Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GPCR; cellular therapeutics; synthetic biology ID TUMOR-INFILTRATING LYMPHOCYTES; RECEIVING ADOPTIVE IMMUNOTHERAPY; NEURAL STEM-CELLS; T-CELLS; COLORECTAL-CANCER; CLINICAL-APPLICATIONS; METASTATIC MELANOMA; EXPRESSION; MIGRATION; RECEPTOR AB Directed migration of diverse cell types plays a critical role in biological processes ranging from development and morphogenesis to immune response, wound healing, and regeneration. However, techniques to direct, manipulate, and study cell migration in vitro and in vivo in a specific and facile manner are currently limited. We conceived of a strategy to achieve direct control over cell migration to arbitrary user-defined locations, independent of native chemotaxis receptors. Here, we show that genetic modification of cells with an engineered G protein-coupled receptor allows us to redirect their migration to a bioinert drug-like small molecule, clozapine-N-oxide (CNO). The engineered receptor and small-molecule ligand form an orthogonal pair: The receptor does not respond to native ligands, and the inert drug does not bind to native cells. CNO-responsive migration can be engineered into a variety of cell types, including neutrophils, T lymphocytes, keratinocytes, and endothelial cells. The engineered cells migrate up a gradient of the drug CNO and transmigrate through endothelial monolayers. Finally, we demonstrate that T lymphocytes modified with the engineered receptor can specifically migrate in vivo to CNO-releasing beads implanted in a live mouse. This technology provides a generalizable genetic tool to systematically perturb and control cell migration both in vitro and in vivo. In the future, this type of migration control could be a valuable module for engineering therapeutic cellular devices. C1 [Park, Jason S.; Rhau, Benjamin; Hermann, Aynur; McNally, Krista A.; Zhou, Carmen; Conklin, Bruce R.; Onuffer, James; Lim, Wendell A.] Univ Calif San Francisco, Nanomed Dev Ctr, NIH, Dept Mol & Cellular Pharmacol, San Francisco, CA 94158 USA. [Park, Jason S.; Rhau, Benjamin; Hermann, Aynur; McNally, Krista A.; Zhou, Carmen; Gong, Delquin; Weiner, Orion D.; Conklin, Bruce R.; Onuffer, James; Lim, Wendell A.] Univ Calif San Francisco, Nanomed Dev Ctr, NIH, Cell Prop Lab, San Francisco, CA 94158 USA. [Park, Jason S.; Conklin, Bruce R.] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA. [Gong, Delquin; Weiner, Orion D.; Conklin, Bruce R.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Gong, Delquin; Weiner, Orion D.; Conklin, Bruce R.] Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94143 USA. [Conklin, Bruce R.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA. [Lim, Wendell A.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA. RP Lim, WA (reprint author), Univ Calif San Francisco, Nanomed Dev Ctr, NIH, Dept Mol & Cellular Pharmacol, San Francisco, CA 94158 USA. EM wendell.lim@ucsf.edu RI Weiner, Orion/F-2576-2011 OI Weiner, Orion/0000-0002-1778-6543 FU National Institutes of Health (NIH) [R01 HL60664-07]; NIH Nanomedicine Development Center [PN2EY016546]; NIH [P50 GM08187]; National Science Foundation Synthetic Biology Engineering Research Center, NIH [R01 GM084040]; California Institute for Regenerative Medicine fellowship [TG2-01153]; Howard Hughes Medical Institute; Gladstone Institutes FX We thank the University of California, San Francisco (UCSF) Preclinical Therapeutics Core Facility (especially Byron Hann, Don Hom, Donghui Wang, and Paul Phojanakong) for mouse experimental support and helpful discussions. We also acknowledge the 2009 UCSF International Genetically Engineered Machine (iGEM) competition team (especially Katja Kolar, Ryan Liang, Cathy Liu, Hansi Liu, Jackie Tam, and Eric Wong) for their work on HL-60 neutrophil chemotaxis experiments and molecular cloning. This work was supported by National Institutes of Health (NIH) Grant R01 HL60664-07 (to B. R. C.), pilot study funds from the Gladstone Institutes, NIH Nanomedicine Development Center Grant PN2EY016546 (The Cell Propulsion Laboratory: Center for Synthetic Signaling and Motility Systems Engineering) (to W. A. L.), NIH Grant P50 GM08187 (to W. A. L.), the National Science Foundation Synthetic Biology Engineering Research Center, NIH Grant R01 GM084040 (to O.D.W.), a California Institute for Regenerative Medicine fellowship (Grant TG2-01153) (to J.S.P.), and the Howard Hughes Medical Institute (W.A.L.). NR 55 TC 24 Z9 24 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 22 PY 2014 VL 111 IS 16 BP 5896 EP 5901 DI 10.1073/pnas.1402087111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF4OV UT WOS:000334694000046 PM 24711398 ER PT J AU Cinghu, S Yellaboina, S Freudenberg, JM Ghosh, S Zheng, XF Oldfield, AJ Lackford, BL Zaykin, DV Hu, G Jothi, R AF Cinghu, Senthilkumar Yellaboina, Sailu Freudenberg, Johannes M. Ghosh, Swati Zheng, Xiaofeng Oldfield, Andrew J. Lackford, Brad L. Zaykin, Dmitri V. Hu, Guang Jothi, Raja TI Integrative framework for identification of key cell identity genes uncovers determinants of ES cell identity and homeostasis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE pluripotency; RNA-binding protein; transcription; ROS; computational biology ID EMBRYONIC STEM-CELLS; CHROMATIN REMODELING COMPLEX; RNAI SCREEN; SELF-RENEWAL; DNA-DAMAGE; TRANSCRIPTIONAL NETWORK; NANOG EXPRESSION; MESSENGER-RNAS; PLURIPOTENCY; P53 AB Identification of genes associated with specific biological phenotypes is a fundamental step toward understanding the molecular basis underlying development and pathogenesis. Although RNAi-based high-throughput screens are routinely used for this task, false discovery and sensitivity remain a challenge. Here we describe a computational framework for systematic integration of published gene expression data to identify genes defining a phenotype of interest. We applied our approach to rank-order all genes based on their likelihood of determining ES cell (ESC) identity. RNAi-mediated loss-of-function experiments on top-ranked genes unearthed many novel determinants of ESC identity, thus validating the derived gene ranks to serve as a rich and valuable resource for those working to uncover novel ESC regulators. Underscoring the value of our gene ranks, functional studies of our top-hit Nucleolin (Ncl), abundant in stem and cancer cells, revealed Ncl's essential role in the maintenance of ESC homeostasis by shielding against differentiation-inducing redox imbalance-induced oxidative stress. Notably, we report a conceptually novel mechanism involving a Nucleolin-dependent Nanog-p53 bistable switch regulating the homeostatic balance between self-renewal and differentiation in ESCs. Our findings connect the dots on a previously unknown regulatory circuitry involving genes associated with traits in both ESCs and cancer and might have profound implications for understanding cell fate decisions in cancer stem cells. The proposed computational framework, by helping to prioritize and preselect candidate genes for tests using complex and expensive genetic screens, provides a powerful yet inexpensive means for identification of key cell identity genes. C1 [Cinghu, Senthilkumar; Yellaboina, Sailu; Freudenberg, Johannes M.; Ghosh, Swati; Oldfield, Andrew J.; Jothi, Raja] NIEHS, Syst Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. [Zheng, Xiaofeng; Lackford, Brad L.; Hu, Guang] NIEHS, Stem Cell Biol Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Yellaboina, Sailu; Zaykin, Dmitri V.; Jothi, Raja] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Yellaboina, Sailu] CR Rao Adv Inst Math Stat & Comp Sci, Hyderabad 500046, Andhra Pradesh, India. RP Hu, G (reprint author), NIEHS, Stem Cell Biol Sect, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM hug4@niehs.nih.gov; jothi@mail.nih.gov RI Jothi, Raja/G-3780-2015; Hu, Guang/E-7474-2016 OI Hu, Guang/0000-0003-0437-4723 FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [1ZIAES102625, 1ZIAES10274, 1ZIAES101866]; Department of Science and Technology, India (DST-CMS GoI Project) [SR/S4/MS: 516/07] FX We thank K. Adelman and P. A. Wade for valuable suggestions and K. Adelman, T. K. Archer, A. Barski, M. B. Fessler, T. A. Kunkel, L. Ho, and P. A. Wade for critical comments on the manuscript. We thank H. Kinyamu and J. Yang for guidance on RNA-IP experiments and NIEHS Microarray, Confocal Microscopy, Flow Cytometry, Viral, and Protein cores for support. Nanog and p21 luciferase vectors are kind gifts from J. Huang (National Cancer Institute) and M. Resnick (National Institute of Environmental Health Sciences), respectively. This work was supported by Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences Grants 1ZIAES102625 (to R.J.), 1ZIAES10274 (to G.H.), and 1ZIAES101866 (to D.V.Z.), and the Department of Science and Technology, India (DST-CMS GoI Project SR/S4/MS: 516/07, to S.Y.). NR 64 TC 7 Z9 7 U1 0 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 22 PY 2014 VL 111 IS 16 BP E1581 EP E1590 DI 10.1073/pnas.1318598111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF4OV UT WOS:000334694000007 PM 24711389 ER PT J AU Al-Herz, W Bousfiha, A Casanova, JL Chatila, T Conley, ME Cunningham-Rundles, C Etzioni, A Franco, JL Gaspar, HB Holland, SM Klein, C Nonoyama, S Ochs, HD Oksenhendler, E Picard, C Puck, JM Sullivan, K Tang, MLK AF Al-Herz, Waleed Bousfiha, Aziz Casanova, Jean-Laurent Chatila, Talal Conley, Mary Ellen Cunningham-Rundles, Charlotte Etzioni, Amos Franco, Jose Luis Gaspar, H. Bobby Holland, Steven M. Klein, Christoph Nonoyama, Shigeaki Ochs, Hans D. Oksenhendler, Erik Picard, Capucine Puck, Jennifer M. Sullivan, Kate Tang, Mimi L. K. TI Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE primary immunodeficiencies; IUIS; classification; genetic defects; genotype AB We report the updated classification of primary immunodeficiencies (PIDs) compiled by the Expert Committee of the International Union of Immunological Societies. In comparison to the previous version, more than 30 new gene defects are reported in this updated version. In addition, we have added a table of acquired defects that are phenocopies of PIDs. For each disorder, the key clinical and laboratory features are provided. This classification is the most up-to-date catalog of all known PIDs and acts as a current reference of the knowledge of these conditions and is an important aid for the molecular diagnosis of patients with these rare diseases. C1 [Al-Herz, Waleed] Kuwait Univ, Dept Pediat, Kuwait, Kuwait. [Al-Herz, Waleed] Al Sabah Hosp, Dept Pediat, Allergy & Clin Immunol Unit, Kuwait, Kuwait. [Bousfiha, Aziz] King Hassan II Univ, Ibn Rochd Med Sch, Casablanca Childrens Hosp, Clin Immunol Unit, Casablanca, Morocco. [Casanova, Jean-Laurent; Conley, Mary Ellen] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10021 USA. [Casanova, Jean-Laurent; Picard, Capucine] Univ Paris 05, Lab Human Genet Infect Dis, Necker Med Sch, Necker Branch,INSERM,Imagine Inst,UMR1163, Paris, France. [Chatila, Talal] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Cunningham-Rundles, Charlotte] Mt Sinai Sch Med, Dept Med & Pediat, New York, NY USA. [Etzioni, Amos] Technion Israel Inst Technol, Meyer Childrens Hosp, Haifa, Israel. [Franco, Jose Luis] Univ Antioquia, Grp Primary Immunodeficiencies, Medellin, Colombia. [Gaspar, H. Bobby] UCL Inst Child Hlth, London WC1N 1EH, England. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Klein, Christoph] Univ Munich, Dr von Hauner Childrens Hosp, Munich, Germany. [Nonoyama, Shigeaki] Natl Def Med Coll, Dept Pediat, Saitama, Japan. [Ochs, Hans D.] Univ Washington, Dept Pediat, Seattle Childrens Res Inst, Seattle, WA 98195 USA. [Oksenhendler, Erik] Hop St Louis, AP HP, Dept Clin Immunol, Paris, France. [Oksenhendler, Erik] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Picard, Capucine] Hop Necker Enfants Malad, AP HP, CEDI, Paris, France. [Puck, Jennifer M.] Univ Calif San Francisco, Dept Pediat, UCSF Benioff Childrens Hosp, San Francisco, CA USA. [Sullivan, Kate] Childrens Hosp Philadelphia, Dept Pediat, Div Allergy Immunol, Philadelphia, PA 19104 USA. [Tang, Mimi L. K.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Tang, Mimi L. K.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Tang, Mimi L. K.] Royal Childrens Hosp, Dept Allergy & Immunol, Melbourne, Vic, Australia. RP Gaspar, HB (reprint author), UCL Inst Child Hlth, Mol Immunol Unit, 30 Guilford St, London WC1N 1EH, England. EM h.gaspar@ucl.ac.uk OI Picard, Capucine/0000-0001-8788-5056 FU NIAID NIH HHS [P01 AI061093, R01 AI105776, R18 AI048693] NR 0 TC 195 Z9 205 U1 1 U2 14 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD APR 22 PY 2014 VL 5 AR 162 DI 10.3389/fimmu.2014.00162 PG 33 WC Immunology SC Immunology GA CH6GK UT WOS:000354134300001 PM 24795713 ER PT J AU Henry, SC Schmidt, EA Fessler, MB Taylor, GA AF Henry, Stanley C. Schmidt, Elyse A. Fessler, Michael B. Taylor, Gregory A. TI Palmitoylation of the Immunity Related GTPase, Irgm1: Impact on Membrane Localization and Ability to Promote Mitochondrial Fission SO PLOS ONE LA English DT Article ID CELL-AUTONOMOUS IMMUNITY; TOXOPLASMA-GONDII; PROTEIN PALMITOYLATION; RESISTANCE MECHANISM; HOST-RESISTANCE; MOUSE CELLS; LRG-47; MACROPHAGES; AUTOPHAGY; MICE AB The Immunity-Related GTPases (IRG) are a family of large GTPases that mediate innate immune responses. Irgm1 is particularly critical for immunity to bacteria and protozoa, and for inflammatory homeostasis in the intestine. Although precise functions for Irgm1 have not been identified, prior studies have suggested roles in autophagy/mitophagy, phagosome remodeling, cell motility, and regulating the activity of other IRG proteins. These functions ostensibly hinge on the ability of Irgm1 to localize to intracellular membranes, such as those of the Golgi apparatus and mitochondria. Previously, it has been shown that an amphipathic helix, the alpha K helix, in the C-terminal portion of the protein partially mediates membrane binding. However, in absence of alpha K, there is still substantial binding of Irgm1 to cellular membranes, suggesting the presence of other membrane binding motifs. In the current work, an additional membrane localization motif was found in the form of palmitoylation at a cluster of cysteines near the alpha K. An Irgm1 mutant possessing alanine to cysteine substitutions at these amino acids demonstrated little residual palmitoylation, yet it displayed only a small decrease in localization to the Golgi and mitochondria. In contrast, a mutant containing the palmitoylation mutations in combination with mutations disrupting the amphipathic character of the alpha K displayed a complete loss of apparent localization to the Golgi and mitochondria, as well as an overall loss of association with cellular membranes in general. Additionally, Irgm1 was found to promote mitochondrial fission, and this function was undermined in Irgm1 mutants lacking the palmitoylation domain, and to a greater extent in those lacking the alpha K, or the alpha K and palmitoylation domains combined. Our data suggest that palmitoylation together with the alpha K helix firmly anchor Irgm1 in the Golgi and mitochondria, thus facilitating function of the protein. C1 [Henry, Stanley C.; Taylor, Gregory A.] VA Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC 27705 USA. [Schmidt, Elyse A.; Taylor, Gregory A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Schmidt, Elyse A.; Taylor, Gregory A.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC USA. [Schmidt, Elyse A.; Taylor, Gregory A.] Duke Univ, Med Ctr, Dept Immunol, Div Geriatr, Durham, NC USA. [Schmidt, Elyse A.; Taylor, Gregory A.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. [Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Taylor, GA (reprint author), VA Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC 27705 USA. EM gregory.taylor@duke.edu FU National Institutes of Health [AI57831]; VA Merit Review grant; National Institute of Environmental Health Sciences, NIH [Z01 ES102005] FX This work was supported by National Institutes of Health grant AI57831 (GAT), a VA Merit Review grant (GAT), and by the Intramural Research Program of the National Institute of Environmental Health Sciences, NIH, Z01 ES102005 (MBF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 9 Z9 9 U1 1 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 21 PY 2014 VL 9 IS 4 AR e95021 DI 10.1371/journal.pone.0095021 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2DX UT WOS:000335227400024 PM 24751652 ER PT J AU Kim, MH Rebbert, ML Ro, H Won, M Dawid, IB AF Kim, Mi Ha Rebbert, Martha L. Ro, Hyunju Won, Minho Dawid, Igor B. TI Cell Adhesion in Zebrafish Embryos Is Modulated by March8 SO PLOS ONE LA English DT Article ID E3 UBIQUITIN LIGASE; E-CADHERIN; CLASS-II; XENOPUS EMBRYOS; DOWN-REGULATION; B-CELLS; C-MIR; EXPRESSION; MOVEMENTS; PROTEIN AB March8 is a member of a family of transmembrane E3 ubiquitin ligases that have been studied mostly for their role in the immune system. We find that March8 is expressed in the zebrafish egg and early embryo, suggesting a role in development. Both knock-down and overexpression of March8 leads to abnormal development. The phenotype of zebrafish embryos and Xenopus animal explants overexpressing March8 implicates impairment of cell adhesion as a cause of the effect. In zebrafish embryos and in cultured cells, overexpression of March8 leads to a reduction in the surface levels of E-cadherin, a major cell-cell adhesion molecule. Experiments in cell culture further show that E-cadherin can be ubiquitinated by March8. On the basis of these observations we suggest that March8 functions in the embryo to modulate the strength of cell adhesion by regulating the localization of E-cadherin. C1 [Kim, Mi Ha; Rebbert, Martha L.; Ro, Hyunju; Won, Minho; Dawid, Igor B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM idawid@nih.gov FU National Institute for Child Health and Human Development FX This research has been funded by the intramural research program of the National Institute for Child Health and Human Development. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 1 Z9 1 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 21 PY 2014 VL 9 IS 4 AR e94873 DI 10.1371/journal.pone.0094873 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2DX UT WOS:000335227400020 PM 24752240 ER PT J AU Yu, XZ Strub, MP Barnard, TJ Noinaj, N Piszczek, G Buchanan, SK Taraska, JW AF Yu, Xiaozhen Strub, Marie-Paule Barnard, Travis J. Noinaj, Nicholas Piszczek, Grzegorz Buchanan, Susan K. Taraska, Justin W. TI An Engineered Palette of Metal Ion Quenchable Fluorescent Proteins SO PLOS ONE LA English DT Article ID ENERGY-TRANSFER; CALCIUM INDICATORS; BINDING PROTEINS; STRUCTURAL BASIS; ZINC; PREDICTION; CHEMISTRY; SITES; CELLS; FRET AB Many fluorescent proteins have been created to act as genetically encoded biosensors. With these sensors, changes in fluorescence report on chemical states in living cells. Transition metal ions such as copper, nickel, and zinc are crucial in many physiological and pathophysiological pathways. Here, we engineered a spectral series of optimized transition metal ion-binding fluorescent proteins that respond to metals with large changes in fluorescence intensity. These proteins can act as metal biosensors or imaging probes whose fluorescence can be tuned by metals. Each protein is uniquely modulated by four different metals (Cu2+, Ni2+, Co2+, and Zn2+). Crystallography revealed the geometry and location of metal binding to the engineered sites. When attached to the extracellular terminal of a membrane protein VAMP2, dimeric pairs of the sensors could be used in cells as ratiometric probes for transition metal ions. Thus, these engineered fluorescent proteins act as sensitive transition metal ion-responsive genetically encoded probes that span the visible spectrum. C1 [Yu, Xiaozhen; Strub, Marie-Paule; Taraska, Justin W.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Barnard, Travis J.; Noinaj, Nicholas; Buchanan, Susan K.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Piszczek, Grzegorz] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Taraska, JW (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. EM justin.taraska@nih.gov RI Taraska, Justin/H-8876-2016 OI Taraska, Justin/0000-0001-5355-9535 FU National Heart Lung and Blood Institute; National Institute Diabetes and Digestive and Kidney Diseases; National Cancer Institute [Y1-CO1020]; National Institute of General Medical Sciences [Y1-GM-1104]; U.S. Department of Energy, Basic Energy Sciences, Office of Science [DE- AC02- 06CH11357] FX J.W.T. is supported by the intramural research program of the National Heart Lung and Blood Institute, and S.K.B. is supported by the National Institute Diabetes and Digestive and Kidney Diseases. GM/CA at the APS has been funded in whole or in part with Federal funds from the National Cancer Institute (Y1-CO1020) and the National Institute of General Medical Sciences (Y1-GM-1104). Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Basic Energy Sciences, Office of Science, under contract DE- AC02- 06CH11357. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 4 Z9 4 U1 3 U2 18 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 21 PY 2014 VL 9 IS 4 AR e95808 DI 10.1371/journal.pone.0095808 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2DX UT WOS:000335227400133 PM 24752441 ER PT J AU Brzeska, H Pridham, K Chery, G Titus, MA Korn, ED AF Brzeska, Hanna Pridham, Kevin Chery, Godefroy Titus, Margaret A. Korn, Edward D. TI The Association of Myosin IB with Actin Waves in Dictyostelium Requires Both the Plasma Membrane-Binding Site and Actin-Binding Region in the Myosin Tail SO PLOS ONE LA English DT Article ID ACANTHAMOEBA MYOSIN; FLUORESCENT PROTEIN; CELL LOCOMOTION; F-ACTIN; DISCOIDEUM; DYNAMICS; PHOSPHORYLATION; MUTANTS; TRANSFORMATION; ORGANIZATION AB F-actin structures and their distribution are important determinants of the dynamic shapes and functions of eukaryotic cells. Actin waves are F-actin formations that move along the ventral cell membrane driven by actin polymerization. Dictyostelium myosin IB is associated with actin waves but its role in the wave is unknown. Myosin IB is a monomeric, non-filamentous myosin with a globular head that binds to F-actin and has motor activity, and a non-helical tail comprising a basic region, a glycine-proline-glutamine-rich region and an SH3-domain. The basic region binds to acidic phospholipids in the plasma membrane through a short basic-hydrophobic site and the Gly-Pro-Gln region binds F-actin. In the current work we found that both the basic-hydrophobic site in the basic region and the Gly-Pro-Gln region of the tail are required for the association of myosin IB with actin waves. This is the first evidence that the Gly-Pro-Gln region is required for localization of myosin IB to a specific actin structure in situ. The head is not required for myosin IB association with actin waves but binding of the head to F-actin strengthens the association of myosin IB with waves and stabilizes waves. Neither the SH3-domain nor motor activity is required for association of myosin IB with actin waves. We conclude that myosin IB contributes to anchoring actin waves to the plasma membranes by binding of the basic-hydrophobic site to acidic phospholipids in the plasma membrane and binding of the Gly-Pro-Gln region to F-actin in the wave. C1 [Brzeska, Hanna; Pridham, Kevin; Chery, Godefroy; Korn, Edward D.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Titus, Margaret A.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. RP Brzeska, H (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM brzeskah@mail.nih.gov FU National Institutes of Health (NIH) intramural program FX Research was funded by National Institutes of Health (NIH) intramural program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 5 Z9 5 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 18 PY 2014 VL 9 IS 4 AR e94306 DI 10.1371/journal.pone.0094306 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2DP UT WOS:000335226500023 PM 24747353 ER PT J AU Pawar, SA Shao, LJ Chang, JH Wang, WZ Pathak, R Zhu, XY Wang, JR Hendrickson, H Boerma, M Sterneck, E Zhou, DH Hauer-Jensen, M AF Pawar, Snehalata A. Shao, Lijian Chang, Jianhui Wang, Wenze Pathak, Rupak Zhu, Xiaoyan Wang, Junru Hendrickson, Howard Boerma, Marjan Sterneck, Esta Zhou, Daohong Hauer-Jensen, Martin TI C/EBP delta Deficiency Sensitizes Mice to Ionizing Radiation-Induced Hematopoietic and Intestinal Injury SO PLOS ONE LA English DT Article ID BINDING-PROTEIN-DELTA; BONE-MARROW INJURY; TOTAL-BODY IRRADIATION; DNA-DAMAGE RESPONSE; STEM-CELLS; IN-VIVO; GASTROINTESTINAL-SYNDROME; SELECTIVELY PROTECTS; PLASMA CITRULLINE; CELLULAR-RESPONSE AB Knowledge of the mechanisms involved in the radiation response is critical for developing interventions to mitigate radiation-induced injury to normal tissues. Exposure to radiation leads to increased oxidative stress, DNA-damage, genomic instability and inflammation. The transcription factor CCAAT/enhancer binding protein delta (Cebpd; C/EBP delta is implicated in regulation of these same processes, but its role in radiation response is not known. We investigated the role of C/EBP delta in radiation-induced hematopoietic and intestinal injury using a Cebpd knockout mouse model. Cebpd-/- mice showed increased lethality at 7.4 and 8.5 Gy total-body irradiation (TBI), compared to Cebpd+/+ mice. Two weeks after a 6 Gy dose of TBI, Cebpd-/- mice showed decreased recovery of white blood cells, neutrophils, platelets, myeloid cells and bone marrow mononuclear cells, decreased colony-forming ability of bone marrow progenitor cells, and increased apoptosis of hematopoietic progenitor and stem cells compared to Cebpd+/+ controls. Cebpd-/- mice exhibited a significant dose-dependent decrease in intestinal crypt survival and in plasma citrulline levels compared to Cebpd+/+ mice after exposure to radiation. This was accompanied by significantly decreased expression of gamma-H2AX in Cebpd-/- intestinal crypts and villi at 1 h post-TBI, increased mitotic index at 24 h post-TBI, and increase in apoptosis in intestinal crypts and stromal cells of Cebpd-/- compared to Cebpd+/+ mice at 4 h post-irradiation. This study uncovers a novel biological function for C/EBP delta in promoting the response to radiation-induced DNA-damage and in protecting hematopoietic and intestinal tissues from radiation-induced injury. C1 [Pawar, Snehalata A.; Shao, Lijian; Chang, Jianhui; Wang, Wenze; Pathak, Rupak; Zhu, Xiaoyan; Wang, Junru; Boerma, Marjan; Zhou, Daohong; Hauer-Jensen, Martin] Univ Arkansas Med Sci, Div Radiat Hlth, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. [Hendrickson, Howard] Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. [Sterneck, Esta] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Hauer-Jensen, Martin] Cent Arkansas Vet Healthcare Syst, Surg Serv, Little Rock, AR USA. RP Pawar, SA (reprint author), Univ Arkansas Med Sci, Div Radiat Hlth, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. EM SAPawar@uams.edu FU Arkansas Bioscience Institute; UAMS Medical Research Endowment Funds; Center for Microbial Pathogenesis and Host Inflammatory Responses COBRE Grant [1P20GM103625]; Edward P. Evan's Foundation; NIH, National Cancer Institute; Veterans Administration FX Grant support by Arkansas Bioscience Institute (SAP), UAMS Medical Research Endowment Funds (SAP), Center for Microbial Pathogenesis and Host Inflammatory Responses COBRE Grant 1P20GM103625 (SAP) and the Edward P. Evan's Foundation (DZ, MHJ), Veterans Administration (MHJ) is gratefully acknowledged. ES is supported by the Intramural Research Program of the NIH, National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 4 Z9 4 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 18 PY 2014 VL 9 IS 4 AR e94967 DI 10.1371/journal.pone.0094967 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2DP UT WOS:000335226500047 PM 24747529 ER PT J AU Szabova, L Bupp, S Kamal, M Householder, DB Hernandez, L Schlomer, JJ Baran, ML Yi, M Stephens, RM Annunziata, CM Martin, PL Van Dyke, TA Ohler, ZW Difilippantonio, S AF Szabova, Ludmila Bupp, Sujata Kamal, Muhaymin Householder, Deborah B. Hernandez, Lidia Schlomer, Jerome J. Baran, Maureen L. Yi, Ming Stephens, Robert M. Annunziata, Christina M. Martin, Philip L. Van Dyke, Terry A. Ohler, Zoe Weaver Difilippantonio, Simone TI Pathway-Specific Engineered Mouse Allograft Models Functionally Recapitulate Human Serous Epithelial Ovarian Cancer SO PLOS ONE LA English DT Article ID ADP-RIBOSE POLYMERASE; MAMMARY-TUMORS; CELL-LINES; POLY(ADP-RIBOSE) POLYMERASE-1; BREAST-CANCER; BRCA1; CHEMOTHERAPY; INHIBITOR; MUTATIONS; THERAPY AB The high mortality rate from ovarian cancers can be attributed to late-stage diagnosis and lack of effective treatment. Despite enormous effort to develop better targeted therapies, platinum-based chemotherapy still remains the standard of care for ovarian cancer patients, and resistance occurs at a high rate. One of the rate limiting factors for translation of new drug discoveries into clinical treatments has been the lack of suitable preclinical cancer models with high predictive value. We previously generated genetically engineered mouse (GEM) models based on perturbation of Tp53 and Rb with or without Brca1 or Brca2 that develop serous epithelial ovarian cancer (SEOC) closely resembling the human disease on histologic and molecular levels. Here, we describe an adaptation of these GEM models to orthotopic allografts that uniformly develop tumors with short latency and are ideally suited for routine preclinical studies. Ovarian tumors deficient in Brca1 respond to treatment with cisplatin and olaparib, a PARP inhibitor, whereas Brca1-wild type tumors are non-responsive to treatment, recapitulating the relative sensitivities observed in patients. These mouse models provide the opportunity for evaluation of effective therapeutics, including prediction of differential responses in Brca1-wild type and Brca1-deficient tumors and development of relevant biomarkers. C1 [Szabova, Ludmila; Bupp, Sujata; Kamal, Muhaymin; Householder, Deborah B.; Schlomer, Jerome J.; Baran, Maureen L.; Martin, Philip L.; Van Dyke, Terry A.; Ohler, Zoe Weaver; Difilippantonio, Simone] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Ctr Adv Preclin Res, Frederick, MD USA. [Hernandez, Lidia; Annunziata, Christina M.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Yi, Ming; Stephens, Robert M.] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD USA. [Van Dyke, Terry A.] Frederick Natl Lab Canc Res, Mouse Canc Genet Program, Frederick, MD USA. RP Szabova, L (reprint author), Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Ctr Adv Preclin Res, Frederick, MD USA. EM lszabova@mail.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole with federal funds from the National Cancer Institute, National Institutes of Health, under contract number 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. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 3 Z9 3 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 18 PY 2014 VL 9 IS 4 AR e95649 DI 10.1371/journal.pone.0095649 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2DP UT WOS:000335226500133 PM 24748377 ER PT J AU Fields, RD AF Fields, R. Douglas TI Myelin-More than Insulation SO SCIENCE LA English DT Editorial Material ID CORTEX C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bldg 35,Room 2A211,MSC 3713, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU Intramural NIH HHS [Z01 HD000713-13] NR 12 TC 7 Z9 7 U1 0 U2 18 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 18 PY 2014 VL 344 IS 6181 BP 264 EP 266 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF1LD UT WOS:000334474500024 PM 24744365 ER PT J AU Mailankody, S Prasad, V AF Mailankody, Sham Prasad, Vinay TI Comparative Effectiveness Questions in Oncology SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INCREASED SURVIVAL; PROSTATE-CANCER C1 [Mailankody, Sham; Prasad, Vinay] NCI, Med Oncol Serv, Bethesda, MD 20892 USA. RP Mailankody, S (reprint author), NCI, Med Oncol Serv, Bethesda, MD 20892 USA. NR 5 TC 15 Z9 15 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 17 PY 2014 VL 370 IS 16 BP 1478 EP 1481 DI 10.1056/NEJMp1400104 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AF3HE UT WOS:000334601600004 PM 24738667 ER PT J AU Hoofnagle, JH Sherker, AH AF Hoofnagle, Jay H. Sherker, Averell H. TI Therapy for Hepatitis C - The Costs of Success SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID UNITED-STATES; INTERFERON; INFECTION AB Welcomed and exciting results from three large, controlled trials of different regimens of oral antiviral agents for chronic hepatitis C, genotype 1, have now been published in the Journal.(1)-(3) The regimens all included the combination of ledipasvir and sofosbuvir, two new direct-acting antiviral agents with potent activity against hepatitis C virus (HCV). The two drugs were given as a single tablet once daily for 8, 12, or 24 weeks, with or without ribavirin. The results were consistent and striking: the various regimens yielded rates of sustained virologic response of 93% to 99%. The combination of ledipasvir and sofosbuvir ... C1 [Hoofnagle, Jay H.; Sherker, Averell H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. NR 13 TC 75 Z9 76 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 17 PY 2014 VL 370 IS 16 BP 1552 EP 1553 DI 10.1056/NEJMe1401508 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AF3HE UT WOS:000334601600013 PM 24725236 ER PT J AU Klauer, SG Guo, F Simons-Morton, BG AF Klauer, Sheila G. Guo, Feng Simons-Morton, Bruce G. TI Distracted Driving and Crash Risk REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Klauer, Sheila G.; Guo, Feng] Virginia Tech, Transportat Inst, Blacksburg, VA 24061 USA. [Simons-Morton, Bruce G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Klauer, SG (reprint author), Virginia Tech, Transportat Inst, Blacksburg, VA 24061 USA. EM cklauer@vtti.vt.edu NR 3 TC 0 Z9 0 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 17 PY 2014 VL 370 IS 16 BP 1565 EP 1566 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AF3HE UT WOS:000334601600026 PM 24738680 ER PT J AU Savage, SA AF Savage, Sharon A. TI Genomic clues to ethnic differences in ALL SO BLOOD LA English DT Editorial Material ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDHOOD LEUKEMIA; KIR GENES; CHILDREN; SURVIVAL C1 NCI, Bethesda, MD 20892 USA. RP Savage, SA (reprint author), NCI, Bethesda, MD 20892 USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 10 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD APR 17 PY 2014 VL 123 IS 16 BP 2440 EP 2442 DI 10.1182/blood-2014-02-557330 PG 5 WC Hematology SC Hematology GA AH1PX UT WOS:000335894500003 PM 24744246 ER PT J AU Wayne, AS FitzGerald, DJ Kreitman, RJ Pastan, I AF Wayne, Alan S. FitzGerald, David J. Kreitman, Robert J. Pastan, Ira TI Immunotoxins for leukemia SO BLOOD LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HAIRY-CELL LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; PHASE-I TRIAL; RECOMBINANT IMMUNOTOXIN; ANTI-CD22 IMMUNOTOXIN; HEMATOLOGIC MALIGNANCIES; PSEUDOMONAS EXOTOXIN; VASCULAR LEAK; MOXETUMOMAB PASUDOTOX AB Unconjugated monoclonal antibodies that target hematopoietic differentiation antigens have been developed to treat hematologic malignancies. Although some of these have activity against chronic lymphocytic leukemia and hairy cell leukemia, in general, monoclonal antibodies have limited efficacy as single agents in the treatment of leukemia. To increase their potency, the binding domains of monoclonal antibodies can be attached to protein toxins. Such compounds, termed immunotoxins, are delivered to the interior of leukemia cells based on antibody specificity for cell surface target antigens. Recombinant immunotoxins have been shown to be highly cytotoxic to leukemic blasts in vitro, in xenograft model systems, and in early-phase clinical trials in humans. These agents will likely play an increasing role in the treatment of leukemia. C1 [Wayne, Alan S.] Univ So Calif, Keck Sch Med,Norris Comprehens Canc Ctr, Div Hematol Oncol & Blood & Marrow Transplantat, Childrens Ctr Canc & Blood Dis,Childrens Hosp Los, Los Angeles, CA 90033 USA. [Wayne, Alan S.; FitzGerald, David J.; Kreitman, Robert J.; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wayne, AS (reprint author), Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, 4650 Sunset Blvd,Mailstop 54, Los Angeles, CA 90027 USA. EM awayne@chla.usc.edu FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Cancer Institute; MedImmune, LLC. FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Research support for development of some of the immunotoxins described was provided through a Cooperative Research and Development Agreement between the National Cancer Institute and MedImmune, LLC. NR 77 TC 43 Z9 43 U1 1 U2 16 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 17 PY 2014 VL 123 IS 16 BP 2470 EP 2477 DI 10.1182/blood-2014-01-492256 PG 8 WC Hematology SC Hematology GA AH1PX UT WOS:000335894500012 PM 24578503 ER PT J AU Bild, DE McClelland, R Kaufman, JD Blumenthal, R Burke, GL Carr, JJ Post, WS Register, TC Shea, S Szklo, M AF Bild, Diane E. McClelland, Robyn Kaufman, Joel D. Blumenthal, Roger Burke, Gregory L. Carr, J. Jeffrey Post, Wendy S. Register, Thomas C. Shea, Steven Szklo, Moyses TI Ten-Year Trends in Coronary Calcification in Individuals without Clinical Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis SO PLOS ONE LA English DT Article ID DENSITY-LIPOPROTEIN-CHOLESTEROL; ARTERY RISK DEVELOPMENT; HEART-DISEASE; YOUNG-ADULTS; MYOCARDIAL-INFARCTION; UNITED-STATES; CARDIA; REGRESSION; CALCIUM; MESA AB Background: Coronary heart disease (CHD) incidence has declined significantly in the US, as have levels of major coronary risk factors, including LDL-cholesterol, hypertension and smoking, but whether trends in subclinical atherosclerosis mirror these trends is not known. Methods and Findings: To describe recent secular trends in subclinical atherosclerosis as measured by serial evaluations of coronary artery calcification (CAC) prevalence in a population over 10 years, we measured CAC using computed tomography (CT) and CHD risk factors in five serial cross-sectional samples of men and women from four race/ethnic groups, aged 55-84 and without clinical cardiovascular disease, who were members of Multi-Ethnic Study of Atherosclerosis (MESA) cohort from 2000 to 2012. Sample sizes ranged from 1062 to 4837. After adjusting for age, gender, and CT scanner, the prevalence of CAC increased across exams among African Americans, whose prevalence of CAC was 52.4% in 2000-02, 50.4% in 2003-04, 60.0% is 2005-06, 57.4% in 2007-08, and 61.3% in 2010-12 (p for trend <0.001). The trend was strongest among African Americans aged 55-64 [prevalence ratio for 2010-12 vs. 2000-02, 1.59 (95% confidence interval 1.06, 2.39); p = 0.005 for trend across exams]. There were no consistent trends in any other ethnic group. Risk factors generally improved in the cohort, and adjustment for risk factors did not change trends in CAC prevalence. Conclusions: There was a significant secular trend towards increased prevalence of CAC over 10 years among African Americans and no change in three other ethnic groups. Trends did not reflect concurrent general improvement in risk factors. The trend towards a higher prevalence of CAC in African Americans suggests that CHD risk in this population is not improving relative to other groups. C1 [Bild, Diane E.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [McClelland, Robyn] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Kaufman, Joel D.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Blumenthal, Roger; Post, Wendy S.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Post, Wendy S.; Szklo, Moyses] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Burke, Gregory L.; Register, Thomas C.] Wake Forest Sch Med, Winston Salem, NC USA. [Carr, J. Jeffrey] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Shea, Steven] Columbia Univ, New York, NY USA. RP Bild, DE (reprint author), NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA. EM dbild@pcori.org RI Kaufman, Joel/B-5761-2008; Carr, John/A-1938-2012 OI Kaufman, Joel/0000-0003-4174-9037; Carr, John/0000-0002-4398-8237 FU NCATS NIH HHS [UL1-TR-000040]; NCRR NIH HHS [UL1-RR-025005] NR 33 TC 6 Z9 6 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 17 PY 2014 VL 9 IS 4 AR e94916 DI 10.1371/journal.pone.0094916 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG3IK UT WOS:000335309100050 PM 24743658 ER PT J AU Guo, XG Park, Y Freedman, ND Sinha, R Hollenbeck, AR Blair, A Chen, HL AF Guo, Xuguang Park, Yikyung Freedman, Neal D. Sinha, Rashmi Hollenbeck, Albert R. Blair, Aaron Chen, Honglei TI Sweetened Beverages, Coffee, and Tea and Depression Risk among Older US Adults SO PLOS ONE LA English DT Article ID HEALTH-AMERICAN-ASSOCIATION; RETIRED-PERSONS DIET; CAFFEINE INTAKE; DECAFFEINATED COFFEE; NATIONAL-INSTITUTES; PARKINSON-DISEASE; MENTAL-HEALTH; WEIGHT-GAIN; SOFT DRINK; CONSUMPTION AB Sweetened beverages, coffee, and tea are the most consumed non-alcoholic beverages and may have important health consequences. We prospectively evaluated the consumption of various types of beverages assessed in 1995-1996 in relation to self-reported depression diagnosis after 2000 among 263,923 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions. The OR (95% CI) comparing >= 4 cans/cups per day with none were 1.30 (95% CI: 1.17-1.44) for soft drinks, 1.38 (1.15-1.65) for fruit drinks, and 0.91 (0.84-0.98) for coffee (all P for trend < 0.0001). Null associations were observed for iced-tea and hot tea. In stratified analyses by drinkers of primarily diet versus regular beverages, the ORs were 1.31 (1.16-1.47) for diet versus 1.22 (1.03-1.45) for regular soft drinks, 1.51 (1.18-1.92) for diet versus 1.08 (0.79-1.46) for regular fruit drinks, and 1.25 (1.10-1.41) for diet versus 0.94 (0.83-1.08) for regular sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea without any sweetener was associated with a lower risk for depression, adding artificial sweeteners, but not sugar or honey, was associated with higher risks. Frequent consumption of sweetened beverages, especially diet drinks, may increase depression risk among older adults, whereas coffee consumption may lower the risk. C1 [Guo, Xuguang] Westat Corp, Dept Hlth Studies, Res Triangle Pk, NC USA. [Park, Yikyung; Freedman, Neal D.; Sinha, Rashmi] NCI, Nutr Epidemiol Branch, Rockville, MD USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Rockville, MD USA. [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. EM chenh2@niehs.nih.gov RI Sinha, Rashmi/G-7446-2015; Freedman, Neal/B-9741-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Freedman, Neal/0000-0003-0074-1098; Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X FU National Institute of Environmental Health Sciences; National Cancer Institute FX The work reported in this manuscript was supported by the intramural research funding from the National Institute of Environmental Health Sciences and the National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 15 Z9 16 U1 4 U2 38 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 17 PY 2014 VL 9 IS 4 AR e94715 DI 10.1371/journal.pone.0094715 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG3IK UT WOS:000335309100042 PM 24743309 ER PT J AU Killeen, GF Seyoum, A Gimnig, JE Stevenson, JC Drakeley, CJ Chitnis, N AF Killeen, Gerry F. Seyoum, Aklilu Gimnig, John E. Stevenson, Jennifer C. Drakeley, Christopher J. Chitnis, Nakul TI Made-to-measure malaria vector control strategies: rational design based on insecticide properties and coverage of blood resources for mosquitoes SO MALARIA JOURNAL LA English DT Review DE Plasmodium; Anopheles; Vector control; Mosquito; Malaria; Target product profile ID TREATED NETS; BEHAVIORAL RESILIENCE; ANOPHELES-ARABIENSIS; HUMAN EXPOSURE; TRANSMISSION; POPULATIONS; PREVENTION; RESISTANCE; IMPACT; TRIAL AB Eliminating malaria from highly endemic settings will require unprecedented levels of vector control. To suppress mosquito populations, vector control products targeting their blood hosts must attain high biological coverage of all available sources, rather than merely high demographic coverage of a targeted resource subset, such as humans while asleep indoors. Beyond defining biological coverage in a measurable way, the proportion of blood meals obtained from humans and the proportion of bites upon unprotected humans occurring indoors also suggest optimal target product profiles for delivering insecticides to humans or livestock. For vectors that feed only occasionally upon humans, preferred animal hosts may be optimal targets for mosquito-toxic insecticides, and vapour-phase insecticides optimized to maximize repellency, rather than toxicity, may be ideal for directly protecting people against indoor and outdoor exposure. However, for vectors that primarily feed upon people, repellent vapour-phase insecticides may be inferior to toxic ones and may undermine the impact of contact insecticides applied to human sleeping spaces, houses or clothing if combined in the same time and place. These concepts are also applicable to other mosquito-borne anthroponoses so that diverse target species could be simultaneously controlled with integrated vector management programmes. Measurements of these two crucial mosquito behavioural parameters should now be integrated into programmatically funded, longitudinal, national-scale entomological monitoring systems to inform selection of available technologies and investment in developing new ones. C1 [Killeen, Gerry F.] Ifakara Hlth Inst, Environm Hlth & Ecol Sci Themat Grp, Morogoro, Tanzania. [Killeen, Gerry F.; Seyoum, Aklilu] Univ Liverpool, Liverpool Sch Trop Med, Vector Biol Dept, Liverpool L3 5QA, Merseyside, England. [Gimnig, John E.] Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Atlanta, GA 30333 USA. [Stevenson, Jennifer C.; Drakeley, Christopher J.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Immunol & Infect, London WC1E 7HT, England. [Stevenson, Jennifer C.] Johns Hopkins Bloomberg Sch Publ Hlth, Johns Hopkins Malaria Res Inst, Baltimore, MD 21205 USA. [Chitnis, Nakul] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland. [Chitnis, Nakul] Univ Basel, Basel, Switzerland. [Chitnis, Nakul] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Killeen, GF (reprint author), Ifakara Hlth Inst, Environm Hlth & Ecol Sci Themat Grp, Morogoro, Tanzania. EM gkilleen@ihi.or.tz RI Smith, Thomas/B-5569-2015; Chitnis, Nakul/B-3105-2013 OI Smith, Thomas/0000-0002-3650-9381; FU Bill & Melinda Gates Foundation [45114, 52644, OPP1032350] FX We thank Dr K Aultman for stimulating discussions that led to this manuscript, Dr T Burkot and Dr D Malone for comments upon an early draft, and two anonymous reviewers whose insightful comments significantly improved the final text and figures. This work was funded by the Bill & Melinda Gates Foundation (award numbers 45114, 52644 and OPP1032350). NR 65 TC 13 Z9 13 U1 0 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD APR 16 PY 2014 VL 13 AR 146 DI 10.1186/1475-2875-13-146 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AL8AA UT WOS:000339357700001 PM 24739261 ER PT J AU Alstott, J Madnick, S Velu, C AF Alstott, Jeff Madnick, Stuart Velu, Chander TI Homophily and the Speed of Social Mobilization: The Effect of Acquired and Ascribed Traits SO PLOS ONE LA English DT Article ID NETWORKS; IDENTITY; SEARCH; COMMUNICATION; BEHAVIOR; GROWTH AB Large-scale mobilization of individuals across social networks is becoming increasingly prevalent in society. However, little is known about what affects the speed of social mobilization. Here we use a framed field experiment to identify and measure properties of individuals and their relationships that predict mobilization speed. We ran a global social mobilization contest and recorded personal traits of the participants and those they recruited. We studied the effects of ascribed traits (gender, age) and acquired traits (geography, and information source) on the speed of mobilization. We found that homophily, a preference for interacting with other individuals with similar traits, had a mixed role in social mobilization. Homophily was present for acquired traits, in which mobilization speed was faster when the recuiter and recruit had the same trait compared to different traits. In contrast, we did not find support for homophily for the ascribed traits. Instead, those traits had other, non-homophily effects: Females mobilized other females faster than males mobilized other males. Younger recruiters mobilized others faster, and older recruits mobilized slower. Recruits also mobilized faster when they first heard about the contest directly from the contest organization, and decreased in speed when hearing from less personal source types (e. g. family vs. media). These findings show that social mobilization includes dynamics that are unlike other, more passive forms of social activity propagation. These findings suggest relevant factors for engineering social mobilization tasks for increased speed. C1 [Alstott, Jeff] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. [Alstott, Jeff] Univ Cambridge, Dept Expt Psychol, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. [Alstott, Jeff] Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge, England. [Madnick, Stuart] MIT, Informat Technol Grp, Sloan Sch Management, Cambridge, MA 02139 USA. [Madnick, Stuart] MIT, Sch Engn, Engn Syst Div, Cambridge, MA 02139 USA. [Velu, Chander] Univ Cambridge, Dept Engn, Inst Mfg, Cambridge CB2 1PZ, England. RP Madnick, S (reprint author), MIT, Informat Technol Grp, Sloan Sch Management, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM smadnick@mit.edu FU NIH-Oxford-Cambridge Scholarship Program; John Norris Maguire Professorship in Information Technologies Chair account; Langley Castle Hotel FX The authors were partially funded by the NIH-Oxford-Cambridge Scholarship Program and by the John Norris Maguire Professorship in Information Technologies Chair account. Langley Castle Hotel funded the awards for the contest used in this study and gathered the data. Other than this, the funders had no role in the subsequent study design, data analysis, decision to publish, or preparation of the manuscript. NR 38 TC 8 Z9 8 U1 2 U2 18 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 16 PY 2014 VL 9 IS 4 AR e95140 DI 10.1371/journal.pone.0095140 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI4VW UT WOS:000336863900109 PM 24740123 ER PT J AU Yin, HF Jin, CF Fang, XY Miao, Q Zhao, YY Chen, ZQ Su, ZA Ye, PP Wang, Y Yin, JF AF Yin, Houfa Jin, Chongfei Fang, Xiaoyun Miao, Qi Zhao, Yingying Chen, Zhiqing Su, Zhaoan Ye, Panpan Wang, Yao Yin, Jinfu TI Molecular Analysis and Phenotypic Study in 14 Chinese Families with Bietti Crystalline Dystrophy SO PLOS ONE LA English DT Article ID CORNEO-RETINAL DYSTROPHY; CHOROIDAL NEOVASCULARIZATION; FUNDUS DYSTROPHY; CYP4V2 MUTATIONS; RETINOPATHY; GENE; TIMP3 AB Purpose: To investigate the clinical features and cytochrome P450 family 4 subfamily V polypeptide 2 (CYP4V2) gene mutations in 14 Chinese families with Bietti crystalline dystrophy (BCD). Methods: Seventeen patients from 14 unrelated Chinese families with BCD were recruited for complete clinical ophthalmic examination and genetic study. The 11 exons of CYP4V2 were amplified from genomic DNA of all patients and their family members by polymerase chain reaction (PCR) and then sequenced. Exons of TIMP3 were also sequenced in BCD patient associated with choroidal neovascularization (CNV). One hundred and seventy unrelated healthy Chinese subjects were screened for mutations in CYP4V2. Results: All 17 patients with BCD had mutations in CYP4V2; one of these mutations was novel (c.219T>A, p.F73L) and four other mutations had been reported. The p.F73L mutation was a commonly detected mutation in our study (seven out of 34 alleles), either in the homozygous state or in the heterozygous state. Among the patients, considerable phenotypic variability was detected, both within and between families. Screening of TIMP3 did not find any mutation in the BCD patient associated with CNV. Conclusion: The novel CYP4V2 c.219T>A (p.F73L) mutation may be another recurrent mutation in Chinese patients with BCD. Our study expands the mutation spectrum of CYP4V2 and characterizes novel genotype-phenotype associations in Chinese patients with BCD. C1 [Yin, Houfa; Jin, Chongfei; Fang, Xiaoyun; Miao, Qi; Zhao, Yingying; Chen, Zhiqing; Su, Zhaoan; Ye, Panpan; Wang, Yao; Yin, Jinfu] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Ctr Eye, Hangzhou 310003, Zhejiang, Peoples R China. [Yin, Houfa; Fang, Xiaoyun; Miao, Qi; Zhao, Yingying; Chen, Zhiqing; Su, Zhaoan; Ye, Panpan; Wang, Yao; Yin, Jinfu] Zhejiang Prov Key Lab Ophthalmol, Hangzhou, Zhejiang, Peoples R China. [Jin, Chongfei] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Fang, XY (reprint author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Ctr Eye, Hangzhou 310003, Zhejiang, Peoples R China. EM xiaoyun.fang88@gmail.com FU Qianjiang Talents Project of Zhejiang province [2010R10067]; Zhejiang Key Innovation Team Project of China [2009R50039]; Zhejiang Key Laboratory Fund of China [2011E10006]; National Natural Science Foundation of China [81100640]; Public Welfare Technology Project of Science Technology Department of Zhejiang Province [2012C23068] FX This work was supported by the Qianjiang Talents Project of Zhejiang province (Grant No. 2010R10067), Zhejiang Key Innovation Team Project of China (Grant No. 2009R50039), Zhejiang Key Laboratory Fund of China (Grant No. 2011E10006), National Natural Science Foundation of China (Grant No. 81100640) and Public Welfare Technology Project of Science Technology Department of Zhejiang Province (Grant No. 2012C23068). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 8 Z9 8 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 16 PY 2014 VL 9 IS 4 AR e94960 DI 10.1371/journal.pone.0094960 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI4VW UT WOS:000336863900088 PM 24739949 ER PT J AU Kwon, HS Nakaya, N Abu-Asab, M Kim, HS Tomarev, SI AF Kwon, Heung Sun Nakaya, Naoki Abu-Asab, Mones Kim, Hong Sug Tomarev, Stanislav I. TI Myocilin Is Involved in NgR1/Lingo-1-Mediated Oligodendrocyte Differentiation and Myelination of the Optic Nerve SO JOURNAL OF NEUROSCIENCE LA English DT Article DE astrocyte; differentiation; Lingo-1; myelin; myocilin; oligodendrocyte ID OPEN-ANGLE GLAUCOMA; GLUCOCORTICOID RESPONSE PROTEIN; HUMAN TRABECULAR MESHWORK; MOUSE MODEL; ER STRESS; EXPRESSION; GENE; LINGO-1; IDENTIFICATION; GLYCOPROTEIN AB Myocilin is a secreted glycoprotein that belongs to a family of olfactomedin domain-containing proteins. Although myocilin is detected in several ocular and nonocular tissues, the only reported human pathology related to mutations in the MYOCILIN gene is primary open-angle glaucoma. Functions of myocilin are poorly understood. Here we demonstrate that myocilin is a mediator of oligodendrocyte differentiation and is involved in the myelination of the optic nerve in mice. Myocilin is expressed and secreted by optic nerve astrocytes. Differentiation of optic nerve oligodendrocytes is delayed in Myocilin-null mice. Optic nerves of Myocilin-null mice contain reduced levels of several myelin-associated proteins including myelin basic protein, myelin proteolipid protein, and 2 ' 3 ' -cyclic nucleotide 3 ' -phosphodiesterase compared with those of wild-type littermates. This leads to reduced myelin sheath thickness of optic nerve axons in Myocilin-null mice compared with wild-type littermates, and this difference is more pronounced at early postnatal stages compared with adult mice. Myocilin also affects differentiation of oligodendrocyte precursors in vitro. Its addition to primary cultures of differentiating oligodendrocyte precursors increases levels of tested markers of oligodendrocyte differentiation and stimulates elongation of oligodendrocyte processes. Myocilin stimulation of oligodendrocyte differentiation occurs through the NgR1/Lingo-1 receptor complex. Myocilin physically interacts with Lingo-1 and may be considered as a Lingo-1 ligand. Myocilin-induced elongation of oligodendrocyte processes may be mediated by activation of FYN and suppression of RhoA GTPase. C1 [Kwon, Heung Sun; Nakaya, Naoki; Tomarev, Stanislav I.] NEI, Lab Retinal Cell & Mol Biol, Retinal Gangl Cell Biol Sect, NIH, Bethesda, MD 20892 USA. [Abu-Asab, Mones] NEI, Histol Core, NIH, Bethesda, MD 20892 USA. [Kim, Hong Sug] NCI, Neuro Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Tomarev, SI (reprint author), NEI, NIH, Bldg 6,Room 212,6 Ctr Dr, Bethesda, MD 20892 USA. EM tomarevs@nei.nih.gov FU National Eye Institute, National Institutes of Health FX This work was supported by the Intramural Research Programs of the National Eye Institute, National Institutes of Health. We thank Drs. Haohua Qian for help with flash visual evoked potentials recording and Thomas V. Johnson for critical reading of this manuscript. NR 48 TC 12 Z9 12 U1 0 U2 7 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 16 PY 2014 VL 34 IS 16 BP 5539 EP 5551 DI 10.1523/JNEUROSCI.4731-13.2014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AF7WN UT WOS:000334926000015 PM 24741044 ER PT J AU Starke, RM Chalouhi, N Jabbour, PM Tjoumakaris, SI Gonzalez, LF Rosenwasser, RH Wada, K Shimada, K Hasan, DM Greig, NH Owens, GK Dumont, AS AF Starke, Robert M. Chalouhi, Nohra Jabbour, Pascal M. Tjoumakaris, Stavropoula I. Gonzalez, L. Fernando Rosenwasser, Robert H. Wada, Kosuke Shimada, Kenji Hasan, David M. Greig, Nigel H. Owens, Gary K. Dumont, Aaron S. TI Critical role of TNF-alpha in cerebral aneurysm formation and progression to rupture SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Cerebral; Aneurysm; Rupture; Subarachnoid hemorrhage; TNF-alpha; Tumor necrosis factor ID SMOOTH-MUSCLE-CELLS; INTRACRANIAL ANEURYSMS; MATRIX METALLOPROTEINASES; PHENOTYPIC MODULATION; MICE; ATHEROSCLEROSIS; RATS; NEUROINFLAMMATION; HYPERTENSION; INFLAMMATION AB Background: Alterations in TNF-alpha expression have been associated with cerebral aneurysms, but a direct role in formation, progression, and rupture has not been established. Methods: Cerebral aneurysms were induced through hypertension and a single stereotactic injection of elastase into the basal cistern in mice. To test the role of TNF-alpha in aneurysm formation, aneurysms were induced in TNF-alpha knockout mice and mice pretreated with the synthesized TNF-alpha inhibitor 3,6' dithiothalidomide (DTH). To assess the role of TNF-alpha in aneurysm progression and rupture, DTH was started 6 days after aneurysm induction. TNF-alpha expression was assessed through real-time PCR and immunofluorescence staining. Results: TNF-alpha knockout mice and those pre-treated with DTH had significantly decreased incidence of aneurysm formation and rupture as compared to sham mice. As compared with sham mice, TNF-alpha protein and mRNA expression was not significantly different in TNF-alpha knockout mice or those pre-treated with DTH, but was elevated in unruptured and furthermore in ruptured aneurysms. Subarachnoid hemorrhage (SAH) occurred between 7 and 21 days following aneurysm induction. To ensure aneurysm formation preceded rupture, additional mice underwent induction and sacrifice after 7 days. Seventy-five percent had aneurysm formation without evidence of SAH. Initiation of DTH treatment 6 days after aneurysm induction did not alter the incidence of aneurysm formation, but resulted in aneurysmal stabilization and a significant decrease in rupture. Conclusions: These data suggest a critical role of TNF-alpha in the formation and rupture of aneurysms in a model of cerebral aneurysm formation. Inhibitors of TNF-alpha could be beneficial in preventing aneurysmal progression and rupture. C1 [Starke, Robert M.; Chalouhi, Nohra; Jabbour, Pascal M.; Tjoumakaris, Stavropoula I.; Gonzalez, L. Fernando; Rosenwasser, Robert H.; Dumont, Aaron S.] Thomas Jefferson Univ, Dept Neurol Surg, Joseph & Marie Field Cerebrovasc Res Lab, Div Neurovasc & Endovasc Surg, Philadelphia, PA 19107 USA. [Starke, Robert M.] Univ Virginia, Dept Neurol Surg, Charlottesville, VA 22908 USA. [Wada, Kosuke; Shimada, Kenji] Univ Calif San Francisco, Ctr Cerebrovasc Res, San Francisco, CA 94143 USA. [Hasan, David M.] Univ Iowa, Dept Neurosurg, Cedar Rapids, IA USA. [Greig, Nigel H.] NIA, NIH, Translat Gerontol Branch, Intramural Res Program, Washington, DC USA. [Owens, Gary K.] Univ Virginia, Dept Mol Physiol & Biophys, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA USA. [Dumont, Aaron S.] Tulane Univ, Dept Neurol Surg, New Orleans, LA 70118 USA. RP Starke, RM (reprint author), Thomas Jefferson Univ, Dept Neurol Surg, Joseph & Marie Field Cerebrovasc Res Lab, Div Neurovasc & Endovasc Surg, Philadelphia, PA 19107 USA. EM bobby.starke@gmail.com FU National Institutes of Health (NIH) [K08NS067072, R03NS079227-01A1, K08NS082363-01A1, R01 HL57353, R01 HL098538, R01 HL087867]; NIH FX This work was supported by National Institutes of Health (NIH) grants K08NS067072 to AD, R03NS079227-01A1 and K08NS082363-01A1 to DH, and R01 HL57353, R01 HL098538, and R01 HL087867 to GO. NG is supported by the Intramural Research Program of the NIH. NR 35 TC 23 Z9 25 U1 2 U2 3 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 16 PY 2014 VL 11 AR 77 DI 10.1186/1742-2094-11-77 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA AF8GX UT WOS:000334954900003 PM 24739142 ER PT J AU Rinaldi, C Bott, LC Fischbeck, KH AF Rinaldi, Carlo Bott, Laura C. Fischbeck, Kenneth H. TI Muscle Matters in Kennedy's Disease SO NEURON LA English DT Editorial Material ID BULBAR MUSCULAR-ATROPHY; ANDROGEN RECEPTOR; MOUSE MODEL; OVEREXPRESSION; PATHOLOGY; PROTEIN AB Polyglutamine expansion in the androgen receptor causes Kennedy's disease. Two recent reports, Cortes et al. (2014) in this issue of Neuron and Lieberman et al. (2014) in Cell Reports, raise the possibility that targeting expression of the mutant protein in skeletal muscle, instead of the nervous system, may mitigate manifestations of this disorder. C1 [Rinaldi, Carlo; Bott, Laura C.; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Bott, Laura C.] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. RP Fischbeck, KH (reprint author), NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. EM kf@ninds.nih.gov FU Intramural NIH HHS [ZIA NS003038-07] NR 16 TC 3 Z9 3 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD APR 16 PY 2014 VL 82 IS 2 BP 251 EP 253 DI 10.1016/j.neuron.2014.04.005 PG 3 WC Neurosciences SC Neurosciences & Neurology GA AF1XI UT WOS:000334506800001 PM 24742452 ER PT J AU Lackford, B Yao, CG Charles, GM Weng, LJ Zheng, XF Choi, EA Xie, XH Wan, J Xing, Y Freudenberg, JM Yang, PY Jothi, R Hu, G Shi, YS AF Lackford, Brad Yao, Chengguo Charles, Georgette M. Weng, Lingjie Zheng, Xiaofeng Choi, Eun-A Xie, Xiaohui Wan, Ji Xing, Yi Freudenberg, Johannes M. Yang, Pengyi Jothi, Raja Hu, Guang Shi, Yongsheng TI Fip1 regulates mRNA alternative polyadenylation to promote stem cell self-renewal SO EMBO JOURNAL LA English DT Article DE alternative polyadenylation; stem cell; reprogramming; mRNA processing ID 3' UNTRANSLATED REGIONS; GENOME-WIDE ANALYSIS; EMBRYONIC-DEVELOPMENT; PROCESSING COMPLEX; CLEAVAGE; PLURIPOTENCY; REVEALS; SITES; DIFFERENTIATION; EXPRESSION AB Synopsis image Alternative polyadenylation is an emerging key post-transcriptional regulatory mechanism. The essential role for mRNA 3 ' end processing factor Fip1 in stem cell self-renewal and pluripotency reveals the importance of poly(A) site choice. mRNA alternative polyadenylation is critical for stem cell self-renewal and pluripotency Fip1 is a key regulator of mRNA alternative polyadenylation The direction of alternative polyadenylation switch is controlled by Fip1 binding and the distance between alternative poly(A) sites Abstract mRNA alternative polyadenylation (APA) plays a critical role in post-transcriptional gene control and is highly regulated during development and disease. However, the regulatory mechanisms and functional consequences of APA remain poorly understood. Here, we show that an mRNA 3 ' processing factor, Fip1, is essential for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Fip1 promotes stem cell maintenance, in part, by activating the ESC-specific APA profiles to ensure the optimal expression of a specific set of genes, including critical self-renewal factors. Fip1 expression and the Fip1-dependent APA program change during ESC differentiation and are restored to an ESC-like state during somatic reprogramming. Mechanistically, we provide evidence that the specificity of Fip1-mediated APA regulation depends on multiple factors, including Fip1-RNA interactions and the distance between APA sites. Together, our data highlight the role for post-transcriptional control in stem cell self-renewal, provide mechanistic insight on APA regulation in development, and establish an important function for APA in cell fate specification. C1 [Lackford, Brad; Charles, Georgette M.; Zheng, Xiaofeng; Freudenberg, Johannes M.; Yang, Pengyi; Jothi, Raja; Hu, Guang] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Yao, Chengguo; Choi, Eun-A; Shi, Yongsheng] Univ Calif Irvine, Sch Med, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. [Weng, Lingjie; Xie, Xiaohui] Univ Calif Irvine, Inst Genom & Bioinformat, Irvine, CA USA. [Weng, Lingjie; Xie, Xiaohui] Univ Calif Irvine, Dept Comp Sci, Irvine, CA USA. [Wan, Ji; Xing, Yi] Univ Iowa, Interdept Grad Program Genet, Iowa City, IA USA. [Wan, Ji; Xing, Yi] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Xing, Yi] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. RP Hu, G (reprint author), NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. EM hug4@niehs.nih.gov; yongshes@uci.edu RI Wan, Ji/K-1344-2014; Jothi, Raja/G-3780-2015; Hu, Guang/E-7474-2016; OI Hu, Guang/0000-0003-0437-4723; Yang, Pengyi/0000-0003-1098-3138 FU National Institute of Environmental Health Sciences; National Institutes of Health Intramural Research Program [1ZIAES102745-02, 1ZIAES102625-03]; NIH [GM090056, GM088342]; American Cancer Society [RSG-12-186]; National Science Foundation [DBI-084621]; Edward Mallinckrodt Jr. Foundation FX We thank Drs. M. Waterman, K. Hertel, K. Adelman, T. Hall, T. Kunkel, and P. Wade for critically reading of the manuscript; Drs. J. Ward and D. Fargo for assistance with bioinformatics analysis; Dr. C. Limoli for sharing equipment. This study was supported in part by the National Institute of Environmental Health Sciences, National Institutes of Health Intramural Research Program 1ZIAES102745-02 (to G. H., G. M. C., B. L., X. Z.), 1ZIAES102625-03 (to R. J., J. F.), NIH Grants GM090056 (to Y.S) and GM088342 (to Y.X.), American Cancer Society Grant RSG-12-186 (to Y.S), National Science Foundation Grant DBI-084621 (to X. X.), and a junior faculty grant from the Edward Mallinckrodt Jr. Foundation (to Y.X.). NR 37 TC 25 Z9 28 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD APR 16 PY 2014 VL 33 IS 8 BP 878 EP 889 DI 10.1002/embj.201386537 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AF2IR UT WOS:000334536300008 PM 24596251 ER PT J AU Nayak, RK Pearson, SD Miller, FG AF Nayak, Rahul K. Pearson, Steven D. Miller, Franklin G. TI Cost-Related Motivations for Conducting Research Participants Should Be Informed SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MACULAR DEGENERATION; BEVACIZUMAB C1 [Nayak, Rahul K.; Pearson, Steven D.; Miller, Franklin G.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Pearson, Steven D.] Inst Clin & Econ Review, Boston, MA USA. RP Miller, FG (reprint author), NIH, Ctr Clin, Dept Bioeth, 10 Ctr Dr,Bldg 10,Rm 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov OI Nayak, Rahul/0000-0001-6725-7634 NR 8 TC 3 Z9 3 U1 0 U2 0 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 16 PY 2014 VL 311 IS 15 BP 1491 EP 1492 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AE9DX UT WOS:000334306000012 PM 24615527 ER PT J AU Cao, S Xiao, L Rao, JN Zou, TT Liu, L Zhang, D Turner, DJ Gorospe, M Wang, JY AF Cao, Shan Xiao, Lan Rao, Jaladanki N. Zou, Tongtong Liu, Lan Zhang, Dee Turner, Douglas J. Gorospe, Myriam Wang, Jian-Ying TI Inhibition of Smurf2 translation by miR-322/503 modulates TGF-beta/Smad2 signaling and intestinal epithelial homeostasis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID MESSENGER-RNA STABILITY; BINDING PROTEIN HUR; UBIQUITIN LIGASE; POLYAMINE DEPLETION; DEPENDENT DEGRADATION; MUCOSAL GROWTH; CELLS; TARGETS; ACTIVATION; APOPTOSIS AB Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that regulates transforming growth factor beta (TGF-beta)/Smad signaling and is implicated in a wide variety of cellular responses, but the exact mechanisms that control Smurf2 abundance are largely unknown. Here we identify microRNA-322 (miR-322) and miR-503 as novel factors that regulate Smurf2 expression posttranscriptionally. Both miR-322 and miR-503 interact with Smurf2 mRNA via its 3'-untranslated region (UTR) and repress Smurf2 translation but do not affect total Smurf2 mRNA levels. Studies using heterologous reporter constructs reveal a greater repressive effect of miR-322/503 through a single binding site in the Smurf2 3'-UTR, whereas point mutation of this site prevents miR-322/503-induced repression of Smurf2 translation. Increased levels of endogenous Smurf2 via antagonism of miR-322/503 inhibits TGF-beta-induced Smad2 activation by increasing degradation of phosphorylated Smad2. Furthermore, the increase in Smurf2 in intestinal epithelial cells (IECs) expressing lower levels of miR-322/503 is associated with increased resistance to apoptosis, which is abolished by Smurf2 silencing. These findings indicate that miR-322/503 represses Smurf2 translation, in turn affecting intestinal epithelial homeostasis by altering TGF-beta/Smad2 signaling and IEC apoptosis. C1 [Cao, Shan; Xiao, Lan; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Zhang, Dee; Turner, Douglas J.; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA. [Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Cao, Shan; Xiao, Lan; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Zhang, Dee; Turner, Douglas J.; Wang, Jian-Ying] Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA. [Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Wang, JY (reprint author), Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA. EM jwang@smail.umaryland.edu FU Department of Veterans Affairs; National Institutes of Health [DK-57819, DK-61972, DK-68491]; National Institute on Aging-Intramural Research Program, National Institutes of Health FX We thank Jennifer L. Martindale for technical support in studies of polysome analysis. This work was supported by Merit Review Awards (to J.Y.W., D.J.T., and J.N.R.) from the Department of Veterans Affairs and by National Institutes of Health Grants DK-57819, DK-61972, and DK-68491 (to J.Y.W.). J.Y.W. is a Senior Research Career Scientist, Medical Research Service, U.S. Department of Veterans Affairs. M. G. is supported by the National Institute on Aging-Intramural Research Program, National Institutes of Health. NR 57 TC 22 Z9 22 U1 0 U2 5 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR 15 PY 2014 VL 25 IS 8 BP 1234 EP 1243 DI 10.1091/mbc.E13-09-0560 PG 10 WC Cell Biology SC Cell Biology GA AM2AC UT WOS:000339649400004 PM 24554769 ER PT J AU Lin, FR Ferrucci, L An, Y Goh, JO Doshi, J Metter, EJ Davatzikos, C Kraut, MA Resnick, SM AF Lin, F. R. Ferrucci, L. An, Y. Goh, J. O. Doshi, Jimit Metter, E. J. Davatzikos, C. Kraut, M. A. Resnick, S. M. TI Association of hearing impairment with brain volume changes in older adults SO NEUROIMAGE LA English DT Article DE Hearing loss; Hearing impairment; MRI Brain volume; Aging ID VOXEL-BASED MORPHOMETRY; AUDITORY-CORTEX; SPEECH COMPREHENSION; INCIDENT DEMENTIA; COGNITIVE DECLINE; UNITED-STATES; PATHWAY; STRESS; AGE; POPULATION AB Hearing impairment in older adults is independently associated in longitudinal studies with accelerated cognitive decline and incident dementia, and in cross-sectional studies, with reduced volumes in the auditory cortex. Whether peripheral hearing impairment is associated with accelerated rates of brain atrophy is unclear. We analyzed brain volume measurements from magnetic resonance brain scans of individuals with normal hearing versus hearing impairment (speech-frequency pure tone average > 25 dB) followed in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging for a mean of 6.4 years after the baseline scan (n = 126, age 56-86 years). Brain volume measurements were performed with semi-automated region-ofinterest (ROI) algorithms, and brain volume trajectories were analyzed with mixed-effect regression models adjusted for demographic and cardiovascular factors. We found that individuals with hearing impairment (n = 51) compared to those with normal hearing (n = 75) had accelerated volume declines in whole brain and regional volumes in the right temporal lobe (superior, middle, and inferior temporal gyri, parahippocampus, p <.05). These results were robust to adjustment for multiple confounders and were consistent with voxel-based analyses, which also implicated right greater than left temporal regions. These findings demonstrate that peripheral hearing impairment is independently associated with accelerated brain atrophy in whole brain and regional volumes concentrated in the right temporal lobe. Further studies investigating the mechanistic basis of the observed associations are needed. 0 2014 Elsevier Inc. All rights reserved. C1 [Lin, F. R.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA. [Lin, F. R.] Johns Hopkins Univ, Dept Geriatr Med, Baltimore, MD USA. [Lin, F. R.] Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD USA. [Lin, F. R.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Lin, F. R.] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. [Ferrucci, L.; Metter, E. J.] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [An, Y.; Goh, J. O.; Resnick, S. M.] NIA, Lab Behav Neurosci, Intramural Res Program, Baltimore, MD 21224 USA. [Goh, J. O.] Natl Taiwan Univ, Coll Med, Grad Inst Brain & Mind Sci, Taipei, Taiwan. [Doshi, Jimit; Davatzikos, C.] Univ Penn, Dept Radiol, Sect Biomed Image Anal, Philadelphia, PA 19104 USA. [Kraut, M. A.] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21205 USA. RP Lin, FR (reprint author), Johns Hopkins Ctr Aging & Hlth, 2024 E Monument St,Suite 2-700, Baltimore, MD 21205 USA. EM flin1@jhmi.edu RI GOH, JOSHUA/C-8063-2016 OI GOH, JOSHUA/0000-0001-7808-5452 FU intramural research program of the National Institute on Aging; NIH [K23DC011279]; Triological Society/American College of Surgeons Clinician Scientist Award; Eleanor Schwartz Charitable Foundation FX This study was supported by the intramural research program of the National Institute on Aging. Dr. Lin was supported by NIH K23DC011279, a Triological Society/American College of Surgeons Clinician Scientist Award, and the Eleanor Schwartz Charitable Foundation. NR 48 TC 33 Z9 37 U1 7 U2 23 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2014 VL 90 BP 84 EP 92 DI 10.1016/j.neuroimage.2013.12.059 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AL1TP UT WOS:000338909500009 PM 24412398 ER PT J AU Banerjee, A Pillai, AS Sperling, JR Smith, JF Horwitz, B AF Banerjee, Arpan Pillai, Ajay S. Sperling, Justin R. Smith, Jason F. Horwitz, Barry TI Temporal microstructure of cortical networks (TMCN) underlying task-related differences (vol 62, pg 1643, 2012) SO NEUROIMAGE LA English DT Correction C1 [Banerjee, Arpan; Pillai, Ajay S.; Sperling, Justin R.; Smith, Jason F.; Horwitz, Barry] NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. RP Banerjee, A (reprint author), NIDCD, Brain Imaging & Modeling Sect, NIH, 10 Ctr Dr,Room 5D39, Bethesda, MD 20892 USA. EM Arpan.Banerjee@nih.gov NR 1 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2014 VL 90 BP 469 EP 469 DI 10.1016/j.neuroimage.2013.12.034 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AL1TP UT WOS:000338909500045 ER PT J AU Malee, KM Mellins, CA Huo, Y Tassiopoulos, K Smith, R Sirois, PA Allison, SM Kacanek, D Kapetanovic, S Williams, PL Grant, ML Marullo, D Aidala, AA AF Malee, Kathleen M. Mellins, Claude A. Huo, Yanling Tassiopoulos, Katherine Smith, Renee Sirois, Patricia A. Allison, Susannah M. Kacanek, Deborah Kapetanovic, Suad Williams, Paige L. Grant, Mitzie L. Marullo, Daniel Aidala, Angela A. CA Pediat HIV AIDS Cohort Study PHACS TI Prevalence, Incidence, and Persistence of Psychiatric and Substance Use Disorders Among Mothers Living With HIV SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; women; psychiatric disorder; substance use disorders; prevalence ID MENTAL-HEALTH; ANTIRETROVIRAL THERAPY; DEPRESSIVE SYMPTOMS; SEROPOSITIVE WOMEN; ANXIETY DISORDERS; POSITIVE WOMEN; INFECTED WOMEN; SELF-REPORT; MORTALITY; TRAUMA AB Objective: To evaluate prevalence, incidence, remission, and persistence of psychiatric and substance use disorders among HIV-infected mothers and identify biopsychosocial correlates. Methods: HIV-infected mothers (n = 1223) of HIV-exposed uninfected children enrolled in a prospective cohort study; HIV-uninfected mothers (n = 128) served as a comparison group. Mothers provided sociodemographic and health information and completed the Client Diagnostic Questionnaire (CDQ). Prevalence of any psy-chiatric or substance use disorder at initial evaluation was compared between the 2 groups. Incident, remitting, and persisting disorders were identified for 689 mothers with HIV who completed follow-up CDQs. We used logistic regression to evaluate adjusted associations of biopsychosocial characteristics with presence, incidence, remission, and persistence of disorders. Results: Thirty-five percent of mothers screened positive for any psychiatric or substance use disorder at initial evaluation, with no difference by maternal HIV status (P = 1.00). Among HIV-infected mothers, presence of any disorder was associated with younger age [adjusted odds ratio (aOR): 1.39; 95% CI: 1.09 to 1.75], single parenthood (aOR: 1.35; 95% CI: 1.08 to 1.68), and functional limitations (aOR: 2.29; 95% CI: 1.81 to 2.90). Incident disorders were associated with functional limitations (aOR: 1.92; 95% CI: 1.10 to 3.30). Among HIV-infected mothers with a disorder at initial evaluation (n = 238), 61% had persistent disorders. Persistent disorders were associated with lower income (aOR: 2.44; 95% CI: 1.33 to 4.76) and functional limitations (aOR: 3.19; 95% CI: 1.87 to 5.48). Receipt of treatment for any disorder was limited: 4.5% at study entry, 7% at follow-up, 5.5% at both entry and follow-up. Conclusions: Psychiatric and substance use disorders remain significant comorbid conditions among HIV-infected mothers and require accessible evidence-informed treatment. C1 [Malee, Kathleen M.] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Mellins, Claude A.] New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, Div Gender Sexual & Hlth, New York, NY 10032 USA. [Mellins, Claude A.] Columbia Univ, New York, NY USA. [Huo, Yanling; Kacanek, Deborah; Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Tassiopoulos, Katherine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Smith, Renee] Univ Illinois, Dept Pediat, Chicago, IL USA. [Sirois, Patricia A.] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. [Allison, Susannah M.; Kapetanovic, Suad] NIMH, NIH, Bethesda, MD 20892 USA. [Grant, Mitzie L.] Drexel Univ, Coll Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Marullo, Daniel] Childrens Alabama, Dept Childrens Behav Hlth, Birmingham, AL USA. [Aidala, Angela A.] Columbia Univ, Dept Sociomed Sci, Mailman Sch Publ Hlth, New York, NY USA. RP Malee, KM (reprint author), Ann & Robert H Lurie Childrens Hosp, 215 East Chicago Ave,Box 155, Chicago, IL 60614 USA. EM kmalee@luriechildrens.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Drug Abuse; National Institute of Allergy and Infectious Diseases; Office of AIDS Research; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Heart Lung and Blood Institute; National Institute of Dental and Craniofacial Research; National Institute on Alcohol Abuse and Alcoholism; Harvard University School of Public Health [HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3]; Tulane University School of Medicine [HD052104, 3U01HD052104-06S1]; Intramural Research Program of the National Institute of Mental Health FX The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard University School of Public Health (HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3) and the Tulane University School of Medicine (HD052104, 3U01HD052104-06S1). This project was also supported in part by the Intramural Research Program of the National Institute of Mental Health. NR 43 TC 4 Z9 4 U1 3 U2 4 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 15 PY 2014 VL 65 IS 5 BP 526 EP 534 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AJ4XX UT WOS:000337684400007 PM 24759063 ER PT J AU Vogler, MA Smeaton, LM Wright, RL Cardoso, SW Sanchez, J Infante, R Moran, LE Godfrey, C Demeter, LM Johnson, VA AF Vogler, Mary A. Smeaton, Laura M. Wright, Rodney L. Cardoso, Sandra W. Sanchez, Jorge Infante, Rosa Moran, Laura E. Godfrey, Catherine Demeter, Lisa M. Johnson, Victoria A. TI Combination Antiretroviral Treatment for Women Previously Treated Only in Pregnancy: Week 24 Results of AIDS Clinical Trials Group Protocol A5227 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral therapy; postpartum women; efavirenz; adherence; pMTCT ID STRUCTURED TREATMENT INTERRUPTIONS; SINGLE-DOSE NEVIRAPINE; DRUG-RESISTANT HIV-1; VERTICAL TRANSMISSION; RECEIVING NEVIRAPINE; HIV-1-INFECTED WOMEN; THERAPY; ZIDOVUDINE; MUTATIONS; ADHERENCE AB Background: Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of mother-to-child transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and coformulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). Methods: Nonpregnant women with plasma HIV-1 RNA of >= 500 copies per milliliter, previously cART exposed for pMTCT only, were eligible if they were off ART for >= 24 weeks before entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA < 400 copies/mL) at 24 weeks. Results: Fifty-four women were enrolled between October 2007 and December 2009; 52 of 54 completed 24 weeks of follow-up. Median baseline CD4+ T-cell count was 265/mm(3) and baseline plasma HIV-1 RNA was 4.6 log(10) copies per milliliter. Median prior cART duration was 14 weeks, and median time elapsed from the last pMTCT dose to entry was 22 months. Virologic response at 24 weeks was observed in 42 of 52 women or 81% (exact 95% confidence interval: 68% to 90%). There were no differences in response by country, by number, or class of prior pMTCT exposures. Although confirmed virologic failure occurred in 8 women, no virologic failures were observed in women reporting perfect early adherence. Conclusions: In this first prospective clinical trial studying combination antiretroviral retreatment in women with a history of pregnancy-limited cART, the observed virologic response to TDF/FTC and EFV at 24 weeks was 81%. Virologic failures occurred and correlated with self-reported nonadherence. C1 [Vogler, Mary A.] Cornell Univ, Weill Cornell Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA. [Smeaton, Laura M.] Harvard Univ, Sch Publ Hlth, Ctr Biostat & AIDS Res, Boston, MA 02115 USA. [Wright, Rodney L.] Albert Einstein Coll Med, Dept Obstet & Gynecol, Bronx, NY 10467 USA. [Cardoso, Sandra W.] Fundacao Oswaldo Cruz, Inst Pesquisa Clin Evandro Chagas, STD AIDS Clin Res Lab, Rio De Janeiro, Brazil. [Sanchez, Jorge; Infante, Rosa] Asociac Civil IMPACTA Salud & Educ, Lima, Peru. [Moran, Laura E.] Social & Sci Syst Inc, Silver Spring, MD USA. [Godfrey, Catherine] NIAID, HIV Res Branch, Div Aids, NIH, Bethesda, MD 20892 USA. [Demeter, Lisa M.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Johnson, Victoria A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Johnson, Victoria A.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. RP Vogler, MA (reprint author), Cornell Univ, Weill Cornell Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA. EM mav9046@med.cornell.edu FU National Institute of Allergy and Infectious Diseases [U01AI068636]; National Institute of Mental Health, National Institute of Dental and Craniofacial Research; Statistical and Data Management Center of the AIDS Clinical Trials Group under the National Institute of Allergy and Infectious Diseases [1 U01AI068634]; University of Alabama at Birmingham ACTG CTU grant [U01 AI069918]; Instituto de Pesquisa Clinica Evandro Chagas CRS Fiocruz Therapeutic and Prevention HIV AIDS CTU grant [12101, 1 U01 AI069476-01]; IMPACTA Peru CTU grant [1U01AI069438-01]; Weill Cornell Medical College ACTG CTU grant [5U01AI069419]; University of Rochester CTU grant [1U01 AI069511] FX Supported by Award no. U01AI068636 from the National Institute of Allergy and Infectious Diseases and supported by National Institute of Mental Health, National Institute of Dental and Craniofacial Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. Supported by the Statistical and Data Management Center of the AIDS Clinical Trials Group under the National Institute of Allergy and Infectious Diseases grant no. 1 U01AI068634. UAB Virology Specialty Laboratory 54 support VSL UM1 AI068636 and UAB CFAR P30; AI27767 for laboratory support and core research facilities within UAB Center for AIDS Research/University of Alabama at Birmingham School of Medicine and Birmingham Veterans Affairs Medical Center, Birmingham Alabama; University of Alabama at Birmingham ACTG CTU grant no. U01 AI069918; Instituto de Pesquisa Clinica Evandro Chagas CRS (12101) Fiocruz Therapeutic and Prevention HIV AIDS CTU grant no. 1 U01 AI069476-01; IMPACTA Peru CTU grant no. 1U01AI069438-01; Weill Cornell Medical College ACTG CTU grant no. 5U01AI069419; University of Rochester CTU grant no. 1U01 AI069511; Bristol Myers Squibb Company, Gilead Sciences, Inc, and Merck & Co, Inc, provided study drugs. NR 31 TC 0 Z9 0 U1 0 U2 1 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 15 PY 2014 VL 65 IS 5 BP 542 EP 550 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AJ4XX UT WOS:000337684400009 PM 24759064 ER PT J AU Zhu, N Jacobs, DR Schreiner, PJ Yaffe, K Bryan, N Launer, LJ Whitmer, RA Sidney, S Demerath, E Thomas, W Bouchard, C He, K Reis, J Sternfeld, B AF Zhu, Na Jacobs, David R., Jr. Schreiner, Pamela J. Yaffe, Kristine Bryan, Nick Launer, Lenore J. Whitmer, Rachel A. Sidney, Stephen Demerath, Ellen Thomas, William Bouchard, Claude He, Ka Reis, Jared Sternfeld, Barbara TI Cardiorespiratory fitness and cognitive function in middle age The CARDIA Study SO NEUROLOGY LA English DT Article ID YOUNG-ADULTS CARDIA; ARTERY RISK DEVELOPMENT; ALZHEIMER-DISEASE; OLDER-ADULTS; MRI FINDINGS; IMPAIRMENT; EXERCISE; ASSOCIATION; RECRUITMENT; PREDICTION AB Objective:To investigate whether greater cardiorespiratory fitness (CRF) is associated with better cognitive function 25 years later.Methods:We studied 2,747 participants in the community-based Coronary Artery Risk Development in Young Adults Study of black and white men and women aged 18 to 30 years at recruitment in 1985-1986 (baseline year 0). Symptom-limited maximal treadmill test durations at years 0 and 20 provided measures of CRF. Cognitive tests at year 25 measured verbal memory (Rey Auditory Verbal Learning Test [RAVLT]), psychomotor speed (Digit Symbol Substitution Test [DSST]), and executive function (Stroop Test).Results:Per minute of baseline CRF, the RAVLT was 0.12 words recalled higher (standard error [SE] = 0.03, p < 0.0001), the DSST was 0.92 digits higher (SE = 0.13, p < 0.0001), and the Stroop Test score was 0.52 lower (better performance, SE = 0.11, p < 0.0001), after accounting for race, sex, age, education, and clinical center. Compared with the lowest quartile of CRF, each cognitive test was 21% to 34% of an SD better in the highest CRF quartile. Further adjustment for lifestyle and clinical measures attenuated coefficients for RAVLT and DSST slightly, while the coefficient predicting the Stroop Test lost more than half its value (p = 0.07). Analysis in the subset of 1,957 participants who also completed the year-20 treadmill test showed that 20-year change in CRF was positively associated only with DSST (p < 0.001).Conclusions:Better verbal memory and faster psychomotor speed at ages 43 to 55 years were clearly associated with better CRF 25 years earlier. C1 [Zhu, Na; Jacobs, David R., Jr.; Schreiner, Pamela J.; Demerath, Ellen] Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. [Thomas, William] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, N-0316 Oslo, Norway. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bryan, Nick] Univ Penn Hlth Syst, Dept Radiol, Philadelphia, PA USA. [Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Whitmer, Rachel A.; Sidney, Stephen; Sternfeld, Barbara] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. [Bouchard, Claude] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70808 USA. [He, Ka] Indiana Univ, Dept Epidemiol & Biostat, Bloomington, IN USA. [Reis, Jared] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Jacobs, DR (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. EM Jacob004@umn.edu RI He, Ka/I-9906-2014; Bouchard, Claude/A-7637-2009 FU National Heart, Lung, and Blood Institute [HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, HHSN268200900041C]; Intramural Research Program of the National Institute on Aging; [R01 HL 078972] FX The Coronary Artery Risk Development in Young Adults (CARDIA) Study is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Institute on Aging, plus a grant for the CARDIA Fitness Study R01 HL 078972. NR 40 TC 15 Z9 16 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD APR 15 PY 2014 VL 82 IS 15 BP 1339 EP 1346 DI 10.1212/WNL.0000000000000310 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AH9XG UT WOS:000336498000013 PM 24696506 ER PT J AU Dominic, EA Ramezani, A Anker, SD Verma, M Mehta, N Rao, M AF Dominic, Elizabeth A. Ramezani, Ali Anker, Stefan D. Verma, Mukesh Mehta, Nehal Rao, Madhumathi TI Mitochondrial cytopathies and cardiovascular disease SO HEART LA English DT Review DE Heart Failure; Coronary Artery Disease ID DILATED CARDIOMYOPATHY; RESPIRATORY-CHAIN; HEART-FAILURE; CARDIAC-HYPERTROPHY; DNA MUTATIONS; MYOCARDIUM; MTDNA; AMPLIFICATION; MECHANISMS; MUSCLE AB The global epidemic of cardiovascular disease remains the leading cause of death in the USA and across the world. Functional and structural integrity of mitochondria are essential for the physiological function of the cardiovascular system. The metabolic adaptation observed in normal heart is lost in the failing myocardium, which becomes progressively energy depleted leading to impaired myocardial contraction and relaxation. Uncoupling of electron transfer from ATP synthesis leads to excess generation of reactive species, leading to widespread cellular injury and cardiovascular disease. Accumulation of mitochondrial DNA mutation has been linked to ischaemic heart disease, cardiomyopathy and atherosclerotic vascular disease. Mitochondria are known to regulate apoptotic and autophagic pathways that have been shown to play an important role in the development of cardiomyopathy and atherosclerosis. A number of pharmacological and non-pharmacological treatment options have been explored in the management of mitochondrial diseases with variable success. C1 [Dominic, Elizabeth A.; Ramezani, Ali] George Washington Sch Med, Washington, DC USA. [Anker, Stefan D.] Campus Virchow Klinikum, CharitA, Dept Cardiol, Berlin, Germany. [Verma, Mukesh] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Mehta, Nehal] NHLBI, Sect Inflammat & Cardiometabol Dis, Bethesda, MD 20892 USA. [Rao, Madhumathi] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. RP Ramezani, A (reprint author), George Washington Univ, Dept Med, 2300 1 St NW, Washington, DC 20037 USA. EM Ramezani@gwu.edu NR 30 TC 11 Z9 14 U1 1 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD APR 15 PY 2014 VL 100 IS 8 BP 611 EP 618 DI 10.1136/heartjnl-2013-304657 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AE0RA UT WOS:000333672600006 PM 24449718 ER PT J AU Shahbazi, S Peer, CJ Polizzotto, MN Uldrick, TS Roth, J Wyvill, KM Aleman, K Zeldis, JB Yarchoan, R Figg, WD AF Shahbazi, Shandiz Peer, Cody J. Polizzotto, Mark N. Uldrick, Thomas S. Roth, Jeffrey Wyvill, Kathleen M. Aleman, Karen Zeldis, Jerome B. Yarchoan, Robert Figg, William D. TI A sensitive and robust HPLC assay with fluorescence detection for the quantification of pomalidomide in human plasma for pharmacokinetic analyses SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Pomalidomide; HPLC; Fluorescence; Pharmacokinetics; Liquid extraction ID REFRACTORY MULTIPLE-MYELOMA; LOW-DOSE DEXAMETHASONE; PHASE-I; THALIDOMIDE ANALOG; CELL-ACTIVATION; LENALIDOMIDE; CC-4047; MYELOFIBROSIS; COMBINATION; MECHANISM AB Pomalidomide is a second generation IMiD (immunomodulatory agent) that has recently been granted approval by the Food and Drug Administration for treatment of relapsed multiple myeloma after prior treatment with two antimyeloma agents, including lenalidomide and bortezomib. A simple and robust HPLC assay with fluorescence detection for pomalidomide over the range of 1-500 ng/mL has been developed for application to pharmacokinetic studies in ongoing clinical trials in various other malignancies. A liquid-liquid extraction from human plasma alone or pre-stabilized with 0.1% HCl was performed, using propyl paraben as the internal standard. From plasma either pre-stabilized with 0.1% HCl or not, the assay was shown to be selective, sensitive, accurate, precise, and have minimal matrix effects (<20%). Pomalidomide was stable in plasma through 4 freeze-thaw cycles (<12% change), in plasma at room temperature for up to 2 h for samples not pre-stabilized with 0.1% HCl and up to 8 h in samples pre-stabilized with 0.1% HCl, 24h post-preparation at 4 degrees C (<2% change), and showed excellent extraction recovery (similar to 90%). This is the first reported description of the freeze/thaw and plasma stability of pomalidomide in plasma either pre-stabilized with 0.1% HCl or not. The information presented in this manuscript is important when performing pharmacokinetic analyses. The method was used to analyze clinical pharmacokinetics samples obtained after a 5 mg oral dose of pomalidomide. This relatively simple HPLC-FL assay allows a broader range of laboratories to measure pomalidomide for application to clinical pharmacokinetics. Published by Elsevier B.V. C1 [Shahbazi, Shandiz; Peer, Cody J.; Roth, Jeffrey; Figg, William D.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Polizzotto, Mark N.; Uldrick, Thomas S.; Wyvill, Kathleen M.; Aleman, Karen; Yarchoan, Robert] NCI, HIV AIDS Malignancy Branch, Bethesda, MD 20892 USA. [Zeldis, Jerome B.] Celgene Corp & Celgene Global Hlth, Summit, NJ USA. RP Figg, WD (reprint author), Clin Pharmacol Program, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM figgw@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU NIH, National Cancer Institute; National Cancer Institute; Celgene Corporation FX This study was funded in part by the Intramural Research Program of the NIH, National Cancer Institute, and a CRADA between the National Cancer Institute and Celgene Corporation. This is a US Government work and there are no restrictions on its use. The views expressed within this paper do not necessarily reflect those of the US Government. We thank the medical research staff of the HIV and AIDS Malignancy Branch, the Center for Cancer Research, and the NIH Clinical Center who helped with the study. We also thank the nursing staff of the National Cancer Institute and the fellows of the Medical Oncology Branch at the National Cancer Institute for their care of our patients; Cynthia Graves for data management assistance; and Cancer Therapy and Evaluation Program for sponsoring the trial. Most importantly, we appreciate the patients with cancer who enroll in investigational trials to advance the knowledge of this disease. NR 29 TC 6 Z9 6 U1 2 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 EI 1873-264X J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 15 PY 2014 VL 92 BP 63 EP 68 DI 10.1016/j.jpba.2014.01.001 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA AG5VR UT WOS:000335487300009 PM 24486861 ER PT J AU Petersen, EJ Henry, TB Zhao, J MacCuspie, RI Kirschling, TL Dobrovolskaia, MA Hackley, V Xing, BS White, JC AF Petersen, Elijah J. Henry, Theodore B. Zhao, Jian MacCuspie, Robert I. Kirschling, Teresa L. Dobrovolskaia, Marina A. Hackley, Vincent Xing, Baoshan White, Jason C. TI Identification and Avoidance of Potential Artifacts and Misinterpretations in Nanomaterial Ecotoxicity Measurements SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Review ID WALLED CARBON NANOTUBES; TITANIUM-DIOXIDE NANOPARTICLES; AQUEOUS C-60 CLUSTERS; TROUT ONCORHYNCHUS-MYKISS; DISSOLVED ORGANIC-MATTER; CELL-CULTURE MEDIA; SILVER NANOPARTICLES; ENGINEERED NANOMATERIALS; IN-VITRO; RAINBOW-TROUT AB Novel physicochemistries of engineered nanomaterials (ENMs) offer considerable commercial potential for new products and processes, but also the possibility of unforeseen and negative consequences upon ENM release into the environment. Investigations of ENM ecotoxicity have revealed that the unique properties of ENMs and a lack of appropriate test methods can lead to results that are inaccurate or not reproducible. The occurrence of spurious results or misinterpretations of results from ENM toxicity tests that are unique to investigations of ENMs (as opposed to traditional toxicants) have been reported, but have not yet been systemically reviewed. Our objective in this manuscript is to highlight artifacts and misinterpretations that can occur at each step of ecotoxicity testing: procurement or synthesis of the ENMs and assessment of potential toxic impurities such as metals or endotoxins, ENM storage, dispersion of the ENMs in the test medium, direct interference with assay reagents and unacknowledged indirect effects such as nutrient depletion during the assay, and assessment of the ENM biodistribution in organisms. We recommend thorough characterization of initial ENMs including measurement of impurities, implementation of steps to minimize changes to the ENMs during storage, inclusion of a set of experimental controls (e.g., to assess impacts of nutrient depletion, ENM specific effects, impurities in ENM formulation, desorbed surface coatings, the dispersion process, and direct interference of ENM with toxicity assays), and use of orthogonal measurement methods when available to assess ENMs fate and distribution in organisms. C1 [Petersen, Elijah J.] NIST, Biosyst & Biomat Div, Gaithersburg, MD 20899 USA. [Henry, Theodore B.] Heriot Watt Univ, Sch Life Sci, Edinburgh, Midlothian, Scotland. [Henry, Theodore B.] Univ Tennessee, Ctr Environm Biotechnol, Knoxville, TN 37932 USA. [Henry, Theodore B.] Univ Tennessee, Dept Forestry Wildlife & Fisheries, Knoxville, TN USA. [Zhao, Jian; Xing, Baoshan] Univ Massachusetts, Stockbridge Sch Agr, Amherst, MA 01003 USA. [MacCuspie, Robert I.; Hackley, Vincent] NIST, Mat Measurement Sci Div, Gaithersburg, MD 20899 USA. [MacCuspie, Robert I.] Florida Polytech Univ, Nanotechnol Program, Lakeland, FL 33801 USA. [Kirschling, Teresa L.] NIST, Appl Chem & Mat Div, Boulder, CO 80305 USA. [Dobrovolskaia, Marina A.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick, MD 21702 USA. [White, Jason C.] Connecticut Agr Expt Stn, Dept Analyt Chem, New Haven, CT 06504 USA. RP Petersen, EJ (reprint author), NIST, Biosyst & Biomat Div, Gaithersburg, MD 20899 USA. EM elijah.petersen@nist.gov RI Petersen, Elijah/E-3034-2013; Zhao, Jian/D-2798-2012; Nanotechnology Characterization Lab, NCL/K-8454-2012; OI Henry, Theodore/0000-0002-9675-9454; MacCuspie, Robert/0000-0002-6618-6499; Kirschling, Teresa/0000-0003-1695-0521 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; EU [604602] FX Certain commercial equipment or materials are identified in this paper in order to specify adequately the experimental procedure. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose. The study was supported in part by federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. T.B. Henry acknowledges EU FP7-NMP-2013-LARGE-7 Project Number 604602. J.C. White also acknowledges USDA AFRI 2011-67006-30181. NR 233 TC 79 Z9 79 U1 13 U2 167 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X EI 1520-5851 J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD APR 15 PY 2014 VL 48 IS 8 BP 4226 EP 4246 DI 10.1021/es4052999 PG 21 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA AF4CG UT WOS:000334658400002 PM 24617739 ER PT J AU Liu, SL Zhang, LJ Wang, ZG Zhang, ZL Wu, QM Sun, EZ Shi, YB Pang, DW AF Liu, Shu-Lin Zhang, Li-Juan Wang, Zhi-Gang Zhang, Zhi-Ling Wu, Qiu-Mei Sun, En-Ze Shi, Yun-Bo Pang, Dai-Wen TI Globally Visualizing the Microtubule-Dependent Transport Behaviors of Influenza Virus in Live Cells SO ANALYTICAL CHEMISTRY LA English DT Article ID A H7N9 VIRUS; AVIAN INFLUENZA; CARGO TRANSPORT; DYNEIN; INFECTION; DYNAMICS; PATHWAY; MOTOR; MOTILITY; REVEALS AB Understanding the microtubule-dependent behaviors of viruses in live cells is very meaningful for revealing the mechanisms of virus infection and endocytosis. Herein, we used a quantum dots-based single-particle tracking technique to dynamically and globally visualize the microtubule-dependent transport behaviors of influenza virus in live cells. We found that the intersection configuration of microtubules can interfere with the transport behaviors of the virus in live cells, which lead to the changing and long-time pausing of the transport behavior of viruses. Our results revealed that most of the viruses moved along straight microtubules rapidly and unidirectionally from the cell periphery to the microtubule organizing center (MTOC) near the bottom of the cell, and the viruses were confined in the grid of microtubules near the top of the cell and at the MTOC near the bottom of the cell. These results provided deep insights into the influence of entire microtubule geometry on the virus infection. C1 [Liu, Shu-Lin; Zhang, Li-Juan; Wang, Zhi-Gang; Zhang, Zhi-Ling; Wu, Qiu-Mei; Sun, En-Ze; Pang, Dai-Wen] Wuhan Univ, Key Lab Analyt Chem Biol & Med, State Key Lab Virol, Coll Chem & Mol Sci,Minist Educ, Wuhan 430072, Hubei, Peoples R China. [Liu, Shu-Lin; Zhang, Li-Juan; Wang, Zhi-Gang; Zhang, Zhi-Ling; Wu, Qiu-Mei; Sun, En-Ze; Pang, Dai-Wen] Wuhan Univ, Wuhan Inst Biotechnol, Wuhan 430072, Hubei, Peoples R China. [Shi, Yun-Bo] NICHD, Sect Mol Morphogenesis, PCRM, NIH, Bethesda, MD 20892 USA. RP Pang, DW (reprint author), Wuhan Univ, Key Lab Analyt Chem Biol & Med, State Key Lab Virol, Coll Chem & Mol Sci,Minist Educ, Wuhan 430072, Hubei, Peoples R China. EM dwpang@whu.edu.cn RI Zhang, Zhi-Ling/B-3135-2010; OI Zhang, Zhi-Ling/0000-0001-7807-2264; Liu, Shu-Lin/0000-0002-1043-4238 FU National Basic Research Program of China (973 Program) [2011CB933600]; Science Fund for Creative Research Groups of NSFC [20921062]; 111 Project; 3551 Talent Program of the Administrative Committee of East Lake Hi-Tech Development Zone [[2011]137]; Intramural Research Program of NICHD, National Institutes of Health FX This work was supported by the National Basic Research Program of China (973 Program, No. 2011CB933600), the Science Fund for Creative Research Groups of NSFC (No. 20921062), the 111 Project, and the 3551 Talent Program of the Administrative Committee of East Lake Hi-Tech Development Zone ([2011]137). Y.-B.S. was supported by the Intramural Research Program of NICHD, National Institutes of Health. NR 31 TC 13 Z9 14 U1 5 U2 48 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD APR 15 PY 2014 VL 86 IS 8 BP 3902 EP 3908 DI 10.1021/ac500640u PG 7 WC Chemistry, Analytical SC Chemistry GA AF4CC UT WOS:000334658000034 PM 24678700 ER PT J AU Zhang, M Khripin, CY Fagan, JA McPhie, P Ito, Y Zheng, M AF Zhang, Min Khripin, Constantine Y. Fagan, Jeffrey A. McPhie, Peter Ito, Yoichiro Zheng, Ming TI Single-Step Total Fractionation of Single-Wall Carbon Nanotubes by Countercurrent Chromatography SO ANALYTICAL CHEMISTRY LA English DT Article ID PARTITION CHROMATOGRAPHY; CHIRALITY SEPARATION; GEL CHROMATOGRAPHY; RECOGNITION; EVOLUTION AB Development of simple processes to fractionate synthetic mixtures of single-wall carbon nanotubes (SWCNTs) into individual species is crucial to many applications. Existing methods for single-chirality SWCNT purification are cumbersome, often requiring multiple steps and different conditions for different species. Here, we report a method to achieve total fractionation of a synthetic SWCNT mixture by countercurrent chromatography, resulting in purification of many single-chirality SWCNT species in a single run. This method is based on a tunable partition of sodium deoxycholate dispersed SWCNTs in a polyethylene glycol/dextran aqueous two-phase system. By running the mobile phase with 0.02% of sodium deoxycholate and a gradient of sodium dodecyl sulfate from 0.1% to 0.7% (w/w), we observe clear diameter-dependent elution, with similar to 90% total recovery. Among all the fractions collected, a number of them are enriched in single-chirality (9,4), (7,5), (7,6), (8,3), (6,5) species, while most of the remaining ones contain no more than 2-3 major species. We also observe strong (n,m)-dependent elution peak width due to the enantiomer-resolved partition. These results demonstrate countercurrent chromatography (CCC) as an effective way to obtain high purity (n, m) species, and suggest the potential of CCC as an analytical tool for chirality distribution mapping of synthetic SWCNT mixtures. C1 [Zhang, Min] E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China. [Zhang, Min; Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Khripin, Constantine Y.; Fagan, Jeffrey A.; Zheng, Ming] NIST, Mat Sci & Engn Div, Gaithersburg, MD 20899 USA. [McPhie, Peter] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov; ming.zheng@nist.gov OI Fagan, Jeffrey/0000-0003-1483-5554 FU Intramural NIH HHS [ZIA HL005107-06, Z01 HL001054-05] NR 21 TC 18 Z9 19 U1 5 U2 60 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD APR 15 PY 2014 VL 86 IS 8 BP 3980 EP 3984 DI 10.1021/ac5003189 PG 5 WC Chemistry, Analytical SC Chemistry GA AF4CC UT WOS:000334658000044 PM 24673411 ER PT J AU Selvin, E Parrinello, CM Sacks, DB Coresh, J AF Selvin, Elizabeth Parrinello, Christina M. Sacks, David B. Coresh, Josef TI Trends in Prevalence and Control of Diabetes in the United States, 1988-1994 and 1999-2010 SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID FASTING PLASMA-GLUCOSE; NATIONAL-HEALTH; PREDIABETES PREVALENCE; ATHEROSCLEROSIS RISK; GLYCATED HEMOGLOBIN; ADULTS; MELLITUS; US; A1C; CLASSIFICATION AB Background: Trends in the prevalence and control of diabetes defined by hemoglobin A(1c) (HbA(1c)) levels are important for health care policy and planning. Objective: To update trends in the prevalence of diabetes, prediabetes, and glycemic control. Design: Cross-sectional. Setting: NHANES (National Health and Nutrition Examination Survey) in 1988-1994 and 1999-2010. Participants: Adults aged 20 years or older. Measurements: We used calibrated HbA(1c) levels to define undiagnosed diabetes (>= 6.5%); prediabetes (5.7% to 6.4%); and, among persons with diagnosed diabetes, glycemic control (<7.0% or <8.0%). Trends in HbA(1c) categories were compared with fasting glucose levels (>= 7.0 mmol/L [>= 126 mg/dL] and 5.6 to 6.9 mmol/L [100 to 125 mg/dL]). Results: In 2010, approximately 21 million U. S. adults aged 20 years or older had total confirmed diabetes (self-reported diabetes or diagnostic levels for both fasting glucose and calibrated HbA(1c)). During 2 decades, the prevalence of total confirmed diabetes in-creased, but the prevalence of undiagnosed diabetes remained fairly stable, reducing the proportion of total diabetes cases that are undiagnosed to 11% in 2005-2010. The prevalence of prediabetes was lower when defined by calibrated HbA(1c) levels than when defined by fasting glucose levels but has increased from 5.8% in 1988-1994 to 12.4% in 2005-2010 when defined by HbA(1c) levels. Glycemic control improved overall, but total diabetes prevalence was greater and diabetes was less controlled among non-Hispanic blacks and Mexican Americans compared with non-Hispanic whites. Limitation: Cross-sectional design. Conclusion: Over the past 2 decades, the prevalence of total diabetes has increased substantially. However, the proportion of undiagnosed diabetes cases decreased, suggesting improvements in screening and diagnosis. Among the growing number of persons with diagnosed diabetes, glycemic control improved but remains a challenge, particularly among non-Hispanic blacks and Mexican Americans. C1 [Selvin, Elizabeth] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21287 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA. Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. RP Selvin, E (reprint author), Welch Ctr Prevent Epidemiol & Clin Res, 2024 East Monument St,Suite 2-600, Baltimore, MD 21287 USA. EM lselvin@jhsph.edu OI Sacks, David/0000-0003-3100-0735 FU National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK089174]; National Heart, Lung, and Blood Institute [T32 HL007024]; Intramural Program of the National Institutes of Health FX By the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01 DK089174) to Dr. Selvin. Ms. Parrinello was supported by the National Heart, Lung, and Blood Institute (grant T32 HL007024). Dr. Sacks was supported by the Intramural Program of the National Institutes of Health. NR 43 TC 150 Z9 152 U1 6 U2 28 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 2014 VL 160 IS 8 BP 517 EP + DI 10.7326/M13-2411 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AG0ZE UT WOS:000335143700001 PM 24733192 ER PT J AU Palmore, TN Henderson, DK AF Palmore, Tara N. Henderson, David K. TI Carbapenem-Resistant Enterobacteriaceae: A Call for Cultural Change SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Palmore, Tara N.; Henderson, David K.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Ctr Clin, Bldg 10,Room 6-1480,10 Ctr Dr, Bethesda, MD 20892 USA. EM dkh@nih.gov NR 11 TC 4 Z9 4 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 2014 VL 160 IS 8 BP 567 EP + DI 10.7326/M13-1910 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AG0ZE UT WOS:000335143700008 PM 24733200 ER PT J AU Kirby, TW DeRose, EF Beard, WA Shock, DD Wilson, SH London, RE AF Kirby, Thomas W. DeRose, Eugene F. Beard, William A. Shock, David D. Wilson, Samuel H. London, Robert E. TI Substrate Rescue of DNA Polymerase beta Containing a Catastrophic L22P Mutation SO BIOCHEMISTRY LA English DT Article ID BASE EXCISION-REPAIR; ENZYME SPECIFICITY; GASTRIC-CANCER; ACTIVE-SITE; AMINO-ACIDS; INDUCED FIT; BINDING; MUTANT; DOMAIN; MECHANISM AB DNA polymerase (pol) beta is a multidomain enzyme with two enzymatic activities that plays a central role in the overlapping base excision repair and single-strand break repair pathways. The high frequency of pol beta variants identified in tumor-derived tissues suggests a possible role in the progression of cancer, making the determination of the functional consequences of these variants of interest. Pol beta containing a proline substitution for leucine 22 in the lyase domain (LD), identified in gastric tumors, has been reported to exhibit severe impairment of both lyase and polymerase activities. Nuclear magnetic resonance (NMR) spectroscopic evaluations of both pol beta and the isolated LD containing the L22P mutation demonstrate destabilization sufficient to result in LD-selective unfolding with minimal structural perturbations to the polymerase domain. Unexpectedly, addition of single-stranded or hairpin DNA resulted in partial refolding of the mutated lyase domain, both in isolation and for the full-length enzyme. Further, formation of an abortive ternary complex using Ca2+ and a complementary dNTP indicates that the fraction of pol beta(L22P) containing the folded LD undergoes conformational activation similar to that of the wild-type enzyme. Kinetic characterization of the polymerase activity of L22P pol beta indicates that the L22P mutation compromises DNA binding, but nearly wild-type catalytic rates can be observed at elevated substrate concentrations. The organic osmolyte trimethylamine N-oxide (TMAO) is similarly able to induce folding and kinetic activation of both polymerase and lyase activities of the mutant. Kinetic data indicate synergy between the TMAO cosolvent and substrate binding. NMR data indicate that the effect of the DNA results primarily from interaction with the folded LD(L22P), while the effect of the TMAO results primarily from destabilization of the unfolded LD(L22P). These studies illustrate that substrate-induced catalytic activation of pol beta provides an optimal enzyme conformation even in the presence of a strongly destabilizing point mutation. Accordingly, it remains to be determined whether this mutation alters the threshold of cellular repair activity needed for routine genome maintenance or whether the "inactive" variant interferes with DNA repair. C1 [Kirby, Thomas W.; DeRose, Eugene F.; Beard, William A.; Shock, David D.; Wilson, Samuel H.; London, Robert E.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), 111 TW Alexander Dr,POB 12233,MD MR 01, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) [Z01-ES050147, ZO1-ES050158, ZO1-ES050159]; National Institutes of Health, NIEHS [HHSN273200700046U] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS), under Research Project Z01-ES050147 to R.E.L. and Research Projects ZO1-ES050158 and ZO1-ES050159 to S.H.W. E.F.D. is supported by the National Institutes of Health, NIEHS, under Delivery Order HHSN273200700046U. NR 43 TC 4 Z9 4 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 15 PY 2014 VL 53 IS 14 BP 2413 EP 2422 DI 10.1021/bi5001855 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AF4CB UT WOS:000334657900022 PM 24655288 ER PT J AU Kodet, JG Beutler, JA Wiemer, DF AF Kodet, John G. Beutler, John A. Wiemer, David F. TI Synthesis and structure activity relationships of schweinfurthin indoles SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Schweinfurthin; Indole; Stilbene analogues; SAR ID MACARANGA-SCHWEINFURTHII; STILBENE; ANALOGS AB As part of a program to explore the biological activity of analogues of the natural schweinfurthins, a set of compounds has been prepared where an indole system can be viewed as a substitution for the resorcinol substructure of the schweinfurthin's D-ring. Twelve of these schweinfurthin indoles have been prepared and evaluated in the 60 cell line screen of the National Cancer Institute. While a range of activity has been observed, it is now clear that schweinfurthin indoles can demonstrate the intriguing pattern of activity associated with the natural stilbenes. In the best cases, these indole analogues display both potency and differential activity across the various cell lines comparable to the best resorcinol analogues. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Kodet, John G.; Wiemer, David F.] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. [Beutler, John A.] NCI Frederick, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Wiemer, DF (reprint author), Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. EM david-wiemer@uiowa.edu FU UI Graduate College for a Presidential Fellowship; Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research; Roy J. Carver Charitable Trust as a Research Program of Excellence FX We thank the UI Graduate College for a Presidential Fellowship (to J.G.K.). This research was supported in part by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. Financial support from the Roy J. Carver Charitable Trust as a Research Program of Excellence is gratefully acknowledged. We thank the Developmental Therapeutics Program, NCI, for the 60-cell testing. NR 25 TC 3 Z9 3 U1 1 U2 16 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 15 PY 2014 VL 22 IS 8 BP 2542 EP 2552 DI 10.1016/j.bmc.2014.02.043 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA AE9OT UT WOS:000334338000019 PM 24656801 ER PT J AU Tajuddin, SM Amaral, AFS Fernandez, AF Chanock, S Silverman, DT Tardon, A Carrato, A Garcia-Closas, M Jackson, BP Torano, EG Marquez, M Urdinguio, RG Garcia-Closas, R Rothman, N Kogevinas, M Real, FX Fraga, MF Malats, N AF Tajuddin, S. M. Amaral, A. F. S. Fernandez, A. F. Chanock, S. Silverman, D. T. Tardon, A. Carrato, A. Garcia-Closas, M. Jackson, B. P. Torano, E. G. Marquez, M. Urdinguio, R. G. Garcia-Closas, R. Rothman, N. Kogevinas, M. Real, F. X. Fraga, M. F. Malats, N. CA Spanish Bladder Canc EPICURO Study TI LINE-1 methylation in leukocyte DNA, interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risk SO BRITISH JOURNAL OF CANCER LA English DT Article DE bladder cancer; LINE-1 repetitive sequences; DNA methylation; one-carbon metabolism; epigenetic-gene interaction ID GENOME-WIDE ASSOCIATION; ONE-CARBON METABOLISM; PANCREATIC-CANCER; CHOLINE METABOLISM; PROSTATE-CANCER; SUSCEPTIBILITY; HYPOMETHYLATION; GENE; EPIGENETICS; INSTABILITY AB Background: Aberrant global DNA methylation is shown to increase cancer risk. LINE-1 has been proven a measure of global DNA methylation. The objectives of this study were to assess the association between LINE-1 methylation level and bladder cancer risk and to evaluate effect modification by environmental and genetic factors. Methods: Bisulphite-treated leukocyte DNA from 952 cases and 892 hospital controls was used to measure LINE-1 methylation level at four CpG sites by pyrosequencing. Logistic regression model was fitted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Interactions between LINE-1 methylation levels and environmental and genetic factors were assessed. Results: The risk of bladder cancer followed a nonlinear association with LINE-1 methylation. Compared with subjects in the middle tertile, the adjusted OR for subjects in the lower and the higher tertiles were 1.26 (95% CI 0.99-1.60, P = 0.06) and 1.33 (95% CI 1.05-1.69, P = 0.02), respectively. This association significantly increased among individuals homozygous for the major allele of five single-nucleotide polymorphisms located in the phosphatidylethanolamine N-methyltransferase gene (corrected P-interactiono<0.05). Conclusions: The findings from this large-scale study suggest that both low and high levels of global DNA methylation are associated with the risk of bladder cancer. C1 [Tajuddin, S. M.; Amaral, A. F. S.; Marquez, M.; Malats, N.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain. [Fernandez, A. F.; Torano, E. G.; Urdinguio, R. G.; Fraga, M. F.] Univ Oviedo, HUCA, Inst Univ Oncol Principado Asturias, Canc Epigenet Lab, E-33006 Oviedo, Asturias, Spain. [Chanock, S.; Silverman, D. T.; Rothman, N.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Tardon, A.] Univ Oviedo, Inst Univ Oncol, Mol Epidemiol Grp, E-33006 Oviedo, Asturias, Spain. [Tardon, A.] CIBERESP, Barcelona, Spain. [Carrato, A.] Hosp Gen Univ Elche, Mol Oncol Grp, Alicante 03203, Spain. [Carrato, A.] Hosp Ramon & Cajal, Dept Med Oncol, E-28034 Madrid, Spain. [Garcia-Closas, M.] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England. [Jackson, B. P.] Dartmouth Coll, Dept Earth Sci, Trace Element Anal Core, Hanover, NH 03755 USA. [Garcia-Closas, R.] Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna 38320, Spain. [Kogevinas, M.] Ctr Res Environm Epidemiol CREAL, Barcelona 08003, Spain. [Real, F. X.] Spanish Natl Canc Res Ctr CNIO, Epithelial Carcinogenesis Grp, Madrid 28029, Spain. [Real, F. X.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona 08002, Spain. [Fraga, M. F.] Ctr Nacl Biotecnol CNB CSIC, Dept Immunol & Oncol, Madrid 28049, Spain. RP Malats, N (reprint author), Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain. EM mffraga@cnb.csic.es; nmalats@cnio.es RI Hernandez-Llodra, S/H-6863-2014; Murta-Nascimento, Cristiane/G-3738-2012; Garcia-Closas, Montserrat /F-3871-2015; Malats, Nuria/H-7041-2015; Real Arribas, Francisco/H-5275-2015; Fernandez , Irene/E-5705-2016; Fernandez, Agustin/N-7302-2014; Martinez, Esther/H-2562-2013; Kogevinas, Manolis/C-3918-2017; Amaral, Andre/A-7662-2008 OI Tajuddin, Salman M./0000-0002-7919-8528; Hernandez-Llodra, S/0000-0003-3963-3756; Soto, Jose Luis/0000-0003-0234-9188; Puente, Diana/0000-0003-4725-537X; Garcia-Closas, Montserrat /0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Real Arribas, Francisco/0000-0001-9501-498X; Fernandez, Agustin/0000-0002-3792-4085; Amaral, Andre/0000-0002-0369-9449 FU Association for International Cancer Research [09-0780]; Fondo de Investigacion Sanitaria, Spain [00/0745, PI051436, PI061614, G03/174]; Red Tematica de Investigacion Cooperativa en Cancer, Spain [RD12/0036/0050-RTICC]; European Commission [EU-FP7-HEALTH-F2-2008-201663-UROMOL, EU-FP7-HEALTH-F2-2008-201333-DECanBio]; Fundacion Cientifica de la AECC, Spain; US National Institutes of Health [USA-NIH-RO1-CA089715]; Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute at the National Institutes of Health, USA FX We acknowledge the coordinators, field and administrative workers, technicians and patients of the Spanish Bladder Cancer/EPICURO Study. This work was supported by the Association for International Cancer Research (grant number 09-0780); Fondo de Investigacion Sanitaria, Spain (grant numbers 00/0745, PI051436, PI061614, G03/174); Red Tematica de Investigacion Cooperativa en Cancer (grant number RD12/0036/0050-RTICC), Spain; European Commission (grant numbers EU-FP7-HEALTH-F2-2008-201663-UROMOL; EU-FP7-HEALTH-F2-2008-201333-DECanBio); Fundacion Cientifica de la AECC, Spain; US National Institutes of Health (grant number USA-NIH-RO1-CA089715); and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute at the National Institutes of Health, USA. NR 46 TC 7 Z9 7 U1 0 U2 10 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 15 PY 2014 VL 110 IS 8 BP 2123 EP 2130 DI 10.1038/bjc.2014.67 PG 8 WC Oncology SC Oncology GA AF3CA UT WOS:000334587900026 PM 24595004 ER PT J AU Wongtrakoongate, P Li, J Andrews, PW AF Wongtrakoongate, P. Li, J. Andrews, P. W. TI Aza-deoxycytidine induces apoptosis or differentiation via DNMT3B and targets embryonal carcinoma cells but not their differentiated derivatives SO BRITISH JOURNAL OF CANCER LA English DT Article DE Human teratocarcinoma stem cells; embryonic stem cells; nullipotent; pluripotent; DNMT3B ID STEM-CELLS; IN-SITU; DNA METHYLTRANSFERASE; EXPRESSION PROFILES; RNA INTERFERENCE; GERM-CELLS; TERATOCARCINOMA; METHYLATION; TUMORS; 5-AZA-2-DEOXYCYTIDINE AB Background: Teratocarcinoma is a malignant male germ cell tumour, which contains stem cells and differentiated cancer tissues. DNMT3B has been shown to be highly expressed in human teratocarcinoma stem cells, and to mediate cytotoxicity of Azadeoxycytidine (Aza-dC) in a pluripotent stem cell line NTERA2. Methods: We have established DNMT3B or POU5F1 (hereafter referred to as OCT4) knockdown in teratocarcinoma stem cells N2102Ep and TERA1 and in the pluripotent NTERA2 by a doxycycline-inducible system, and tested the cytotoxicity induced by Aza-dC. Results: Silencing of DNMT3B led to apoptosis of human teratocarcinoma stem cells N2102Ep and TERA1. Further, we found that induction of apoptosis or differentiation in NTERA2 and human embryonic stem cells by Aza-dC requires DNMT3B. To test whether Aza-dC inhibits proliferation of differentiated teratocarcinoma cells, we depleted OCT4 expression in N2102Ep and TERA1 cells treated with Aza-dC. Treatment with Aza-dC reduced cell number of differentiated cells to a lesser extent than their undifferentiated parental stem cells. Moreover, in contrast to the stem cells, Aza-dC failed to induce apoptosis of differentiated cells. Conclusions: Our finding suggests that DNMT3B acts as an antiapoptotic gene in teratocarcinoma stem cells, and mediates apoptosis and differentiation of human pluripotent stem cells induced by Aza-dC, and that Aza-dC specifically induces apoptosis of teratocarcinoma stem cells. C1 [Wongtrakoongate, P.; Li, J.; Andrews, P. W.] Univ Sheffield, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England. RP Wongtrakoongate, P (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM p.wongtrakoongate@gmail.com FU Thai Commission on Higher Education FX This research was supported by the Thai Commission on Higher Education to PW. NR 38 TC 3 Z9 3 U1 0 U2 3 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 15 PY 2014 VL 110 IS 8 BP 2131 EP 2138 DI 10.1038/bjc.2014.128 PG 8 WC Oncology SC Oncology GA AF3CA UT WOS:000334587900027 PM 24603304 ER PT J AU Lowe, JM Menendez, D Bushel, PR Shatz, M Kirk, EL Troester, MA Garantziotis, S Fessler, MB Resnick, MA AF Lowe, Julie M. Menendez, Daniel Bushel, Pierre R. Shatz, Maria Kirk, Erin L. Troester, Melissa A. Garantziotis, Stavros Fessler, Michael B. Resnick, Michael A. TI p53 and NF-kappa B Coregulate Proinflammatory Gene Responses in Human Macrophages SO CANCER RESEARCH LA English DT Article ID CANCER-CELLS; RADIATION PNEUMONITIS; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; DNA-DAMAGE; IN-VIVO; ACTIVATION; EXPRESSION; GROWTH; INTERLEUKIN-6 AB Macrophages are sentinel immune cells that survey the tissue microenvironment, releasing cytokines in response to both exogenous insults and endogenous events such as tumorigenesis. Macrophages mediate tumor surveillance and therapy-induced tumor regression; however, tumor-associated macrophages (TAM) and their products may also promote tumor progression. Whereas NF-kappa B is prominent in macrophage-initiated inflammatory responses, little is known about the role of p53 in macrophage responses to environmental challenge, including chemotherapy or in TAMs. Here, we report that NF-kappa B and p53, which generally have opposing effects in cancer cells, coregulate induction of proinflammatory genes in primary human monocytes and macrophages. Using Nutlin-3 as a tool, we demonstrate that p53 and NF-kappa B rapidly and highly induce interleukin (IL)-6 by binding to its promoter. Transcriptome analysis revealed global p53/NF-kappa B co-regulation of immune response genes, including several chemokines, which effectively induced human neutrophil migration. In addition, we show that p53, activated by tumor cell paracrine factors, induces high basal levels of macrophage IL-6 in a TAM model system [tumor-conditioned macrophages (TCM)]. Compared with normal macrophages, TCMs exhibited higher p53 levels, enhanced p53 binding to the IL-6 promoter, and reduced IL-6 levels upon p53 inhibition. Taken together, we describe a mechanism by which human macrophages integrate signals through p53 and NF-kappa B to drive proinflammatory cytokine induction. Our results implicate a novel role for macrophage p53 in conditioning the tumor microenvironment and suggest a potential mechanism by which p53-activating chemotherapeutics, acting upon p53-sufficient macrophages and precursor monocytes, may indirectly impact tumors lacking functional p53. (C) 2014 AACR. C1 [Lowe, Julie M.; Menendez, Daniel; Shatz, Maria; Resnick, Michael A.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. [Bushel, Pierre R.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Garantziotis, Stavros; Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Kirk, Erin L.; Troester, Melissa A.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. RP Resnick, MA (reprint author), NIEHS, MD D3-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM julie.lowe@nih.gov; resnick@niehs.nih.gov RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU NIH, NIEHS, Breast Cancer; Environment Research Program grant [U01-ES109472]; NIEHS Intramural Research Program FX This study was supported by funding from NIH, NIEHS, Breast Cancer and the Environment Research Program grant, U01-ES109472 (M.A. Troester and E.L. Kirk) and the NIEHS Intramural Research Program. NR 50 TC 30 Z9 30 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2014 VL 74 IS 8 BP 2182 EP 2192 DI 10.1158/0008-5472.CAN-13-1070 PG 11 WC Oncology SC Oncology GA AF3AQ UT WOS:000334584200007 PM 24737129 ER PT J AU Yaffe, K Vittinghoff, E Pletcher, MJ Hoang, TD Launer, LJ Whitmer, R Coker, LH Sidney, S AF Yaffe, Kristine Vittinghoff, Eric Pletcher, Mark J. Hoang, Tina D. Launer, Lenore J. Whitmer, Rachel Coker, Laura H. Sidney, Stephen TI Early Adult to Midlife Cardiovascular Risk Factors and Cognitive Function SO CIRCULATION LA English DT Article DE blood pressure; cholesterol; cognition; glucose; risk factors ID CORONARY CALCIUM LATER; LATE-LIFE; ALZHEIMERS-DISEASE; BLOOD-PRESSURE; YOUNG-ADULTS; TEST-PERFORMANCE; DEMENTIA; CHOLESTEROL; HEALTH; AGE AB Background Studies have linked midlife and late-life cardiovascular risk factors (CVRFs) to cognitive function, yet little is known about CVRF exposure in early adulthood and subsequent cognitive function. In addition, most studies rely on single assessments of CVRFs, which may not accurately reflect long-term exposure. We sought to determine the association between cumulative exposure to CVRFs from early to middle adulthood and cognitive function at midlife. Methods and Results In a prospective study of 3381 adults (age, 18-30 years at baseline) with 25 years of follow-up, we assessed cognitive function at year 25 (2010-2011) with the Digit Symbol Substitution Test, Stroop Test, and Rey Auditory Verbal Learning Test analyzed with standardized z scores. The primary predictor was 25-year cumulative exposure estimated by areas under the curve for resting systolic and diastolic blood pressures, fasting blood glucose, and total cholesterol. Higher cumulative systolic and diastolic blood pressures and fasting blood glucose were consistently associated with worse cognition on all 3 tests. These associations were significant primarily for exposures above recommended guidelines; cognitive test z scores were between 0.06 and 0.30 points less, on average, for each 1-SD increase in risk factor area under the curve after adjustment for age, race, sex, and education (P<0.05 for all). Fewer significant associations were observed for cholesterol. Conclusions Cumulative exposure to CVRFs from early to middle adulthood, especially above recommended guidelines, was associated with worse cognition in midlife. The meaning of this association and whether it warrants more aggressive treatment of CVRFs earlier in life require further investigation. C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine; Vittinghoff, Eric; Pletcher, Mark J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Pletcher, Mark J.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94121 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Hoang, Tina D.] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Whitmer, Rachel; Sidney, Stephen] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Coker, Laura H.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu FU National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; Intramural Research Program of the National Institute on Aging (NIA); NIA; NHLBI [AG0005] FX The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C & HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). This manuscript has been reviewed by CARDIA for scientific content. NR 50 TC 37 Z9 39 U1 0 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 15 PY 2014 VL 129 IS 15 BP 1560 EP 1567 DI 10.1161/CIRCULATIONAHA.113.004798 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AE9II UT WOS:000334321100009 PM 24687777 ER PT J AU Malik, SM Maher, VE Bijwaard, KE Becker, RL Zhang, LJ Tang, SHW Song, PF Liu, Q Marathe, A Gehrke, B Helms, W Hanner, D Justice, R Pazdur, R AF Malik, Shakun M. Maher, Virginia Ellen Bijwaard, Karen E. Becker, Robert L. Zhang, Lijun Tang, Shenghui W. Song, Pengfei Liu, Qi Marathe, Anshu Gehrke, Brenda Helms, Whitney Hanner, Diane Justice, Robert Pazdur, Richard TI US Food and Drug Administration Approval: Crizotinib for Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer That Is Anaplastic Lymphoma Kinase Positive SO CLINICAL CANCER RESEARCH LA English DT Article ID EML4-ALK FUSION GENE; ALK; CHEMOTHERAPY; TRANSCRIPTS; CARCINOMAS; EGFR AB On August 26, 2011, the U. S. Food and Drug Administration (FDA) approved crizotinib (XALKORI Capsules, Pfizer Inc.) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as detected by an FDA-approved test. The Vysis ALK Break-Apart FISH Probe Kit (Abbott Molecular, Inc.) was approved concurrently. In two multicenter, single-arm trials, patients with locally advanced or metastatic ALK-positive NSCLC previously treated with one or more systemic therapies received crizotinib orally at a dose of 250 mg twice daily. In 119 patients with ALK-positive NSCLC by local trial assay, the objective response rate (ORR) was 61% [95% confidence intervals (CI), 52%-70%] with a median response duration of 48 weeks. In 136 patients with ALK-positive NSCLC by the to-be-marketed test, the ORR was 50% (95% CI, 42%-59%) with a median response duration of 42 weeks. The most common adverse reactions (>= 25%) were vision disorder, nausea, diarrhea, vomiting, edema, and constipation. Accelerated approval was granted on the basis of the high ORRs and durable responses. On November 20, 2013, crizotinib received full approval based on an improvement in progression-free survival in patients with metastatic ALK-positive NSCLC previously treated with one platinum-based chemotherapy regimen. Clin Cancer Res; 20(8); 2029-34. (C) 2014 AACR. C1 [Malik, Shakun M.] NCI, Clin Investigat Branch, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. [Maher, Virginia Ellen; Gehrke, Brenda; Helms, Whitney; Hanner, Diane; Justice, Robert; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Silver Spring, MD 20993 USA. [Zhang, Lijun; Tang, Shenghui W.] US FDA, Off Biostat, Silver Spring, MD 20993 USA. [Song, Pengfei; Liu, Qi; Marathe, Anshu] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Bijwaard, Karen E.; Becker, Robert L.] US FDA, Off In Vitro Diagnost & Radiol Hlth, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Justice, R (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 22,Room 2125, Silver Spring, MD 20993 USA. EM robert.justice@fda.hhs.gov NR 17 TC 41 Z9 41 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2014 VL 20 IS 8 BP 2029 EP 2034 DI 10.1158/1078-0432.CCR-13-3077 PG 6 WC Oncology SC Oncology GA AF3AJ UT WOS:000334583500004 PM 24573551 ER PT J AU Kennedy-Nasser, AA Ku, S Castillo-Caro, P Hazrat, Y Wu, MF Liu, H Melenhorst, J Barrett, AJ Ito, S Foster, A Savoldo, B Yvon, E Carrum, G Ramos, CA Krance, RA Leung, K Heslop, HE Brenner, MK Bollard, CM AF Kennedy-Nasser, Alana A. Ku, Stephanie Castillo-Caro, Paul Hazrat, Yasmin Wu, Meng-Fen Liu, Hao Melenhorst, Jos Barrett, A. John Ito, Sawa Foster, Aaron Savoldo, Barbara Yvon, Eric Carrum, George Ramos, Carlos A. Krance, Robert A. Leung, Kathryn Heslop, Helen E. Brenner, Malcolm K. Bollard, Catherine M. TI Ultra Low-Dose IL-2 for GVHD Prophylaxis after Allogeneic Hematopoietic Stem Cell Transplantation Mediates Expansion of Regulatory T Cells without Diminishing Antiviral and Antileukemic Activity SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; RECOMBINANT INTERLEUKIN-2; HEMATOLOGICAL MALIGNANCY; CHEMO-RADIOTHERAPY; PEDIATRIC-PATIENTS; IMMUNE-RESPONSES; HEALTHY DONORS; HOST-DISEASE AB Purpose: GVHD after allogeneic hematopoietic stem cell transplantation (alloSCT) has been associated with low numbers of circulating CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs). Because Tregs express high levels of the interleukin (IL)-2 receptor, they may selectively expand in vivo in response to doses of IL-2 insufficient to stimulate T effector T-cell populations, thereby preventing GVHD. Experimental Design: We prospectively evaluated the effects of ultra low-dose (ULD) IL-2 injections on Treg recovery in pediatric patients after alloSCT and compared this recovery with Treg reconstitution post alloSCT in patients without IL-2. Sixteen recipients of related (n = 12) or unrelated (n = 4) donor grafts received ULD IL-2 post hematopoietic stem cell transplantation (HSCT; 100,000-200,000 IU/m(2) x 3 per week), starting