FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Mercado, CI Cogswell, ME Valderrama, AL Wang, CY Loria, CM Moshfegh, AJ Rhodes, DG Carriquiry, AL AF Mercado, Carla I. Cogswell, Mary E. Valderrama, Amy L. Wang, Chia-Yih Loria, Catherine M. Moshfegh, Alanna J. Rhodes, Donna G. Carriquiry, Alicia L. TI Difference between 24-h diet recall and urine excretion for assessing population sodium and potassium intake in adults aged 18-39 y SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE biomarker; diet; sodium; urine; validation study ID CHRONIC KIDNEY-DISEASE; BLOOD-PRESSURE; H RECALLS; CARDIOVASCULAR RISK; RACIAL-DIFFERENCES; CALCIUM INTAKE; FOOD-INTAKE; VALIDATION; BALANCE; COLLECTION AB Background: Limited data are available on the accuracy of 24-h dietary recalls used to monitor US sodium and potassium intakes. Objective: We examined the difference in usual sodium and potassium intakes estimated from 24-h dietary recalls and urine collections. Design: We used data from a cross-sectional study in 402 participants aged 18-39 y (similar to 50% African American) in the Washington, DC, metropolitan area in 2011. We estimated means and percentiles of usual intakes of daily dietary sodium (dNa) and potassium (dK) and 24-h urine excretion of sodium (uNa) and potassium (uK). We examined Spearman's correlations and differences between estimates from dietary and urine measures. Multiple linear regressions were used to evaluate the factors associated with the difference between dietary and urine measures. Results: Mean differences between diet and urine estimates were higher in men [dNa uNa (95% CI) = 936.8 (787.1, 1086.5) mg/d and dK - uK = 571.3 (448.3, 694.3) mg/d] than in women [dNa uNa (95% CI) = 108.3 (11.1, 205.4) mg/d and dK uK = 163.4 (85.3, 241.5 mg/d)]. Percentile distributions of diet and urine estimates for sodium and potassium differed for men. Spearman's correlations between measures were 0.16 for men and 0.25 for women for sodium and 0.39 for men and 0.29 for women for potassium. Urinary creatinine, total caloric intake, and percentages of nutrient intake from mixed dishes were independently and consistently associated with the differences between diet and urine estimates of sodium and potassium intake. For men, body mass index was also associated. Race was associated with differences in estimates of potassium intake. Conclusions: Low correlations and differences between dietary and urinary sodium or potassium may be due to measurement error in one or both estimates. Future analyses using these methods to assess sodium and potassium intake in relation to health outcomes may consider stratifying by factors associated with the differences in estimates from these methods. This trial was registered at clinicaltrials.gov as NCT01631240. C1 [Mercado, Carla I.; Cogswell, Mary E.; Valderrama, Amy L.] Ctr Dis Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Heart Dis & Stroke Prevent, Atlanta, GA 30333 USA. [Wang, Chia-Yih] Natl Ctr Hlth Stat, Div Hlth & Nutr Examinat Surveys, Hyattsville, MD 20782 USA. [Loria, Catherine M.] NHLBI, Ctr Dis Control & Prevent, NIH, Bethesda, MD 20892 USA. [Moshfegh, Alanna J.; Rhodes, Donna G.] USDA ARS, Beltsville Human Nutr Res Ctr, Beltsville, MD USA. [Carriquiry, Alicia L.] Iowa State Univ, Dept Stat, Ames, IA USA. RP Mercado, CI (reprint author), Ctr Dis Control & Prevent, Mailstop F-72,4770 Buford Highway NE, Atlanta, GA 30341 USA. EM cmercado@cdc.gov FU CDC FX Data collection and laboratory analyses were funded by the CDC. NR 52 TC 8 Z9 8 U1 7 U2 11 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 FEB PY 2015 VL 101 IS 2 BP 376 EP 386 DI 10.3945/ajcn.113.081604 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CA5US UT WOS:000348973900018 PM 25646336 ER PT J AU Blair, A Hines, CJ Thomas, KW Alavanja, MCR Freeman, LEB Hoppin, JA Kamel, F Lynch, CF Lubin, JH Silverman, DT Whelan, E Zahm, SH Sandler, DP AF Blair, A. Hines, C. J. Thomas, K. W. Alavanja, M. C. R. Freeman, L. E. Beane Hoppin, J. A. Kamel, F. Lynch, C. F. Lubin, J. H. Silverman, D. T. Whelan, E. Zahm, S. H. Sandler, D. P. TI Investing in Prospective Cohorts for Etiologic Study of Occupational Exposures SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Editorial Material DE prospective cohorts; agricultural exposures; occupational epidemiology ID NON-HODGKINS-LYMPHOMA; LICENSED PESTICIDE APPLICATORS; SOFT-TISSUE SARCOMA; AGRICULTURAL RISK-FACTORS; BREAST-CANCER RISK; UNITED-STATES; PROSTATE-CANCER; DIESEL EXHAUST; IOWA FARMERS; LUNG-CANCER AB Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures. Am. J. Ind. Med. 58:113-122, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Blair, A.; Alavanja, M. C. R.; Freeman, L. E. Beane; Lubin, J. H.; Silverman, D. T.; Zahm, S. H.] NCI, Div Epidemiol & Genet, Rockville, MD 20892 USA. [Hines, C. J.; Whelan, E.] NIOSH, Cincinnati, OH 45226 USA. [Thomas, K. W.] US EPA, Natl Exposure Res Lab, Raleigh, NC USA. [Hoppin, J. A.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA. [Kamel, F.; Sandler, D. P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC USA. [Lynch, C. F.] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. RP Blair, A (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20892 USA. EM blaira@mail.nih.gov OI Sandler, Dale/0000-0002-6776-0018 FU Intramural CDC HHS [CC999999]; Intramural NIH HHS NR 120 TC 1 Z9 1 U1 3 U2 9 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 FEB PY 2015 VL 58 IS 2 BP 113 EP 122 DI 10.1002/ajim.22403 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AZ9UW UT WOS:000348563100001 PM 25603935 ER PT J AU Kavanagh, BP Suffredini, AF AF Kavanagh, Brian P. Suffredini, Anthony F. TI Management of Pediatric Septic Shock Progress through Applied Insight SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID MONOCLONAL ANTIENDOTOXIN ANTIBODY; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; INFECTION; THERAPY; HA-1A C1 [Kavanagh, Brian P.] Univ Toronto, Hosp Sick Children, Dept Crit Care Med, Toronto, ON M5S 1A1, Canada. [Kavanagh, Brian P.] Univ Toronto, Hosp Sick Children, Dept Anesthesia, Toronto, ON M5S 1A1, Canada. [Suffredini, Anthony F.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kavanagh, BP (reprint author), Univ Toronto, Hosp Sick Children, Dept Crit Care Med, Toronto, ON M5S 1A1, Canada. FU Canadian Institutes of Health Research; Intramural NIH HHS NR 12 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2015 VL 191 IS 3 BP 247 EP 248 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CA3SS UT WOS:000348827000004 PM 25635486 ER PT J AU Thannickal, VJ Murthy, M Balch, WE ChandeI, NS Meiners, I Eickelberg, O Selman, M Pardo, A White, ES Levy, BD Busse, PJ Tuder, RM Antony, VB Sznajder, JI Budinger, GRS AF Thannickal, Victor J. Murthy, Mahadev Balch, William E. Chande, Navdeep S., I Meiners, Ike Eickelberg, Oliver Selman, Moises Pardo, Annie White, Eric S. Levy, Bruce D. Busse, Paula J. Tuder, Rubin M. Antony, Veena B. Sznajder, Jacob I. Budinger, G. R. Scott TI Blue Journal Conference Aging and Susceptibility to Lung Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID IDIOPATHIC PULMONARY-FIBROSIS; STEM-CELLS; EXTRACELLULAR-MATRIX; UNITED-STATES; ALPHA(1)-ANTITRYPSIN DEFICIENCY; CELLULAR SENESCENCE; MITOCHONDRIAL-DNA; TELOMERE LENGTH; GENE-EXPRESSION; VIRUS-INFECTION AB The aging of the population in the United States and throughout the developed world has increased morbidity and mortality attributable to lung disease, while the morbidity and mortality from other prevalent diseases has declined or remained stable. Recognizing the importance of aging in the development of lung disease, the American Thoracic Society (ATS) highlighted this topic as a core theme for the 2014 annual meeting. The relationship between aging and lung disease was discussed in several oral symposiums and poster sessions at the annual ATS meeting. In this article, we used the input gathered at the conference to develop a broad framework and perspective to stimulate basic, clinical, and translational research to understand how the aging process contributes to the onset and/or progression of lung diseases. A consistent theme that emerged from the conference was the need to apply novel, systems-based approaches to integrate a growing body of genomic, epigenomic, transcriptomic, and proteomic data and elucidate the relationship between biologic hallmarks of aging, altered lung function, and increased susceptibility to lung diseases in the older population. The challenge remains to causally link the molecular and cellular changes of aging with age-related changes in lung physiology and disease susceptibility. The purpose of this review is to stimulate further research to identify new strategies to prevent or treat age-related lung disease. C1 [Thannickal, Victor J.; Antony, Veena B.] Univ Alabama Birmingham, Birmingham, AL USA. [Murthy, Mahadev] NIA, NIH, Bethesda, MD 20892 USA. [Balch, William E.] Scripps Res Inst, Dept Cell Biol & Chem Physiol, La Jolla, CA 92037 USA. [Chande, Navdeep S., I; Sznajder, Jacob I.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Meiners, Ike; Eickelberg, Oliver] Univ Munich, Univ Hosp, Comprehens Pneumol Ctr, Helmholtz Ctr Munich, Munich, Germany. [Selman, Moises] Natl Inst Resp Dis Ismael Cosio Villegas, Mexico City, DF, Mexico. [Pardo, Annie] Univ Nacl Autonoma Mexico, Fac Sci, Mexico City 04510, DF, Mexico. [White, Eric S.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Levy, Bruce D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Busse, Paula J.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Tuder, Rubin M.] Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Program Translat Lung Res, Aurora, CO USA. RP Budinger, GRS (reprint author), Northwestern Univ, 240 E Huron,M300, Chicago, IL 60611 USA. EM s-buding@northwestern.edu OI White, Eric/0000-0003-4060-8443 FU BLRD VA [I01 BX000201]; NHLBI NIH HHS [P01 HL114470]; NIA NIH HHS [P01 AG049665, R01 AG046210]; NIEHS NIH HHS [R01 ES013995] NR 108 TC 26 Z9 26 U1 1 U2 8 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2015 VL 191 IS 3 BP 261 EP 269 DI 10.1164/rccm.201410-1876PP PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CA3SS UT WOS:000348827000009 PM 25590812 ER PT J AU Zhang, L Pacheco-Rodriguez, G Steagall, WK Kato, J Haughey, M Fontana, JR Manganiello, VC Moss, J AF Zhang, Li Pacheco-Rodriguez, Gustavo Steagall, Wendy K. Kato, Jiro Haughey, Mary Fontana, Joseph R. Manganiello, Vincent C. Moss, Joel TI Tuberous Sclerosis Complex 2 Loss of Heterozygosity in Patients with Lung Disease and Cancer SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID MICROSATELLITE DNA INSTABILITY; TUMOR-SUPPRESSOR LOCI; LYMPHANGIOLEIOMYOMATOSIS; TSC2; BENIGN; GENES; CELLS; ADENOCARCINOMA; DELETION; 16P13 C1 [Zhang, Li; Pacheco-Rodriguez, Gustavo; Steagall, Wendy K.; Kato, Jiro; Haughey, Mary; Fontana, Joseph R.; Manganiello, Vincent C.; Moss, Joel] NHLBI, Bethesda, MD 20892 USA. RP Zhang, L (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. RI Zhang, Li/P-9646-2015 OI Zhang, Li/0000-0002-4138-1511 FU Intramural NIH HHS NR 25 TC 0 Z9 0 U1 1 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2015 VL 191 IS 3 BP 352 EP 355 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CA3SS UT WOS:000348827000022 PM 25635494 ER PT J AU Lu, GF Lomonosova, E Cheng, XH Moran, EA Meyers, MJ Le Grice, SFJ Thomas, CJ Jiang, JK Meck, C Hirsch, DR D'Erasmo, MP Suyabatmaz, DM Murelli, RP Tavis, JE AF Lu, Gaofeng Lomonosova, Elena Cheng, Xiaohong Moran, Eileen A. Meyers, Marvin J. Le Grice, Stuart F. J. Thomas, Craig J. Jiang, Jian-kang Meck, Christine Hirsch, Danielle R. D'Erasmo, Michael P. Suyabatmaz, Duygu M. Murelli, Ryan P. Tavis, John E. TI Hydroxylated Tropolones Inhibit Hepatitis B Virus Replication by Blocking Viral Ribonuclease H Activity SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; LONG-TERM EFFICACY; RNASE-H; ALPHA-HYDROXYTROPOLONES; NATURAL-HISTORY; DNA; INTEGRASE; SITE; EPIDEMIOLOGY; SUPERFAMILY AB Hepatitis B virus (HBV) remains a major human pathogen despite the development of both antiviral drugs and a vaccine, in part because the current therapies do not suppress HBV replication far enough to eradicate the virus. Here, we screened 51 troponoid compounds for their ability to suppress HBV RNaseH activity and HBV replication based on the activities of alpha-hydroxytropolones against HIV RNaseH, with the goal of determining whether the tropolone pharmacophore may be a promising scaffold for anti-HBV drug development. Thirteen compounds inhibited HBV RNaseH, with the best 50% inhibitory concentration (IC50) being 2.3 mu M. Similar inhibition patterns were observed against HBV genotype D and C RNaseHs, implying limited genotype specificity. Six of 10 compounds tested against HBV replication in culture suppressed replication via blocking of viral RNaseH activity, with the best 50% effective concentration (EC50) being 0.34 mu M. Eighteen compounds inhibited recombinant human RNaseH1, and moderate cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC50] = 25 to 79 mu M). Therapeutic indexes ranged from 3.8 to 94. Efficient inhibition required an intact alpha-hydroxytropolone moiety plus one or more short appendages on the tropolone ring, but a wide variety of constituents were permissible. These data indicate that troponoids and specifically alpha-hydroxytropolones are promising lead candidates for development as anti-HBV drugs, providing that toxicity can be minimized. Potential anti-RNaseH drugs are envisioned to be employed in combination with the existing nucleos(t) ide analogs to suppress HBV replication far enough to block genomic maintenance, with the goal of eradicating infection. C1 [Lu, Gaofeng] Zhengzhou Univ, Affiliated Hosp 2, Dept Gastroenterol, Zhengzhou 450052, Henan, Peoples R China. [Lu, Gaofeng; Lomonosova, Elena; Cheng, Xiaohong; Moran, Eileen A.; Tavis, John E.] St Louis Univ, Sch Med, Dept Mol Microbiol & Immunol, St Louis, MO 63103 USA. [Lomonosova, Elena; Tavis, John E.] St Louis Univ, Sch Med, Ctr Liver, St Louis, MO 63103 USA. [Meyers, Marvin J.] St Louis Univ, Sch Med, Ctr World Hlth & Med, St Louis, MO 63103 USA. [Le Grice, Stuart F. J.] NCI, Basic Res Lab, Frederick, MD 21701 USA. [Thomas, Craig J.; Jiang, Jian-kang] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Meck, Christine; Hirsch, Danielle R.; D'Erasmo, Michael P.; Suyabatmaz, Duygu M.; Murelli, Ryan P.] CUNY, Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 USA. [Meck, Christine; Hirsch, Danielle R.; D'Erasmo, Michael P.; Murelli, Ryan P.] CUNY, Grad Ctr, Dept Chem, New York, NY 11210 USA. RP Tavis, JE (reprint author), St Louis Univ, Sch Med, Dept Mol Microbiol & Immunol, St Louis, MO 63103 USA. EM tavisje@slu.edu FU Saint Louis University funds from the School of Medicine; Cancer Center; Friends of the Saint Louis University Liver Center; NIH/National Center for Advancing Translational Sciences (NCATS) [UL1 TR000448, R01 AI104494]; Henan Province, China, medical technology fund; NIH [SC2 GM09959]; Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX The work at Saint Louis University was supported by Saint Louis University funds from the School of Medicine and the Cancer Center and by grants from the Friends of the Saint Louis University Liver Center, NIH/National Center for Advancing Translational Sciences (NCATS) (UL1 TR000448), and R01 AI104494 to J.T. G.L. was partially supported by the Henan Province, China, medical technology fund. R. M. was supported by NIH grant SC2 GM09959, and S.L.G. was funded by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 53 TC 14 Z9 14 U1 0 U2 8 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 FEB PY 2015 VL 59 IS 2 BP 1070 EP 1079 DI 10.1128/AAC.04617-14 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CA0LT UT WOS:000348610000039 PM 25451058 ER PT J AU Kindrachuk, J Ork, B Hart, BJ Mazur, S Holbrook, MR Frieman, MB Traynor, D Johnson, RF Dyall, J Kuhn, JH Olinger, GG Hensley, LE Jahrling, PB AF Kindrachuk, Jason Ork, Britini Hart, Brit J. Mazur, Steven Holbrook, Michael R. Frieman, Matthew B. Traynor, Dawn Johnson, Reed F. Dyall, Julie Kuhn, Jens H. Olinger, Gene G. Hensley, Lisa E. Jahrling, Peter B. TI Antiviral Potential of ERK/MAPK and PI3K/AKT/mTOR Signaling Modulation for Middle East Respiratory Syndrome Coronavirus Infection as Identified by Temporal Kinome Analysis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MERS-COV; RHESUS MACAQUES; ACTIVATION; INTERFERON; VIRUSES; PATHWAY; PROTEIN; EXPRESSION; ALPHA; STORM AB Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus, and infections with this virus can result in acute respiratory syndrome with renal failure. Globally, MERS-CoV has been responsible for 877 laboratory-confirmed infections, including 317 deaths, since September 2012. As there is a paucity of information regarding the molecular pathogenesis associated with this virus or the identities of novel antiviral drug targets, we performed temporal kinome analysis on human hepatocytes infected with the Erasmus isolate of MERS-CoV with peptide kinome arrays. bioinformatics analysis of our kinome data, including pathway overrepresentation analysis (ORA) and functional network analysis, suggested that extracellular signalregulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling responses were specifically modulated in response to MERS-CoV infection in vitro throughout the course of infection. The overrepresentation of specific intermediates within these pathways determined by pathway and functional network analysis of our kinome data correlated with similar patterns of phosphorylation determined through Western blot array analysis. In addition, analysis of the effects of specific kinase inhibitors on MERS-CoV infection in tissue culture models confirmed these cellular response observations. Further, we have demonstrated that a subset of licensed kinase inhibitors targeting the ERK/MAPK and PI3K/AKT/mTOR pathways significantly inhibited MERS-CoV replication in vitro whether they were added before or after viral infection. Taken together, our data suggest that ERK/MAPK and PI3K/AKT/mTOR signaling responses play important roles in MERS-CoV infection and may represent novel drug targets for therapeutic intervention strategies. C1 [Kindrachuk, Jason; Ork, Britini; Hart, Brit J.; Mazur, Steven; Holbrook, Michael R.; Traynor, Dawn; Dyall, Julie; Kuhn, Jens H.; Olinger, Gene G.; Hensley, Lisa E.; Jahrling, Peter B.] NIAID, Integrated Res Facil, NIH, Frederick, MD 21702 USA. [Frieman, Matthew B.] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Johnson, Reed F.; Jahrling, Peter B.] NIAID, Emerging Viral Pathogens Sect, NIH, Frederick, MD USA. RP Kindrachuk, J (reprint author), NIAID, Integrated Res Facil, NIH, Frederick, MD 21702 USA. EM kindrachuk.kenneth@nih.gov RI Hart, Brit/G-6205-2015; OI Hart, Brit/0000-0002-9389-2786; Kindrachuk, Jason/0000-0002-3305-7084; Kuhn, Jens H./0000-0002-7800-6045 FU NIAID Division of Intramural Research; NIAID [HHSN272200700016I] FX This study was supported in part by the NIAID Division of Intramural Research.; B.J.H., J.D., and J.H.K. performed this work as employees of Tunnell Consulting, Inc., and D.T. and S.M. performed this work as employees of MRI Global. Tunnell Consulting, Inc., and MRI Global are subcontractors to Battelle Memorial Institute. J.K., B.O., and M.H. performed this work as employees of Battelle Memorial Institute. All work was performed under the Battelle Memorial Institute prime contract with NIAID (contract no. HHSN272200700016I). NR 48 TC 8 Z9 9 U1 1 U2 6 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 FEB PY 2015 VL 59 IS 2 BP 1088 EP 1099 DI 10.1128/AAC.03659-14 PG 12 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CA0LT UT WOS:000348610000041 PM 25487801 ER PT J AU Holz, L Rehermann, B AF Holz, Lauren Rehermann, Barbara TI T cell responses in hepatitis C virus infection: Historical overview and goals for future research SO ANTIVIRAL RESEARCH LA English DT Review DE Hepatitis C virus; T cell; Infection; Immunological techniques; History ID ACUTE HCV INFECTION; EX-VIVO ANALYSIS; IMMUNE-RESPONSES; VIRAL PERSISTENCE; CLASS-I; NONSTRUCTURAL PROTEIN-3; FUNCTIONAL RESTORATION; LYMPHOCYTE RESPONSE; GENETIC-VARIATION; PERIPHERAL-BLOOD AB Hepatitis C virus (HCV)-specific T cells are key factors in the outcome of acute HCV infection and in protective immunity. This review recapitulates the steps that immunologists have taken in the past 25 years to dissect the role of T cell responses in HCV infection. It describes technical as well as disease-specific challenges that were caused by the inapparent onset of acute HCV infection, the difficulty to identify subjects who spontaneously clear HCV infection, the low frequency of HCV-specific T cells in the blood of chronically infected patients, and the lack of small animal models with intact immune systems to study virus-host interaction. The review provides a historical perspective on techniques and key findings, and identifies areas for future research. Published by Elsevier B.V. C1 [Holz, Lauren; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bldg 10,Room 9B16,10 Ctr Dr, Bethesda, MD 20892 USA. EM Rehermann@nih.gov FU Intramural Research Program of the NIH, NIDDK FX This work was supported in part by the Intramural Research Program of the NIH, NIDDK. NR 96 TC 10 Z9 11 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD FEB PY 2015 VL 114 BP 96 EP 105 DI 10.1016/j.antiviral.2014.11.009 PG 10 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA CA5PM UT WOS:000348960300011 PM 25433310 ER PT J AU Barry, KP Ngu, A Cohn, EF Cote, JM Burroughs, AM Gerbino, JP Taylor, EA AF Barry, Kevin Patrick Ngu, Abraham Cohn, Erin Frances Cote, Joy Marie Burroughs, A. Maxwell Gerbino, Jason Paul Taylor, Erika Anne TI Exploring allosteric activation of LigAB from Sphingobium sp strain SYK-6 through kinetics, mutagenesis and computational studies SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Protocatechuate 4,5-dioxygenase; Dioxygenase; Vanillin; Allosteric activation; Lignin; PCAD superfamily ID SPHINGOMONAS-PAUCIMOBILIS SYK-6; EXTRADIOL CATECHOL DIOXYGENASE; PROTOCATECHUATE 4,5-DIOXYGENASE; INDOLEAMINE 2,3-DIOXYGENASE; SUBSTRATE-SPECIFICITY; 2,3-DIHYDROXYBIPHENYL 1,2-DIOXYGENASE; ESCHERICHIA-COLI; TRYPTOPHAN 2,3-DIOXYGENASE; FRUCTOSE 2,6-BISPHOSPHATE; EFFECTOR INTERACTIONS AB The protocatechuate 4,5-dioxygenase (LigAB) from Sphingobium sp. strain SYK-6 is the defining member of the Type II extradiol dioxygenase superfamily (a.k.a. PCA Dioxygenase Superfamily or PCADSF) and plays a key aromatic ring-opening role in the metabolism of several lignin derived aromatic compounds. In our search for alternate substrates and inhibitors of LigAB, we discovered allosteric rate enhancement in the presence of non-substrate protocatechuate-like aldehydes such as vanillin. LigAB has the broadest substrate utilization profile of all protocatechuate (PCA) 4,5-dioxygenase described in the literature, however, the rate enhancement is only observed with PCA, with vanillin increasing k(cat) for LigAB by 36%. Computational docking has identified a potential site of allosteric binding near the entrance to the active site. Examination of a multiple sequence alignment reveals that many of the residues contributing to this newly identified allosteric pocket are highly conserved within the LigB family of the PCADSF. Point mutants of Phe103 alpha and Ala18 beta, two residues located in the putative allosteric pocket, display altered rate enhancement as compared to LigAB-WT, providing support for the computationally identified allosteric binding site. Further investigation of this binding site may provide insight into the mechanism of this never before observed allosteric activation in extradiol dioxygenases. (C) 2014 Elsevier Inc. All rights reserved. C1 [Barry, Kevin Patrick; Ngu, Abraham; Cohn, Erin Frances; Cote, Joy Marie; Gerbino, Jason Paul; Taylor, Erika Anne] Wesleyan Univ, Dept Chem, Middletown, CT 06459 USA. [Burroughs, A. Maxwell] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Taylor, EA (reprint author), Wesleyan Univ, Dept Chem, Middletown, CT 06459 USA. EM eataylor@wesleyan.edu RI Taylor, Erika/F-5635-2015 OI Taylor, Erika/0000-0001-5598-640X FU Intramural Research Program of the NIH, National Library of Medicine; Wesleyan University FX We would like to thank Carlos A. Ramirez-Mondragon for calculating the surface accessibility of the tryptophan residues of LigAB and Ishita Mukerji for providing us access to her Horiba SPEX Fluoromax-4 spectrofluorometer. Support for this research project was provided by Wesleyan University. AMB is supported by the Intramural Research Program of the NIH, National Library of Medicine. NR 77 TC 2 Z9 2 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 1 PY 2015 VL 567 BP 35 EP 45 DI 10.1016/j.abb.2014.12.019 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CA5UV UT WOS:000348974200005 PM 25562402 ER PT J AU Chae, JJ Park, YH Park, C Hwang, IY Hoffmann, P Kehrl, JH Aksentijevich, I Kastner, DL AF Chae, Jae Jin Park, Yong Hwan Park, Chung Hwang, Il-Young Hoffmann, Patrycja Kehrl, John H. Aksentijevich, Ivona Kastner, Daniel L. TI Connecting Two Pathways Through Ca2+ Signaling: NLRP3 Inflammasome Activation Induced by a Hypermorphic PLCG2 Mutation SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID AUTOINFLAMMATORY DISEASES; NALP3 INFLAMMASOME; CRYSTALS AB Objective. We previously reported that p.Ser707Tyr, a novel variant in phospholipase C gamma 2 (PLC gamma 2), is the cause of a dominantly inherited auto-inflammatory disease, autoinflammation and PLC gamma 2-associated antibody deficiency and immune dysregulation (APLAID). The hypermorphic mutation enhances PLC gamma 2 activity and causes an increase in intracellular Ca2+ release from endoplasmic reticulum stores. Because increased intracellular Ca2+ signaling has been associated with NLRP3 inflammasome activation, we studied the role of the NLRP3 inflammasome in the pathogenesis of APLAID. Methods. Human peripheral blood mononuclear cells (PBMCs) were isolated from healthy control subjects and 2 patients with APLAID. Inflammasome activation was analyzed by Western blotting. Intracellular Ca2+ levels were measured with a FLIPR Calcium 4 assay kit. Results. Cells from the patients had elevated basal levels of intracellular Ca2+, and the intracellular Ca2+ flux triggered by extracellular CaCl2 was substantially enhanced. Patient PBMCs secreted interleukin-1 beta in response to lipopolysaccharide priming alone, and this effect was attenuated by treatment with a PLC inhibitor, intracellular Ca2+ blockers, or an adenylate cyclase activator. Conclusion. Our findings suggest that the inflammation in patients with APLAID is partially driven by activation of the NLRP3 inflammasome. These data link 2 seemingly distinct molecular pathways and provide new insights into the pathogenesis of APLAID and autoinflammation. C1 [Chae, Jae Jin; Park, Yong Hwan; Hoffmann, Patrycja; Aksentijevich, Ivona; Kastner, Daniel L.] NHGRI, NIH, Bethesda, MD 20892 USA. [Park, Chung; Hwang, Il-Young; Kehrl, John H.] NIAID, NIH, Bethesda, MD 20892 USA. RP Kastner, DL (reprint author), Bldg 50,Room 5222,South Dr MSC 8002, Bethesda, MD 20892 USA. EM aksentil@exchange.nih.gov; kastnerd@mail.nih.gov FU Intramural Research Programs of the National Human Genome Research Institute; National Institute of Allergy and Infectious Diseases, NIH FX Supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Institute of Allergy and Infectious Diseases, NIH. NR 12 TC 3 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD FEB PY 2015 VL 67 IS 2 BP 563 EP 567 DI 10.1002/art.38961 PG 5 WC Rheumatology SC Rheumatology GA CA9CR UT WOS:000349218500029 PM 25418813 ER PT J AU Gao, F Kim, HW Igarashi, M Kiesewetter, D Chang, L Ma, KZ Rapoport, SI AF Gao, Fei Kim, Hyung-Wook Igarashi, Miki Kiesewetter, Dale Chang, Lisa Ma, Kaizong Rapoport, Stanley I. TI Liver conversion of docosahexaenoic and arachidonic acids from their 18-carbon precursors in rats on a DHA-free but alpha-LNA-containing n-3 PUFA adequate diet (Retraction of vol 1811, pg 484, 2011) SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Correction C1 [Gao, Fei; Kim, Hyung-Wook; Igarashi, Miki; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. [Kiesewetter, Dale] Natl Inst Biomed Imaging & Bioengn, Positron Emiss Tomog Radiochem Grp, NIH, Bethesda, MD 20892 USA. RP Gao, F (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,Room 1S126, Bethesda, MD 20892 USA. EM gaof@mail.nih.gov NR 1 TC 0 Z9 0 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 EI 0006-3002 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD FEB PY 2015 VL 1851 IS 2 BP 238 EP 238 DI 10.1016/j.bbalip.2014.12.009 PG 1 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CA5QT UT WOS:000348963600014 ER PT J AU Varga, ZV Giricz, Z Liaudet, L Hasko, G Ferdinandy, P Pacher, P AF Varga, Zoltan V. Giricz, Zoltan Liaudet, Lucas Hasko, Gyoergy Ferdinandy, Peter Pacher, Pal TI Interplay of oxidative, nitrosative/nitrative stress, inflammation, cell death and autophagy in diabetic cardiomyopathy SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE Diabetic cardiomyopathy; Protein oxidation; Autophagy; Oxidative stress ID NITRIC-OXIDE SYNTHASE; GLYCATION END-PRODUCTS; POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; CARDIAC PATHOLOGICAL-CHANGES; LEFT-VENTRICULAR DYSFUNCTION; SOLUBLE GUANYLATE-CYCLASE; OXYGEN SPECIES MEDIATE; NECROSIS-FACTOR-ALPHA; ENDOTHELIAL DYSFUNCTION; NADPH OXIDASE AB Diabetes is a recognized risk factor for cardiovascular diseases and heart failure. Diabetic cardiovascular dysfunction also underscores the development of diabetic retinopathy, nephropathy and neuropathy. Despite the broad availability of antidiabetic therapy, glycemic control still remains a major challenge in the management of diabetic patients. Hyperglycemia triggers formation of advanced glycosylation end products (AGEs), activates protein kinase C, enhances polyol pathway, glucose autoxidation, which coupled with elevated levels of free fatty acids, and leptin have been implicated in increased generation of superoxide anion by mitochondria, NADPH oxidases and xanthine oxidoreductase in diabetic vasculature and myocardium. Superoxide anion interacts with nitric oxide forming the potent toxin peroxynitrite via diffusion limited reaction, which in concert with other oxidants triggers activation of stress kinases, endoplasmic reticulum stress, mitochondrial and poly(ADP-ribose) polymerase 1-dependent cell death, dysregulates autophagy/mitophagy, inactivates key proteins involved in myocardial calcium handling/contractility and antioxidant defense, activates matrix metalloproteinases and redox-dependent pro-inflammatory transcription factors (e.g. nuclear factor kappaB) promoting inflammation, AGEs formation, eventually culminating in myocardial dysfunction, remodeling and heart failure. Understanding the complex interplay of oxidative/nitrosative stress with pro-inflammatory, metabolic and cell death pathways is critical to devise novel targeted therapies for diabetic cardiomyopathy, which will be overviewed in this brief synopsis. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases. Published by Elsevier B.V. C1 [Varga, Zoltan V.; Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. [Varga, Zoltan V.; Giricz, Zoltan; Ferdinandy, Peter] Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, Cardiometab Res Grp, H-1085 Budapest, Hungary. [Liaudet, Lucas] Univ Hosp Med Ctr, Dept Intens Care Med, Lausanne, Switzerland. [Hasko, Gyoergy] Rutgers NJ Med Sch, Dept Surg, Newark, NJ 07103 USA. [Hasko, Gyoergy] Rutgers NJ Med Sch, Ctr Immun & Inflammat, Newark, NJ 07103 USA. [Ferdinandy, Peter] Pharmahungwy Grp, Szeged, Hungary. RP Pacher, P (reprint author), Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, 5625 Fishers Lane,Room 2N-17, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017; OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930; Giricz, Zoltan/0000-0003-2036-8665 FU Intramural Research Program of NIH/NIAAA; New Horizons Grant of the European Foundation for the Study of Diabetes; Hungarian Scientific Research Fund [OTKA K109737]; Hungarian Academy of Sciences; National Program of Excellence [TAMOP 4.2.4.A/2-11-1-2012-0001] FX This study was supported by Intramural Research Program of NIH/NIAAA (to PP), the New Horizons Grant of the European Foundation for the Study of Diabetes, and Hungarian Scientific Research Fund (OTKA K109737) (to PF, ZG, and ZVV). ZG holds a "Janos Bolyai Fellowship" from the Hungarian Academy of Sciences. PF is a Szentagothai Fellow of the National Program of Excellence (TAMOP 4.2.4.A/2-11-1-2012-0001). Authors are indebted to Dr. George Kunos, the Scientific Director of NIAAA for continuous support NR 176 TC 23 Z9 29 U1 5 U2 49 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 EI 0006-3002 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD FEB PY 2015 VL 1852 IS 2 SI SI BP 232 EP 242 DI 10.1016/j.bbadis.2014.06.030 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CA5QR UT WOS:000348963400007 PM 24997452 ER PT J AU Yan, XF Niu, G Lin, J Jin, AJ Hu, H Tang, YX Zhang, YJ Wu, AG Lu, J Zhang, SL Huang, P Shen, BZ Chen, XY AF Yan, Xuefeng Niu, Gang Lin, Jing Jin, Albert J. Hu, Hao Tang, Yuxia Zhang, Yujie Wu, Aiguo Lu, Jie Zhang, Shaoliang Huang, Peng Shen, Baozhong Chen, Xiaoyuan TI Enhanced fluorescence imaging guided photodynamic therapy of sinoporphyrin sodium loaded graphene oxide SO BIOMATERIALS LA English DT Article DE Photosensitizer; Sinoporphyrin sodium (DVDMS); Graphene oxide (GO); Photodynamic therapy; Fluorescence imaging ID BIOMEDICAL APPLICATIONS; PHOTOTHERMAL THERAPY; TUMOR VASCULATURE; SMALL MOLECULES; NANO-GRAPHENE; GOLD NANORODS; PHOTOSENSITIZER; THERANOSTICS; AGENTS; NANOPARTICLES AB Extensive research indicates that graphene oxide (GO) can effectively deliver photosensitives (PSs) by pi-pi stacking for photodynamic therapy (PDT). However, due to the tight complexes of GO and PSs, the fluorescence of PSs are often drastically quenched via an energy/charge transfer process, which limits GO-PS systems for photodiagnostics especially in fluorescence imaging. To solve this problem, we herein strategically designed and prepared a novel photo-theranostic agent based on sinoporphyrin sodium (DVDMS) loaded PEGylated GO (GO-PEG-DVDMS) with improved fluorescence property for enhanced optical imaging guided PDT. The fluorescence of loaded DVDMS is drastically enhanced via intramolecular charge transfer. Meanwhile, the GO-PEG vehicles can significantly increase the tumor accumulation efficiency of DVDMS and lead to an improved PDT efficacy as compared to DVDMS alone. The cancer theranostic capability of the as-prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. Most intriguingly, 100% in vivo tumor elimination was achieved by intravenous injection of GO-PEG-DVDMS (2 mg/kg of DVDMS, 50 J) without tumor recurrence, loss of body weight or other noticeable toxicity. This novel GO-PEG-DVDMS theranostics is well suited for enhanced fluorescence imaging guided PDT. Published by Elsevier Ltd. C1 [Yan, Xuefeng; Shen, Baozhong] Harbin Med Univ, Mol Imaging Ctr, Harbin, Heilongjiang, Peoples R China. [Jin, Albert J.] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. [Zhang, Yujie; Wu, Aiguo] Chinese Acad Sci, Key Lab Magnet Mat & Devices, Ningbo Inst Mat Technol & Engn, Ningbo 315201, Zhejiang, Peoples R China. [Zhang, Yujie; Wu, Aiguo] Chinese Acad Sci, Div Funct Mat & Nanodevices, Ningbo Inst Mat Technol & Engn, Ningbo 315201, Zhejiang, Peoples R China. [Zhang, Shaoliang] Jiangxi Qinglong Grp Co Ltd, Yichun 336000, Jiangxi, Peoples R China. RP Chen, XY (reprint author), NIBIB, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. EM peng.huang@nih.gov; shenbzh@vip.sina.com; shawn.chen@nih.gov RI Wu, Aiguo/A-5414-2008; Huang, Peng/H-9985-2013; Huang, Peng/R-2480-2016; OI Huang, Peng/0000-0003-3651-7813; Jin, Albert/0000-0003-3826-1081; Wu, Aiguo/0000-0001-7200-8923 FU National Basic Research Program of China [2013CB733802, 2014CB744503, 2015CB931800, 2015CB931803]; National Natural Science Foundation of China [81371596, 81401465, 81130028, 31210103913]; Key Grant Project of Heilongjiang Province [GA12C302]; Ph.D. Programs Foundation of Ministry of Education of China [201123071100203]; Key Laboratory of Molecular Imaging Foundation(College of Heilongjiang Province); intramural research program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported, in part, by the National Basic Research Program of China (2013CB733802, 2014CB744503, 2015CB931800 and 2015CB931803), National Natural Science Foundation of China (81371596, 81401465, 81130028, 31210103913), the Key Grant Project of Heilongjiang Province (GA12C302), the Ph.D. Programs Foundation of Ministry of Education of China (201123071100203), the Key Laboratory of Molecular Imaging Foundation(College of Heilongjiang Province) and by the intramural research program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 48 TC 28 Z9 29 U1 17 U2 130 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2015 VL 42 BP 94 EP 102 DI 10.1016/j.biomaterials.2014.11.040 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA CA4OH UT WOS:000348883700010 PM 25542797 ER PT J AU Puligujja, P Balkundi, SS Kendrick, LM Baldridge, HM Hilaire, JR Bade, AN Dash, PK Zhang, G Poluektova, LY Gorantla, S Liu, XM Ying, TL Feng, Y Wang, YP Dimitrov, DS McMillan, JM Gendelman, HE AF Puligujja, Pavan Balkundi, Shantanu S. Kendrick, Lindsey M. Baldridge, Hannah M. Hilaire, James R. Bade, Aditya N. Dash, Prasanta K. Zhang, Gang Poluektova, Larisa Y. Gorantla, Santhi Liu, Xin-Ming Ying, Tianlei Feng, Yang Wang, Yanping Dimitrov, Dimiter S. McMillan, JoEllyn M. Gendelman, Howard E. TI Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir-boosted atazanavir nanoformulations SO BIOMATERIALS LA English DT Article DE Folic acid receptor; Long-acting nanoformulated antiretroviral therapy; Human immunodeficiency virus type one; Pharmacokinetics; Pharmacodynamics; Non-obese diabetic severe combined; immunodeficient mice ID ANTIRETROVIRAL DRUG-DELIVERY; HUMANIZED MICE; VIRAL PERSISTENCE; FOLATE RECEPTOR; HIV-1 INFECTION; MURINE MODEL; THERAPY; ADHERENCE; MACROPHAGES; TRAFFICKING AB Long-acting nanoformulated antiretroviral therapy (nanoART) that targets monocyte-macrophages could improve the drug's half-life and protein-binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly increased drug bioavailability and PD by five and 100 times, respectively. Drug particles administered to human peripheral blood lymphocyte reconstituted NOD.Cg-Prkdc(scid)Il2rg(tm1wil)/SzJ mice and infected with HIV-1ADA led to ATV/r drug concentrations that paralleled FA receptor beta staining in both the macrophage-rich parafollicular areas of spleen and lymph nodes. Drug levels were higher in these tissues than what could be achieved by either native drug or untargeted nanoART particles. The data also mirrored potent reductions in viral loads, tissue viral RNA and numbers of HIV-1p24+ cells in infected and treated animals. We conclude that FA-P407 coating of ART nanoparticles readily facilitates drug carriage and antiretroviral responses. (C) 2014 The Authors. Published by Elsevier Ltd. C1 [Puligujja, Pavan; Balkundi, Shantanu S.; Kendrick, Lindsey M.; Baldridge, Hannah M.; Hilaire, James R.; Bade, Aditya N.; Dash, Prasanta K.; Zhang, Gang; Poluektova, Larisa Y.; Gorantla, Santhi; Liu, Xin-Ming; McMillan, JoEllyn M.; Gendelman, Howard E.] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA. [Balkundi, Shantanu S.] Kansas Univ Innovat & Collaborat, Lawrence, KS 66045 USA. [Liu, Xin-Ming; Gendelman, Howard E.] Univ Nebraska Med Ctr, Dept Pharmaceut Sci, Omaha, NE 68198 USA. [Ying, Tianlei; Feng, Yang; Wang, Yanping; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Expt Immunol Lab, Canc & Inflammat Program,Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Ying, Tianlei] Fudan Univ, Key Lab Med Mol Virol Minist Educ & Hlth, Shanghai Med Coll, Shanghai 200032, Peoples R China. [Ying, Tianlei] Fudan Univ, Inst Med Microbiol, Shanghai 200032, Peoples R China. RP Gendelman, HE (reprint author), Dept Pharmacol & Expt Neurosci, 985880 Nebraska Med Ctr, Omaha, NE 68198 USA. EM hegendel@unmc.edu OI Poluektova, Larisa/0000-0001-7339-8732 FU University of Nebraska Foundation; National Institutes of Health (NIH), USA [P01 MH64570, RO1 MH104147, P01 DA028555, R01 NS36126, P01 NS31492, 2R01 N5034239, P01 NS43985, P30 MH062261, RO1 AG043540] FX This work was supported by the University of Nebraska Foundation that includes individual donations from Dr. Carol Swarts and Frances and Louie Blumkin; the Vice Chancellor for Research office, UNMC; ViiV Healthcare; and National Institutes of Health (NIH), USA grants P01 MH64570, RO1 MH104147, P01 DA028555, R01 NS36126, P01 NS31492, 2R01 N5034239, P01 NS43985, P30 MH062261, RO1 AG043540 (H.E.G.) and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (D.S.D). NR 47 TC 16 Z9 16 U1 2 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2015 VL 41 BP 141 EP 150 DI 10.1016/.biomaterials.2014.11.012 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA CA6XY UT WOS:000349062100014 PM 25522973 ER PT J AU Schaffer, A Isometsa, ET Tondo, L Moreno, DH Turecki, G Reis, C Cassidy, F Sinyor, M Azorin, JM Kessing, LV Ha, K Goldstein, T Weizman, A Beautrais, A Chou, YH Diazgranados, N Levitt, AJ Zarate, CA Rihmer, Z Yatham, LN AF Schaffer, Ayal Isometsae, Erkki T. Tondo, Leonardo Moreno, Doris H. Turecki, Gustavo Reis, Catherine Cassidy, Frederick Sinyor, Mark Azorin, Jean-Michel Kessing, Lars Vedel Ha, Kyooseob Goldstein, Tina Weizman, Abraham Beautrais, Annette Chou, Yuan-Hwa Diazgranados, Nancy Levitt, Anthony J. Zarate, Carlos A., Jr. Rihmer, Zoltan Yatham, Lakshmi N. TI International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; meta-analysis; suicide ID NATIONAL EPIDEMIOLOGIC SURVEY; COMORBID ANXIETY DISORDERS; SUBSTANCE USE DISORDERS; AGE-OF-ONSET; RISK-FACTORS; ATTEMPT HISTORY; PSYCHIATRIC-INPATIENTS; GENDER-DIFFERENCES; SPECTRUM DISORDER; CONDITIONS NESARC AB ObjectivesBipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder. MethodsWithin the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and suicide attempts' or suicide', was conducted, and data extracted for analysis from all eligible articles. Demographic and clinical variables for which 3 studies with usable data were available were meta-analyzed using fixed or random-effects models for association with suicide attempts and suicide deaths. There was considerable heterogeneity in the methods employed by the included studies. ResultsVariables significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use, comorbid cluster B/borderline personality disorder, and first-degree family history of suicide. Suicide deaths were significantly associated with male gender and first-degree family history of suicide. ConclusionsThis paper reports on the presence and magnitude of the correlates of suicide attempts and suicide deaths in bipolar disorder. These findings do not address causation, and the heterogeneity of data sources should limit the direct clinical ranking of correlates. Our results nonetheless support the notion of incorporating diagnosis-specific data in the development of models of understanding suicide in bipolar disorder. C1 [Schaffer, Ayal; Reis, Catherine; Sinyor, Mark; Levitt, Anthony J.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Psychiat, Toronto, ON, Canada. [Schaffer, Ayal; Reis, Catherine; Sinyor, Mark; Levitt, Anthony J.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Isometsae, Erkki T.] Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. [Tondo, Leonardo] Lucio Bini Ctr, Cagliari, Italy. [Tondo, Leonardo] Harvard Univ, Sch Med, McLean Hosp, Boston, MA USA. [Moreno, Doris H.] Univ Sao Paulo, Dept & Inst Psychiat, Sao Paulo, Brazil. [Turecki, Gustavo] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Turecki, Gustavo] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Turecki, Gustavo] McGill Univ, Dept Neurosurg, Montreal, PQ, Canada. [Cassidy, Frederick] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Azorin, Jean-Michel] Univ Aix Marseille 2, Dept Psychiat, F-13284 Marseille 07, France. [Kessing, Lars Vedel] Univ Copenhagen, Fac Hlth Sci, Ctr Psychiat, Copenhagen Dept, Copenhagen, Denmark. [Ha, Kyooseob] Seoul Natl Univ, Dept Psychiat, Bundang Hosp, Seoul, South Korea. [Goldstein, Tina] Univ Pittsburgh, Sch Med, Dept Child & Adolescent Psychiat, Pittsburgh, PA USA. [Weizman, Abraham] Tel Aviv Univ, Sackler Fac Med, Dept Psychiat, IL-69978 Tel Aviv, Israel. [Beautrais, Annette] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. [Chou, Yuan-Hwa] Taipei Vet Gen Hosp, Dept Psychiat, Taipei, Taiwan. [Chou, Yuan-Hwa] Natl Yang Ming Univ, Taipei 112, Taiwan. [Diazgranados, Nancy] NIAAA, Bethesda, MD USA. [Zarate, Carlos A., Jr.] NIMH, Bethesda, MD USA. [Rihmer, Zoltan] Semmelweis Univ, Dept Clin & Theoret Mental Hlth, Budapest, Hungary. [Rihmer, Zoltan] Semmelweis Univ, Dept Psychiat & Psychotherapy, Budapest, Hungary. [Yatham, Lakshmi N.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. RP Schaffer, A (reprint author), Sunnybrook Hlth Sci Ctr, Dept Psychiat, Mood & Anxiety Disorders Program, 2075 Bayview Ave,Room FG 52, Toronto, ON M4N 3M5, Canada. EM ayal.schaffer@sunnybrook.ca FU Brenda Smith Bipolar Disorder Research Fund, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada FX The authors wish to thank the International Society for Bipolar Disorders executive and staff who assisted with the organization of the task force, and the students who assisted with the literature review and provided statistical work (Jessika Lenchyshyn, BSc, Randy Rovinski, MSc). Partial support for this project was provided by the Brenda Smith Bipolar Disorder Research Fund, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada. NR 100 TC 29 Z9 30 U1 6 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD FEB PY 2015 VL 17 IS 1 BP 1 EP 16 DI 10.1111/bdi.12271 PG 16 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CA1HH UT WOS:000348662900001 PM 25329791 ER PT J AU Wennerberg, E Kremer, V Childs, R Lundqvist, A AF Wennerberg, Erik Kremer, Veronika Childs, Richard Lundqvist, Andreas TI CXCL10-induced migration of adoptively transferred human natural killer cells toward solid tumors causes regression of tumor growth in vivo SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Adoptive cell therapy; Natural killer cells; Migration; CXCL10; CXCR3 ID HUMAN NK CELLS; CXCR3 LIGANDS; IFN-GAMMA; T-CELLS; PROGNOSTIC-SIGNIFICANCE; MEDIATED CYTOTOXICITY; COLORECTAL-CARCINOMA; ACTIVATING RECEPTORS; CHEMOKINE RECEPTORS; IMMUNE-RESPONSES AB Adoptive infusion of natural killer (NK) cells is being increasingly explored as a therapy in patients with cancer, although clinical responses are thus far limited to patients with hematological malignancies. Inadequate homing of infused NK cells to the tumor site represents a key factor that may explain the poor anti-tumor effect of NK cell therapy against solid tumors. One of the major players in the regulation of lymphocyte chemotaxis is the chemokine receptor chemokine (C-X-C motif) receptor 3 (CXCR3) which is expressed on activated NK cells and induces NK cell migration toward gradients of the chemokine (C-X-C motif) ligand (CXCL9, 10 and 11). Here, we show that ex vivo expansion of human NK cells results in a tenfold increased expression of the CXCR3 receptor compared with resting NK cells (p = 0.04). Consequently, these NK cells displayed an improved migratory capacity toward solid tumors, which was dependent on tumor-derived CXCL10. In xenograft models, adoptively transferred NK cells showed increased migration toward CXCL10-transfected melanoma tumors compared with CXCL10-negative wild-type tumors, resulting in significantly reduced tumor burden and increased survival (median survival 41 vs. 32 days, p = 0.03). Furthermore, administration of interferon-gamma locally in the tumor stimulated the production of CXCL10 in subcutaneous melanoma tumors resulting in increased infiltration of adoptively transferred CXCR3-positive expanded NK cells. Our findings demonstrate the importance of CXCL10-induced chemoattraction in the anti-tumor response of adoptively transferred expanded NK cells against solid melanoma tumors. C1 [Wennerberg, Erik; Kremer, Veronika; Lundqvist, Andreas] Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, S-17176 Stockholm, Sweden. [Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Lundqvist, A (reprint author), Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, R8 01, S-17176 Stockholm, Sweden. EM andreas.lundqvist@ki.se OI Lundqvist, Andreas/0000-0002-9709-2970; Wennerberg, Erik/0000-0001-7689-5988 FU Swedish Research Council [522-208-2377]; Swedish Cancer Society [CAN 2012/474]; FP7 Marie Curie re-integration Grant [246759]; Cancer Society in Stockholm [121132]; Swedish Society of Medicine [325751]; Karolinska Institutet; Jeanssons Stiftelser; Ake Wibergs Stiftelse; Magnus Bergvalls Stiftelse; Fredrik och Ingrid Thurings Stiftelse; Stiftelsen Clas Groschinskys Minnesfond; Division of Intramural Research at the Hematology Branch of the National Heart Blood and Lung Institute FX We would like to acknowledge the staff at the animal facility at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. Dhifaf Sarhan and Rolf Kiessling at the Department of Oncology-Pathology, Karolinska Institutet for intellectual input. This work was supported by funding from The Swedish Research Council (# 522-208-2377), The Swedish Cancer Society (# CAN 2012/474), FP7 Marie Curie re-integration Grant (# 246759), The Cancer Society in Stockholm (# 121132), the Swedish Society of Medicine (# 325751), Karolinska Institutet, Jeanssons Stiftelser, Ake Wibergs Stiftelse, Magnus Bergvalls Stiftelse, Fredrik och Ingrid Thurings Stiftelse, Stiftelsen Clas Groschinskys Minnesfond, and the Division of Intramural Research at the Hematology Branch of the National Heart Blood and Lung Institute. NR 53 TC 20 Z9 20 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD FEB PY 2015 VL 64 IS 2 BP 225 EP 235 DI 10.1007/s00262-014-1629-5 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA CA9GW UT WOS:000349231200009 PM 25344904 ER PT J AU Chandran, SS Paria, BC Srivastava, AK Rothermel, LD Stephens, DJ Dudley, ME Somerville, R Wunderlich, JR Sherry, RM Yang, JC Rosenberg, SA Kammula, US AF Chandran, Smita S. Paria, Biman C. Srivastava, Abhishek K. Rothermel, Luke D. Stephens, Daniel J. Dudley, Mark E. Somerville, Robert Wunderlich, John R. Sherry, Richard M. Yang, James C. Rosenberg, Steven A. Kammula, Udai S. TI Persistence of CTL Clones Targeting Melanocyte Differentiation Antigens Was Insufficient to Mediate Significant Melanoma Regression in Humans SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL TRANSFER THERAPY; CD8(+) T-CELLS; RECOMBINANT INTERLEUKIN-2 THERAPY; METASTATIC MELANOMA; ADOPTIVE TRANSFER; CANCER REGRESSION; TUMOR-REGRESSION; INFILTRATING LYMPHOCYTES; PERIPHERAL-BLOOD; PHASE-I AB Purpose: Adoptive transfer of autologous tumor infiltrating lymphocytes (TIL) can mediate durable cancer regression in selected patients with metastatic melanoma. However, the tumor antigens associated with these favorable responses remain unclear. We hypothesized that a clinical strategy involving the iterative adoptive transfer of selected autologous antigen-specific T-cell clones could help systematically define immunologic targets associated with successful cancer therapy, without the interpretative ambiguity of transferring polyclonal populations. Here, we evaluated the clinical efficacy of CD8(+) T-cell clones specific for the melanocyte differentiation antigens (MDA), gp100 and MART-1, respectively. Experimental Design: We conducted two consecutive phase II clinical trials involving the adoptive transfer of highly selected autologous antigen-specificCD8(+) T-cell clones against gp100 and MART-1, respectively. Fifteen patients with HLA-A2(+) treatment-refractory metastatic melanoma received highly avid MDA-specific CD8(+) T-cell clones specific for either gp100 (n = 10) or MART-1 (n = 5) with or without intravenous interleukin-2 (IL2) after a lymphodepleting myeloablative preparative regimen. Results: Of the 15 treated patients, we observed immune-mediated targeting of skin melanocytes in 11 patients (73%) and clonal engraftment in eight patients (53%) after cell transfer. There were only transient minor tumor regressions observed, but no objective tumor responses based on Response Evaluation Criteria in Solid Tumor (RECIST) criteria. Conclusions: Despite successful clonal repopulation and evidence of in vivo antigen targeting, the poor therapeutic efficacy after the adoptive transfer of autologous MDA-specific T cells raises significant concerns regarding future immunotherapy efforts targeting this class of tumor antigens. (C) 2014 AACR. C1 [Chandran, Smita S.; Paria, Biman C.; Srivastava, Abhishek K.; Rothermel, Luke D.; Stephens, Daniel J.; Dudley, Mark E.; Somerville, Robert; Wunderlich, John R.; Sherry, Richard M.; Yang, James C.; Rosenberg, Steven A.; Kammula, Udai S.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kammula, US (reprint author), NCI, Surg Branch, Ctr Canc Res, 10 Ctr Dr,Bldg 10-Hatfield CRC,Room 3-5930, Bethesda, MD 20892 USA. EM udai_kammula@nih.gov RI Srivastava, Abhishek/M-7577-2014 FU Intramural NIH HHS [ZIA BC010766-08] NR 42 TC 10 Z9 10 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2015 VL 21 IS 3 BP 534 EP 543 DI 10.1158/1078-0432.CCR-14-2208 PG 10 WC Oncology SC Oncology GA CA4WR UT WOS:000348908500007 PM 25424856 ER PT J AU Kim, HS Kwon, HJ Jung, I Yun, MR Ahn, MJ Kang, BW Sun, JM Kim, SB Yoon, DH Park, KU Lee, SH Koh, YW Kim, SH Choi, EC Koo, DH Sohn, JH Kim, B Kwon, NJ Yun, HJ Lee, MG Lee, JH Kim, TM Kim, HR Kim, JH Paik, S Cho, BC AF Kim, Han Sang Kwon, Hyeong Ju Jung, Inkyung Yun, Mi Ran Ahn, Myung-Ju Kang, Byung Woog Sun, Jong-Mu Kim, Sung Bae Yoon, Dok-Hyun Park, Keon Uk Lee, Se-Hoon Koh, Yoon Woo Kim, Se Hun Choi, Eun Chang Koo, Dong Hoe Sohn, Jin Hee Kim, Bomi Kwon, Nak-Jung Yun, Hwan Jung Lee, Min Goo Lee, Ji Hyun Kim, Tae-Min Kim, Hye Ryun Kim, Joo Hang Paik, Soonmyung Cho, Byoung Chul TI Phase II Clinical and Exploratory Biomarker Study of Dacomitinib in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; COOPERATIVE-ONCOLOGY-GROUP; CHEMOTHERAPY PLUS CETUXIMAB; TYROSINE KINASE INHIBITOR; PIK3CA MUTATION; LUNG-CANCER; SOMATIC MUTATIONS; MESSENGER-RNA; COPY NUMBER; OPEN-LABEL AB Purpose: The goals of this study were to investigate the clinical activity, safety, and biomarkers of dacomitinib, an irreversible tyrosine kinase inhibitor of EGFR, HER2, and HER4, in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). Experimental Design: Patients were eligible if the diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, and were treated with dacomitinib 45 mg/day. The primary endpoint was objective response rate by RECISTv1.1. Exploratory analysis included the characterization of somatic mutation, gene copy number, gene expression, p16(INK4A) expression by IHC, and investigation of their relationship with clinical outcomes. Results: Forty-eight patients were evaluable for efficacy and toxicity. Ten patients (20.8%) had partial responses and 31 patients (65%) had stable diseases. The median progressionfree survival (PFS) and overall survival (OS) were 3.9 months [95% confidence interval (CI), 2.9-5.0] and 6.6 months (95% CI, 5.4-10.3). Adverse events were mostly grade 1-2. Mutations in the PI3K pathway (PIK3CA, PTEN) and high expression of inflammatory cytokines (IL6, IL8, IL1A, IL1B, IL4, and TNF) were significantly associated with shorter PFS (2.9 vs. 4.9 months without mutations, P = 0.013; 2.8 vs. 9.9 months with low expression, P = 0.004). Those harboring PI3K pathway mutations or high inflammatory cytokine expression had shorter median OS (6.1 vs. 12.5 months lacking PI3K pathway mutations and with low inflammatory cytokine expression, P = 0.005). Conclusions: Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-SCCHN patients. Screening of PI3K pathway mutation and inflammatory cytokine expression may help identify which R/M-SCCHN patients are likely to gain benefit from dacomitinib. (C) 2014 AACR. C1 [Kim, Han Sang; Kim, Hye Ryun; Kim, Joo Hang; Cho, Byoung Chul] Yonsei Canc Ctr, Dept Internal Med, Div Med Oncol, Seoul, South Korea. [Kim, Han Sang; Lee, Min Goo] Pharmacogen Res Ctr Membrane Transporters, Dept Pharmacol, Brain Korea PLUS Project Med Sci 21, Seoul, South Korea. [Kwon, Hyeong Ju] Yonsei Univ, Coll Med, Dept Pathol, Seoul 120752, South Korea. [Jung, Inkyung] Yonsei Univ, Coll Med, Dept Biostat, Seoul 120752, South Korea. [Yun, Mi Ran] JE UK Inst Canc Res, Gumi, Kyungbuk, South Korea. [Ahn, Myung-Ju; Sun, Jong-Mu] Samsung Med Ctr, Seoul, South Korea. [Kang, Byung Woog] Kyungpook Natl Univ Hosp, Taegu, South Korea. [Kim, Sung Bae; Yoon, Dok-Hyun] Asan Med Ctr, Seoul, South Korea. [Park, Keon Uk] Keimyung Univ, Taegu, South Korea. [Lee, Se-Hoon] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Koh, Yoon Woo; Kim, Se Hun; Choi, Eun Chang] Yonsei Univ, Coll Med, Dept Otorhinolaryngol, Seoul 120752, South Korea. [Koo, Dong Hoe] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol, Seoul, South Korea. [Sohn, Jin Hee] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Med Ctr, Dept Pathol, Seoul, South Korea. [Kim, Bomi] Yonsei Univ, Brain Korea PLUS Project Med Sci 21, Seoul 120752, South Korea. [Kwon, Nak-Jung] Macrogen Inc, Seoul, South Korea. [Yun, Hwan Jung] Chungnam Natl Univ, Dept Hematol Oncol, Taejon, South Korea. [Lee, Ji Hyun] Yonsei Univ, Coll Dent, Dept Oral Biol, Seoul 120749, South Korea. [Kim, Tae-Min] Catholic Univ Korea, Coll Med, Dept Med Informat, Seoul, South Korea. [Paik, Soonmyung] NSABP, Div Pathol, Pittsburgh, PA USA. [Paik, Soonmyung] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul 120752, South Korea. RP Cho, BC (reprint author), Yonsei Univ, Coll Med, Yonsei Canc Ctr, Div Med Oncol, 50 Yonsei Ro, Seoul 120752, South Korea. EM cbc1971@yuhs.ac RI Lee, Min Goo/D-5635-2012; sun, jm/O-5938-2014; OI Lee, Min Goo/0000-0001-7436-012X; Kim, Han Sang/0000-0002-6504-9927; Koo, Dong-Hoe/0000-0001-9913-8883 FU Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI12C1440]; National Research Foundation of Korea (NRF) - Korean government(MEST) [2012R1A2A2A01046927] FX This work was supported in part by a grant from the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C1440; to B.C. Cho) and the National Research Foundation of Korea (NRF) funded by the Korean government (MEST; 2012R1A2A2A01046927; to B.C. Cho). Pfizer provided dacomitinib. NR 48 TC 10 Z9 10 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2015 VL 21 IS 3 BP 544 EP 552 DI 10.1158/1078-0432.CCR-14-1756 PG 9 WC Oncology SC Oncology GA CA4WR UT WOS:000348908500008 PM 25424851 ER PT J AU Candido-dos-Reis, FJ Song, HL Goode, EL Cunningham, JM Fridley, BL Larson, MC Alsop, K Dicks, E Harrington, P Ramus, SJ de Fazio, A Mitchell, G Fereday, S Bolton, KL Gourley, C Michie, C Karlan, B Lester, J Walsh, C Cass, I Olsson, H Gore, M Benitez, JJ Garcia, MJ Andrulis, I Mulligan, AM Glendon, G Blanco, I Lazaro, C Whittemore, AS McGuire, V Sieh, W Montagna, M Alducci, E Sadetzki, S Chetrit, A Kwong, A Kjaer, SK Jensen, A Hogdall, E Neuhausen, S Nussbaum, R Daly, M Greene, MH Mai, PL Loud, JT Moysich, K Toland, AE Lambrechts, D Ellis, S Frost, D Brenton, JD Tischkowitz, M Easton, DF Antoniou, A Chenevix-Trench, G Gayther, SA Bowtell, D Pharoah, PDP AF Candido-dos-Reis, Francisco J. Song, Honglin Goode, Ellen L. Cunningham, Julie M. Fridley, Brooke L. Larson, Melissa C. Alsop, Kathryn Dicks, Ed Harrington, Patricia Ramus, Susan J. de Fazio, Anna Mitchell, Gillian Fereday, Sian Bolton, Kelly L. Gourley, Charlie Michie, Caroline Karlan, Beth Lester, Jenny Walsh, Christine Cass, Ilana Olsson, Hakan Gore, Martin Benitez, Javier J. Garcia, Maria J. Andrulis, Irene Mulligan, Anna Marie Glendon, Gord Blanco, Ignacio Lazaro, Conxi Whittemore, Alice S. McGuire, Valerie Sieh, Weiva Montagna, Marco Alducci, Elisa Sadetzki, Siegal Chetrit, Angela Kwong, Ava Kjaer, Susanne K. Jensen, Allan Hogdall, Estrid Neuhausen, Susan Nussbaum, Robert Daly, Mary Greene, Mark H. Mai, Phuong L. Loud, Jennifer T. Moysich, Kirsten Toland, Amanda E. Lambrechts, Diether Ellis, Steve Frost, Debra Brenton, James D. Tischkowitz, Marc Easton, Douglas F. Antoniou, Antonis Chenevix-Trench, Georgia Gayther, Simon A. Bowtell, David Pharoah, Paul D. P. CA EMBRACE KConFab Investigators Australian Ovarian Cancer Study Gr TI Germline Mutation in BRCA1 or BRCA2 and Ten-Year Survival for Women Diagnosed with Epithelial Ovarian Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SOMATIC MUTATIONS; POPULATION; CARCINOMAS; RESISTANCE; CISPLATIN; GENES; RAD51 AB Purpose: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis. Experimental Design: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model. Results: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality. Conclusions: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/ 2 mutation carriers. (C) 2014 AACR. C1 [Candido-dos-Reis, Francisco J.] Univ Sao Paulo, Dept Gynecol & Obstet, Ribeirao Preto Med Sch, Sao Paulo, Brazil. [Song, Honglin; Dicks, Ed; Harrington, Patricia; Ellis, Steve; Frost, Debra; Easton, Douglas F.; Antoniou, Antonis; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England. [Goode, Ellen L.; Cunningham, Julie M.; Larson, Melissa C.] Mayo Clin, Rochester, MN USA. [Fridley, Brooke L.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Alsop, Kathryn; Mitchell, Gillian; Fereday, Sian; Bowtell, David] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Ramus, Susan J.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [de Fazio, Anna] Univ Sydney, Dept Gynecol Oncol, Crown Princess Mary Canc Ctr, Sydney, NSW 2006, Australia. [de Fazio, Anna] Univ Sydney, Inst Canc Res, Westmead Millennium Inst, Sydney, NSW 2006, Australia. [Bolton, Kelly L.; Greene, Mark H.; Mai, Phuong L.; Loud, Jennifer T.] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. [Gourley, Charlie] Univ Edinburgh, Canc Res UK Ctr, MRC IGMM, Edinburgh, Midlothian, Scotland. [Michie, Caroline] Ninewells Hosp, Dundee DD1 9SY, Scotland. [Michie, Caroline] Sch Med, Dundee, Scotland. [Karlan, Beth; Lester, Jenny; Walsh, Christine; Cass, Ilana] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Olsson, Hakan] Lund Univ, Dept Canc Epidemiol, Lund, Sweden. [Olsson, Hakan] Lund Univ, Dept Oncol, Lund, Sweden. [Gore, Martin] Royal Marsden NHS Fdn Trust, London, England. [Benitez, Javier J.; Garcia, Maria J.] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid, Spain. [Benitez, Javier J.; Garcia, Maria J.] Spanish Natl Canc Res Ctr CNIO, Human Genotyping Unit, Madrid, Spain. [Andrulis, Irene] Univ Toronto, Mt Sinai Hosp, Lunenfeld TanenbaumResearch Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 1X5, Canada. [Mulligan, Anna Marie; Glendon, Gord] Univ Toronto, Univ Hlth Network, Lab Med Program, Toronto, ON M5G 1X5, Canada. [Mulligan, Anna Marie; Glendon, Gord] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 1X5, Canada. [Blanco, Ignacio; Lazaro, Conxi] Catalan Inst Oncol, Hereditary Canc Program, Barcelona, Spain. [Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [Montagna, Marco; Alducci, Elisa] Ist Oncol Veneto IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Sadetzki, Siegal; Chetrit, Angela] Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, Tel Hashomer, Israel. [Kwong, Ava] Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China. [Kjaer, Susanne K.; Jensen, Allan] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark. [Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark. [Neuhausen, Susan] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA. [Nussbaum, Robert] Univ Calif San Francisco, Canc Risk Program, San Francisco, CA 94143 USA. [Daly, Mary] Fox Chase Canc Ctr, Dept Clin Genet, Philadelphia, PA 19111 USA. [Moysich, Kirsten] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Dept Mol Virol, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Dept Immunol, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Dept Med Genet, Columbus, OH 43210 USA. [Lambrechts, Diether] Univ Leuven, VIBVesalius Res Ctr, Leuven, Belgium. [Brenton, James D.] Cambridge Univ Hosp Fdn Trust, Dept Oncol, Cambridge, England. [Brenton, James D.] Cambridge Univ Hosp Fdn Trust, Dept Radiol, Cambridge, England. [Brenton, James D.] Univ Cambridge, CR UK Cambridge Inst, Cambridge, England. [Brenton, James D.] NIHR Cambridge Biomed Res Ctr, Cambridge, England. [Tischkowitz, Marc] Univ Cambridge, Dept Med Genet, Cambridge CB1 8RN, England. [Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Herston, Qld, Australia. RP Pharoah, PDP (reprint author), Univ Cambridge, Strangeways Res Lab, Dept Oncol, Worths Causeway, Cambridge CB1 8RN, England. EM paul.pharoah@srl.cam.ac.uk RI Fridley, Brooke/D-8315-2015; montagna, marco/E-2225-2012; Garcia, Maria/G-1361-2016; Bowtell, David/H-1007-2016; Andrulis, Irene/E-7267-2013; Candido dos Reis, Francisco/K-7024-2016; OI Fridley, Brooke/0000-0001-7739-7956; montagna, marco/0000-0002-4929-2150; Garcia, Maria/0000-0002-2236-9912; Bowtell, David/0000-0001-9089-7525; Candido dos Reis, Francisco/0000-0001-5758-5917; Brenton, James/0000-0002-5738-6683; Blanco, Ignacio/0000-0002-7414-7481; Kjaer, Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798 FU Sao Paulo Research Foundation (FAPESP); American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; Asociacion Espanola Contra el Cancer; Cancer Australia [509303]; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Research UK [C490/A10119, C490/A10124, C490/A16561]; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia [ISCIIIRETIC RD06/0020/105, PI10/01422, PI10/31488, 2009SGR290]; European Research Council [310018, 2011294576]; Mermaid Project (Mermaid 1); Ministero della Salute of Italy "5 x 1000" fund; National Breast Cancer Foundation of Australia; National Cancer Institute [UM1CA164920, R01CA178535, R01CA61107, U01CA71966, R01CA16056, K07CA143047, U01CA69417, P50CA136393, R01CA122443]; NIHR Biomedical Research Centres at the University of Cambridge; Royal Marsden NHS Foundation Trust; Institute of Cancer Research; National Health and Medical Research Council of Australia [400281, 400413]; Ovarian Cancer Research Program of the US Department of Defense [W81XWH-08-1-0684, W81XWH-08-10685]; Peter MacCallum Cancer Centre Foundation; Scottish Funding Council; Seventh Framework Programme of the European Union (FP); Swedish Cancer Society; Spanish Health Research Fund; Swedish Research Council; University of Sydney Cancer Research Fund; U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729] FX F.J. Candido-dos-Reis was funded by the Sao Paulo Research Foundation (FAPESP). The contributing studies were funded by grants from The American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN); Asociacion Espanola Contra el Cancer; Cancer Australia (509303); the Cancer Council Victoria; the Cancer Council Queensland, the Cancer Council New South Wales; Cancer Research UK (C490/A10119, C490/A10124, C490/A16561); Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. (ISCIIIRETIC RD06/0020/105, PI10/01422, PI10/31488, 2009SGR290); the European Research Council (310018, 2011294576); the Mermaid Project (Mermaid 1); Ministero della Salute of Italy "5 x 1000" fund; the National Breast Cancer Foundation of Australia; National Cancer Institute (UM1CA164920, R01CA178535, R01CA61107, U01CA71966, R01CA16056, K07CA143047, and U01CA69417, P50CA136393, R01CA122443); the NIHR Biomedical Research Centres at the University of Cambridge and the Royal Marsden NHS Foundation Trust and Institute of Cancer Research; the National Health and Medical Research Council of Australia (400281, 400413); Ovarian Cancer Research Program of the US Department of Defense (W81XWH-08-1-0684 and W81XWH-08-10685); the Peter MacCallum Cancer Centre Foundation; Scottish Funding Council; the Seventh Framework Programme of the European Union (FP/2007-2013); Swedish Cancer Society; Spanish Health Research Fund; Swedish Research Council; the University of Sydney Cancer Research Fund; and U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729). NR 29 TC 20 Z9 21 U1 0 U2 11 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 FEB 1 PY 2015 VL 21 IS 3 BP 652 EP 657 DI 10.1158/1078-0432.CCR-14-2497 PG 6 WC Oncology SC Oncology GA CA4WR UT WOS:000348908500020 PM 25398451 ER PT J AU Shin, D Protano, MA Polydorides, AD Dawsey, SM Pierce, MC Kim, MK Schwarz, RA Quang, T Parikh, N Bhutani, MS Zhang, F Wang, GQ Xue, LY Wang, XS Xu, H Anandasabapathy, S Richards-Kortum, RR AF Shin, Dongsuk Protano, Marion-Anna Polydorides, Alexandros D. Dawsey, Sanford M. Pierce, Mark C. Kim, Michelle Kang Schwarz, Richard A. Quang, Timothy Parikh, Neil Bhutani, Manoop S. Zhang, Fan Wang, Guiqi Xue, Liyan Wang, Xueshan Xu, Hong Anandasabapathy, Sharmila Richards-Kortum, Rebecca R. TI Quantitative Analysis of High-Resolution Microendoscopic Images for Diagnosis of Esophageal Squamous Cell Carcinoma SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Esophageal Cancer; HRME; Quantitative Diagnosis; Diagnostic ID GASTROINTESTINAL EPITHELIAL NEOPLASIA; HIGH-GRADE DYSPLASIA; BARRETTS-ESOPHAGUS; CANCER STATISTICS; LOW-COST; IN-VIVO; ENDOMICROSCOPY AB BACKGROUND & AIMS: High-resolution microendoscopy is an optical imaging technique with the potential to improve the accuracy of endoscopic screening for esophageal squamous neoplasia. Although these microscopic images can be interpreted readily by trained personnel, quantitative image analysis software could facilitate the use of this technology in low-resource settings. In this study, we developed and evaluated quantitative image analysis criteria for the evaluation of neoplastic and non-neoplastic squamous esophageal mucosa. METHODS: We performed an image analysis of 177 patients undergoing standard upper endoscopy for screening or surveillance of esophageal squamous neoplasia, using high-resolution microendoscopy, at 2 hospitals in China and at 1 hospital in the United States from May 2010 to October 2012. Biopsy specimens were collected from imaged sites (n = 375), and a consensus diagnosis was provided by 2 expert gastrointestinal pathologists and used as the standard. RESULTS: Quantitative information from the high-resolution images was used to develop an algorithm to identify high-grade squamous dysplasia or invasive squamous cell cancer, based on histopathology findings. Optimal performance was obtained using the mean nuclear area as the basis for classification, resulting in sensitivities and specificities of 93% and 92% in the training set, 87% and 97% in the test set, and 84% and 95% in an independent validation set, respectively. CONCLUSIONS: High-resolution microendoscopy with quantitative image analysis can aid in the identification of esophageal squamous neoplasia. Use of software-based image guides may overcome issues of training and expertise in low-resource settings, allowing for widespread use of these optical biopsy technologies. C1 [Shin, Dongsuk; Schwarz, Richard A.; Quang, Timothy; Richards-Kortum, Rebecca R.] Rice Univ, Dept Bioengn, Houston, TX 77005 USA. [Protano, Marion-Anna; Kim, Michelle Kang; Parikh, Neil; Anandasabapathy, Sharmila] Mt Sinai Med Ctr, Div Gastroenterol, New York, NY 10029 USA. [Polydorides, Alexandros D.] Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA. [Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Pierce, Mark C.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. [Bhutani, Manoop S.] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. [Zhang, Fan; Wang, Xueshan; Xu, Hong] Jilin Univ, Hosp 1, Dept Gastrointestinal Med, Changchun 130023, Jilin, Peoples R China. [Wang, Guiqi] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Endoscopy, Beijing 100730, Peoples R China. [Xue, Liyan] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Pathol, Beijing 100730, Peoples R China. RP Richards-Kortum, RR (reprint author), Rice Univ, 6100 Main St, Houston, TX 77005 USA. EM rkortum@rice.edu FU National Cancer Institute [R21CA156704]; National Institute of Biomedical Imaging and Bioengineering [R01EB007594] FX Supported by grants R21CA156704 from the National Cancer Institute and R01EB007594 from the National Institute of Biomedical Imaging and Bioengineering. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, the National Institute of Biomedical Imaging and Bioengineering, or the National Institutes of Health. NR 23 TC 12 Z9 12 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD FEB PY 2015 VL 13 IS 2 BP 272 EP U93 DI 10.1016/j.cgh.2014.07.030 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ9BB UT WOS:000348505100014 PM 25066838 ER PT J AU Martinez, MA Vuppalanchi, R Fontana, RJ Stolz, A Kleiner, DE Hayashi, PH Gu, J Hoofnagle, JH Chalasani, N AF Martinez, Melissa A. Vuppalanchi, Raj Fontana, Robert J. Stolz, Andrew Kleiner, David E. Hayashi, Paul H. Gu, Jiezhun Hoofnagle, Jay H. Chalasani, Naga TI Clinical and Histologic Features of Azithromycin-Induced Liver Injury SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE DILI; Antibiotic; Liver Toxicity; Macrolide ID STEVENS-JOHNSON-SYNDROME; INDUCED INTRAHEPATIC CHOLESTASIS; TOXIC EPIDERMAL NECROLYSIS; UNITED-STATES; CASE-SERIES; HEPATOTOXICITY; ERYTHROMYCIN; FAILURE; NETWORK; SAFETY AB BACKGROUND & AIMS: Rare cases of azithromycin-induced hepatotoxicity have been reported, with variable clinical and histologic features. We characterized clinical features and outcomes of azithromycin-induced liver injury. METHODS: We identified patients with azithromycin-induced liver injury from the Drug-Induced Liver Injury Network Prospective Study who had causality scores of definite, highly likely, or probable. Demographic, clinical, and laboratory data and 6-month outcomes were examined. RESULTS: Eighteen patients (72% female; mean age, 37 y) had causality scores of definite (n = 1), highly likely (n = 9), or probable (n = 8). Common presenting symptoms were jaundice, abdominal pain, nausea, and/or pruritus. For 16 patients, abnormal results from liver tests were first detected 14 days after azithromycin cessation (range, 9-20 d). The median duration of azithromycin treatment was 4 days (range, 2-7 d). The pattern of injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in 2 patients. The mean peak level of alanine aminotransferase was 2127 IU/L, of alkaline phosphatase was 481 IU/L, and of total bilirubin was 9.2 mg/dL. Liver histology showed ductopenia and veno-occlusive changes in a few patients. Two individuals had severe hypersensitivity cutaneous reactions. After 6 months, 8 patients had recovered, 4 patients had chronic injury, 1 patient died, and 1 patient underwent liver transplantation (outcomes were unavailable for 4 patients). Two of the patients who died or underwent liver transplantation had underlying chronic liver disease. CONCLUSIONS: Azithromycin-induced liver injury occurs within 1 to 3 weeks after azithromycin initiation and predominantly is hepatocellular in nature. Although most patients recover fully, severe cutaneous reactions, chronic injury, and serious complications leading to death or liver transplantation can occur C1 [Martinez, Melissa A.; Vuppalanchi, Raj; Chalasani, Naga] Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. [Fontana, Robert J.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Stolz, Andrew] Univ So Calif, Dept Med, Los Angeles, CA USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Natl Inst Hlth, Bethesda, MD USA. [Hayashi, Paul H.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Gu, Jiezhun] Duke Clin Res Inst, Durham, NC USA. RP Chalasani, N (reprint author), Indiana Univ Sch Med, Div Gastroenterol & Hepatol, 702 Rotary Bldg,Suite 225, Indianapolis, IN 46202 USA. EM nchalasa@iupui.edu OI Vuppalanchi, Raj/0000-0003-0637-1577 FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [U01s, 2U01-DK065176-06, 2U01-DK065201-06, 2U01-DK065184-06, 2U01-DK065211-06, 5U01DK065193-04, 5U01-DK065238-08, 1U01-DK083023-01, 1U01-DK083020-01]; CTSA [UL1 RR025761, UL1 RR025747, UL1 RR024134, UL1 RR024986, UL1 RR024982, UL1 RR024150]; National Cancer Institute, National Institutes of Health FX The Drug-Induced Liver Injury Network (https://dilin.dcri.duke.edu/) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health as a Cooperative Agreement (U01s) under grants: 2U01-DK065176-06 (Duke), 2U01-DK065201-06 (University of North Carolina), 2U01-DK065184-06 (Michigan), 2U01-DK065211-06 (Indiana), 5U01DK065193-04 (University of Connecticut), 5U01-DK065238-08 (University of California at San Francisco California Pacific Medical Center), 1U01-DK083023-01 (University of Texas Southwestern), 1U01-DK083027-01 (Thomas Jefferson Hospital/University of Pennsylvania), 1U01-DK082992-01 (Mayo), and 1U01-DK083020-01 (USC). Additional funding was provided by CTSA grants UL1 RR025761 (Indiana), UL1 RR025747 (University of North Carolina), UL1 RR024134 (University of Pennsylvania), UL1 RR024986 (Michigan), UL1 RR024982 (UTSW), and UL1 RR024150 (Mayo), and by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 33 TC 6 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD FEB PY 2015 VL 13 IS 2 BP 369 EP U219 DI 10.1016/j.cgh.2014.07.054 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ9BB UT WOS:000348505100028 PM 25111234 ER PT J AU Shiloh, S deHeer, HD Peleg, S Alford, SH Skapinsky, K Roberts, JS Hadley, DW AF Shiloh, S. deHeer, H. D. Peleg, S. Alford, S. Hensley Skapinsky, K. Roberts, J. S. Hadley, D. W. TI The impact of multiplex genetic testing on disease risk perceptions SO CLINICAL GENETICS LA English DT Article DE family history; genetic testing; multiplex; risk perception ID MANAGED CARE ORGANIZATION; BREAST-CANCER; HEREDITARY BREAST; DECISION-MAKING; FAMILY-HISTORY; LIFETIME RISK; HEALTH-RISK; INFORMATION; WOMEN; STRATEGIES AB This study assessed the effects of multiplex genetic testing on disease risk perceptions among 216 healthy adults. Participants, aged 25-40, were recruited through the Multiplex Initiative, which offered a genetic susceptibility test for eight common diseases. Participants completed baseline telephone and web-based surveys prior to making the testing decision. Three months after the receipt of mailed test results, participants completed a follow-up telephone survey. Risk perceptions for the eight diseases were measured at baseline and follow-up, along with beliefs about genetic causation of those diseases. The main results were: (i) mean risk perceptions were considerably stable from baseline to follow-up; (ii) the best predictors of follow-up risk perceptions were the corresponding baseline perceptions and family history; and (iii) within-individuals, most participants increased or decreased their risk perceptions for specific diseases in concordance with the number of risk markers they carry, their family history and their beliefs about genetic causality of diseases. In conclusion, participants presented a vigilant approach to the interpretation of genetic test results, which provides reassurance with regard to a potential inflation of risk perceptions in the population because of multiplex genetic testing. C1 [Shiloh, S.; Peleg, S.] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. [deHeer, H. D.; Skapinsky, K.; Hadley, D. W.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [deHeer, H. D.] No Arizona Univ, Coll Hlth & Human Serv, Dept Phys Therapy & Athlet Training, Flagstaff, AZ 86011 USA. [Alford, S. Hensley] Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI USA. [Skapinsky, K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Roberts, J. S.] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Hadley, D. W.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Shiloh, S (reprint author), Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. EM shoshi@freud.tau.ac.il FU National Human Genome Research Institute (NHGRI); National Cancer Institute [U19 CA 079689]; National Institutes of Health [HHSN268200782096C] FX This work was supported by the intramural Research Program of the National Human Genome Research Institute (NHGRI). However, the proposed research was made possible by collaboration with the Cancer Research Network funded by the National Cancer Institute (U19 CA 079689). Additional infrastructural resources were provided by Group health Research Institute and henry Ford Hospital. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (HHSN268200782096C). We also thank the Multiplex steering committee (Drs Colleen McBride, Lawrence Brody, Sharon Hensley Alford, Robert Reid, Eric Larson, Andreas Baxevanis and Sharon Kardia) who provided critical review of this report. This research was additionally supported by an appointment of S.S. to the Senior Fellowship Program at the National Institutes of Health. This program is administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the National Institutes of Health. Our thanks also go to Yasmin Alkalay for her excellent statistical guidance and to the study participants who were all members of the Henry Ford Health System. NR 50 TC 3 Z9 3 U1 0 U2 3 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 FEB PY 2015 VL 87 IS 2 BP 117 EP 123 DI 10.1111/cge.12403 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA CA2EB UT WOS:000348720600004 PM 24720448 ER PT J AU Yaffe, RB Borger, P Megevand, P Groppe, DM Kramer, MA Chu, CJ Santaniello, S Meisel, C Mehta, AD Sarma, SV AF Yaffe, Robert B. Borger, Philip Megevand, Pierre Groppe, David M. Kramer, Mark A. Chu, Catherine J. Santaniello, Sabato Meisel, Christian Mehta, Ashesh D. Sarma, Sridevi V. TI Physiology of functional and effective networks in epilepsy SO CLINICAL NEUROPHYSIOLOGY LA English DT Review DE Effective connectivity; Functional connectivity; Networks; Brain; Epilepsy ID TEMPORAL-LOBE EPILEPSY; CORTICOCORTICAL EVOKED-POTENTIALS; SMALL-WORLD NETWORKS; GRAPH-THEORETICAL ANALYSIS; DEFAULT-MODE NETWORK; HUMAN BRAIN; NEURONAL AVALANCHES; SEIZURE-ONSET; NEOCORTICAL EPILEPSY; COMPLEX NETWORKS AB Epilepsy is a network phenomenon characterized by atypical activity during seizure both at the level of single neurons and neural populations. The etiology of epilepsy is not completely understood but a common theme among proposed mechanisms is abnormal synchronization between neuronal populations. Recent advances in novel imaging and recording technologies have enabled the inference of comprehensive maps of both the anatomical and physiological inter-relationships between brain regions. Clinical protocols established for diagnosis and treatment of epilepsy utilize both advanced neuroimaging techniques and neurophysiological data. These growing clinical datasets can be further exploited to better understand the complex connectivity patterns in the epileptic brain. In this article, we review results and insights gained from the growing body of research focused on epilepsy from a network perspective. In particular, we put an emphasis on two different notions of network connectivity: functional and effective; and studies investigating these notions in epilepsy are highlighted. We also discuss limitations and opportunities in data collection and analyses that will further our understanding of epileptic networks and the mechanisms of seizures. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Yaffe, Robert B.; Santaniello, Sabato; Sarma, Sridevi V.] Johns Hopkins Univ, Inst Computat Med, Dept Biomed Engn, Baltimore, MD 21218 USA. [Borger, Philip; Megevand, Pierre; Groppe, David M.; Mehta, Ashesh D.] Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Borger, Philip; Megevand, Pierre; Groppe, David M.; Mehta, Ashesh D.] Hofstra North Shore LIJ Sch Med, Dept Neurosurg, Manhasset, NY 11030 USA. [Kramer, Mark A.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Chu, Catherine J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Chu, Catherine J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Meisel, Christian] NIMH, Bethesda, MD 20892 USA. RP Yaffe, RB (reprint author), Johns Hopkins Univ, Inst Computat Med, Dept Biomed Engn, Hackerman Hall,Room 318,3400 North Charles St, Baltimore, MD 21218 USA. EM yaffer@jhu.edu OI Santaniello, Sabato/0000-0002-2133-9471; Megevand, Pierre/0000-0002-0427-547X FU Epilepsy Foundation Predoctoral Research Training Fellowship; Swiss National Science Foundation [P3SMP3_148388]; Career Award at the Scientific Interface from the Burroughs Wellcome Fund; Page and Otto Marx Jr. Foundation; US NSF Grant [ECCS 1346888]; US NSF Career Award [1055560]; Burroughs Wellcome Fund CASI Award [1007274] FX R.B. Yaffe was supported by the Epilepsy Foundation Predoctoral Research Training Fellowship. P. Megevand was supported by the Swiss National Science Foundation (Grant P3SMP3_148388). M. A. Kramer was supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. A. D. Mehta and D. M. Groppe are supported by the Page and Otto Marx Jr. Foundation. S. Santaniello was supported by the US NSF Grant ECCS 1346888. S. V. Sarma was supported by the US NSF Career Award 1055560 and the Burroughs Wellcome Fund CASI Award 1007274. NR 110 TC 14 Z9 14 U1 9 U2 30 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD FEB PY 2015 VL 126 IS 2 BP 227 EP 236 DI 10.1016/j.clinph.2014.09.009 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AZ9UL UT WOS:000348562000004 PM 25283711 ER PT J AU Porter, JN Roy, AK Benson, B Carlisi, C Collins, PF Leibenluft, E Pine, DS Luciana, M Ernst, M AF Porter, James N. Roy, Amy K. Benson, Brenda Carlisi, Christina Collins, Paul F. Leibenluft, Ellen Pine, Daniel S. Luciana, Monica Ernst, Monique TI Age-related changes in the intrinsic functional connectivity of the human ventral vs. dorsal striatum from childhood to middle age SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Article DE Resting-state; Adolescence; Development; Functional-connectivity; Striatum; Prefrontal-cortex ID DUAL SYSTEMS-MODEL; BASAL GANGLIA; HUMAN BRAIN; ADOLESCENT BRAIN; INDIVIDUAL-DIFFERENCES; INCENTIVE MOTIVATION; SENSATION SEEKING; RISK-TAKING; NETWORKS; FMRI AB The striatum codes motivated behavior. Delineating age-related differences within striatal circuitry can provide insights into neural mechanisms underlying ontogenic behavioral changes and vulnerabilities to mental disorders. To this end, a dual ventral/dorsal model of striatal function was examined using resting state intrinsic functional connectivity (iFC) imaging in 106 healthy individuals, ages 9-44. Broadly, the dorsal striatum (DS) is connected to prefrontal and parietal cortices and contributes to cognitive processes; the ventral striatum (VS) is connected to medial orbitofrontal and anterior cingulate cortices, and contributes to affective valuation and motivation. Findings revealed patterns of age-related changes that differed between VS and DS iFCs. We found an age-related increase in DS iFC with posterior cingulate cortex (pCC) that stabilized after the mid-twenties, but a decrease in VS iFC with anterior insula (aIns) and dorsal anterior cingulate cortex (dACC) that persisted into mid-adulthood. These distinct developmental trajectories of VS vs. DS iFC might underlie adolescents' unique behavioral patterns and vulnerabilities to psychopathology, and also speaks to changes in motivational networks that extend well past 25 years old. (C) 2014 Published by Elsevier Ltd. C1 [Porter, James N.] Univ Iowa Hosp & Clin, Dept Neurol, Iowa City, IA 52242 USA. [Collins, Paul F.; Luciana, Monica] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Luciana, Monica] Univ Minnesota, Ctr Neurobehav Dev, Minneapolis, MN 55455 USA. [Roy, Amy K.] Fordham Univ, Dept Psychol, Bronx, NY 10458 USA. [Benson, Brenda; Carlisi, Christina; Leibenluft, Ellen; Pine, Daniel S.; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, NIH, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, NIH, Sect Neurobiol Fear & Anxiety NFA, Emot Dev & Affect Neurosci Branch EDAN, 15K North Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov OI Carlisi, Christina/0000-0002-0942-8586 NR 73 TC 15 Z9 15 U1 5 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1878-9293 EI 1878-9307 J9 DEV COGN NEUROS-NETH JI Dev. Cogn. Neurosci. PD FEB PY 2015 VL 11 BP 83 EP 95 DI 10.1016/j.dcn.2014.08.011 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CB1QN UT WOS:000349403000010 PM 25257972 ER PT J AU Thomason, ME Grove, LE Lozon, TA Vila, AM Ye, YQ Nye, MJ Manning, JH Pappas, A Hernandez-Andrade, E Yeo, LM Mody, S Berman, S Hassan, SS Romero, R AF Thomason, Moriah E. Grove, Lauren E. Lozon, Tim A., Jr. Vila, Angela M. Ye, Yongquan Nye, Matthew J. Manning, Janessa H. Pappas, Athina Hernandez-Andrade, Edgar Yeo, Lami Mody, Swati Berman, Susan Hassan, Sonia S. Romero, Roberto TI Age-related increases in long-range connectivity in fetal functional neural connectivity networks in utero SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Article DE Fetus; fMRI; Human; Prenatal; Resting-state; Connectome ID RESTING-STATE NETWORKS; GLOBAL SIGNAL REGRESSION; DEFAULT MODE NETWORK; HUMAN BRAIN; STRUCTURAL CONNECTIVITY; NOISE CORRECTION; ANTICORRELATIONS; MOTION; MRI; CONSTRUCTION AB Formation of operational neural networks is one of the most significant accomplishments of human fetal brain growth. Recent advances in functional magnetic resonance imaging (fMRI) have made it possible to obtain information about brain function during fetal development. Specifically, resting-state fMRI and novel signal covariation approaches have opened up a new avenue for non-invasive assessment of neural functional connectivity (FC) before birth. Early studies in this area have unearthed new insights about principles of prenatal brain function. However, very little is known about the emergence and maturation of neural networks during fetal life. Here, we obtained cross-sectional rs-fMRI data from 39 fetuses between 24 and 38 weeks postconceptual age to examine patterns of connectivity across ten neural FC networks. We identified primitive forms of motor, visual, default mode, thalamic, and temporal networks in the human fetal brain. We discovered the first evidence of increased long-range, cerebral-cerebellar, cortical-subcortical, and intra-hemispheric FC with advancing fetal age. Continued aggregation of data about fundamental neural connectivity systems in utero is essential to establishing principles of connectomics at the beginning of human life. Normative data provides a vital context against which to compare instances of abnormal neurobiological development. (C) 2014 The Authors. Published by Elsevier Ltd. C1 [Thomason, Moriah E.; Grove, Lauren E.; Vila, Angela M.; Manning, Janessa H.] Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA. [Thomason, Moriah E.; Pappas, Athina] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48202 USA. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Thomason, Moriah E.; Grove, Lauren E.; Manning, Janessa H.; Pappas, Athina; Hernandez-Andrade, Edgar; Yeo, Lami; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48202 USA. [Lozon, Tim A., Jr.; Mody, Swati] Michigan State Univ, Sch Med, E Lansing, MI 48824 USA. [Ye, Yongquan] Wayne State Univ, Sch Med, Dept Radiol, Detroit, MI 48202 USA. [Nye, Matthew J.] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. [Hernandez-Andrade, Edgar; Yeo, Lami; Berman, Susan; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. RP Thomason, ME (reprint author), Merrill Palmer Skillman Inst, 71 E Ferry St, Detroit, MI 48202 USA. EM moriah@wayne.edu OI Nye, Matthew/0000-0001-8203-3049 FU Merrill Palmer Skillman Institute for Child and Family Development; Department of Pediatrics, Wayne State University (WSU) School of Medicine; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services; WSU's Perinatology Virtual Discovery Grant; WSU's President's BRAIN Research Enhancement Program FX This research was supported, in part, by the Merrill Palmer Skillman Institute for Child and Family Development, by the Department of Pediatrics, Wayne State University (WSU) School of Medicine, and by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. This project was also supported by WSU's Perinatology Virtual Discovery Grant (made possible by the W.K. Kellogg Foundation) and WSU's President's BRAIN Research Enhancement Program awards to MET. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 43 TC 14 Z9 15 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1878-9293 EI 1878-9307 J9 DEV COGN NEUROS-NETH JI Dev. Cogn. Neurosci. PD FEB PY 2015 VL 11 BP 96 EP 104 DI 10.1016/j.dcn.2014.09.001 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CB1QN UT WOS:000349403000011 PM 25284273 ER PT J AU Chase, HP Maahs, D Wadwa, P Buckingham, B Wilson, D Ly, T Lum, J Calhoun, P Raghinaru, D Cameron, F Bequette, BW Hramiak, I Beck, R AF Chase, H. P. Maahs, D. Wadwa, P. Buckingham, B. Wilson, D. Ly, T. Lum, J. Calhoun, P. Raghinaru, D. Cameron, F. Bequette, B. W. Hramiak, I. Beck, R. CA J D R F Home Closed-Loop Study Grp TI HYPOGLYCEMIA REDUCTION WITH CLOSED-LOOP SYSTEMS BY AGE SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 [Chase, H. P.; Maahs, D.; Wadwa, P.] Univ Colorado, Barbara Davis Ctr Diabet, Denver, CO 80202 USA. [Buckingham, B.; Wilson, D.; Ly, T.] Stanford, Dept Peds Endo, Stanford, CA USA. [Lum, J.; Calhoun, P.; Raghinaru, D.; Beck, R.] JAEB, JDRF Artificial Pancreas Project, Tampa, FL USA. [Cameron, F.; Bequette, B. W.] Rensselaer Polytech Inst, Troy, NY USA. [Hramiak, I.] St Josephs Healthcare, Internal Med, London, ON, Canada. [J D R F Home Closed-Loop Study Grp] NIDDK, ROI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD FEB 1 PY 2015 VL 17 SU 1 MA 10 BP A4 EP A4 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CB0LL UT WOS:000349317500011 ER PT J AU Reith, MEA Blough, BE Hong, WMC Jones, KT Schmitt, KC Baumann, MH Partilla, JS Rothman, RB Katz, JL AF Reith, Maarten E. A. Blough, Bruce E. Hong, Weimin C. Jones, Kymry T. Schmitt, Kyle C. Baumann, Michael H. Partilla, John S. Rothman, Richard B. Katz, Jonathan L. TI Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter SO DRUG AND ALCOHOL DEPENDENCE LA English DT Review DE DAT inhibitors; DA releasers; Dopamine transporter; Atypical effects; Molecular mechanisms; Stimulant abuse treatment compounds ID BIOGENIC-AMINE TRANSPORTERS; OUTWARD-FACING CONFORMATION; UPTAKE INHIBITORS COCAINE; PLACEBO-CONTROLLED TRIAL; RAT NUCLEUS-ACCUMBENS; RHESUS-MONKEYS; MONOAMINE TRANSPORTER; BENZTROPINE ANALOGS; D-AMPHETAMINE; DOUBLE-BLIND AB Background: Treatment of stimulant-use disorders remains a formidable challenge, and the dopamine transporter (DAT) remains a potential target for antagonist or agonist-like substitution therapies. Methods: This review focuses on DAT ligands, such as benztropine, GBR 12909, modafinil, and DAT substrates derived from phenethylamine or cathinone that have atypical DAT-inhibitor effects, either in vitro or in vivo. The compounds are described from a molecular mechanistic, behavioral, and medicinal-chemical perspective. Results: Possible mechanisms for atypicality at the molecular level can be deduced from the conformational cycle for substrate translocation. For each conformation, a crystal structure of a bacterial homolog is available, with a possible role of cholesterol, which is also present in the crystal of Drosophila DAT. Although there is a direct relationship between behavioral potencies of most DAT inhibitors and their DAT affinities, a number of compounds bind to the DAT and inhibit dopamine uptake but do not share cocaine-like effects. Such atypical behavior, depending on the compound, may be related to slow DAT association, combined sigma-receptor actions, or bias for cytosol-facing DAT. Some structures are sterically small enough to serve as DAT substrates but large enough to also inhibit transport. Such compounds may display partial DA releasing effects, and may be combined with release or uptake inhibition at other monoamine transporters. Conclusions: Mechanisms of atypical DAT inhibitors may serve as targets for the development of treatments for stimulant abuse. These mechanisms are novel and their further exploration may produce compounds with unique therapeutic potential as treatments for stimulant abuse. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Reith, Maarten E. A.; Jones, Kymry T.; Schmitt, Kyle C.] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. [Reith, Maarten E. A.] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA. [Blough, Bruce E.] Res Triangle Inst, Ctr Drug Discovery, Res Triangle Pk, NC 27709 USA. [Hong, Weimin C.; Katz, Jonathan L.] NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Baumann, Michael H.; Partilla, John S.; Rothman, Richard B.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Reith, MEA (reprint author), NYU, Sch Med, Dept Psychiat, Alexandria Ctr Life Sci, 450 E 29th St,Room 803, New York, NY 10016 USA. EM Maarten.Reith@nyumc.org OI Katz, Jonathan/0000-0002-1068-1159 FU National Institutes of Health [R01 DA019676, MH083840, DA12970]; National Institute on Drug Abuse [R13DA029347]; NIDA Intramural Research Programs FX The research was supported by National Institutes of Health grants R01 DA019676 (MEAR), MH083840 (MEAR), DA12970 (BEB), as well as travel support from the Behavior, Biology, and Chemistry: Translational Research in Addiction 2014 symposium. Funding for the BBC conference was made possible, in part, by R13DA029347 from the National Institute on Drug Abuse. The research of JLK, WCH, MHB, JSP, and RBH is supported by the NIDA Intramural Research Programs. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Health and Human Services, the National Institute on Drug Abuse, the National Institute of Mental Health, or the University of Texas at San Antonio Health Sciences Center. Mention of trade names, commercial practices, or organization does not imply endorsement by the U.S. Government. The funding sources had no role in writing the review or in the decision to submit the review for publication. NR 141 TC 17 Z9 18 U1 3 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD FEB 1 PY 2015 VL 147 BP 1 EP 19 DI 10.1016/j.drugalcdep.2014.12.005 PG 19 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CA4RU UT WOS:000348893000001 PM 25548026 ER PT J AU Anizan, S Bergamaschi, MM Barnes, AJ Milman, G Desrosiers, N Lee, D Gorelick, DA Huestis, MA AF Anizan, Sebastien Bergamaschi, Mateus M. Barnes, Allan J. Milman, Garry Desrosiers, Nathalie Lee, Dayong Gorelick, David A. Huestis, Marilyn A. TI Impact of oral fluid collection device on cannabinoid stability following smoked cannabis SO DRUG TESTING AND ANALYSIS LA English DT Article DE oral fluid; cannabis; cannabinoids; stability; THC ID 2-DIMENSIONAL GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; SIMULTANEOUS QUANTIFICATION; SATIVA L; DELTA-9-TETRAHYDROCANNABINOL; DELTA(9)-TETRAHYDROCANNABINOL; TETRAHYDROCANNABINOL; CONSTITUENTS; DRUGS; ABUSE AB Evaluation of cannabinoid stability in authentic oral fluid (OF) is critical, as most OF stability studies employed fortified or synthetic OF. Participants (n=16) smoked a 6.8% delta-9-tetrahydrocannabinol (THC) cigarette, and baseline concentrations of THC, 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), and cannabinol (CBN) were determined within 24h in 16 separate pooled samples (collected 1h before to 10.5 or 13h after smoking). OF was collected with the StatSure Saliva Sampler and Oral-Eze (R) devices. Oral-Eze samples were re-analyzed after room temperature (RT) storage for 1week, and for both devices after 4 degrees C for 1 and 4weeks, and -20 degrees C for 4 and 24weeks. Concentrations +/- 20% from initial concentrations were considered stable. With the StatSure device, all cannabinoids were within 80-120% median %baseline for all storage conditions. Individual THC, CBD, CBN and THCCOOH pool concentrations were stable in 100%, 100%, 80-94% and >85%, respectively, across storage conditions. With the Oral-Eze device, at RT or refrigerated storage (for 1 and 4weeks), THC, CBD and THCCOOH were stable in 94-100%, 78-89%, and 93-100% of samples, respectively, while CBN concentrations were 53-79% stable. However, after 24weeks at -20 degrees C, stability decreased, especially for CBD, with a median of 56% stability. Overall, the collection devices' elution/stabilizing buffers provided good stability for OF cannabinoids, with the exception of the more labile CBN. To ensure OF cannabinoid concentration accuracy, these data suggest analysis within 4weeks at 4 degrees C storage for Oral-Eze collection and within 4weeks at 4 degrees C or 24weeks at -20 degrees C for StatSure collection. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. C1 [Anizan, Sebastien; Bergamaschi, Mateus M.; Barnes, Allan J.; Milman, Garry; Desrosiers, Nathalie; Lee, Dayong; Gorelick, David A.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Natl Inst Hlth, Chem & Drug Metab Intramural Res Program, Baltimore, MD 21224 USA. [Desrosiers, Nathalie] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA. [Gorelick, David A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Huestis, MA (reprint author), NIDA, NIH, Biomed Res Ctr, Chem & Drug Metab Intramural Res Program, 251 Bayview Blvd,Room 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural Research Program, National Institute on Drug Abuse, NIH; CAPES; FAPESP (Brazil); Fondation Baxter et Alma Ricard (Canada) FX The authors acknowledge the contribution of the Chemistry and Drug Metabolism Section staff, and the clinical staff of the National Institute on Drug Abuse, Intramural Research Program and the Behavioral Pharmacology Research Unit and Clinical Research Unit, Johns Hopkins Bayview Medical Center. This research was supported by the Intramural Research Program, National Institute on Drug Abuse, NIH. MMB received grants from CAPES and FAPESP (Brazil) and NAD received a fellowship from the Fondation Baxter et Alma Ricard (Canada). NR 29 TC 6 Z9 6 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1942-7603 EI 1942-7611 J9 DRUG TEST ANAL JI Drug Test. Anal. PD FEB PY 2015 VL 7 IS 2 BP 114 EP 120 DI 10.1002/dta.1688 PG 7 WC Biochemical Research Methods; Chemistry, Analytical; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA CA8EW UT WOS:000349150800004 PM 24995604 ER PT J AU Furlong, M Tanner, CM Goldman, SM Bhudhikanok, GS Blair, A Chade, A Comyns, K Hoppin, JA Kasten, M Korell, M Langston, JW Marras, C Meng, C Richards, M Ross, GW Umbach, DM Sandler, DP Kamel, F AF Furlong, Melissa Tanner, Caroline M. Goldman, Samuel M. Bhudhikanok, Grace S. Blair, Aaron Chade, Anabel Comyns, Kathleen Hoppin, Jane A. Kasten, Meike Korell, Monica Langston, J. William Marras, Connie Meng, Cheryl Richards, Marie Ross, G. Webster Umbach, David M. Sandler, Dale P. Kamel, Freya TI Protective glove use and hygiene habits modify the associations of specific pesticides with Parkinson's disease SO ENVIRONMENT INTERNATIONAL LA English DT Article DE Personal protective equipment; Parkinson's disease; Pesticides; Neurodegenerative diseases; Movement disorders ID AGRICULTURAL HEALTH; INCOMPLETE REMOVAL; EXPOSURE; RISK; DETERMINANTS; APPLICATORS; FARMWORKERS; CALIFORNIA; CAPTAN; SKIN AB Pesticides have been associated with Parkinson's disease (PD), and protective gloves and workplace hygiene can reduce pesticide exposure. We assessed whether use of gloves and workplace hygiene modified associations between pesticides and PD. The Farming and Movement Evaluation (FAME) study is a nested case-control study within the Agricultural Health Study. Use of protective gloves, other PPE, and hygiene practices were determined by questionnaire (69 cases and 237 controls were included). We considered interactions of gloves and hygiene with ever-use of pesticides for all pesticides with >= 5 exposed and unexposed cases and controls in each glove-use stratum (paraquat, permethrin, rotenone, and trifluralin). 61% of respondents consistently used protective gloves and 87% consistently used >= 2 hygiene practices. Protective glove use modified the associations of paraquat and permethrin with PD: neither pesticide was associated with PD among protective glove users, while both pesticides were associated with PD among non-users (paraquat OR 3.9 [95% CI 13, 11.7], interaction p = 0.15; permethrin OR 4.3 [95% CI 1.2, 15.6] interaction p = 0.05). Rotenone was associated with PD regardless of glove use. Trifluralin was associated with PD among participants who used <2 hygiene practices (OR 5.5 [95% CI 1.1, 27.1]) but was not associated with PD among participants who used 2 or more practices (interaction p = 0.02). Although sample size was limited in the FAME study, protective glove use and hygiene practices appeared to be important modifiers of the association between pesticides and PD and may reduce risk of PD associated with certain pesticides. Published by Elsevier Ltd C1 [Furlong, Melissa] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Tanner, Caroline M.; Meng, Cheryl] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Tanner, Caroline M.; Goldman, Samuel M.; Comyns, Kathleen; Korell, Monica; Meng, Cheryl] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA. [Bhudhikanok, Grace S.; Langston, J. William] Parkinsons Inst & Clin Ctr, Sunnyvale, CA USA. [Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. [Chade, Anabel] Favaloro Univ, Inst Neurosci, Buenos Aires, DF, Argentina. [Hoppin, Jane A.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA. [Kasten, Meike] Univ Lubeck, Dept Psychiat, Lubeck, Germany. [Marras, Connie] Univ Toronto, Toronto, ON, Canada. [Richards, Marie] Westat Corp, Durham, NC USA. [Ross, G. Webster] VA Pacific Isl Hlth Care Syst, Honolulu, HI USA. [Umbach, David M.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Sandler, Dale P.; Kamel, Freya] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Furlong, M (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Box 7435, Chapel Hill, NC 27599 USA. EM furlongm@med.unc.edu OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 FU NIEHS [R01-ES10803, ES07018]; National Institutes of Health [National Institute of Environmental Health Sciences (NIEHS)] [Z01-ES044007, Z01-ES049030]; National Institutes of Health [National Cancer Institute] [Z01-CP010119] FX This study was supported by the NIEHS grant R01-ES10803, the James and Sharron Clark, and the Intramural Research Program of the National Institutes of Health [National Institute of Environmental Health Sciences (NIEHS) grants Z01-ES044007 and Z01-ES049030, and the National Cancer Institute grant Z01-CP010119]. M Furlong was partly supported by the NIEHS institutional training grant ES07018. The authors would also like to thank the participants and the research team. We are indebted to Kent Thomas at the US EPA for valuable discussions about PPE and hygiene. NR 36 TC 7 Z9 7 U1 0 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-4120 EI 1873-6750 J9 ENVIRON INT JI Environ. Int. PD FEB PY 2015 VL 75 BP 144 EP 150 DI 10.1016/j.envint.2014.11.002 PG 7 WC Environmental Sciences SC Environmental Sciences & Ecology GA CA2OD UT WOS:000348746600014 PM 25461423 ER PT J AU Wen, L Fu, LZ Guo, XG Chen, YL Shi, YB AF Wen, Luan Fu, Liezhen Guo, Xiaogang Chen, Yonglong Shi, Yun-Bo TI Histone methyltransferase Dot1L plays a role in postembryonic development in Xenopus tropicalis SO FASEB JOURNAL LA English DT Article DE epigenetics; histone modification; activation mark; organogenesis ID THYROID-HORMONE RECEPTOR; EFFECTOR NUCLEASES TALENS; INTESTINAL STEM-CELLS; SET-DOMAIN; H3K79 METHYLATION; HUMAN GENOME; TRANSCRIPTION; GENE; CHROMATIN; H3 AB Histone methylations have been implicated to play important roles in diverse cellular processes. Of particular interest is the methylation of histone H3K79, which is catalyzed by an evolutionarily conserved methyltransferase, disruptor of telomeric silencing (Dot1)-like (Dot1L). To investigate the role of Dot1L during vertebrate development, we have generated a Dot1L-specific transcription activator-like effector nuclease (TALEN) nuclease to knockdown endogenous Dot1L in Xenopus tropicalis, a diploid species highly related to the well-known developmental model Xenopus laevis, a pseudotetraploid amphibian. We show that the TALEN was extremely efficient in mutating Dot1L when expressed in fertilized eggs, creating essentially Dot1L knockout embryos with little H3K79 methylation. Importantly, we observed that Dot1L knockdown had no apparent effect on embryogenesis because normally feeding tadpoles were formed, consistent with the lack of maternal Dot1L expression. On the other hand, Dot1L knockdown severely retarded the growth of the tadpoles and led to tadpole lethality prior to metamorphosis. These findings suggest that Dot1L and H3K79 methylation play an important role for tadpole growth and development prior to metamorphosis into a frog. Our findings further reveal interesting similarities and differences between Xenopus and mouse development and suggest the existence of 2 separate phases of vertebrate development with distinct requirements for epigenetic modifications. C1 [Wen, Luan; Fu, Liezhen; Shi, Yun-Bo] NICHHD, NIH, Program Cellular Regulat & Metab, Sect Mol Morphogenesis, Bethesda, MD 20892 USA. [Guo, Xiaogang; Chen, Yonglong] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou, Guangdong, Peoples R China. RP Shi, YB (reprint author), NICHHD, NIH, Bldg 18T Room 106,18 Lib Dr MSC 5431, Bethesda, MD 20892 USA. EM shi@helix.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, U.S. National Institutes of Health FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, U.S. National Institutes of Health. The authors declare no conflicts of interest. NR 33 TC 7 Z9 7 U1 3 U2 15 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD FEB PY 2015 VL 29 IS 2 BP 385 EP 393 DI 10.1096/fj.14-252171 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CB1ET UT WOS:000349370400005 PM 25366346 ER PT J AU Chen, X Willette-Brown, J Wu, XQ Hu, Y Howard, MZ Hu, YL Oppenheim, JJ AF Chen, Xin Willette-Brown, Jami Wu, Xueqiang Hu, Ya Howard, M. Zack Hu, Yinling Oppenheim, Joost J. TI IKK alpha is required for the homeostasis of regulatory T cells and for the expansion of both regulatory and effector CD4 T cells SO FASEB JOURNAL LA English DT Article DE Foxp3; proliferation; colitis; lymphopenic mouse ID NF-KAPPA-B; SIGNALING PATHWAY; KINASE-ALPHA; C-REL; ACTIVATION; TNFR2; DIFFERENTIATION; EXPRESSION; PHOSPHORYLATION; COSTIMULATION AB It was reported that TNF receptor type II signaling, which has the capacity to stimulate CD4(+) fork-head box P3(+) (Foxp3(+)) regulatory T cells (Tregs), activated the noncanonical NF-kappa B pathway in an IKK alpha-dependent manner. Therefore, we studied the role of IKK alpha in the homeostasis of Treg population. To this end, we generated a mouse strain with conditional knockout of IKK alpha in CD4 cells (Ikk alpha(f/f): CD4.Cre) that showed a >60% reduction in the number of Tregs in the thymus and peripheral lymphoid tissues, whereas the number of Foxp3(-) effector T cells (Teffs) remained at a normal level. The function of Tregs deficient in IKK alpha was examined using Rag1(-/-) mice cotransferred with naive CD4 cells (nCD4s). Although wild-type (WT) Tregs inhibited colitis induced by transfer of WT nCD4s, IKK alpha-deficient Tregs failed to do so, which was associated with their inability to reconstitute Rag1(-/-) mice. Furthermore, nCD4s deficient in IKK alpha also failed to reconstitute Rag1(-/-) mice and were defective in proliferative responses in vitro and in vivo. Thus, our study reveals a novel role of IKK alpha in the maintenance of a normal Treg population and in the control of expansion of CD4 T cells. These properties of IKK alpha may be exploited as therapeutic strategies in the treatment of major human diseases. C1 [Chen, Xin] NCI, Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21701 USA. [Willette-Brown, Jami; Wu, Xueqiang; Hu, Ya; Howard, M. Zack; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Frederick, MD USA. [Willette-Brown, Jami; Hu, Yinling] NCI, Ctr Canc Res, Canc Inflammat Program, Expt Immunol Lab, Frederick, MD USA. [Chen, Xin] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa, Macao Sar, Peoples R China. RP Chen, X (reprint author), Univ Macau, Inst Chinese Med Sci, Bldg N22, Taipa, Macao Sar, Peoples R China. EM xchen@umac.mo; oppenhej@mail.nih.gov RI Chen, Xin/I-6601-2015 OI Chen, Xin/0000-0002-2628-4027 FU U.S. National Institutes of Health (NIH) NCI [HHSN261200800001E]; Intramural Research Program of the NIHNCI, Center for Cancer Research FX The authors thank Dr. Na-Young Song, Trivett L. Anna, and Czarra T. Kelli for their help in this study. The authors thank the U. S. National Cancer Institute (NCI)-Frederick Cancer Inflammation Program Fluorescence Cytometry Core (Kathleen B. Noer, Roberta M. Matthai, and Guity Mohammadi) for expert technical assistance with flow cytometry. This project has been funded in whole or in part with federal funds from the U.S. National Institutes of Health (NIH) NCI, under contract HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the NIHNCI, Center for Cancer Research. NR 46 TC 7 Z9 8 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD FEB PY 2015 VL 29 IS 2 BP 443 EP 454 DI 10.1096/fj.14-259564 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CB1ET UT WOS:000349370400010 PM 25376833 ER PT J AU Kapogiannis, D Boxer, A Schwartz, JB Abner, EL Biragyn, A Masharani, U Frassetto, L Petersen, RC Miller, BL Goetzl, EJ AF Kapogiannis, Dimitrios Boxer, Adam Schwartz, Janice B. Abner, Erin L. Biragyn, Arya Masharani, Umesh Frassetto, Lynda Petersen, Ronald C. Miller, Bruce L. Goetzl, Edward J. TI Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer's disease SO FASEB JOURNAL LA English DT Article DE insulin resistance; dementia; senescence ID SERINE/THREONINE PHOSPHORYLATION; TAU-HYPERPHOSPHORYLATION; GLUCOSE-METABOLISM; CLINICAL-TRIALS; ADAS-COG; IN-VIVO; RESISTANCE; IRS-1; MECHANISMS; SENSITIVITY AB Insulin resistance causes diminished glucose uptake in similar regions of the brain in Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2). Brain tissue studies suggested that insulin resistance is caused by low insulin receptor signaling attributable to its abnormal association with more phospho (P)-serine-type 1 insulin receptor substrate (IRS-1) and less P-tyrosine-IRS-1. Plasma exosomes enriched for neural sources by immunoabsorption were obtained once from 26 patients with AD, 20 patients with DM2, 16 patients with frontotemporal dementia (FTD), andmatched case control subjects. At 2 time points, they were obtained from 22 others when cognitively normal and 1 to 10 yr later when diagnosed with AD. Mean exosomal levels of extracted P-serine 312-IRS-1 and P-pantyrosine- IRS-1 by ELISA and the ratio of P-serine 312-IRS-1 to P-pan-tyrosine-IRS-1 (insulin resistance factor, R) for AD and DM2 and P-serine 312-IRS-1 and R for FTD were significantly different from those for case control subjects. The levels of R for AD were significantly higher than those for DM2 or FTD. Stepwise discriminant modeling showed correct classification of 100% of patients with AD, 97.5% of patients with DM2, and 84% of patients with FTD. In longitudinal studies of 22 patients with AD, exosomal levels of P-serine 312-IRS-1, P-pan-tyrosine-IRS-1, and R were significantly different 1 to 10 yr before and at the time of diagnosis comparedwith control subjects. Insulin resistance reflected in R values from this blood test is higher for patients with AD, DM2, and FTD than case control subjects; higher for patients with AD than patients with DM2 or FTD; and accurately predicts development of AD up to 10 yr prior to clinical onset.-Kapogiannis, D., Boxer, A., Schwartz, J. B., Abner, E. L., Biragyn, A., Masharani, U., Frassetto, L., Petersen, R. C., Miller, B. L., Goetzl, E. J. Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer's disease. C1 [Kapogiannis, Dimitrios; Biragyn, Arya; Goetzl, Edward J.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Boxer, Adam; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Schwartz, Janice B.; Goetzl, Edward J.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Schwartz, Janice B.; Masharani, Umesh; Frassetto, Lynda; Goetzl, Edward J.] Jewish Home San Francisco, San Francisco, CA USA. [Abner, Erin L.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Petersen, Ronald C.] Mayo Clin, Rochester, MN USA. RP Goetzl, EJ (reprint author), UCSF, Geriatr Res Ctr, 1719 Broderick St, San Francisco, CA 94115 USA. EM edward.goetzl@ucsf.edu FU U.S.National Institutes of Health (NIH) NIA; United Kingdom Alzheimer's Disease Center [P30-AG028383] FX The authors are grateful to Lynn Kane (JHSF), Anna Karydas (UCSF MAC), Dana Swenson-Dravis and Matthew Miller (Mayo Clinic), Sonya Anderson (University of Kentucky), and Olga Carlson and Melissa Swaby Intramural Research Program of the National Institute on Aging (NIA) for organizing and distributing clinical materials and data and for providing access to analytical systems.They also thank Judith H.Goetzl for expert preparation of graphic illustrations.This studywas funded by the U.S.National Institutes of Health (NIH) NIA (to A.Bi., D.K.), United Kingdom Alzheimer's Disease Center grant P30-AG028383 (to E.L.A.), and an unrestricted supply grant for methodologic development from Nanosomix, Incorporated (to E.J.G.).D.K., J.B.S., E.L.A., A.Bi., U.M., L.F., R.C.P., and B.L.M.declare no potential conflicts of interest. E.J.G. has filed a provisional application with the U.S. Patent Office for the methodology described in this report; Nanosomix, Incorporated, supports the research but provides no salary, expense reimbursement, or fees and does not influence the processes of research or publication. A. B. reports grants from the NIH/NIA; grants from Tau Research Consortium; grants from Corticobasal Degeneration Solutions; grants, personal fees, and nonfinancial support from Archer Biosciences; grants from Allon Therapeutics; personal fees from Acetylon; personal fees from Ipierian; grants from Genentech; grants from Bristol-Myers Squibb; grants from TauRx; grants from Alzheimer's Association; grants from Bluefield Project to Cure FTD; grants from Association for Frontotemporal Degeneration; grants from Alzheimer's Drug Discovery Foundation; grants from EnVivo; grants from C2N Diagnostics; grants from Pfizer; grants from Eli Lilly for support outside the submitted work. NR 39 TC 32 Z9 32 U1 2 U2 18 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD FEB PY 2015 VL 29 IS 2 BP 589 EP 596 DI 10.1096/fj.14-262048 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CB1ET UT WOS:000349370400021 PM 25342129 ER PT J AU Devine, K Stillman, RJ DeCherney, AH AF Devine, Kate Stillman, Robert J. DeCherney, Alan H. TI Building a family through in vitro fertilization-economic realities SO FERTILITY AND STERILITY LA English DT Editorial Material C1 [Devine, Kate; Stillman, Robert J.] Shady Grove Fertil Ctr, Rockville, MD 20850 USA. [DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Devine, K (reprint author), Shady Grove Fertil Ctr, Rockville, MD 20850 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2015 VL 103 IS 2 BP 357 EP 358 DI 10.1016/j.fertnstert.2014.12.092 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CA5RY UT WOS:000348966700011 PM 25527233 ER PT J AU Schliep, KC Mumford, SL Ahrens, KA Hotaling, JM Carrell, DT Link, M Hinkle, SN Kissell, K Porucznik, CA Hammoud, AO AF Schliep, Karen C. Mumford, Sunni L. Ahrens, Katherine A. Hotaling, James M. Carrell, Douglas T. Link, Megan Hinkle, Stefanie N. Kissell, Kerri Porucznik, Christina A. Hammoud, Ahmad O. TI Effect of male and female body mass index on pregnancy and live birth success after in vitro fertilization SO FERTILITY AND STERILITY LA English DT Article DE Body mass index; obesity; in vitro fertilization; pregnancy; live birth ID ASSISTED REPRODUCTIVE TECHNOLOGY; INFERTILITY TREATMENT; EMBRYO QUALITY; OVERWEIGHT; OBESITY; METAANALYSIS; OUTCOMES; IMPACT; RISK; MEN AB Objective: To assess the effects of both male and female body mass index (BMI), individually and combined, on IVF outcomes. Design: Prospective cohort study. Setting: University fertility center. Patient(s): All couples undergoing first fresh IVF cycles, 2005-2010, for whom male and female weight and height information were available (n = 721 couples). Intervention(s): None. Main Outcome Measure(s): Embryologic parameters, clinical pregnancy, and live birth incidence. Result(s): The average male BMI among the study population was 27.5 +/- 4.8 kg/m(2) (range, 17.3-49.3 kg/m(2)), while the average female BMI (n = 721) was 25.2 +/- 5.9 kg/m(2) (range, 16.2-50.7 kg/m(2)). Neither male nor female overweight (25-29.9 kg/m(2)), class I obese (30-34.9 kg/m(2)), or class II/III obese (>= 35 kg/m(2)) status was significantly associated with fertilization rate, embryo score, or incidence of pregnancy or live birth compared with normal weight (18.5-24.9 kg/m(2)) status after adjusting for male and female age, partner BML and parity. Similar null findings were found between combined couple BM categories and IVF success. Conclusion(s): Our findings support the notion that weight status does not influence fecundity among couples undergoing infertility treatment. Given the limited and conflicting research on BMI and pregnancy success among IVF couples, further research augmented to include other adiposity measures is needed. (C) 2015 by American Society for Reproductive Medicine. C1 [Schliep, Karen C.; Mumford, Sunni L.; Ahrens, Katherine A.; Hinkle, Stefanie N.; Kissell, Kerri] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA. [Hotaling, James M.; Carrell, Douglas T.] Univ Utah, Sch Med, Androl & In Vitro Fertilizat Labs, Salt Lake City, UT USA. [Hotaling, James M.; Carrell, Douglas T.] Univ Utah, Sch Med, Dept Surg, Salt Lake City, UT USA. [Hotaling, James M.; Carrell, Douglas T.; Link, Megan; Hammoud, Ahmad O.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. [Hotaling, James M.; Carrell, Douglas T.] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84132 USA. [Porucznik, Christina A.] Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84112 USA. RP Schliep, KC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, 6100 Execut Blvd,Room 7B05 MSC 7510, Rockville, MD 20852 USA. EM schliepkc2@mail.nih.gov RI Hinkle, Stefanie/F-8253-2013 OI Hinkle, Stefanie/0000-0003-4312-708X FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Rockville, Maryland FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Rockville, Maryland (K.C.S., S.L.M., K.A.A., S.N.H., and K.K.). NR 32 TC 15 Z9 16 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2015 VL 103 IS 2 BP 388 EP 395 DI 10.1016/j.fertnstert.2014.10.048 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CA5RY UT WOS:000348966700017 PM 25497445 ER PT J AU Rijal, K Maraia, RJ Arimbasseri, AG AF Rijal, Keshab Maraia, Richard J. Arimbasseri, Aneeshkumar G. TI A methods review on use of nonsense suppression to study 3 ' end formation and other aspects of tRNA biogenesis SO GENE LA English DT Review DE RNA polymerase III; Transcription termination; RPC11; RPC53; RPC37; RPC2 ID POLYMERASE-III TRANSCRIPTION; PRECURSOR TRANSFER-RNAS; SERINE TRANSFER-RNA; YEAST SCHIZOSACCHAROMYCES-POMBE; TRANSFER RNAIMET GENE; SACCHAROMYCES-CEREVISIAE; LA PROTEIN; FISSION YEAST; IN-VITRO; XENOPUS-LAEVIS AB Suppressor tRNAs bear anticodon mutations that allow them to decode premature stop codons in metabolic marker gene mRNAs, that can be used as in vivo reporters of functional tRNA biogenesis. Here, we review key components of a suppressor tRNA system specific to Schizosaccharomyces pombe and its adaptations for use to study specific steps in tRNA biogenesis. Eukaryotic tRNA biogenesis begins with transcription initiation by RNA polymerase (p01)111. The nascent pre-tRNAs must undergo folding, 5' and 3' processing to remove the leader and trailer, nuclear export, and splicing if applicable, while multiple complex chemical modifications occur throughout the process. We review evidence that precursor-tRNA processing begins with transcription termination at the oligo(T) terminator element, which forms a 3' oligo(U) tract on the nascent RNA, a sequence-specific binding site for the RNA chaperone, La protein. The processing pathway bifurcates depending on a poorly understood property of pal III termination that determines the 3' oligo(U) length and therefore the affinity for La. We thus review the pol III termination process and the factors involved including advances using gene-specific random mutagenesis by dNTP analogs that identify key residues important for transcription termination in certain pol III subunits. The review ends with a 'technical approaches' section that includes a parts lists of suppressortRNA alleles, strains and plasmids, and graphic examples of its diverse uses. Published by Elsevier B.V. C1 [Rijal, Keshab; Maraia, Richard J.; Arimbasseri, Aneeshkumar G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Genom Differentiat, NIH, Bethesda, MD USA. RP Maraia, RJ (reprint author), 31 Ctr Dr,Rm 2A25, Bethesda, MD 20892 USA. EM maraiar@mail.nih.gov; arimbasseriag@mail.nih.gov OI Arimbasseri, Gopalakrishnan Aneeshkumar/0000-0001-5266-2688 FU Intramural Research Program on Genomics of Differentiation in the Eunice Kennedy Shriver National Institute of Child Health and Human Development, at the National Institutes of Health [HD000412-24 PGD] FX We thank former and current lab members, M. Bayfield, R. Intine, Y. Huang, A. Sakulich, S. Koduru, S. Hasson, A. Mozlin, and J. Mazeika for their contributions toward developing TMS. This work was supported by the Intramural Research Program on Genomics of Differentiation (HD000412-24 PGD) in the Eunice Kennedy Shriver National Institute of Child Health and Human Development, at the National Institutes of Health. NR 173 TC 4 Z9 4 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD FEB 1 PY 2015 VL 556 IS 1 SI SI BP 35 EP 50 DI 10.1016/j.gene.2014.11.034 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA CA5TQ UT WOS:000348971100006 PM 25447915 ER PT J AU Hulihan, MM Feuchtbaum, L Jordan, L Kirby, RS Snyder, A Young, W Greene, Y Telfair, J Wang, Y Cramer, W Werner, EM Kenney, K Creary, M Grant, AM AF Hulihan, Mary M. Feuchtbaum, Lisa Jordan, Lanetta Kirby, Russell S. Snyder, Angela Young, William Greene, Yvonne Telfair, Joseph Wang, Ying Cramer, William Werner, Ellen M. Kenney, Kristy Creary, Melissa Grant, Althea M. TI State-based surveillance for selected hemoglobinopathies SO GENETICS IN MEDICINE LA English DT Article DE hemoglobinopathies; newborn screening; sickle cell disease; surveillance; thalassemia ID SICKLE-CELL-DISEASE; UNITED-STATES; VISITS; US AB Purpose: The lack of an ongoing surveillance system for hemoglobinopathies in the United States impedes the ability of public health organizations to identify individuals with these conditions, monitor their health-care utilization and clinical outcomes, and understand the effect these conditions have on the health-care system. This article describes the results of a pilot program that supported the development of the infrastructure and data collection methods for a state-based surveillance system for selected hemoglobinopathies. Methods: The system was designed to identify and gather information on all people living with a hemoglobinopathy diagnosis (sickle cell diseases or thalassemias) in the participating states during 2004-2008. Novel, three-level case definitions were developed, and multiple data sets were used to collect information. Results: In total, 31,144 individualS who had a hemoglobinopathy diagnosis during the study period were identified in California; 39,633 in Florida; 20,815 in Georgia; 12,680 in Michigan; 34,853 in New York, and 8,696 in North Carolina. Conclusion: This approach provides a possible model for the development of state-based hemoglobinopathy surveillance systems. C1 [Hulihan, Mary M.; Kenney, Kristy; Creary, Melissa; Grant, Althea M.] Ctr Dis Control & Prevent, Div Blood Disorders, Atlanta, GA 30329 USA. [Feuchtbaum, Lisa] Calif Dept Publ Hlth, Genet Dis Screening Program, Richmond, CA USA. [Jordan, Lanetta] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Kirby, Russell S.] Univ S Florida, Coll Publ Hlth, Tampa, FL USA. [Snyder, Angela] Georgia State Univ, Andrew Young Sch Policy Studies, Georgia Hlth Policy Ctr, Atlanta, GA 30303 USA. [Young, William] Michigan Dept Community Hlth, Lansing, MI USA. [Greene, Yvonne] North Carolina Dept Hlth & Human Serv, Raleigh, NC USA. [Telfair, Joseph] Georgia So Univ, Jiann Ping Hsu Coll Publ Hlth, Statesboro, GA 30460 USA. [Wang, Ying] New York State Dept Hlth, Albany, NY USA. [Cramer, William] Penn Dept Hlth, Harrisburg, PA 17108 USA. [Werner, Ellen M.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Hulihan, MM (reprint author), Ctr Dis Control & Prevent, Div Blood Disorders, Atlanta, GA 30329 USA. EM ibx5@cdc.gov FU US Centers for Disease Control and Prevention; National Heart, Lung and Blood Institute [DD09-909, DD10-1017] FX This work was supported by the US Centers for Disease Control and Prevention and the National Heart, Lung and Blood Institute cooperative agreements DD09-909 and DD10-1017. We gratefully acknowledge the assistance of the following individuals and institutions: California: Susan Paulukonis, William Harris, Fred Lorey, Elliott Vichinsky, Lynne Neumayr, Marsha Treadwell, Shanda Robertson, Gabriel Wong, Ashley Holley, Thomas Coates, Sheree Schrager, and Kelly Russell. Florida: Ofelia Alvarez, Robert Hayden, Hua Li, Anthony Panzera, Jean Paul Tanner, and Lois Taylor. Georgia: Sharon Quary, James Eckman, Peter Lane, Robert Gibson, Jackie George, Mei Zhou, Jane Branscomb, JoAnn Beasley, Janeth Spurlin, Beverly Sinclair, Holly Avey, Eldrida Randall, Rodney Theodore, Christopher Perry, Brendan Noggle, Abdullah Kutlar, the Office of Health Indicators for Planning, the Georgia Department of Public Health, and the Georgia Department of Community Health. Michigan: Karen Andruszewski, Janice Bach, Erika Garcia, Violanda Grigorescu, Mary Kleyn, Robin Stottlemyer, and Wanda Whitten Shurney. New York: Michele Caggana and Gang Liu. North Carolina: Daisy Morris and the North Carolina Sickle Cell Program. NR 10 TC 3 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD FEB PY 2015 VL 17 IS 2 BP 125 EP 130 DI 10.1038/gim.2014.81 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA CA5QJ UT WOS:000348962600005 PM 24991875 ER PT J AU Pfaender, S Cavalleri, JMV Walter, S Doerrbecker, J Campana, B Brown, RJP Burbelo, PD Postel, A Hahn, K Anggakusuma Riebesehl, N Baumgartner, W Becher, P Heim, MH Pietschmann, T Feige, K Steinmann, E AF Pfaender, Stephanie Cavalleri, Jessika M. V. Walter, Stephanie Doerrbecker, Juliane Campana, Benedetta Brown, Richard J. P. Burbelo, Peter D. Postel, Alexander Hahn, Kerstin Anggakusuma Riebesehl, Nina Baumgaertner, Wolfgang Becher, Paul Heim, Markus H. Pietschmann, Thomas Feige, Karsten Steinmann, Eike TI Clinical Course of Infection and Viral Tissue Tropism of Hepatitis C Virus-Like Nonprimate Hepaciviruses in Horses SO HEPATOLOGY LA English DT Article ID GLOBAL EPIDEMIOLOGY; IDENTIFICATION; PATHOGENESIS; PEGIVIRUSES; CHALLENGES; RNA AB Hepatitis C virus (HCV) has a very narrow species and tissue tropism and efficiently replicates only in humans and the chimpanzee. Recently, several studies identified close relatives to HCV in different animal species. Among these novel viruses, the nonprimate hepaciviruses (NPHV) that infect horses are the closest relatives of HCV described to date. In this study, we analyzed the NPHV prevalence in northern Germany and characterized the clinical course of infection and viral tissue tropism to explore the relevance of HCV-related horse viruses as a model for HCV infection. We found that approximately 31.4% of 433 horses were seropositive for antibodies (Abs) against NPHV and approximately 2.5% carried viral RNA. Liver function analyses revealed no indication for hepatic impairment in 7 of 11 horses. However, serum gamma-glutamyl transferase (GGT) concentrations were mildly elevated in 3 horses, and 1 horse displayed even highly elevated GGT levels. Furthermore, we observed that NPHV infection could be cleared in individual horses with a simultaneous emergence of nonstructural (NS)3-specific Abs and transient elevation of serum levels of liver-specific enzymes indicative for a hepatic inflammation. In other individual horses, chronic infections could be observed with the copresence of viral RNA and NS3-specific Abs for over 6 months. For the determination of viral tissue tropism, we analyzed different organs and tissues of 1 NPHV-positive horse using quantitative real-time polymerase chain reaction and fluorescent in situ hydridization and detected NPHV RNA mainly in the liver and at lower amounts in other organs. Conclusion: Similar to HCV infections in humans, this work demonstrates acute and chronic stages of NPHV infection in horses with viral RNA detectable predominantly within the liver. (Hepatology 2015;61:447-459) C1 [Pfaender, Stephanie; Walter, Stephanie; Doerrbecker, Juliane; Brown, Richard J. P.; Anggakusuma; Riebesehl, Nina; Pietschmann, Thomas; Steinmann, Eike] TWINCORE, Ctr Expt & Clin Infect Res, Inst Expt Virol, D-30625 Hannover, Germany. [Cavalleri, Jessika M. V.; Feige, Karsten] Univ Vet Med Hannover, Clin Horses, D-30559 Hannover, Germany. [Campana, Benedetta; Heim, Markus H.] Univ Basel, Dept Biomed, Basel, Switzerland. [Campana, Benedetta; Heim, Markus H.] Univ Basel Hosp, Div Gastroenterol & Hepatol, CH-4031 Basel, Switzerland. [Burbelo, Peter D.] Natl Inst Dent Craniofacial Res, Dent Clin Res Core, NIH, Bethesda, MD USA. [Postel, Alexander; Becher, Paul] Univ Vet Med Hannover, Inst Virol, Hannover, Germany. [Hahn, Kerstin; Baumgaertner, Wolfgang] Univ Vet Med Hannover, Dept Pathol, Hannover, Germany. RP Steinmann, E (reprint author), TWINCORE, Ctr Expt & Clin Infect Res, Inst Expt Virol, Feodor Lynen Str 7, D-30625 Hannover, Germany. EM Karsten.Feige@tiho-hannover.de; Eike.Steinmann@twincore.de RI Pietschmann, Thomas/E-9241-2015; OI Pietschmann, Thomas/0000-0001-5138-6239; Heim, Markus/0000-0002-7523-4894; Becher, Paul/0000-0001-7857-1354; Brown, Richard/0000-0002-3292-6671 FU International Research Training Group by DFG [1273 (IRTG 1273)]; DFG [STE 1954/1-1]; Helmholtz Center for Infection Research; Helmholtz Association [SO-024]; European Research Council [ERC-2011-StG_281473-VIRAFRONT]; Intramural Research Program, National Institute of Dental and Craniofacial Research, National Institutes of Health; Niedersachsen Research Network on Neuroinfectiology (N-RENNT) of the Ministry of Science and Culture of Lower Saxony FX S.P. was supported by a stipend from the International Research Training Group 1273 (IRTG 1273) provided by the DFG. E.S. was supported by the DFG (STE 1954/1-1) and an intramural young investigator award of the Helmholtz Center for Infection Research. T.P. was supported by a grant from the Helmholtz Association (SO-024) and by a grant from the European Research Council (ERC-2011-StG_281473-VIRAFRONT). P.D.B. was supported by the Intramural Research Program, National Institute of Dental and Craniofacial Research, National Institutes of Health. K.H. was supported by the Niedersachsen Research Network on Neuroinfectiology (N-RENNT) of the Ministry of Science and Culture of Lower Saxony. NR 29 TC 21 Z9 24 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD FEB PY 2015 VL 61 IS 2 BP 447 EP 459 DI 10.1002/hep.27440 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ9UX UT WOS:000348563200010 PM 25212983 ER PT J AU Lee, SM Zhang, YX Tsuchiya, H Smalling, R Jetten, AM Wang, L AF Lee, Sang Min Zhang, Yuxia Tsuchiya, Hiroyuki Smalling, Rana Jetten, Anton M. Wang, Li TI Small Heterodimer Partner/Neuronal PAS Domain Protein 2 Axis Regulates the Oscillation of Liver Lipid Metabolism SO HEPATOLOGY LA English DT Article ID NUCLEAR-RECEPTOR-SHP; REV-ERB-ALPHA; CIRCADIAN CLOCK; GENE-EXPRESSION; IN-VIVO; TRANSCRIPTION; PATHWAYS; PARTNER; NPAS2; MOUSE AB In mammals, circadian rhythms are essential for coordinating the timing of various metabolic processes. The Clock gene regulates diurnal plasma triglyceride fluctuation through nuclear receptor small heterodimer partner (Shp; Nr0b2). Given that SHP is a critical regulator of metabolism in the liver, it is unknown whether SHP is necessary to coordinate metabolism and circadian rhythms. Shp(+/+) and Shp(-/-) mice on a C57BL/6 background (n=3-5/group) were fed a standard chow diet and water ad libitum. Serum and livers were collected at zeitgeber time 2, 6, 10, 14, 18, and 22. In vivo and in vitro assays included RNA sequencing, quantitative polymerase chain reaction, very-low-density lipoprotein production, adenovirus overexpression and small interfering RNA knockdown, serum parameters, circadian locomotor activity, Oil Red O staining, transient transfection, luciferase reporter assay, chromatin immunoprecipitation assay, gel-shift assay, coimmunoprecipitation, and western blottings. Shp deficiency had a robust global impact on major liver metabolic genes. Several components of the liver clock, including peroxisome proliferator-activated receptor-, coactivator 1 (Pgc-1), neuronal PAS domain-containing protein 2 (Npas2), and retinoic acid-related orphan receptor (Ror)/ were sharply induced in Shp(-/-) liver. At the molecular level, SHP inhibited Npas2 gene transcription and promoter activity through interaction with Ror to repress Ror transactivation and by interacting with Rev-erb to enhance its inhibition of Ror activity. Conversely, Npas2 controlled the circadian rhythm of Shp expression by binding rhythmically to the Shp promoter, which was enhanced by nicotinamide adenine dinucleotide, but not nicotinamide adenine dinucleotide phosphate. Phenotypically, Npas2 deficiency induced severe steatosis in Shp(-/-) mice, which was attributed to the dysregulation of lipoprotein metabolism. Conclusion: Shp and Npas2 crosstalk is essential to maintain hepatic lipid homeostasis. (Hepatology 2015;61:497-505) C1 [Lee, Sang Min; Wang, Li] Univ Connecticut, Dept Physiol & Neurobiol, Storrs, CT 06269 USA. [Zhang, Yuxia; Tsuchiya, Hiroyuki; Smalling, Rana] Univ Utah, Sch Med, Dept Med, Salt Lake City, UT USA. [Jetten, Anton M.] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Wang, Li] Yale Univ, Dept Internal Med, Sect Digest Dis, New Haven, CT USA. [Wang, Li] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. RP Wang, L (reprint author), Univ Connecticut, Dept Physiol & Neurobiol, 75 North Eagleville Rd,U3156, Storrs, CT 06269 USA. EM li.wang@uconn.edu OI Jetten, Anton/0000-0003-0954-4445 FU NIH [DK080440]; AHA [13GRNT14700043, 13POST14630070, 14PRE17930013]; VA Merit Award by Diabetes Research Center at Washington University [1I01BX002634, P30 DK020579]; Huntsman Cancer Institute [P30 CA042014]; Manpei Suzuki Diabetes Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research FX L.W. is supported by NIH DK080440, AHA 13GRNT14700043, VA Merit Award 1I01BX002634, P30 DK020579 by the Diabetes Research Center at Washington University, and P30 CA042014 from Huntsman Cancer Institute. S.L. is supported by AHA Postdoctoral fellowship 13POST14630070. H.T. is supported by the Manpei Suzuki Diabetes Foundation and the Mochida Memorial Foundation for Medical and Pharmaceutical Research. R.S. is supported by AHA Predoctoral fellowship 14PRE17930013. NR 47 TC 12 Z9 12 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD FEB PY 2015 VL 61 IS 2 BP 497 EP 505 DI 10.1002/hep.27437 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ9UX UT WOS:000348563200015 PM 25212631 ER PT J AU Li, L Liu, YX Guo, Y Liu, B Zhao, YR Li, P Song, FJ Zheng, H Yu, JP Song, TQ Niu, RF Li, Q Wang, XW Zhang, W Chen, KX AF Li, Lian Liu, Yuexin Guo, Yan Liu, Ben Zhao, Yanrui Li, Pei Song, Fengju Zheng, Hong Yu, Jingpu Song, Tianqiang Niu, Ruifang Li, Qiang Wang, Xin Wei Zhang, Wei Chen, Kexin TI Regulatory MiR-148a-ACVR1/BMP Circuit Defines a Cancer Stem Cell-Like Aggressive Subtype of Hepatocellular Carcinoma SO HEPATOLOGY LA English DT Article ID FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; HEPATIC PROGENITOR CELLS; TUMOR-INITIATING CELLS; LIVER-CANCER; THERAPEUTIC TARGET; GENE-EXPRESSION; MICRORNA-148A SUPPRESSES; METASTASIS; ACVR1; IDENTIFICATION AB Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third most common cancer in Asia. HCC has heterogeneous etiologic and molecular profiles and a varied response to therapeutics. The high recurrence rate and curtailed survival in this cancer are attributed to its resistance to therapy. The ultimate goal is to develop a more effective personalized therapeutic strategy for HCC, but the first step is to develop a system for classifying the disease on the basis of molecular biomarkers. To that end, we performed mRNA and microRNA (miRNA) expression profiling in 100 HCC tissues. Clustering analysis of informative genes identified two robust subtypes, which were validated by an independent dataset. The subtype characterized by a cancer stem cell-like signature was clinically aggressive and associated with poor survival. Integrated analysis of miRNA and mRNA expression in this subtype showed that miR-148a was expressed at a significantly lower level in these tumors than in the other subtype. MiR-148a has been shown to directly suppress the expression of activin A receptor type 1 (ACVR1), a key receptor in the signaling pathway of the bone morphogenetic proteins (BMPs), which regulate many stem cell markers as well as the clinically important cytokine interleukin-8 (IL-8). Increased expression of ACVR1 and its downstream genes EPCAM, CD24, CD90, and IL-8 was associated with shorter survival in a larger cohort of 227 HCC cases. Introduction of miR-148a resulted in suppressed tumor phenotypes both in vitro and in vivo. Conclusion: We identified a clinically aggressive stem cell-like subtype of HCC that is characterized by an miR-148a-ACVR1-BMP-Wnt circuit. We propose that miR-148a may serve as a prognostic biomarker and therapeutic target for this subtype of HCC. (Hepatology 2015;61:574-584) C1 [Li, Lian; Guo, Yan; Liu, Ben; Zhao, Yanrui; Li, Pei; Song, Fengju; Zheng, Hong; Chen, Kexin] Tianjin Med Univ, Key Lab Canc Prevent & Therapy Tianjin, Natl Clin Res Ctr Canc, Dept Epidemiol & Biostat,Canc Inst & Hosp, Tianjin 300060, Peoples R China. [Liu, Yuexin; Zhang, Wei] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Yu, Jingpu] Tianjin Med Univ, Key Lab Canc Prevent & Therapy Tianjin, Natl Clin Res Ctr Canc, Dept Immunol,Canc Inst & Hosp, Tianjin 300060, Peoples R China. [Yu, Jingpu] Tianjin Med Univ, TMUCIH J&J Joint Lab, Canc Inst & Hosp, Tianjin 300060, Peoples R China. [Song, Tianqiang; Li, Qiang] Tianjin Med Univ, Key Lab Canc Prevent & Therapy Tianjin, Natl Clin Res Ctr Canc, Dept Liver Canc,Canc Inst & Hosp, Tianjin 300060, Peoples R China. [Niu, Ruifang] Tianjin Med Univ, Key Lab Canc Prevent & Therapy Tianjin, Natl Clin Res Ctr Canc, Publ Lab,Canc Inst & Hosp, Tianjin 300060, Peoples R China. [Wang, Xin Wei] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Chen, KX (reprint author), Tianjin Med Univ, Key Lab Canc Prevent & Therapy Tianjin, Natl Clin Res Ctr Canc, Dept Epidemiol & Biostat,Canc Inst & Hosp, Tianjin 300060, Peoples R China. EM wzhang@mdanderson.org; chenkexin@tjmuch.com RI Wang, Xin/B-6162-2009 FU Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) in China [IRT1076]; National Key Scientific and Technological Project [2011ZX09307-001-04]; National Natural Science Foundation of China [81172762]; China Postdoctoral Science Foundation [2012M510757]; University of Texas MD Anderson Cancer Center Core Support Grant from U.S. National Institutes of Health [CA016672]; Tianjin Cancer Institute and Hospital; U.S. National Foundation for Cancer Research; Intramural Research Program of the Center for Cancer Research, U.S. National Cancer Institute [Z01-BC 010313, Z01-BC010876] FX Partially supported by the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) in China (IRT1076), the National Key Scientific and Technological Project (2011ZX09307-001-04), the National Natural Science Foundation of China (No. 81172762), China Postdoctoral Science Foundation funded Project (2012M510757), and the University of Texas MD Anderson Cancer Center Core Support Grant from the U.S. National Institutes of Health (CA016672). The tissue bank is jointly supported by the Tianjin Cancer Institute and Hospital and the U.S. National Foundation for Cancer Research. X.W.W. was supported by grants (Z01-BC 010313 and Z01-BC010876) from the Intramural Research Program of the Center for Cancer Research, the U.S. National Cancer Institute. NR 49 TC 15 Z9 16 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD FEB PY 2015 VL 61 IS 2 BP 574 EP 584 DI 10.1002/hep.27543 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ9UX UT WOS:000348563200022 PM 25271001 ER PT J AU Xu, MJ Feng, DC Wu, HL Wang, H Chan, Y Kolls, J Borregaard, N Porse, B Berger, T Mak, TW Cowland, JB Kong, XN Gao, B AF Xu, Ming-Jiang Feng, Dechun Wu, Hailong Wang, Hua Chan, Yvonne Kolls, Jay Borregaard, Niels Porse, Bo Berger, Thorsten Mak, Tak W. Cowland, Jack B. Kong, Xiaoni Gao, Bin TI Liver Is the Major Source of Elevated Serum Lipocalin-2 Levels After Bacterial Infection or Partial Hepatectomy: A Critical Role for IL-6/STAT3 SO HEPATOLOGY LA English DT Article ID GELATINASE-ASSOCIATED LIPOCALIN; NF-KAPPA-B; NEUTROPHIL GELATINASE; SIGNAL TRANSDUCER; TRANSCRIPTION 3; HOST-DEFENSE; MICE; INJURY; REGENERATION; INFLAMMATION AB Lipocalin-2 (LCN2) was originally isolated from human neutrophils and termed neutrophil gelatinase-associated lipocalin (NGAL). However, the functions of LCN2 and the cell types that are primarily responsible for LCN2 production remain unclear. To address these issues, hepatocyte-specific Lcn2 knockout (Lcn2(Hep-/-)) mice were generated and subjected to bacterial infection (with Klesbsiella pneumoniae or Escherichia coli) or partial hepatectomy (PHx). Studies of Lcn2(Hep-/-) mice revealed that hepatocytes contributed to 25% of the low basal serum level of LCN2 protein (approximate to 62 ng/mL) but were responsible for more than 90% of the highly elevated serum LCN2 protein level (approximate to 6,000 ng/mL) postinfection and more than 60% post-PHx (approximate to 700 ng/mL). Interestingly, both Lcn2(Hep-/-) and global Lcn2 knockout (Lcn2(-/-)) mice demonstrated comparable increases in susceptibility to infection with K. pneumoniae or E. coli. These mice also had increased enteric bacterial translocation from the gut to the mesenteric lymph nodes and exhibited reduced liver regeneration after PHx. Treatment with interleukin (IL)-6 stimulated hepatocytes to produce LCN2 in vitro and in vivo. Hepatocyte-specific ablation of the IL-6 receptor or Stat3, a major downstream effector of IL-6, markedly abrogated LCN2 elevation in vivo. Furthermore, chromatin immunoprecipitation (ChIP) assay revealed that STAT3 was recruited to the promoter region of the Lcn2 gene upon STAT3 activation by IL-6. Conclusion: Hepatocytes are the major cell type responsible for LCN2 production after bacterial infection or PHx, and this response is dependent on IL-6 activation of the STAT3 signaling pathway. Thus, hepatocyte-derived LCN2 plays an important role in inhibiting bacterial infection and promoting liver regeneration. (Hepatology 2015;61:692-702) C1 [Xu, Ming-Jiang; Feng, Dechun; Wang, Hua; Kong, Xiaoni; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. [Xu, Ming-Jiang] Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol,Hlth Sci Ctr, Minist Educ,Key Lab Mol Cardiovasc Sci, Beijing 100871, Peoples R China. [Wu, Hailong; Kong, Xiaoni] Shanghai Jiao Tong Univ, Renji Med Clin Stem Cell Res Ctr 10, State Key Lab Oncogenes & Related Genes, Ren Ji Hosp,Sch Med, Shanghai 200030, Peoples R China. [Chan, Yvonne] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Kolls, Jay] Childrens Hosp Pittsburgh, Richard King Mellon Fdn, Pediat Res Inst, Pittsburgh, PA 15213 USA. [Borregaard, Niels; Cowland, Jack B.] Rigshosp, Granulocyte Res Lab, DK-2100 Copenhagen, Denmark. [Porse, Bo] Univ Copenhagen, Finsen Lab, Rigshosp, Fac Hlth Sci, DK-1168 Copenhagen, Denmark. [Porse, Bo] Univ Copenhagen, BRIC, DK-1168 Copenhagen, Denmark. [Porse, Bo] Univ Copenhagen, Danish Stem Cell Ctr DanStem, Fac Hlth Sci, DK-1168 Copenhagen, Denmark. [Berger, Thorsten; Mak, Tak W.] Univ Hlth Network, Campbell Family Inst Breast Canc Res, Toronto, ON, Canada. [Kong, Xiaoni] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200030, Peoples R China. [Kong, Xiaoni] Shanghai Jiao Tong Univ, Med Res Inst 10, Shanghai 200030, Peoples R China. RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM xiaonikong@sjtu.edu.cn; bgao@mail.-nih.gov RI Feng, Dechun/Q-5962-2016; OI Cowland, Jack Bernard/0000-0002-7429-5388 FU NIAAA, NIH; NIAAA, NIH (State Key Laboratory of Oncogenes and Related Genes) [90-13-02] FX Supported by the intramural program of NIAAA, NIH (B.G. and the State Key Laboratory of Oncogenes and Related Genes (90-13-02) (X.L.K.). NR 35 TC 29 Z9 29 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD FEB PY 2015 VL 61 IS 2 BP 692 EP 702 DI 10.1002/hep.27447 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ9UX UT WOS:000348563200032 PM 25234944 ER PT J AU Di Bisceglie, AM Lok, AS Martin, P Terrault, N Perrillo, RP Hoofnagle, JH AF Di Bisceglie, Adrian M. Lok, Anna S. Martin, Paul Terrault, Norah Perrillo, Robert P. Hoofnagle, Jay H. TI Recent US Food and Drug Administration Warnings on Hepatitis B Reactivation With Immune-Suppressing and Anticancer Drugs: Just the Tip of the Iceberg? SO HEPATOLOGY LA English DT Review ID VIRUS INFECTION; PREEMPTIVE LAMIVUDINE; CHEMOTHERAPY; THERAPY; TRANSPLANTATION; MANAGEMENT; PSORIASIS; DISEASES; ANTIGEN; TRIAL AB Reactivation of hepatitis B in the context of immunosuppressive therapy may be severe and potentially fatal. The US Food and Drug Administration has recently drawn attention to the potentially fatal risk of hepatitis B reactivation in patients receiving the anti-CD20 agents ofatumumab or rituximab. This action focuses attention on the broader issue of hepatitis B virus reactivation, which may occur with a wide variety of immunosuppressive therapies in benign or malignant disease. This article summarizes the data behind this issue. These data support the recommendation that all patients undergoing chemotherapy, immunosuppressive therapy, hematopoietic stem cell transplantation, or solid organ transplantation be screened for active or prior hepatitis B viral infection by testing for hepatitis B surface antigen and the antibody to hepatitis B core antigen in serum. Those who are found to be hepatitis B surface antigen-positive should start appropriate antiviral therapy to prevent reactivation. Additionally, even those who have recovered from hepatitis B will benefit from antiviral therapy in certain circumstances because of the risks associated with a form of hepatitis B virus reactivation referred to as reverse seroconversion. There remain many uncertain areas that warrant further study, and further advances will benefit from close interactions between various medical specialties, regulatory agencies, and researchers. Conclusions: There is good evidence to support routine screening of all patients for hepatitis B prior to undergoing chemotherapy or immunosuppressive treatment; use of prompt antiviral treatment appears to diminish the risk of severe or fatal reactivation of hepatitis B. (Hepatology 2015;61:703-711) C1 [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO 63104 USA. [Lok, Anna S.] Univ Michigan, Div Gastroenterol & Hepatol, Ann Arbor, MI 48109 USA. [Martin, Paul] Univ Miami, Miami, FL USA. [Terrault, Norah] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Perrillo, Robert P.] Baylor Univ, Med Ctr, Dallas, TX USA. [Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Di Bisceglie, AM (reprint author), St Louis Univ, Sch Med, Dept Internal Med, 1402 South Grand Blvd, St Louis, MO 63104 USA. EM dibiscam@slu.edu FU American Association for the Study of Liver Diseases FX This article was the outcome of an Emerging Trends Conference, entitled "Reactivation of Hepatitis B," held March 21-22, 2013, in Crystal City, Arlington, VA, funded by the American Association for the Study of Liver Diseases. The authors did not receive salary or honoraria for attending this meeting or preparing this article. The manuscript benefited from input from representatives of the American Academy of Dermatology, the American College of Rheumatology, and the American Society of Clinical Oncology, although these associations do not necessarily endorse its full content. NR 25 TC 43 Z9 43 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD FEB PY 2015 VL 61 IS 2 BP 703 EP 711 DI 10.1002/hep.27609 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ9UX UT WOS:000348563200033 PM 25412906 ER PT J AU Rehermann, B Bertoletti, A AF Rehermann, Barbara Bertoletti, Antonio TI Immunological Aspects of Antiviral Therapy of Chronic Hepatitis B Virus and Hepatitis C Virus Infections SO HEPATOLOGY LA English DT Article ID PEGYLATED-INTERFERON-ALPHA; NEGATIVE CHRONIC HEPATITIS; NATURAL-KILLER-CELLS; PERSISTENT LCMV INFECTION; CELLULAR IMMUNE-RESPONSE; E-ANTIGEN SEROCONVERSION; REGULATORY T-CELLS; PEGINTERFERON ALPHA-2A; NUCLEOS(T)IDE ANALOGS; LAMIVUDINE TREATMENT AB Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause a large proportion of acute and chronic liver disease worldwide. Over the past decades many immunological studies defined host immune responses that mediate spontaneous clearance of acute HBV and HCV infection. However, host immune responses are also relevant in the context of treatment-induced clearance of chronic HBV and HCV infection. First, the pretreatment level of interferon-stimulated genes as well as genetic determinants of innate immune responses, such as single nucleotide polymorphisms near the IFNL3 gene, are strong predictors of the response to interferon-alpha (IFN-)-based therapy. Second, IFN-, which has been a mainstay of HBV and HCV therapy over decades, and ribavirin, which has also been included in interferon-free direct antiviral therapy for HCV, modulate host immune responses. Third, both IFN--based and IFN--free treatment regimens of HBV and HCV infection alter the short-term and long-term adaptive immune response against these viruses. Finally, treatment studies have not just improved the clinical outcomes, but also provided opportunities to study virus-host interaction. This review summarizes our current knowledge on how a patient's immune response affects the treatment outcome of HBV and HCV infection and how innate and adaptive immune responses themselves are altered by the different treatment regimens. ( Hepatology 2015;61:712-721) C1 [Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA. [Bertoletti, Antonio] Duke NUS Grad Med Sch, Singapore 169857, Singapore. [Bertoletti, Antonio] ASTAR, Singapore Inst Clin Sci, Singapore, Singapore. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bldg 10,Rm 9B16,10 Ctr Dr, Bethesda, MD 20892 USA. EM Rehermann@nih.gov; antonio@duke-nus.egu.sg OI Bertoletti, Antonio/0000-0002-2942-0485 FU NIH, NIDDK; Singapore Translational Research (STaR) Investigator Award [NMRC/STaR/013/2012] FX Supported in part by the Intramural Research Program of the NIH, NIDDK (to B.R.) and by a Singapore Translational Research (STaR) Investigator Award (NMRC/STaR/013/2012) (to A.B.). NR 116 TC 31 Z9 31 U1 3 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD FEB PY 2015 VL 61 IS 2 BP 712 EP 721 DI 10.1002/hep.27323 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ9UX UT WOS:000348563200034 PM 25048716 ER PT J AU Li, WQ Park, Y McGlynn, KA Hollenbeck, AR Taylor, PR Goldstein, AM Freedman, ND AF Li, Wen-Qing Park, Yikyung McGlynn, Katherine A. Hollenbeck, Albert R. Taylor, Philip R. Goldstein, Alisa M. Freedman, Neal D. TI Protein Intake, Chronic Liver Diseases, and Hepatocellular Carcinoma Reply SO HEPATOLOGY LA English DT Letter ID MORTALITY C1 [Li, Wen-Qing] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. [Li, Wen-Qing; Taylor, Philip R.; Goldstein, Alisa M.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Park, Yikyung; Freedman, Neal D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [McGlynn, Katherine A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Li, WQ (reprint author), Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. RI Freedman, Neal/B-9741-2015 OI Freedman, Neal/0000-0003-0074-1098 NR 2 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD FEB PY 2015 VL 61 IS 2 BP 730 EP 731 DI 10.1002/hep.27261 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ9UX UT WOS:000348563200040 PM 24925716 ER PT J AU Zhou, S Bonner, MA Wang, YD Rapp, S De Ravin, SS Malech, HL Sorrentino, BP AF Zhou, Sheng Bonner, Melissa A. Wang, Yong-Dong Rapp, Samuel De Ravin, Suk See Malech, Harry L. Sorrentino, Brian P. TI Quantitative Shearing Linear Amplification Polymerase Chain Reaction: An Improved Method for Quantifying Lentiviral Vector Insertion Sites in Transplanted Hematopoietic Cell Systems SO HUMAN GENE THERAPY METHODS LA English DT Article ID SCID-X1 GENE-THERAPY; HIGH-THROUGHPUT; INTEGRATION SITES; CLONAL ANALYSIS; STEM-CELLS; RETROVIRAL INTEGRATION; BETA-THALASSEMIA; TRACKING; PCR; RECONSTITUTION AB In gene therapy trials targeting blood disorders, it is important to detect dominance of transduced hematopoietic stem cell (HSC) clones arising from vector insertion site (VIS) effects. Current methods for VIS analysis often do not have defined levels of quantitative accuracy and therefore can fail to detect early clonal dominance. We have developed a rapid and inexpensive method for measuring clone size based on random shearing of genomic DNA, minimal exponential PCR amplification, and shear site counts as a quantitative endpoint. This quantitative shearing linear amplification PCR (qsLAM PCR) assay utilizes an internal control sample containing 19 lentiviral insertion sites per cell that is mixed with polyclonal samples derived from transduced human CD34+ cells. Samples were analyzed from transplanted pigtail macaques and from a participant in our X-linked severe combined immunodeficiency (XSCID) lentiviral vector trial and yielded controlled and quantitative results in all cases. One case of early clonal dominance was detected in a monkey transplanted with limiting numbers of transduced HSCs, while the clinical samples from the XSCID trial participant showed highly diverse clonal representation. These studies demonstrate that qsLAM PCR is a facile and quantitative assay for measuring clonal repertoires in subjects enrolled in human gene therapy trials using lentiviral-transduced HSCs. C1 [Zhou, Sheng; Bonner, Melissa A.; Rapp, Samuel; Sorrentino, Brian P.] St Jude Childrens Res Hosp, Dept Hematol, Div Expt Hematol, Memphis, TN 38120 USA. [Wang, Yong-Dong] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38120 USA. [De Ravin, Suk See; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Zhou, S (reprint author), St Jude Childrens Res Hosp, Dept Hematol, Div Expt Hematol, 262 Danny Thomas Pl, Memphis, TN 38120 USA. EM sheng.zhou@stjude.org RI Wang, Yong-Dong/K-3563-2013; OI Malech, Harry/0000-0001-5874-5775 FU National Heart, Lung, and Blood Institute [P01HL 53749]; Cancer Center [P30 CA 21765]; Assisi Foundation of Memphis; American Lebanese Syrian Associated Charities FX We thank John T. Gray for insightful discussions and advice, Chunlao Tang for data analysis, Virginia Valentine and Marc Valentine for fluorescence in situ hybridization, Dana Roeber and Scott Olsen for genome sequencing, and Taihe Lu for Southern blot analysis and PCR. This work was supported by the National Heart, Lung, and Blood Institute (Grant P01HL 53749), Cancer Center (Support Grant P30 CA 21765), the Assisi Foundation of Memphis, and the American Lebanese Syrian Associated Charities. NR 38 TC 3 Z9 3 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1946-6536 EI 1946-6544 J9 HUM GENE THER METHOD JI Hum. Gene Ther. Methods PD FEB 1 PY 2015 VL 26 IS 1 BP 4 EP 12 DI 10.1089/hgtb.2014.122 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CB0MI UT WOS:000349319900003 PM 25545666 ER PT J AU de Gonzalez, AB Wong, J Kleinerman, R Kim, C Morton, L Bekelman, JE AF de Gonzalez, Amy Berrington Wong, Jeannette Kleinerman, Ruth Kim, Clara Morton, Lindsay Bekelman, Justin E. TI Risk of Second Cancers According to Radiation Therapy Technique and Modality in Prostate Cancer Survivors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID EXTERNAL-BEAM RADIOTHERAPY; CONVENTIONAL RADIOTHERAPY; BRACHYTHERAPY; MALIGNANCIES; MEN AB Purpose: Radiation therapy (RT) techniques for prostate cancer are evolving rapidly, but the impact of these changes on risk of second cancers, which are an uncommon but serious consequence of RT, are uncertain. We conducted a comprehensive assessment of risks of second cancer according to RT technique (> 10 MV vs <= 10 MV and 3-dimensional [3D] vs 2D RT) and modality (external beam RT, brachytherapy, and combined modes) in a large cohort of prostate cancer patients. Methods and Materials: The cohort was constructed using the Surveillance Epidemiology and End Results-Medicare database. We included cases of prostate cancer diagnosed in patients 66 to 84 years of age from 1992 to 2004 and followed through 2009. We used Poisson regression analysis to compare rates of second cancer across RT groups with adjustment for age, follow-up, chemotherapy, hormone therapy, and comorbidities. Analyses of second solid cancers were based on the number of 5-year survivors (n=38,733), and analyses of leukemia were based on number of 2-year survivors (n=52,515) to account for the minimum latency period for radiation-related cancer. Results: During an average of 4.4 years' follow-up among 5-year prostate cancer survivors (2DRT = 5.5 years; 3DRT = 3.9 years; and brachytherapy = 2.7 years), 2933 second solid cancers were diagnosed. There were no significant differences in second solid cancer rates overall between 3DRT and 2DRT patients (relative risk [RR] = 1.00, 95% confidence interval [CI]: 0.91-1.09), but second rectal cancer rates were significantly lower after 3DRT (RR = 0.59, 95% CI: 0.40-0.88). Rates of second solid cancers for higher-and lower-energy RT were similar overall (RR = 0.97, 95% CI: 0.89-1.06), as were rates for site-specific cancers. There were significant reductions in colon cancer and leukemia rates in the first decade after brachytherapy compared to those after external beam RT. Conclusions: Advanced treatment planning may have reduced rectal cancer risks in prostate cancer survivors by approximately 3 cases per 1000 after 15 years. Despite concerns about the neutron doses, we did not find evidence that higher energy therapy was associated with increased second cancer risks. (C) 2015 Elsevier Inc. C1 [de Gonzalez, Amy Berrington; Wong, Jeannette; Kleinerman, Ruth; Kim, Clara; Morton, Lindsay] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Bekelman, Justin E.] Univ Penn, Abramson Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Bekelman, Justin E.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Bekelman, Justin E.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP de Gonzalez, AB (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Room 7E452,MSC 9778,9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM berringtona@mail.nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478 FU National Cancer Institute, National Institutes of Health [KO7-CA16316] FX This study was supported by the intramural research program, National Cancer Institute (KO7-CA16316), National Institutes of Health. NR 22 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2015 VL 91 IS 2 BP 295 EP 302 DI 10.1016/j.ijrobp.2014.10.040 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AZ2DR UT WOS:000348045400009 ER PT J AU Parmar, P Krishnamurthi, R Ikram, MA Hofman, A Mirza, SS Varakin, Y Kravchenko, M Piradov, M Thrift, AG Norrving, B Wang, W Mandal, DK Barker-Collo, S Sahathevan, R Davis, S Saposnik, G Kivipelto, M Sindi, S Bornstein, NM Giroud, M Bejot, Y Brainin, M Poulton, R Narayan, KMV Correia, M Freire, A Kokubo, Y Wiebers, D Mensah, G BinDhim, NF Barber, PA Pandian, JD Hankey, GJ Mehndiratta, MM Azhagammal, S Ibrahim, NM Abbott, M Rush, E Hume, P Hussein, T Bhattacharjee, R Purohit, M Feigin, VL AF Parmar, Priya Krishnamurthi, Rita Ikram, M. Arfan Hofman, Albert Mirza, Saira S. Varakin, Yury Kravchenko, Michael Piradov, Michael Thrift, Amanda G. Norrving, Bo Wang, Wenzhi Mandal, Dipes Kumar Barker-Collo, Suzanne Sahathevan, Ramesh Davis, Stephen Saposnik, Gustavo Kivipelto, Miia Sindi, Shireen Bornstein, Natan M. Giroud, Maurice Bejot, Yannick Brainin, Michael Poulton, Richie Narayan, K. M. Venkat Correia, Manuel Freire, Antonio Kokubo, Yoshihiro Wiebers, David Mensah, George BinDhim, Nasser F. Barber, P. Alan Pandian, Jeyaraj Durai Hankey, Graeme J. Mehndiratta, Man Mohan Azhagammal, Shobhana Ibrahim, Norlinah Mohd Abbott, Max Rush, Elaine Hume, Patria Hussein, Tasleem Bhattacharjee, Rohit Purohit, Mitali Feigin, Valery L. CA Stroke Riskometer Collaboration TI The Stroke Riskometer (TM) App: Validation of a data collection tool and stroke risk predictor SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE prevention; stroke prediction; Stroke Riskometer(TM) App; validation ID CARDIOVASCULAR-DISEASE RISK; PROSPECTIVE OPEN COHORT; EXTERNAL VALIDATION; ALCOHOL-CONSUMPTION; SYSTEMATIC ANALYSIS; PRIMARY PREVENTION; ELDERLY-PEOPLE; GLOBAL BURDEN; PRIMARY-CARE; FOLLOW-UP AB BackgroundThe greatest potential to reduce the burden of stroke is by primary prevention of first-ever stroke, which constitutes three quarters of all stroke. In addition to population-wide prevention strategies (the mass' approach), the high risk' approach aims to identify individuals at risk of stroke and to modify their risk factors, and risk, accordingly. Current methods of assessing and modifying stroke risk are difficult to access and implement by the general population, amongst whom most future strokes will arise. To help reduce the burden of stroke on individuals and the population a new app, the Stroke Riskometer(TM), has been developed. We aim to explore the validity of the app for predicting the risk of stroke compared with current best methods. Methods752 stroke outcomes from a sample of 9501 individuals across three countries (New Zealand, Russia and the Netherlands) were utilized to investigate the performance of a novel stroke risk prediction tool algorithm (Stroke Riskometer(TM)) compared with two established stroke risk score prediction algorithms (Framingham Stroke Risk Score [FSRS] and QStroke). We calculated the receiver operating characteristics (ROC) curves and area under the ROC curve (AUROC) with 95% confidence intervals, Harrels C-statistic and D-statistics for measure of discrimination, R-2 statistics to indicate level of variability accounted for by each prediction algorithm, the Hosmer-Lemeshow statistic for calibration, and the sensitivity and specificity of each algorithm. ResultsThe Stroke Riskometer(TM) performed well against the FSRS five-year AUROC for both males (FSRS=750% (95% CI 723%-776%), Stroke Riskometer(TM)=740(95% CI 713%-767%) and females [FSRS=703% (95% CI 679%-728%, Stroke Riskometer(TM)=715% (95% CI 690%-739%)], and better than QStroke [males - 597% (95% CI 573%-620%) and comparable to females=711% (95% CI 690%-731%)]. Discriminative ability of all algorithms was low (C-statistic ranging from 051-056, D-statistic ranging from 001-012). Hosmer-Lemeshow illustrated that all of the predicted risk scores were not well calibrated with the observed event data (P<0006). ConclusionsThe Stroke Riskometer(TM) is comparable in performance for stroke prediction with FSRS and QStroke. All three algorithms performed equally poorly in predicting stroke events. The Stroke Riskometer(TM) will be continually developed and validated to address the need to improve the current stroke risk scoring systems to more accurately predict stroke, particularly by identifying robust ethnic/race ethnicity group and country specific risk factors. C1 [Parmar, Priya; Krishnamurthi, Rita; Abbott, Max; Rush, Elaine; Hume, Patria; Hussein, Tasleem; Bhattacharjee, Rohit; Purohit, Mitali; Feigin, Valery L.] AUT Univ, Auckland 1142, New Zealand. [Ikram, M. Arfan; Hofman, Albert; Mirza, Saira S.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Varakin, Yury; Kravchenko, Michael; Piradov, Michael] RAMS, Res Ctr Neurol, Moscow, Russia. [Thrift, Amanda G.] Monash Univ, Sch Clin Sci, Dept Med, Clayton, Vic 3800, Australia. [Norrving, Bo] Lund Univ, S-22100 Lund, Sweden. [Wang, Wenzhi] Beijing Neurosurg Inst, Beijing, Peoples R China. [Mandal, Dipes Kumar; Azhagammal, Shobhana] Stroke Fdn Bengal, Kolkata, India. [Barker-Collo, Suzanne; Barber, P. Alan] Univ Auckland, Auckland 1, New Zealand. [Sahathevan, Ramesh; Ibrahim, Norlinah Mohd] Univ Kebangsaan Malaysia, Med Ctr, Kl, Malaysia. [Davis, Stephen] Univ Melbourne, Melbourne, Vic 3010, Australia. [Saposnik, Gustavo] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Kivipelto, Miia; Sindi, Shireen] Karolinska Inst, S-10401 Stockholm, Sweden. [Bornstein, Natan M.] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Giroud, Maurice] Ctr Hosp Univ, Dijon, France. [Bejot, Yannick] Univ Burgundy, Dijon, France. [Brainin, Michael] Danube Univ, Krems An Der Donau, Austria. [Poulton, Richie] Univ Otago, Dunedin, New Zealand. [Narayan, K. M. Venkat] Emory Univ, Atlanta, GA 30322 USA. [Correia, Manuel] Hosp Santo Antonio, Oporto, Portugal. [Freire, Antonio] Univ Hosp Coimbra, Coimbra, Portugal. [Kokubo, Yoshihiro] Natl Cerebral & Cardiovasc Ctr, Suita, Osaka, Japan. [Wiebers, David] Mayo Clin, Rochester, MN USA. [Mensah, George] NHLBI, NIH, Bethesda, MD USA. [BinDhim, Nasser F.] Univ Sydney, Sydney, NSW 2006, Australia. [Pandian, Jeyaraj Durai] Christian Med Coll & Hosp, Ludhiana, Punjab, India. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. [Mehndiratta, Man Mohan] Janakpuri Super Special Hosp, Dept Neurol, New Delhi, India. RP Parmar, P (reprint author), AUT Univ, Natl Inst Stroke & Appl Neurosci, Fac Hlth & Environm Studies, AUT North Shore Campus,AA254,90 Akoranga Dr, Auckland 1142, New Zealand. EM pparmar@aut.ac.nz RI Hankey, Graeme /H-4968-2014; Piradov, Mikhail/B-4407-2012; Thrift, Amanda/I-6251-2012; Kravchenko, Michael/B-2596-2012; Varakin, Yuriy/C-8634-2012 OI Hankey, Graeme /0000-0002-6044-7328; Piradov, Mikhail/0000-0002-6055-8335; Thrift, Amanda/0000-0001-8533-4170; Kravchenko, Michael/0000-0001-5187-5518; FU Faculty of Health and Environmental Studies, AUT University, Auckland, NZ FX Faculty of Health and Environmental Studies, AUT University, Private Bag 92006, Auckland, NZ. NR 56 TC 10 Z9 12 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD FEB PY 2015 VL 10 IS 2 BP 231 EP 244 DI 10.1111/ijs.12411 PG 14 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CA2BH UT WOS:000348713500025 PM 25491651 ER PT J AU Akhmetova, A Kozhamkulov, U Bismilda, V Chingissova, L Abildaev, T Dymova, M Filipenko, M Ramanculov, E AF Akhmetova, A. Kozhamkulov, U. Bismilda, V. Chingissova, L. Abildaev, T. Dymova, M. Filipenko, M. Ramanculov, E. TI Mutations in the pncA and rpsA genes among 77 Mycobacterium tuberculosis isolates in Kazakhstan SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE pyrazinamide; PZA; resistance; Mycobacterium tuberculosis; sequencing ID PYRAZINAMIDE RESISTANCE; DRUG-RESISTANCE; SUSCEPTIBILITY; STRAINS; REGION AB SETTING: Pyrazinamide (PZA), an important first-line drug for anti-tuberculosis treatment, demonstrates potent activity against semi-dormant bacilli in acidic environments. However, the diagnosis of PZA resistance is often impeded by technical difficulties. OBJECTIVE: To characterise mutations in the pncA and rpsA genes among PZA-resistant and PZA-susceptible clinical Mycobacterium tuberculosis isolates circulating in Kazakhstan. The potential use of genotyping to identify PZA resistance was also investigated. DESIGN: PZA drug susceptibility testing and pncA and rpsA gene sequencing were performed on 77 clinical M. tuberculosis isolates; mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing was performed on 74 clinical M. tuberculosis isolates. RESULTS: Of the 77 clinical M. tuberculosis isolates, 41 (53.2%) were phenotypically resistant to PZA, whereas 36 (46.7%) were susceptible; 48 (62.3%) of these isolates were also multidrug-resistant (MDR). Furthermore, 38 (49.3%) clinical isolates showed mutations in the pncA gene and its flanking region; the majority of these isolates (n = 36, 94.7%) were also MDR. Gene sequencing showed that only synonymous substitutions affecting rpsA occurred. MIRU-VNTR typing revealed that 78.4% of isolates were of the Beijing genotype. CONCLUSIONS: Sequencing revealed that mutations in pncA, but not in rpsA, occurred in PZA-resistant M. tuberculosis isolates circulating in the territory of Kazakhstan. C1 [Akhmetova, A.; Kozhamkulov, U.; Ramanculov, E.] Natl Ctr Biotechnol Republ Kazakhstan, Astana, Kazakhstan. [Bismilda, V.; Chingissova, L.; Abildaev, T.] Natl Ctr TB Problems Republ Kazakhstan, Alma Ata, Kazakhstan. [Dymova, M.; Filipenko, M.] Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia. [Dymova, M.; Filipenko, M.] Novosibirsk State Univ, Novosibirsk 630090, Russia. RP Dymova, M (reprint author), Inst Chem Biol & Fundamental Med, 8 Lavrentiev Ave, Novosibirsk 630090, Russia. EM maya.a.rot@gmail.com RI Kozhamkulov, Ulan/H-6805-2016; OI Dymova, Maya/0000-0002-7281-9096 FU Russian 'Living Systems' federal programme [11.519.11.2013]; Programme of the Presidium of Siberian Academy of Science [5, 43] FX This work was supported by the Russian 'Living Systems' federal programme (State Contract no 11.519.11.2013) and by the Programme of the Presidium of Siberian Academy of Science No 5 (Project No 43). NR 32 TC 5 Z9 5 U1 3 U2 15 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 EI 1815-7920 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD FEB PY 2015 VL 19 IS 2 BP 179 EP 184 DI 10.5588/ijtld.14.0305 PG 6 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA CA1UM UT WOS:000348696900011 PM 25574916 ER PT J AU Ghany, MG AF Ghany, Marc G. TI The Ongoing Debate of Who to Treat for Chronic Hepatitis C Virus SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID DISEASE PROGRESSION; UNITED-STATES; INFECTION; HCV; MORTALITY; COHORT C1 Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Ghany, MG (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, NIH, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM MarcG@intra.niddk.nih.gov FU Intramural NIH HHS NR 16 TC 5 Z9 5 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB PY 2015 VL 175 IS 2 BP 169 EP 170 DI 10.1001/jamainternmed.2014.4299 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CA7TL UT WOS:000349120100010 PM 25486410 ER PT J AU Jena, AB Prasad, V Goldman, DP Romley, J AF Jena, Anupam B. Prasad, Vinay Goldman, Dana P. Romley, John TI Mortality and Treatment Patterns Among Patients Hospitalized With Acute Cardiovascular Conditions During Dates of National Cardiology Meetings SO JAMA INTERNAL MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; DUTY HOUR REFORM; MEDICARE BENEFICIARIES; OUTCOMES; RISK; CARE; ADMISSION; TRENDS; VOLUME AB IMPORTANCE Thousands of physicians attend scientific meetings annually. Although hospital physician staffing and composition may be affected by meetings, patient outcomes and treatment patterns during meeting dates are unknown. OBJECTIVE To analyze mortality and treatment differences among patients admitted with acute cardiovascular conditions during dates of national cardiology meetings compared with nonmeeting dates. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 30-day mortality among Medicare beneficiaries hospitalized with acutemyocardial infarction (AMI), heart failure, or cardiac arrest from 2002 through 2011 during dates of 2 national cardiology meetings compared with identical nonmeeting days in the 3 weeks before and after conferences (AMI, 8570 hospitalizations during 82 meeting days and 57 471 during 492 nonmeeting days; heart failure, 19 282 during meeting days and 11 4591 during nonmeeting days; cardiac arrest, 1564 during meeting days and 9580 during nonmeeting days). Multivariable analyses were conducted separately for major teaching hospitals and nonteaching hospitals and for low- and high-risk patients. Differences in treatment utilization were assessed. EXPOSURES Hospitalization during cardiology meeting dates. MAIN OUTCOMES AND MEASURES Thirty-day mortality, procedure rates, charges, length of stay. RESULTS Patient characteristics were similar between meeting and nonmeeting dates. In teaching hospitals, adjusted 30-day mortality was lower among high-risk patients with heart failure or cardiac arrest admitted during meeting vs nonmeeting dates (heart failure, 17.5% [95% CI, 13.7%-21.2%] vs 24.8%[95% CI, 22.9%-26.6%]; P <.001; cardiac arrest, 59.1% [95% CI, 51.4%-66.8%] vs 69.4%[95% CI, 66.2%-72.6%]; P=.01). Adjusted mortality for high-risk AMI in teaching hospitals was similar between meeting and nonmeeting dates (39.2%[95% CI, 31.8%-46.6%] vs 38.5%[95% CI, 35.0%-42.0%]; P=.86), although adjusted percutaneous coronary intervention (PCI) rates were lower during meetings (20.8% vs 28.2%; P = .02). No mortality or utilization differences existed for low-risk patients in teaching hospitals or high- or low-risk patients in nonteaching hospitals. In sensitivity analyses, cardiac mortality was not affected by hospitalization during oncology, gastroenterology, and orthopedics meetings, nor was gastrointestinal hemorrhage or hip fracture mortality affected by hospitalization during cardiology meetings. CONCLUSIONS AND RELEVANCE High-risk patients with heart failure and cardiac arrest hospitalized in teaching hospitals had lower 30-day mortality when admitted during dates of national cardiology meetings. High-risk patients with AMI admitted to teaching hospitals during meetings were less likely to receive PCI, without any mortality effect. C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jena, Anupam B.; Goldman, Dana P.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Goldman, Dana P.; Romley, John] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Goldman, Dana P.; Romley, John] RAND Corp, Santa Monica, CA USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu OI Prasad, Vinay/0000-0002-6110-8221 FU Office of the Director, National Institutes of Health (NIH Early Independence Award) [1DP50D017897-01]; National Institute of Aging [5P01AG033559] FX Dr Jena has received funding from the Office of the Director, National Institutes of Health (NIH Early Independence Award, grant 1DP50D017897-01). Drs Goldman and Romley have received funding from the National Institute of Aging (grant 5P01AG033559). NR 31 TC 16 Z9 16 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB PY 2015 VL 175 IS 2 BP 237 EP 244 DI 10.1001/jamainternmed.2014.6781 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CA7TL UT WOS:000349120100022 PM 25531231 ER PT J AU Baker, TG Roy, S Brandon, CS Kramarenko, IK Francis, SP Taleb, M Marshall, KM Schwendener, R Lee, FS Cunningham, LL AF Baker, Tiffany G. Roy, Soumen Brandon, Carlene S. Kramarenko, Inga K. Francis, Shimon P. Taleb, Mona Marshall, Keely M. Schwendener, Reto Lee, Fu-Shing Cunningham, Lisa L. TI Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE ototoxicity; HSPs; cisplatin; utricles ID ISCHEMIA-REPERFUSION INJURY; HEME OXYGENASE-1 EXPRESSION; INDUCED HEARING-LOSS; AUDITORY CELLS; INDUCED APOPTOSIS; CYTOCHROME-C; INNER-EAR; COBALT-PROTOPORPHYRIN; OXIDATIVE STRESS; SUPPORTING CELLS AB Cisplatin is a highly successful and widely used chemotherapy for the treatment of various solid malignancies in both adult and pediatric patients. Side effects of cisplatin treatment include nephrotoxicity and ototoxicity. Cisplatin ototoxicity results from damage to and death of cells in the inner ear, including sensory hair cells. We showed previously that heat shock inhibits cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice. Since heat shock protein 70 (HSP70) is the most upregulated HSP in response to heat shock, we investigated the role of HSP70 as a potential protectant against cisplatin-induced hair cell death. Our data using utricles from HSP70 (-/-) mice indicate that HSP70 is necessary for the protective effect of heat shock against cisplatin-induced hair cell death. In addition, constitutive expression of inducible HSP70 offered modest protection against cisplatin-induced hair cell death. We also examined a second heat-inducible protein, heme oxygenase-1 (HO-1, also called HSP32). HO-1 is an enzyme responsible for the catabolism of free heme. We previously showed that induction of HO-1 using cobalt protoporphyrin IX (CoPPIX) inhibits aminoglycoside-induced hair cell death. Here, we show that HO-1 also offers significant protection against cisplatin-induced hair cell death. HO-1 induction occurred primarily in resident macrophages, with no detectable expression in hair cells or supporting cells. Depletion of macrophages from utricles abolished the protective effect of HO-1 induction. Together, our data indicate that HSP induction protects against cisplatin-induced hair cell death, and they suggest that resident macrophages mediate the protective effect of HO-1 induction. C1 [Baker, Tiffany G.; Brandon, Carlene S.; Kramarenko, Inga K.; Francis, Shimon P.; Taleb, Mona; Marshall, Keely M.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Roy, Soumen; Cunningham, Lisa L.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. [Schwendener, Reto] Univ Zurich, Inst Mol Canc Res, CH-8057 Zurich, Switzerland. [Lee, Fu-Shing] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. RP Cunningham, LL (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 35A Convent Dr, Bethesda, MD 20892 USA. EM lisa.cunningham@nih.gov FU NIH/NIDCD [R01 DC007613, F30DC010522]; NIH/NCRR from National Center for Research Resources [C06 RR015455, C06 RR14516]; MUSC GAANN; Cancer Center Support Grant [P30 CA138313]; NIDCD Intramural Research Program [ZIA DC00079] FX Thanks to Lindsey May for help with qRT-PCR experiments. Thanks to Dr. Suhua Sha for graciously sharing her lab space during the completion of these studies. This work was supported by NIH/NIDCD R01 DC007613, F30DC010522, and NIH/NCRR extramural research facilities construction (C06) grants C06 RR015455 and C06 RR14516 from the National Center for Research Resources, as well as the MUSC GAANN fellowship in Cell and Neurobiology. Imaging facilities for this research were supported by Cancer Center Support Grant P30 CA138313 to the Hollings Cancer Center, Medical University of South Carolina. Additional support for this work was provided by the NIDCD Intramural Research Program (ZIA DC00079). NR 108 TC 1 Z9 1 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 EI 1438-7573 J9 JARO-J ASSOC RES OTO JI JARO PD FEB PY 2015 VL 16 IS 1 BP 67 EP 80 DI 10.1007/s10162-014-0491-7 PG 14 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA CA6JL UT WOS:000349018500004 PM 25261194 ER PT J AU Marceau, K Narusyte, J Lichtenstein, P Ganiban, JM Spotts, EL Reiss, D Neiderhiser, JM AF Marceau, Kristine Narusyte, Jurgita Lichtenstein, Paul Ganiban, Jody M. Spotts, Erica L. Reiss, David Neiderhiser, Jenae M. TI Parental knowledge is an environmental influence on adolescent externalizing SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Gene-environment correlation; adolescent externalizing; parental monitoring; parental knowledge; extended children of twins ID CHILDREN-OF-TWINS; CONDUCT PROBLEMS; YOUNG ADULTHOOD; AGGRESSIVE BOYS; SUBSTANCE USE; FOLLOW-UP; BEHAVIOR; INTERVENTION; REINTERPRETATION; ASSOCIATIONS AB BackgroundThere is evidence both that parental monitoring is an environmental influence serving to diminish adolescent externalizing problems and that this association may be driven by adolescents' characteristics via genetic and/or environmental mechanisms, such that adolescents with fewer problems tell their parents more, and therefore appear to be better monitored. Without information on how parents' and children's genes and environments influence correlated parent and child behaviors, it is impossible to clarify the mechanisms underlying this association. MethodThe present study used the Extended Children of Twins model to distinguish types of gene-environment correlation and direct environmental effects underlying associations between parental knowledge and adolescent (age 11-22years) externalizing behavior with a Swedish sample of 909 twin parents and their adolescent offspring and a US-based sample of 405 White adolescent siblings and their parents. ResultsResults suggest that more parental knowledge is associated with less adolescent externalizing via a direct environmental influence independent of any genetic influences. There was no evidence of a child-driven explanation of the association between parental knowledge and adolescent externalizing problems. ConclusionsIn this sample of adolescents, parental knowledge exerted an environmental influence on adolescent externalizing after accounting for genetic influences of parents and adolescents. Because the association between parenting and child development originates in the parent, treatment for adolescent externalizing must not only include parents but should also focus on altering their parental style. Thus, findings suggest that teaching parents better knowledge-related monitoring strategies is likely to help reduce externalizing problems in adolescents. C1 [Marceau, Kristine] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Marceau, Kristine] Rhode Isl Hosp, Div Behav Genet, Dept Psychiat, Providence, RI 02903 USA. [Narusyte, Jurgita] Karolinska Inst, Dept Epidemiol & Biostat, Stockholm, Sweden. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. [Ganiban, Jody M.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Spotts, Erica L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Reiss, David] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Neiderhiser, Jenae M.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. RP Marceau, K (reprint author), Brown Univ, Ctr Alcohol & Addict Studies GS121 4, Providence, RI 02912 USA. EM Kristine_Marceau@Brown.edu OI Marceau, Kristine/0000-0002-8924-6597 FU National Institute of Mental Health [R01MH43373, R01MH48825, R01MH54601]; William T. Grant Foundation; National Institute on Drug Abuse [F31 DA033737, T32 DA016184] FX Funding for the Nonshared Environment in Adolescent Development project was provided by National Institute of Mental Health grants R01MH43373, R01MH48825 & the William T. Grant Foundation; funding for the Twin and Offspring Study in Sweden was provided by the National Institute of Mental Health grant R01MH54601. Data analysis and manuscript preparation were supported in part by the National Institute on Drug Abuse (F31 DA033737, T32 DA016184, K. M.). NR 35 TC 4 Z9 4 U1 2 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD FEB PY 2015 VL 56 IS 2 BP 130 EP 137 DI 10.1111/jcpp.12288 PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CA4GX UT WOS:000348863800004 PM 24975929 ER PT J AU Caballero, MT Serra, ME Acosta, PL Marzec, J Gibbons, L Salim, M Rodriguez, A Reynaldi, A Garcia, A Bado, D Buchholz, UJ Hijano, DR Coviello, S Newcomb, D Bellabarba, M Ferolla, FM Libster, R Berenstein, A Siniawaski, S Blumetti, V Echavarria, M Pinto, L Lawrence, A Ossorio, MF Grosman, A Mateu, CG Bayle, C Dericco, A Pellegrini, M Igarza, I Repetto, HA Grimaldi, LA Gudapati, P Polack, NR Althabe, F Shi, M Ferrero, F Berge, E Stein, RT Peebles, RS Boothby, M Kleeberger, SR Polack, FP AF Caballero, Mauricio T. Serra, M. Elina Acosta, Patricio L. Marzec, Jacqui Gibbons, Luz Salim, Maximiliano Rodriguez, Andrea Reynaldi, Andrea Garcia, Alejandro Bado, Daniela Buchholz, Ursula J. Hijano, Diego R. Coviello, Silvina Newcomb, Dawn Bellabarba, Miguel Ferolla, Fausto M. Libster, Romina Berenstein, Ada Siniawaski, Susana Blumetti, Valeria Echavarria, Marcela Pinto, Leonardo Lawrence, Andrea Ossorio, M. Fabiana Grosman, Arnoldo Mateu, Cecilia G. Bayle, Carola Dericco, Alejandra Pellegrini, Mariana Igarza, Ignacio Repetto, Horatio A. Grimaldi, Luciano Alva Gudapati, Prathyusha Polack, Norberto R. Althabe, Fernando Shi, Min Ferrero, Fernando Berge, Eduardo Stein, Renato T. Peebles, R. Stokes Boothby, Mark Kleeberger, Steven R. Polack, Fernando P. TI TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; TOLL-LIKE RECEPTOR-4; ENDOTOXIN EXPOSURE; IMMUNE-RESPONSES; YOUNG-CHILDREN; MOUSE LUNG; HIGH-RISK; DISEASE; POLYMORPHISMS; INFECTION AB While 30%-70% of RSV-infected infants develop bronchiolitis, 2% require hospitalization. It is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and Th2 bias are proposed explanations. While TLR4 is associated with these disease phenotypes, the role of this receptor in respiratory syncytial virus (RSV) pathogenesis is controversial. Here, we evaluated the interaction between TLR4 and environmental factors in RSV disease and defined the immune mediators associated with severe illness. Two independent populations of infants with RSV bronchiolitis revealed that the severity of RSV infection is determined by the TLR4 genotype of the individual and by environmental exposure to LPS. RSV-infected infants with severe disease exhibited a high GATA3/T-bet ratio, which manifested as a high IL-4/IFN-gamma ratio in respiratory secretions. The IL-4/IFN-gamma ratio present in infants with severe RSV is indicative of Th2 polarization. Murine models of RSV infection confirmed that LPS exposure, Tlr4 genotype, and Th2 polarization influence disease phenotypes. Together, the results of this study identify environmental and genetic factors that influence RSV pathogenesis and reveal that a high IL-4/IFN-gamma ratio is associated with severe disease. Moreover, these molecules should be explored as potential targets for therapeutic intervention. C1 [Caballero, Mauricio T.; Serra, M. Elina; Acosta, Patricio L.; Hijano, Diego R.; Coviello, Silvina; Ferolla, Fausto M.; Libster, Romina; Pinto, Leonardo; Mateu, Cecilia G.; Stein, Renato T.; Polack, Fernando P.] Alianza INFANT Argentina Brasil, Buenos Aires, DF, Argentina. [Caballero, Mauricio T.; Serra, M. Elina; Acosta, Patricio L.; Salim, Maximiliano; Rodriguez, Andrea; Reynaldi, Andrea; Garcia, Alejandro; Bado, Daniela; Hijano, Diego R.; Coviello, Silvina; Bellabarba, Miguel; Ferolla, Fausto M.; Libster, Romina; Berenstein, Ada; Siniawaski, Susana; Mateu, Cecilia G.; Polack, Norberto R.; Polack, Fernando P.] Fdn INFANT, Buenos Aires, DF, Argentina. [Acosta, Patricio L.; Ferolla, Fausto M.; Libster, Romina; Echavarria, Marcela; Mateu, Cecilia G.] Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina. [Marzec, Jacqui; Shi, Min; Kleeberger, Steven R.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Gibbons, Luz; Althabe, Fernando; Berge, Eduardo] IECS, Buenos Aires, DF, Argentina. [Salim, Maximiliano] Hosp Evita Pueblo, Buenos Aires, DF, Argentina. [Rodriguez, Andrea] Hosp Mi Pueblo, Buenos Aires, DF, Argentina. [Reynaldi, Andrea; Garcia, Alejandro; Bado, Daniela; Bellabarba, Miguel; Polack, Norberto R.] Hosp Frances Riosa, Buenos Aires, DF, Argentina. [Buchholz, Ursula J.] NIAID, NIH, Bethesda, MD 20892 USA. [Hijano, Diego R.; Newcomb, Dawn; Libster, Romina; Lawrence, Andrea; Peebles, R. Stokes; Polack, Fernando P.] Vanderbilt Univ, Dept Pediat, Nashville, TN USA. [Blumetti, Valeria] Swiss Med Ctr, Buenos Aires, DF, Argentina. [Echavarria, Marcela] CEMIC, Buenos Aires, DF, Argentina. [Pinto, Leonardo] Pontificia Univ Catol Rio Grande Sul, Ctr INFANT, Porto Alegre, RS, Brazil. [Ossorio, M. Fabiana] Hosp Pedro Elizalde, Buenos Aires, DF, Argentina. [Grosman, Arnoldo] Hosp Espanol, Buenos Aires, DF, Argentina. [Bayle, Carola; Dericco, Alejandra; Pellegrini, Mariana; Igarza, Ignacio; Repetto, Horatio A.] Hosp Nacl Prof Alejandro Posadas, Buenos Aires, DF, Argentina. [Grimaldi, Luciano Alva] Hosp Zonal Gen Agudos Lucio Melendez, Buenos Aires, DF, Argentina. [Gudapati, Prathyusha; Boothby, Mark] Vanderbilt Univ, Dept Pathol, Dept Microbiol & Immunol, Nashville, TN 37235 USA. RP Caballero, MT (reprint author), Alianza INFANT Argentina Brasil, Buenos Aires, DF, Argentina. RI Stein, Renato/K-2568-2014; Pinto, Leonardo/C-6866-2008; OI Pinto, Leonardo/0000-0002-3906-5456; Acosta, Patricio/0000-0002-4164-7674; Gudapati, Prathyusha/0000-0003-2545-5194 FU Bill & Melinda Gates Foundation; Intramural Research Program of the NIH; NIEHS, Department of Health and Human Services; NIEHS; Intramural Research Program of the NIAID, NIH; NIAID, NIH [AI-054952, AI-104853] FX This work was supported by grants from the Bill & Melinda Gates Foundation (to F.P. Polack); the Intramural Research Program of the NIH (to U.J. Buchholz); the NIEHS, Department of Health and Human Services (to S.R. Kleeberger, J. Marzec, and M. Shi); a Director's Challenge Award from the NIEHS (to F.P. Polack and S.R. Kleeberger); the Intramural Research Program of the NIAID, NIH (to U.J. Buchholz); and by grants AI-054952 (to F.P. Polack) and AI-104853 (to F.P. Polack) from the NIAID, NIH. NR 59 TC 18 Z9 18 U1 1 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2015 VL 125 IS 2 BP 571 EP 582 DI 10.1172/JCI75183 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CA5QK UT WOS:000348962700016 PM 25555213 ER PT J AU Chandler, RJ LaFave, MC Varshney, GK Trivedi, NS Carrillo-Carrasco, N Senac, JS Wu, WW Hoffmann, V Elkahloun, AG Burgess, SM Venditti, CP AF Chandler, Randy J. LaFave, Matthew C. Varshney, Gaurav K. Trivedi, Niraj S. Carrillo-Carrasco, Nuria Senac, Julien S. Wu, Weiwei Hoffmann, Victoria Elkahloun, Abdel G. Burgess, Shawn M. Venditti, Charles P. TI Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LEBERS CONGENITAL AMAUROSIS; METHYLMALONIC ACIDEMIA; HEPATOCELLULAR-CARCINOMA; AAV VECTORS; MOUSE MODEL; INSERTIONAL MUTAGENESIS; INTEGRATION SITES; MURINE MODEL; LARGE-SCALE; LIVER AB The use of adeno-associated virus (AAV) as a gene therapy vector has been approved recently for clinical use and has demonstrated efficacy in a growing number of clinical trials. However, the safety of AAV as a vector has been challenged by a single study that documented hepatocellular carcinoma (HCC) after AAV gene delivery in mice. Most studies have not noted genotoxicity following AAV-mediated gene delivery; therefore, the possibility that there is an association between AAV and HCC is controversial. Here, we performed a comprehensive study of HCC in a large number of mice following therapeutic AAV gene delivery. Using a sensitive high-throughput integration site-capture technique and global expressional analysis, we found that AAV integration into the RNA imprinted and accumulated in nucleus (Rian) locus, and the resulting overexpression of proximal microRNAs and retrotransposon-like 1 (Rt/l) were associated with HCC. In addition, we demonstrated that the AAV vector dose, enhancer/promoter selection, and the timing of gene delivery are all critical factors for determining HCC incidence after AAV gene delivery. Together, our results define aspects of AAV-mediated gene therapy that influence genotoxicity and suggest that these features should be considered for design of both safer AAV vectors and gene therapy studies. C1 [Chandler, Randy J.; Senac, Julien S.; Venditti, Charles P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [LaFave, Matthew C.; Varshney, Gaurav K.; Burgess, Shawn M.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA. [Trivedi, Niraj S.] NHGRI, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA. [Carrillo-Carrasco, Nuria] Natl Ctr Adv Sci, Therapeut Rare & Neglected Dis, NIH, Bethesda, MD USA. [Wu, Weiwei; Elkahloun, Abdel G.] NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA. [Hoffmann, Victoria] Off Director, Diagnost & Res Serv Branch, NIH, Bethesda, MD USA. RP Venditti, CP (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr Room 4A18, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov RI Varshney, Gaurav/L-5261-2014; Carrillo-Carrasco, Nuria/B-9034-2009; OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808; LaFave, Matthew/0000-0001-9165-041X; Varshney, Gaurav K./0000-0002-0429-1904 FU Intramural Research Program of the National Human Genome Research Institute, NIH FX We thank R.W. Blakesley, A. Young, and the staff of the NIH Intramural Sequencing Center for Sequencing and I. Ginty and S. Hoogstraten-Miller for animal care. R.J. Chandler, M.C. LaFave, G.K. Varshney, N.S. Trivedi, N. Carrillo-Carrasco, J.S. Senac, W. Wu, A.G. Elkahloun, S.M. Burgess, and C.P. Venditti were supported by the Intramural Research Program of the National Human Genome Research Institute, NIH. NR 62 TC 47 Z9 47 U1 2 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2015 VL 125 IS 2 BP 870 EP 880 DI 10.1172/JCI79213 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CA5QK UT WOS:000348962700040 PM 25607839 ER PT J AU Badano, A Revie, C Casertano, A Cheng, WC Green, P Kimpe, T Krupinski, E Sisson, C Skrovseth, S Treanor, D Boynton, P Clunie, D Flynn, MJ Heki, T Hewitt, S Homma, H Masia, A Matsui, T Nagy, B Nishibori, M Penczek, J Schopf, T Yagi, Y Yokoi, H AF Badano, Aldo Revie, Craig Casertano, Andrew Cheng, Wei-Chung Green, Phil Kimpe, Tom Krupinski, Elizabeth Sisson, Christye Skrovseth, Stein Treanor, Darren Boynton, Paul Clunie, David Flynn, Michael J. Heki, Tatsuo Hewitt, Stephen Homma, Hiroyuki Masia, Andy Matsui, Takashi Nagy, Balazs Nishibori, Masahiro Penczek, John Schopf, Thomas Yagi, Yukako Yokoi, Hideto TI Consistency and Standardization of Color in Medical Imaging: a Consensus Report SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE Color imaging; Medical imaging; Color calibration; Color management ID PERFORMANCE; LESIONS; IMAGES; CAMERA AB This article summarizes the consensus reached at the Summit on Color in Medical Imaging held at the Food and Drug Administration (FDA) on May 8-9, 2013, co-sponsored by the FDA and ICC (International Color Consortium). The purpose of the meeting was to gather information on how color is currently handled by medical imaging systems to identify areas where there is a need for improvement, to define objective requirements, and to facilitate consensus development of best practices. Participants were asked to identify areas of concern and unmet needs. This summary documents the topics that were discussed at the meeting and recommendations that were made by the participants. Key areas identified where improvements in color would provide immediate tangible benefits were those of digital microscopy, telemedicine, medical photography (particularly ophthalmic and dental photography), and display calibration. Work in these and other related areas has been started within several professional groups, including the creation of the ICC Medical Imaging Working Group. C1 [Badano, Aldo; Cheng, Wei-Chung] US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Revie, Craig] FFEI Ltd, London, England. [Revie, Craig] Int Color Consortium, London, England. [Casertano, Andrew] SAN Business Consultants LLP, New York, NY USA. [Green, Phil] Gjovik Univ Coll, Tromso, Norway. [Kimpe, Tom] Barco NV, Healthcare Div, Brussels, Belgium. [Krupinski, Elizabeth] Univ Arizona, Dept Med Imaging, Tucson, AZ USA. [Krupinski, Elizabeth] Univ Arizona, Arizona Telemed Program, Tucson, AZ USA. [Sisson, Christye] Rochester Inst Technol, Sch Photog Arts & Sci, Rochester, NY 14623 USA. [Skrovseth, Stein] Univ Hosp North Norway, Norwegian Ctr Integrated Care & Telemed, Tromso, Norway. [Treanor, Darren] Leeds Teaching Hosp NHS Trust, London, England. [Treanor, Darren] Univ Leeds, London, England. [Boynton, Paul] NIST, Gaithersburg, MD 20899 USA. [Clunie, David] PixelMed Publishing, Philadelphia, PA USA. [Flynn, Michael J.] Henry Ford Hlth Syst, New York, NY USA. [Heki, Tatsuo] Fujifilm Corp, Healthcare Business Dev Off, Tokyo, Japan. [Hewitt, Stephen] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Homma, Hiroyuki] Olympus Med Syst Corp, Tokyo, Japan. [Masia, Andy] X Rite, Boston, MA USA. [Matsui, Takashi] Eizo Corp, Tokyo, Japan. [Nagy, Balazs] Inst Psychol, Dept Expt Psychol, Sao Paulo, Brazil. [Nishibori, Masahiro] Int Univ Hlth & Welf, Dept Social Serv & Healthcare Management, Tokyo, Japan. [Penczek, John] NIST, Boulder, CO USA. [Penczek, John] Univ Colorado, Boulder, CO 80309 USA. [Schopf, Thomas] Univ Hosp North Norway, Norwegian Ctr Integrated Care & Telemed, Tromso, Norway. [Yokoi, Hideto] Kagawa Univ Hosp, Dept Med Informat, Tokyo, Japan. [Yagi, Yukako] Harvard Univ, Sch Med, Boston, MA USA. [Yagi, Yukako] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nagy, Balazs] Budapest Univ Technol & Econ, Ctr Neurosci & Behav, Budapest, Hungary. [Nagy, Balazs] Budapest Univ Technol & Econ, Dept Mechatron Opt & Engn Informat, Budapest, Hungary. RP Badano, A (reprint author), US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, 10993 New Hampshire Ave, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov RI NAGY, Balazs Vince/K-6546-2015; Clunie, David/Q-2777-2015; OI NAGY, Balazs Vince/0000-0002-8489-7200; Clunie, David/0000-0002-2406-1145; Skrovseth, Stein Olav/0000-0003-3568-867X; Hewitt, Stephen/0000-0001-8283-1788; badano, aldo/0000-0003-3712-6670 FU Research Council of Norway [174,934] FX SS and TS were funded by the Research Council of Norway grant no. 174,934, Tromso Telemedicine Laboratory. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 30 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0897-1889 EI 1618-727X J9 J DIGIT IMAGING JI J. Digit. Imaging PD FEB PY 2015 VL 28 IS 1 BP 41 EP 52 DI 10.1007/s10278-014-9721-0 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ7KO UT WOS:000348398200007 PM 25005868 ER PT J AU Quick, V McWilliams, R Byrd-Bredbenner, C AF Quick, V. McWilliams, R. Byrd-Bredbenner, C. TI A case-control study of current psychological well-being and weight-teasing history in young adults with and without bowel conditions SO JOURNAL OF HUMAN NUTRITION AND DIETETICS LA English DT Article DE bowel condition; psychological well-being; weight-teasing; young adults ID GENERALIZED ANXIETY DISORDER; QUALITY-OF-LIFE; RISK-FACTOR; DISEASE; DEPRESSION; ADOLESCENTS; POPULATION; IMPACT; SCALE; EPIDEMIOLOGY AB Background: The present study aimed to determine whether psychological well-being and weight-teasing history of young adults with bowel conditions (i.e. coeliac disease, inflammatory bowel diseases and irritable bowel syndrome) differed from those without bowel conditions. Methods: Young adults (aged 18-26 years) completed an online survey that collected demographic information and assessed psychological well-being (mentally and physically unhealthy days, self-esteem, and depression, anxiety and obsessive compulsive disorder severity) and weight-teasing history (Perception of Teasing Scale). Each bowel condition participant (cases = 135) was matched to four healthy participants (controls = 504) based on sex and body mass index (BMI) (+/- 0.50 BMI units). Conditional logistic regression analyses were conducted and odds ratios (OR) and 95% confidence intervals (CI) were presented for all measures and demographics. Results: Cases were significantly more likely to have poorer overall psychological well-being. Specifically, cases were significantly (P <= 0.05) more likely to have more mentally and physical unhealthy days, depression, anxiety, and obsessive compulsive disorder symptoms than controls. Cases were also significantly more likely to recall being weight teased as a child (P = 0.02, OR = 1.26, 95% CI = 1.04-1.53) and being more upset from the weight-teasing insults (P = 0.006, OR = 1.19, 95% CI = 1.05-1.35) than controls. Cases were also more than 1.5 times more likely to be made fun of (P = 0.03, OR = 1.63, 95% CI = 1.09-2.43) or laughed at (P = 0.01, OR = 1.77, 95% CI = 1.15-2.73) because of their weight than controls. Conclusions: The findings of the present study suggest that healthcare providers should monitor the psychological well-being of young adults with bowel conditions and incorporate opportunities for them to develop skills and strategies for coping. C1 [Quick, V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, DHHS, Bethesda, MD USA. [McWilliams, R.] Rutgers State Univ, Dept Human Ecol, New Brunswick, NJ 08903 USA. [Byrd-Bredbenner, C.] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. RP Quick, V (reprint author), NICHHD, Div Populat Hlth Res, NIH, DHHS, Bethesda, MD 20892 USA. EM gingermquick@gmail.com RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU Kappa Omicron Nu Research Fellowship; National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX The present study was funded by the Kappa Omicron Nu Research Fellowship and supported in part by the intramural research programme of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 62 TC 1 Z9 1 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3871 EI 1365-277X J9 J HUM NUTR DIET JI J. Hum. Nutr. Diet. PD FEB PY 2015 VL 28 IS 1 BP 28 EP 36 DI 10.1111/jhn.12202 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CA5AO UT WOS:000348919600003 PM 24387303 ER PT J AU Costello, RB Saldanha, L Dwyer, J Andrews, K Bailen, R Bailey, R Betz, J Burt, V Chang, F Emenaker, N Gahche, J Hardy, C Pehrsson, P AF Costello, R. B. Saldanha, L. Dwyer, J. Andrews, K. Bailen, R. Bailey, R. Betz, J. Burt, V Chang, F. Emenaker, N. Gahche, J. Hardy, C. Pehrsson, P. TI NEW NATIONAL INSTITUTES OF HEALTH DIETARY SUPPLEMENT LABEL DATABASE CAN AID SEARCH FOR INGREDIENT INFORMATION SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 26-28, 2015 CL New Orleans, LA SP Amer Federat Med Res C1 [Costello, R. B.; Saldanha, L.; Dwyer, J.; Bailen, R.; Bailey, R.; Betz, J.; Chang, F.; Emenaker, N.] NIH, Bethesda, MD 20892 USA. [Andrews, K.; Pehrsson, P.] USDA, Beltsville, MD 20705 USA. [Burt, V; Gahche, J.] Ctr Dis Control & Prevent, Hyattsville, MD USA. [Hardy, C.] US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2015 VL 63 IS 2 MA 218 BP 386 EP 386 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CA0GM UT WOS:000348595000229 ER PT J AU Ertunc, ME Sikkeland, J Fenaroli, F Griffiths, G Daniels, MP Cao, HM Saatcioglu, F Hotamisligil, GS AF Ertunc, Meric Erikci Sikkeland, Jorgen Fenaroli, Federico Griffiths, Gareth Daniels, Mathew P. Cao, Haiming Saatcioglu, Fahri Hotamisligil, Goekhan S. TI Secretion of fatty acid binding protein aP2 from adipocytes through a nonclassical pathway in response to adipocyte lipase activity SO JOURNAL OF LIPID RESEARCH LA English DT Article DE adipokine; adipose triglyceride lipase; obesity; hormone-sensitive lipase; lipolysis; hormone ID ADIPOSE TRIGLYCERIDE LIPASE; HORMONE-SENSITIVE LIPASE; INSULIN-RESISTANCE; METABOLIC SYNDROME; APOLIPOPROTEIN-E; ENDOCRINE ORGAN; DEFICIENT MICE; HEART-DISEASE; OBESITY; TISSUE AB Adipocyte fatty acid binding protein 4, aP2, contributes to the pathogenesis of several common diseases including type 2 diabetes, atherosclerosis, fatty liver disease, asthma, and cancer. Although the biological functions of aP2 have classically been attributed to its intracellular action, recent studies demonstrated that aP2 acts as an adipokine to regulate systemic metabolism. However, the mechanism and regulation of aP2 secretion remain unknown. Here, we demonstrate a specific role for lipase activity in aP2 secretion from adipocytes in vitro and ex vivo. Our results show that chemical inhibition of lipase activity, genetic deficiency of adipose triglyceride lipase and, to a lesser extent, hormone-sensitive lipase blocked aP2 secretion from adipocytes. Increased lipolysis and lipid availability also contributed to aP2 release as determined in perilipin1-deficient adipose tissue explants ex vivo and upon treatment with lipids in vivo and in vitro. In addition, we identify a nonclassical route for aP2 secretion in exosome-like vesicles and show that aP2 is recruited to this pathway upon stimulation of lipolysis. Given the effect of circulating aP2 on glucose metabolism, these data support that targeting aP2 or the lipolysis-dependent secretory pathway may present novel mechanistic and translational opportunities in metabolic disease. C1 [Ertunc, Meric Erikci; Hotamisligil, Goekhan S.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Ertunc, Meric Erikci; Hotamisligil, Goekhan S.] Harvard Univ, Sch Publ Hlth, Sabri Ulker Ctr, Boston, MA 02115 USA. [Sikkeland, Jorgen; Fenaroli, Federico; Griffiths, Gareth; Saatcioglu, Fahri] Univ Oslo, Dept Biosci, Oslo, Norway. [Daniels, Mathew P.; Cao, Haiming] NHLBI, NIH, Bethesda, MD 20892 USA. RP Hotamisligil, GS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM ghotamis@hsph.harvard.edu RI Cao, Haiming/P-4634-2016 FU National Institutes of Health [DK064360, R90 DK071507]; Harvard Merit/Term Time Research Fellowship (John Parker Bequest Award); Norwegian Research Council; Norwegian Cancer Society FX This work is supported in part by National Institutes of Health Grant DK064360 (G.S.H.). M.E.E. was supported by the Roadmap Grant R90 DK071507 from the National Institutes of Health and the Harvard Merit/Term Time Research Fellowship (John Parker Bequest Award). F.S. and J.S. are supported by grants from the Norwegian Research Council and Norwegian Cancer Society. NR 63 TC 23 Z9 23 U1 3 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 2015 VL 56 IS 2 BP 423 EP 434 DI 10.1194/jlr.M055798 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CA4VR UT WOS:000348905000021 PM 25535287 ER PT J AU Allister, CA Liu, LF Lamendola, CA Craig, CM Cushman, SW Hellerstein, MK McLaughlin, TL AF Allister, Candice A. Liu, Li-fen Lamendola, Cindy A. Craig, Colleen M. Cushman, Samuel W. Hellerstein, Marc K. McLaughlin, Tracey L. TI In vivo (H2O)-H-2 administration reveals impaired triglyceride storage in adipose tissue of insulin-resistant humans SO JOURNAL OF LIPID RESEARCH LA English DT Article DE obesity; insulin resistance; subcutaneous adipose; triglycerides; de novo; lipogenesis; lipolysis ID OBESE INDIVIDUALS; NONDIABETIC WOMEN; ADIPOGENESIS; FAT; METABOLISM; LIPOLYSIS; TURNOVER; DISEASE; CELLS AB Indirect evidence suggests that impaired triglyceride storage in the subcutaneous fat depot contributes to the development of insulin resistance via lipotoxicity. We directly tested this hypothesis by measuring, in vivo, TG synthesis, de novo lipogenesis (DNL), adipocyte proliferation, and insulin suppression of lipolysis in subcutaneous adipose tissue of BMI-matched individuals classified as insulin resistant (IR) or insulin sensitive (IS). Nondiabetic, moderately obese subjects with BMI 25-35 kg/m(2), classified as IR or IS by the modified insulin suppression test, consumed deuterated water ((H2O)-H-2) for 4 weeks. Deuterium incorporation into glycerol, palmitate, and DNA indicated TG synthesis, DNL, and adipocyte proliferation, respectively. Net TG synthesis and DNL in adipose cells were significantly lower in IR as compared with IS subjects, whereas adipocyte proliferation did not differ significantly. Plasma FFAs measured during an insulin suppression test were 2.5-fold higher in IR subjects, indicating resistance to insulin suppression of lipolysis. Adipose TG synthesis correlated directly with DNL but not with proliferation. These results provide direct in vivo evidence for impaired TG storage in subcutaneous adipose tissue of IR as compared with IS. Relative inability to store TG in the subcutaneous depot may represent a mechanism contributing to the development of insulin resistance in the setting of obesity. C1 [Allister, Candice A.; Hellerstein, Marc K.] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. [Liu, Li-fen; Lamendola, Cindy A.; Craig, Colleen M.; McLaughlin, Tracey L.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Cushman, Samuel W.] Natl Inst Digest Dis & Kidney Dis, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD USA. RP Allister, CA (reprint author), Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. EM callister@berkeley.edu FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK080436, R01DK071309] FX This work was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grants R01 DK080436 and R01DK071309. NR 16 TC 1 Z9 1 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 2015 VL 56 IS 2 BP 435 EP 439 DI 10.1194/jlr.M052860 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CA4VR UT WOS:000348905000022 PM 25418322 ER PT J AU Wakabayashi, KT Myal, SE Kiyatkin, EA AF Wakabayashi, Ken T. Myal, Stephanie E. Kiyatkin, Eugene A. TI Fluctuations in nucleus accumbens extracellular glutamate and glucose during motivated glucose-drinking behavior: dissecting the neurochemistry of reward SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE brain metabolism; electrochemistry; metabolic reward; motivated behavior; sensory reward ID FREELY MOVING RATS; DISCRIMINATIVE STIMULUS TASK; STRIATAL NEURONAL-ACTIVITY; NATURAL AROUSING STIMULI; INTRAVENOUS COCAINE; RAPID CHANGES; BRAIN; DOPAMINE; RELEASE; MICRODIALYSIS AB While motivated behavior involves multiple neurochemical systems, few studies have focused on the role of glutamate, the brain's excitatory neurotransmitter, and glucose, the energetic substrate of neural activity in reward-related neural processes. Here, we used high-speed amperometry with enzyme-based substrate-sensitive and control, enzyme-free biosensors to examine second-scale fluctuations in the extracellular levels of these substances in the nucleus accumbens shell during glucose-drinking behavior in trained rats. Glutamate rose rapidly after the presentation of a glucose-containing cup and before the initiation of drinking (reward seeking), decreased more slowly to levels below baseline during consumption (sensory reward), and returned to baseline when the ingested glucose reached the brain (metabolic reward). When water was substituted for glucose, glutamate rapidly increased with cup presentation and in contrast to glucose drinking, increased above baseline after rats tasted the water and refused to drink further. Therefore, extracellular glutamate show distinct changes associated with key events of motivated drinking behavior and opposite dynamics during sensory and metabolic components of reward. In contrast to glutamate, glucose increased at each stimulus and behavioral event, showing a sustained elevation during the entire behavior and a robust post-ingestion rise that correlated with the gradual return of glutamate levels to their baseline. By comparing active drinking with passive intra-gastric glucose delivery, we revealed that fluctuations in extracellular glucose are highly dynamic, reflecting a balance between rapid delivery because of neural activity, intense metabolism, and the influence of ingested glucose reaching the brain. C1 [Wakabayashi, Ken T.; Myal, Stephanie E.; Kiyatkin, Eugene A.] NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU NIDA-IRP, NIH [DA000566-05] FX This study was supported by the Intramural Research Program of NIDA-IRP, NIH (grant number DA000566-05). The Authors declare no competitive interests in relation to the work described. EAK supervised the project, KTW, SEM, and EAK performed experiments, wrote the manuscript and have approved the submission of this version. NR 59 TC 8 Z9 8 U1 0 U2 2 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 FEB PY 2015 VL 132 IS 3 BP 327 EP 341 DI 10.1111/jnc.12993 PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CA2AU UT WOS:000348712200007 PM 25393775 ER PT J AU Walling, AM Weeks, JC Kahn, KL Tisnado, D Keating, NL Dy, SM Arora, NK Mack, JW Pantoja, PM Malin, JL AF Walling, Anne M. Weeks, Jane C. Kahn, Katherine L. Tisnado, Diana Keating, Nancy L. Dy, Sydney M. Arora, Neeraj K. Mack, Jennifer W. Pantoja, Philip M. Malin, Jennifer L. TI Symptom Prevalence in Lung and Colorectal Cancer Patients SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Cancer; symptoms; prevalence; colorectal neoplasms; lung neoplasms ID LONGITUDINAL FOLLOW-UP; CARE OUTCOMES RESEARCH; PERFORMANCE STATUS; REPORTED OUTCOMES; PALLIATIVE CARE; ONCOLOGY; PAIN; MANAGEMENT; LIFE; INTERVENTIONS AB Context.. Relatively few data are available about symptoms among cancer patients. Objectives. To describe the prevalence and severity of symptoms among a large, representative cohort of newly diagnosed cancer patients. Methods. We collected survey data about symptoms (pain, fatigue, depression, nausea/vomiting, cough, dyspnea, and diarrhea) from 5422 patients with incident lung and colorectal cancer from the diverse, nationally representative Cancer Care Outcomes Research and Surveillance Consortium cohort. We described the prevalence of any symptoms and moderate/severe symptoms approximately four to six months after diagnosis. We used logistic regression to identify patient and clinical characteristics associated with symptoms, and calculated adjusted proportions of patients with symptoms. Results. In total, 5067 (93.5%) patients reported at least one symptom in the four weeks before their survey, with 51% reporting at least one moderate/severe symptom. Lung cancer patients reported more symptoms than colorectal cancer patients. Patients who received treatment or had more comorbidities were more likely to report symptoms. For example, after adjustment, patients who received chemotherapy during the six weeks before the survey were more likely than others to report at least one symptom (97.3% vs. 90.8%, P < 0.001), and at least one moderate/severe symptom (56.8% vs. 46.2%, P < 0.001). After adjustment, early-vs. late-stage patients did not differ in reports of at least one symptom (93.6% vs. 93.4%, P = 0.853) and differed only slightly in reports of at least one moderate/severe symptom (53.3% vs. 49.6%, P = 0.009). Conclusion. Most recently diagnosed lung and colorectal cancer patients have cancer-related symptoms regardless of stage, and more than half have at least one moderate/severe symptom. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. C1 [Walling, Anne M.; Kahn, Katherine L.; Tisnado, Diana] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90024 USA. [Walling, Anne M.; Kahn, Katherine L.; Tisnado, Diana] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Walling, Anne M.; Tisnado, Diana; Pantoja, Philip M.; Malin, Jennifer L.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Walling, Anne M.; Kahn, Katherine L.] RAND Hlth, Santa Monica, CA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Weeks, Jane C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Weeks, Jane C.] Harvard Univ, Sch Med, Dept Hlth Policy & Management, Boston, MA USA. [Weeks, Jane C.; Mack, Jennifer W.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Dy, Sydney M.] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. [Arora, Neeraj K.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. RP Walling, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, 911 Broxton Plaza, Los Angeles, CA 90024 USA. EM awalling@mednet.ucla.edu FU NCATS NIH HHS [U54 TR000123, UL1 TR000124, UL1TR000123]; NCI NIH HHS [U01 CA093348, R01 CA164021, R011CA164021-01A1, U01 CA093324, U01 CA093326, U01 CA093329, U01 CA093332, U01 CA093339, U01 CA093344]; NIA NIH HHS [L30 AG030993] NR 50 TC 11 Z9 11 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2015 VL 49 IS 2 BP 192 EP 202 DI 10.1016/j.jpainsymman.2014.06.003 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AZ8PU UT WOS:000348478200004 PM 24973624 ER PT J AU Levine, D Mandrell, B Symons, H Wendler, D Baker, J AF Levine, Deena Mandrell, Belinda Symons, Heather Wendler, Dave Baker, Justin TI Evaluating Supportive Care for Children with Cancer: A Multi-Institutional Survey Study of Pediatric Oncology Patients and Parents SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY FEB 25-28, 2015 CL Philadelphia, PA SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Levine, Deena; Mandrell, Belinda; Baker, Justin] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Symons, Heather] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Wendler, Dave] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2015 VL 49 IS 2 MA TH346-C BP 350 EP 350 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AZ8PU UT WOS:000348478200049 ER PT J AU Webb, J Weckmann, M Padgett, L AF Webb, Jason Weckmann, Michelle Padgett, Lynne TI Integrating Psychosocial Quality Indicators into Hospice and Palliative Care Programs SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY FEB 25-28, 2015 CL Philadelphia, PA SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Webb, Jason] Duke Univ, Duke Palliat Care, Durham, NC USA. [Weckmann, Michelle] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Padgett, Lynne] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2015 VL 49 IS 2 MA SA546 BP 406 EP 406 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AZ8PU UT WOS:000348478200160 ER PT J AU Grayson, PC AF Grayson, Peter C. TI Lumpers and Splitters: Ongoing Issues in the Classification of Large Vessel Vasculitis SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID GIANT-CELL ARTERITIS; POSITRON-EMISSION-TOMOGRAPHY; COMPLICATION AORTIC-ANEURYSM; TAKAYASU ARTERITIS; INVOLVEMENT; CRITERIA; DISSECTION; SONOGRAPHY; STENOSIS; DISEASES C1 [Grayson, Peter C.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, US Natl Inst Hlth, Vasculitis Translat Res Program, Bethesda, MD USA. RP Grayson, PC (reprint author), NIH, 10 Ctr Dr,Bldg 10,6N Rm 216G, Bethesda, MD 20892 USA. EM peter.grayson@nih.gov NR 21 TC 2 Z9 2 U1 0 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 2015 VL 42 IS 2 BP 149 EP 151 DI 10.3899/jrheum.141376 PG 3 WC Rheumatology SC Rheumatology GA CA6NT UT WOS:000349032200003 PM 25641963 ER PT J AU Rennspiess, D Pujari, S Keijzers, M Abdul-Hamid, MA Hochstenbag, M Dingemans, AM Kurz, AK Speel, EJ Haugg, A Pastrana, DV Buck, CB De Baets, MH zur Hausen, A AF Rennspiess, Dorit Pujari, Sreedhar Keijzers, Marlies Abdul-Hamid, Myrurgia A. Hochstenbag, Monique Dingemans, Anne-Marie Kurz, Anna Kordelia Speel, Ernst-Jan Haugg, Anke Pastrana, Diana V. Buck, Christopher B. De Baets, Marc H. zur Hausen, Axel TI Detection of Human Polyomavirus 7 in Human Thymic Epithelial Tumors SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Human polyomavirus 7; thymomas; thymic follicular hyperplasia; viral tumorigenesis; myasthenia gravis ID EPSTEIN-BARR-VIRUS; MERKEL CELL POLYOMAVIRUS; IN-SITU HYBRIDIZATION; MYASTHENIA-GRAVIS THYMUS; LYMPHOID HYPERPLASIA; GENOME; INFECTION; CARCINOMA; ABSENCE; IDENTIFICATION AB Introduction: Although the molecular genetics possibly underlying the pathogenesis of human thymoma have been extensively studied, its etiology remains poorly understood. Because murine polyomavirus consistently induces thymomas in mice, we assessed the presence of the novel human polyomavirus 7 (HPyV7) in human thymic epithelial tumors. Methods: HPyV7-DNA Fluorescence in situ hybridization (FISH), DNA-polymerase chain reaction (PCR), and immunohistochemistry (IHC) were performed in 37 thymomas. Of these, 26 were previously diagnosed with myasthenia gravis (MG). In addition, 20 thymic hyperplasias and 20 fetal thymic tissues were tested. Results: HPyV7-FISH revealed specific nuclear hybridization signals within the neoplastic epithelial cells of 23 thymomas (62.2%). With some exceptions, the HPyV7-FISH data correlated with the HPyV7-DNA PCR. By IHC, large T antigen expression of HPyV7 was detected, and double staining confirmed its expression in the neoplastic epithelial cells. Eighteen of the 26 MG-positive and 7 of the 11 MG-negative thymomas were HPyV7-positive. Of the 20 hyperplastic thymi, 40% were HPyV7-positive by PCR as confirmed by FISH and IHC in the follicular lymphocytes. All 20 fetal thymi tested HPyV7-negative. Conclusions: The presence of HPyV7-DNA and large T antigen expression in the majority of thymomas possibly link HPyV7 to human thymomagenesis. Further investigations are needed to elucidate the possible associations of HPyV7 and MG. C1 [Rennspiess, Dorit; Pujari, Sreedhar; Abdul-Hamid, Myrurgia A.; Speel, Ernst-Jan; Haugg, Anke; zur Hausen, Axel] Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, Dept Pathol, NL-6202 AZ Maastricht, Netherlands. [Keijzers, Marlies] Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, Dept Cardiothorac Surg, NL-6202 AZ Maastricht, Netherlands. [Keijzers, Marlies; Hochstenbag, Monique; Dingemans, Anne-Marie] Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, Dept Pulmonol, NL-6202 AZ Maastricht, Netherlands. [Kurz, Anna Kordelia] Univ Hosp Aachen, Dept Internal Med 4, Aachen, Germany. [Pastrana, Diana V.; Buck, Christopher B.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. [De Baets, Marc H.] Maastricht Univ, Sch Mental Hlth & Neurosci MHeNS, Dept Neurosci, NL-6202 AZ Maastricht, Netherlands. RP zur Hausen, A (reprint author), Maastricht Univ, Med Ctr, Dept Pathol, P Debyelaan 25,POB 5800, NL-6202 AZ Maastricht, Netherlands. EM axel.zurhau-sen@mumc.nl OI Buck, Christopher/0000-0003-3165-8094 FU Intramural NIH HHS [Z99 CA999999] NR 30 TC 10 Z9 11 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD FEB PY 2015 VL 10 IS 2 BP 360 EP 366 DI 10.1097/JTO.0000000000000390 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CA3TM UT WOS:000348829400023 PM 25526237 ER PT J AU Thomas, A Rajan, A Berman, A Giaccone, G AF Thomas, Anish Rajan, Arun Berman, Arlene Giaccone, Giuseppe TI Multiorgan Autoimmune Manifestations Associated with Thymoma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article ID AIRE C1 [Thomas, Anish; Rajan, Arun; Berman, Arlene] NCI, GI Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Giaccone, Giuseppe] Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20057 USA. RP Giaccone, G (reprint author), Georgetown Univ, Lombardi Canc Ctr, Res Bldg Room W503,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM gg496@georgetown.edu RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Thomas, Anish/0000-0003-3293-3115 FU Intramural Research Program of the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institutes of Health. All the authors declare no conflict of interest. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD FEB PY 2015 VL 10 IS 2 BP E5 EP E7 DI 10.1097/JTO.0000000000000324 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CA3TM UT WOS:000348829400001 PM 25611232 ER PT J AU Nichols, B Jog, P Lee, JH Blackler, D Wilmot, M D'Agati, V Markowitz, G Kopp, JB Alperl, SL Pollak, MR Friedman, DJ AF Nichols, Brendan Jog, Prachi Lee, Jessica H. Blackler, Daniel Wilmot, Michael D'Agati, Vivette Markowitz, Glen Kopp, Jeffrey B. Alperl, Seth L. Pollak, Martin R. Friedman, David J. TI Innate immunity pathways regulate the nephropathy gene Apolipoprotein L1 SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; expression; focal segmental glomerulosclerosis; gene; inflammation ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; TOLL-LIKE RECEPTORS; COLLAPSING GLOMERULOPATHY; AFRICAN-AMERICANS; KIDNEY-DISEASE; CELL-DEATH; IFN-ALPHA; L-I; APOL1; VARIANTS AB Apolipoprotein L1 (APOL1) risk variants greatly elevate the risk of kidney disease in African Americans. Here we report a cohort of patients who developed collapsing focal segmental glomerulosclerosis while receiving therapeutic interferon, all of whom carried the APOL1 high-risk genotype. This finding raised the possibility that interferons and the molecular pattern recognition receptors that stimulate interferon production may contribute to APOL1-associated kidney disease. In cell culture, interferons and Toll-like receptor (TLR) agonists increased APOL1 expression by up to 200-fold, in some cases with the appearance of transcripts not detected under basal conditions. Polyl:C, a double-stranded RNA TLR3 agonist, increased APOL1 expression by upregulating interferons directly or through an interferon-independent, IFN-regulatory factor 3 (IRF3)-dependent pathway. Using pharmacological inhibitors, small hairpin RNA knockdown, and chromatin immunoprecipitation, we found that the interferon-independent TLR3 pathway relied on signaling through TBK1, NF-kappa B, and Jak kinases, and on binding of IRF1, IRF2, and STAT2 at the APOL1 transcription start site. We also demonstrate that overexpression of the APOL1 risk variants is more injurious to cells than overexpression of the wild-type APOL1 protein. Our study illustrates that antiviral pathways may be important inducers of kidney disease in individuals with the APOL1 high-risk genotype and identifies potential targets for prevention or treatment. C1 [Nichols, Brendan; Jog, Prachi; Lee, Jessica H.; Blackler, Daniel; Wilmot, Michael; Alperl, Seth L.; Pollak, Martin R.; Friedman, David J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Renal, Boston, MA 02215 USA. [Nichols, Brendan; Jog, Prachi; Lee, Jessica H.; Blackler, Daniel; Wilmot, Michael; Friedman, David J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Vasc Biol Res, Boston, MA 02215 USA. [D'Agati, Vivette; Markowitz, Glen] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. [Kopp, Jeffrey B.] NIH, Kidney Dis Branch, Bethesda, MD 20892 USA. [Pollak, Martin R.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Friedman, DJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave, Boston, MA 02215 USA. EM dfriedma@bidmc.harvard.edu OI Kopp, Jeffrey/0000-0001-9052-186X FU Doris Duke Charitable Foundation [2011035]; Satellite Healthcare Foundation; National Institutes of Health/Institute of Minority Health Studies [MD007092-01]; National Institutes of Diabetes and Digestive and Kidney Diseases Intramural Research Program; Doris Duke CSD Award FX This work was supported by the Doris Duke Charitable Foundation Grant 2011035 (DJF), a Norman Coplon Award from Satellite Healthcare Foundation (DJF), the National Institutes of Health/Institute of Minority Health Studies (MD007092-01, MRP), and supported in part by the National Institutes of Diabetes and Digestive and Kidney Diseases Intramural Research Program (JBK). DJF is a recipient of the Doris Duke CSD Award. We gratefully acknowledge expert advice from John Doench and David Root at the Broad Institute shRNA platform. Data included in this report were presented at the American Society of Nephrology Renal Week in Atlanta, GA, USA (10 November 2013). NR 34 TC 48 Z9 52 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2015 VL 87 IS 2 BP 332 EP 342 DI 10.1038/ki.2014.270 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA CA5UH UT WOS:000348972800014 PM 25100047 ER PT J AU Madan, R Dahut, WL AF Madan, Ravi Dahut, William L. TI Abiraterone's efficacy confirmed; time to aim higher SO LANCET ONCOLOGY LA English DT Editorial Material ID METASTATIC PROSTATE-CANCER; ENZALUTAMIDE; CHEMOTHERAPY; ACETATE; THERAPY C1 [Madan, Ravi; Dahut, William L.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Madan, R (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. EM madanr@mail.nih.gov NR 9 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD FEB PY 2015 VL 16 IS 2 BP 119 EP 121 DI 10.1016/S1470-2045(15)70005-7 PG 4 WC Oncology SC Oncology GA CA3YR UT WOS:000348841700019 PM 25601338 ER PT J AU Farooqui, MZH Valdez, J Martyr, S Aue, G Saba, N Niemann, CU Herman, SEM Tian, X Marti, G Soto, S Hughes, TE Jones, J Lipsky, A Pittaluga, S Stetler-Stevenson, M Yuan, C Lee, YS Pedersen, LB Geisler, CH Calvo, KR Arthur, DC Maric, I Childs, R Young, NS Wiestner, A AF Farooqui, Mohammed Z. H. Valdez, Janet Martyr, Sabrina Aue, Georg Saba, Nakhle Niemann, Carsten U. Herman, Sarah E. M. Tian, Xin Marti, Gerald Soto, Susan Hughes, Thomas E. Jones, Jade Lipsky, Andrew Pittaluga, Stefania Stetler-Stevenson, Maryalice Yuan, Constance Lee, Yuh Shan Pedersen, Lone B. Geisler, Christian H. Calvo, Katherine R. Arthur, Diane C. Maric, Irina Childs, Richard Young, Neal S. Wiestner, Adrian TI Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial SO LANCET ONCOLOGY LA English DT Article ID INITIAL THERAPY; ELDERLY-PATIENTS; 17P DELETION; OPEN-LABEL; RITUXIMAB; CLL; BTK; CYCLOPHOSPHAMIDE; PROLIFERATION; ALEMTUZUMAB AB Background Patients with chronic lymphocytic leukaemia (CLL) with TP53 aberrations respond poorly to first-line chemoimmunotherapy, resulting in early relapse and short survival. We investigated the safety and activity of ibrutinib in previously untreated and relapsed or refractory CLL with TP53 aberrations. Methods In this investigator-initiated, single-arm phase 2 study, we enrolled eligible adult patients with active CLL with TP53 aberrations at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Patients received 28-day cycles of ibrutinib 420 mg orally once daily until disease progression or the occurrence of limiting toxicities. The primary endpoint was overall response to treatment at 24 weeks in all evaluable patients. This study is registered with ClinicalTrials.gov, number NCT01500733, and is fully enrolled. Findings Between Dec 22, 2011, and Jan 2, 2014, we enrolled 51 patients; 47 had CLL with deletion 17p13.1 and four carried a TP53 mutation in the absence of deletion 17p13.1. All patients had active disease requiring therapy. 35 enrolled patients had previously untreated CLL and 16 had relapsed or refractory disease. Median follow-up was 24 months (IQR 12.9-27.0). 33 previously untreated patients and 15 patients with relapsed or refractory CLL were evaluable for response at 24 weeks. 32 (97%; 95% CI 86-100) of 33 previously untreated patients achieved an objective response, including partial response in 18 patients (55%) and partial response with lymphocytosis in 14 (42%). One patient had progressive disease at 0.4 months. 12 (80%; 95% CI 52-96) of the 15 patients with relapsed or refractory CLL had an objective response: six (40%) achieved a partial response and six (40%) a partial response with lymphocytosis; the remaining three (20%) patients had stable disease. Grade 3 or worse treatment-related adverse events were neutropenia in 12 (24%) patients (grade 4 in one [2%] patient), anaemia in seven (14%) patients, and thrombocytopenia in five (10%) patients (grade 4 in one [2%] patient). Grade 3 pneumonia occurred in three (6%) patients, and grade 3 rash in one (2%) patient. Interpretation The activity and safety profile of single-agent ibrutinib in CLL with TP53 aberrations is encouraging and supports its consideration as a novel treatment option for patients with this high-risk disease in both first-line and second-line settings. C1 [Farooqui, Mohammed Z. H.; Valdez, Janet; Martyr, Sabrina; Aue, Georg; Saba, Nakhle; Niemann, Carsten U.; Herman, Sarah E. M.; Marti, Gerald; Soto, Susan; Jones, Jade; Lipsky, Andrew; Lee, Yuh Shan; Childs, Richard; Young, Neal S.; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Tian, Xin] NHLBI, Office Biostat Res, NIH, Bethesda, MD 20892 USA. [Hughes, Thomas E.] NHLBI, Ctr Clin, Dept Pharm, NIH, Bethesda, MD 20892 USA. [Jones, Jade] NHLBI, Med Scholars Res Program, NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania; Stetler-Stevenson, Maryalice; Yuan, Constance; Arthur, Diane C.] NCI, Ctr Canc Res, Pathol Lab, NIH, Bethesda, MD USA. [Calvo, Katherine R.; Maric, Irina] CRC, Dept Lab Med, NIH, Bethesda, MD USA. [Pedersen, Lone B.; Geisler, Christian H.] Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark. RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM wiestnera@mail.nih.gov RI Niemann, Carsten/P-3497-2015 OI Niemann, Carsten/0000-0001-9880-5242 FU Intramural Research Program of the National Heart, Lung, and Blood Institute; National Cancer Institute (National Institutes of Health); Pharmacyclics Inc FX This work was funded by the Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Cancer Institute (National Institutes of Health). Pharmacyclics Inc provided the study drug and research support. We thank the patients who participated in this trial and their families; Ajunae Wells, Jennifer Gyamfi, Stephanie Housel, Adrian Byrnes, Milena Kirilyuk, and Allison Wise for protocol support; Judith Starling for pharmacy support; Francine Thomas for imaging analysis; Tatyana Sarkisova, Jocelyn Bailey, and Sindhuja Edara for data management; and Olha Katynska, Inna Churbanova, Arman Sabet Kashani, and Jae Hyung Chang for clinical trial monitoring. NR 30 TC 101 Z9 101 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD FEB PY 2015 VL 16 IS 2 BP 169 EP 176 DI 10.1016/S1470-2045(14)71182-9 PG 8 WC Oncology SC Oncology GA CA3YR UT WOS:000348841700033 PM 25555420 ER PT J AU Thomas, A Rajan, A Berman, A Tomita, Y Brzezniak, C Lee, MJ Lee, S Ling, A Spittler, AJ Carter, CA Guha, U Wang, Y Szabo, E Meltzer, P Steinberg, SM Trepel, JB Loehrer, PJ Giaccone, G AF Thomas, Anish Rajan, Arun Berman, Arlene Tomita, Yusuke Brzezniak, Christina Lee, Min-Jung Lee, Sunmin Ling, Alexander Spittler, Aaron J. Carter, Corey A. Guha, Udayan Wang, Yisong Szabo, Eva Meltzer, Paul Steinberg, Seth M. Trepel, Jane B. Loehrer, Patrick J. Giaccone, Giuseppe TI Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial SO LANCET ONCOLOGY LA English DT Article ID TYROSINE KINASE INHIBITOR; ENDOTHELIAL-GROWTH-FACTOR; EPITHELIAL TUMORS; IMMUNE SUPPRESSION; EXPRESSION; CELLS; RECURRENT; CANCER; OUTCOMES; BLOOD AB Background No standard treatments are available for advanced thymic epithelial tumours after failure of platinum-based chemotherapy. We investigated the activity of sunitinib, an orally administered tyrosine kinase inhibitor. Methods Between May 15, 2012, and Oct 2, 2013, we did an open-label phase 2 trial in patients with histologically confirmed chemotherapy-refractory thymic epithelial tumours. Patients were eligible if they had disease progression after at least one previous regimen of platinum-containing chemotherapy, an Eastern Cooperative Oncology Group performance status of two or lower, measurable disease, and adequate organ function. Patients received 50 mg of sunitinib orally once a day, in 6-week cycles (ie, 4 weeks of treatment followed by 2 weeks without treatment), until tumour progression or unacceptable toxic effects arose. The primary endpoint was investigator-assessed best tumour response at any point, which we analysed separately in thymoma and thymic carcinoma cohorts. Patients who had received at least one cycle of treatment and had their disease reassessed were included in the analyses of response. The trial was registered with ClinicalTrials.gov, number NCT01621568. Findings 41 patients were enrolled, 25 with thymic carcinoma and 16 with thymoma. One patient with thymic carcinoma was deemed ineligible after enrolment and did not receive protocol treatment. Of patients who received treatment, one individual with thymic carcinoma was not assessable because she died. Median follow-up on trial was 17 months (IQR 14.0-18.4). Of 23 assessable patients with thymic carcinoma, six (26%, 90% CI 12.1-45.3, 95% CI 10.2-48.4) had partial responses, 15 (65%, 95% CI 42.7-83.6) achieved stable disease, and two (9%, 1.1-28.0) had progressive disease. Of 16 patients with thymoma, one (6%, 95% CI 0.23-0.2) had a partial response, 12 (75%, 47.6-92.7) had stable disease, and three (19%, 4.1-45.7) had progressive disease. The most common grade 3 and 4 treatment-related adverse events were lymphocytopenia (eight [20%] of 40 patients), fatigue (eight [20%]), and oral mucositis (eight [20%]). Five (13%) patients had decreases in left-ventricular ejection fraction, of which three (8%) were grade 3 events. Three (8%) patients died during treatment, including one individual who died of cardiac arrest that was possibly treatment-related. Interpretation Sunitinib is active in previously treated patients with thymic carcinoma. Further studies are needed to identify potential biomarkers of activity. C1 [Thomas, Anish; Rajan, Arun; Berman, Arlene; Guha, Udayan] NCI, Thorac & GI Oncol Branch, NIH, Bethesda, MD USA. [Tomita, Yusuke; Lee, Min-Jung; Lee, Sunmin; Trepel, Jane B.] NCI, Dev Therapeut Branch, NIH, Bethesda, MD USA. [Ling, Alexander] NCI, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD USA. [Szabo, Eva] NCI, Canc Prevent Div, NIH, Bethesda, MD USA. [Meltzer, Paul] NCI, Genet Branch, NIH, Bethesda, MD USA. [Steinberg, Seth M.] NCI, Ctr Canc Res, Biostat & Data Management Sect, NIH, Bethesda, MD USA. [Brzezniak, Christina; Carter, Corey A.] Walter Reed Natl Mil Med Ctr, Dept Hematol & Oncol, Bethesda, MD USA. [Spittler, Aaron J.; Loehrer, Patrick J.] Indiana Univ, Med Ctr, Div Hematol Oncol, Indianapolis, IN USA. [Wang, Yisong; Giaccone, Giuseppe] Georgetown Univ, Lombardi Canc Ctr, Div Hematol Oncol, Washington, DC USA. RP Giaccone, G (reprint author), Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20057 USA. EM gg496@georgetown.edu RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Thomas, Anish/0000-0003-3293-3115 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute (NCI), Center for Cancer Research; Cancer Therapy Evaluation Program (CTEP), NCI FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (NCI), Center for Cancer Research. The study was funded by the Cancer Therapy Evaluation Program (CTEP), NCI. Sunitinib was provided by Pfizer and distributed by CTEP. We thank the patients who took part, Pamela Harris (CTEP, NCI), and Nancy Mansell (Protocol Support Office, NCI). NR 32 TC 28 Z9 28 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD FEB PY 2015 VL 16 IS 2 BP 177 EP 186 DI 10.1016/S1470-2045(14)71181-7 PG 10 WC Oncology SC Oncology GA CA3YR UT WOS:000348841700034 PM 25592632 ER PT J AU Huang, C Petibon, Y Ouyang, J Reese, TG Ahlman, MA Bluemke, DA El Fakhri, G AF Huang, Chuan Petibon, Yoann Ouyang, Jinsong Reese, Timothy G. Ahlman, Mark A. Bluemke, David A. El Fakhri, Georges TI Accelerated acquisition of tagged MRI for cardiac motion correction in simultaneous PET-MR: Phantom and patient studies SO MEDICAL PHYSICS LA English DT Article DE simultaneous PET-MR; motion correction; cardiac PET; cardiac motion; tagged MR ID RESPIRATORY MOTION; MYOCARDIAL-PERFUSION; GATED PET; COMPENSATION; RECONSTRUCTION; FOCUSS; SENSE; ARRAY; CT AB Purpose: Degradation of image quality caused by cardiac and respiratory motions hampers the diagnostic quality of cardiac PET. It has been shown that improved diagnostic accuracy of myocardial defect can be achieved by tagged MR (tMR) based PET motion correction using simultaneous PET-MR. However, one major hurdle for the adoption of tMR-based PET motion correction in the PET-MR routine is the long acquisition time needed for the collection of fully sampled tMR data. In this work, the authors propose an accelerated tMR acquisition strategy using parallel imaging and/or compressed sensing and assess the impact on the tMR-based motion corrected PET using phantom and patient data. Methods: Fully sampled tMR data were acquired simultaneously with PET list-mode data on two simultaneous PET-MR scanners for a cardiac phantom and a patient. Parallel imaging and compressed sensing were retrospectively performed by GRAPPA and kt-FOCUSS algorithms with various acceleration factors. Motion fields were estimated using nonrigid B-spline image registration from both the accelerated and fully sampled tMR images. The motion fields were incorporated into a motion corrected ordered subset expectation maximization reconstruction algorithm with motion-dependent attenuation correction. Results: Although tMR acceleration introduced image artifacts into the tMR images for both phantom and patient data, motion corrected PET images yielded similar image quality as those obtained using the fully sampled tMR images for low to moderate acceleration factors (< 4). Quantitative analysis of myocardial defect contrast over ten independent noise realizations showed similar results. It was further observed that although the image quality of the motion corrected PET images deteriorates for high acceleration factors, the images were still superior to the images reconstructed without motion correction. Conclusions: Accelerated tMR images obtained with more than 4 times acceleration can still provide relatively accurate motion fields and yield tMR-based motion corrected PET images with similar image quality as those reconstructed using fully sampled tMR data. The reduction of tMR acquisition time makes it more compatible with routine clinical cardiac PET-MR studies. (C) 2015 American Association of Physicists in Medicine. C1 [Huang, Chuan; Petibon, Yoann; Ouyang, Jinsong; El Fakhri, Georges] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Huang, Chuan; Ouyang, Jinsong; Reese, Timothy G.; El Fakhri, Georges] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Huang, Chuan] Stony Brook Med, Dept Radiol, Stony Brook, NY 11794 USA. [Reese, Timothy G.] Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ahlman, Mark A.; Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Huang, C (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. EM chuan.huang@stonybrookmedicine.edu OI Bluemke, David/0000-0002-8323-8086 FU NIH [R21-EB012326, R01-CA165221, R01-HL110241, R01-HL118261]; NIH intramural research program; Athinoula A. Martinos Center for Biomedical Imaging; Imaging Sciences Training Program at the National Institutes of Health; Center for Functional Neuroimaging Technologies - NIH [P41-EB015896] FX This research was supported in part by NIH Grant No. R21-EB012326, R01-CA165221, R01-HL110241, R01-HL118261, NIH intramural research program, the Athinoula A. Martinos Center for Biomedical Imaging, the Imaging Sciences Training Program at the National Institutes of Health, and the Center for Functional Neuroimaging Technologies (funded by NIH Grant No. P41-EB015896). The authors would like to thank Wen-TungWang for the help with patient acquisition. NR 46 TC 5 Z9 5 U1 1 U2 8 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD FEB PY 2015 VL 42 IS 2 BP 1087 EP 1097 DI 10.1118/1.4906247 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CA9GJ UT WOS:000349229600055 PM 25652521 ER PT J AU Alekel, DL Genschel, U Koehler, KJ Hofmann, H Van Loan, MD Beer, BS Hanson, LN Peterson, CT Kurzer, MS AF Alekel, D. Lee Genschel, Ulrike Koehler, Kenneth J. Hofmann, Heike Van Loan, Marta D. Beer, Bonnie S. Hanson, Laura N. Peterson, Charles T. Kurzer, Mindy S. TI Soy Isoflavones for Reducing Bone Loss Study: effects of a 3-year trial on hormones, adverse events, and endometrial thickness in postmenopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Soy isoflavone supplements; Safety; Transvaginal ultrasound; 17 beta-Estradiol; Estrone sulfate; Thyroid-stimulating hormone ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; MENOPAUSAL SYMPTOMS; ALCOHOL-CONSUMPTION; PROTEIN ISOLATE; CANCER-RISK; HOT FLUSHES; US ADULTS; BREAST; NUTRITION AB Objective: This study aims to assess the overall safety and potential endometrium-stimulating effects of soy isoflavone tablets consumed (3 y) by postmenopausal women and to determine endometrial thickness response to treatment among compliant women, taking into account hormone concentrations and other hypothesized modifying factors. Methods: We randomized healthy postmenopausal women (aged 45.8-65.0 y) to placebo control or two doses (80 or 120 mg/d) of soy isoflavones at two sites. We used intent-to-treat analysis (N = 224) and compliant analysis (>95%; N = 208) to assess circulating hormone concentrations, adverse events, and endometrial thickness (via transvaginal ultrasound). Results: Median values for endometrial thickness (mm) declined from baseline through 36 months. Nonparametric analysis of variance for treatment differences among groups showed no differences in absolute (or percentage of change) endometrial thickness (chi(2) P ranged from 0.12 to 0.69) or in circulating hormones at any time point. A greater number of adverse events in the genitourinary system (P = 0.005) were noted in the 80 mg/day group compared with the 120 mg/day group, whereas other systems showed no treatment effects. The model predicting endometrial thickness response (using natural logarithm) to treatment among compliant women across time points was significant (P <= 0.0001), indicating that estrogen exposure (P = 0.0013), plasma 17 beta-estradiol (P = 0.0086), and alcohol intake (P = 0.023) contributed significantly to the response. Neither the 80 mg/day dose (P = 0.57) nor the 120 mg/day dose (P = 0.43) exerted an effect on endometrial thickness across time. Conclusions: Our randomized controlled trial verifies the long-term overall safety of soy isoflavone tablet intake by postmenopausal women who display excellent compliance. We find no evidence of treatment effects on endometrial thickness, adverse events, or circulating hormone concentrations, most notably thyroid function, across a 3-year period. C1 [Alekel, D. Lee] NIH, Bethesda, MD 20892 USA. [Genschel, Ulrike; Koehler, Kenneth J.; Hofmann, Heike] Iowa State Univ, Dept Stat, Ames, IA USA. [Van Loan, Marta D.] Univ Calif Davis, USDA, ARS, Western Human Nutr Res Ctr, Davis, CA 95616 USA. [Beer, Bonnie S.] McFarland Clin, Ames, IA USA. [Hanson, Laura N.] Mayo Validat Support Serv, Rochester, MN USA. [Peterson, Charles T.] US FDA, Ctr Devices & Radiol Hlth, White Oak, MD USA. [Kurzer, Mindy S.] Univ Minnesota, Dept Food Sci & Nutr, St Paul, MN USA. RP Alekel, DL (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Suite 401,6707 Democracy Blvd 2, Bethesda, MD 20892 USA. EM Lee.Alekel@nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [RO1 AR046922]; Nutrition and Wellness Research Center at Iowa State University; US Department of Agriculture-Agricultural Research Service Western Human Nutrition Research Center [5306-51530-006-00D]; Clinical and Translational Science Center, Clinical Research Center, University of California [1M01RR19975-01]; National Center for Medical Research [UL1 RR024146] FX Funding/support: This work was supported mainly by a grant (RO1 AR046922) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and was also supported by the Nutrition and Wellness Research Center at Iowa State University; US Department of Agriculture-Agricultural Research Service Western Human Nutrition Research Center (5306-51530-006-00D); Clinical and Translational Science Center, Clinical Research Center, University of California (1M01RR19975-01); and National Center for Medical Research (UL1 RR024146). NR 31 TC 14 Z9 14 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD FEB PY 2015 VL 22 IS 2 BP 185 EP 197 DI 10.1097/gme.0000000000000280 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CA2UY UT WOS:000348764600011 PM 25003624 ER PT J AU Gold, PW AF Gold, P. W. TI The organization of the stress system and its dysregulation in depressive illness SO MOLECULAR PSYCHIATRY LA English DT Review ID CORTICOTROPIN-RELEASING HORMONE; ADULT HIPPOCAMPAL NEUROGENESIS; ENDOPLASMIC-RETICULUM STRESS; PITUITARY-ADRENAL RESPONSES; MEDIAL PREFRONTAL CORTEX; INSULIN-RESISTANCE; MAJOR DEPRESSION; MOOD DISORDERS; BIOCHEMICAL MANIFESTATIONS; EPIGENETIC MECHANISMS AB Stressors are imminent or perceived challenges to homeostasis. The stress response is an innate, stereotypic, adaptive response to stressors that has evolved in the service of restoring the nonstressed homeostatic set point. It is encoded in specific neuroanatomical sites that activate a specific repertoire of cognitive, behavioral and physiologic phenomena. Adaptive responses, though essential for survival, can become dysregulated and result in disease. A clear example is autoimmune disease. I postulate that depression, like autoimmunity, represents a dysregulated adaptive response: a stress response that has gone awry. The cardinal manifestation of the normal stress response is anxiety. Cognitive programs shift from complex associative operations to rapid retrieval of unconscious emotional memories acquired during prior threatening situations. These emerge automatically to promote survival. To prevent distraction during stressful situations, the capacity to seek and experience pleasure is reduced, food intake is diminished and sexual activity and sleep are held in abeyance. Monoamines, cytokines, glutamate, GABA and other central mediators have key roles in the normal stress response. Many central loci are involved. The subgenual prefrontal cortex restrains the amygdala, the corticotropin-releasing hormone/hypothalamic-pituitary-adrenal (CRH/HPA) axis and the sympathomedullary system. The function of the subgenual prefrontal cortex is moderately diminished during normal stress to disinhibit these loci. This disinhibition promotes anxiety and physiological hyperarousal, while diminishing appetite and sleep. The dorsolateral prefrontal cortex is downregulated, diminishing cognitive regulation of anxiety. The nucleus accumbens is also downregulated, to reduce the propensity for distraction by pleasurable stimuli or the capacity to experience pleasure. Insulin resistance, inflammation and a prothrombotic state acutely emerge. These provide increased glucose for the brain and establish premonitory, proinflammatory and prothrombotic states in anticipation of either injury or hemorrhage during a threatening situation. Essential adaptive intracellular changes include increased neurogenesis, enhancement of neuroplasticity and deployment of a successful endoplasmic reticulum stress response. In melancholic depression, the activities of the central glutamate, norepinephrine and central cytokine systems are significantly and persistently increased. The subgenual prefrontal cortex is functionally impaired, and its size is reduced by as much as 40%. This leads to sustained anxiety and activations of the amygdala, CRH/HPA axis, the sympathomedullary system and their sequella, including early morning awakening and loss of appetite. The sustained activation of the amygdala, in turn, further activates stress system neuroendocrine and autonomic functions. The activity of the nucleus accumbens is further decreased and anhedonia emerges. Concomitantly, neurogenesis and neuroplasticity fall significantly. Antidepressants ameliorate many of these processes. The processes that lead to the behavioral and physiological manifestations of depressive illness produce a significant decrease in lifespan, and a doubling of the incidence of premature coronary artery disease. The incidences of premature diabetes and osteoporosis are also substantially increased. Six physiological processes that occur during stress and that are markedly increased in melancholia set into motion six different mechanisms to produce inflammation, as well as sustained insulin resistance and a prothrombotic state. Clinically, melancholic and atypical depression seem to be antithesis of one another. In melancholia, depressive systems are at their worst in the morning when arousal systems, such as the CRH/HPA axis and the noradrenergic systems, are at their maxima. In atypical depression, depressive symptoms are at their worst in the evening, when these arousal systems are at their minima. Melancholic patients experience anorexia and insomnia, whereas atypical patients experience hyperphagia and hypersomnia. Melancholia seems like an activation and persistence of the normal stress response, whereas atypical depression resembles a stress response that has been excessively inhibited. It is important that we stratify clinical studies of depressed patients to compare melancholic and atypical subtypes and establish their differential pathophysiology. Overall, it is important to note that many of the major mediators of the stress response and melancholic depression, such as the subgenual prefrontal cortex, the amygdala, the noradrenergic system and the CRH/HPA axis participate in multiple reinforcing positive feedback loops. This organization permits the establishment of the markedly exaggerated, persistent elevation of the stress response seen in melancholia. Given their pronounced interrelatedness, it may not matter where in this cascade the first abnormality arises. It will spread to the other loci and initiate each of their activations in a pernicious vicious cycle. C1 NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Gold, PW (reprint author), NIMH, Clin Neuroendocrinol Branch, 10 Ctr Dr,Room 2D46, Bethesda, MD 20892 USA. EM philipgold@mail.nih.gov NR 91 TC 65 Z9 66 U1 18 U2 106 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 FEB PY 2015 VL 20 IS 1 BP 32 EP 47 DI 10.1038/mp.2014.163 PG 16 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CB1QR UT WOS:000349403400004 PM 25486982 ER PT J AU Ellegood, J Anagnostou, E Babineau, BA Crawley, JN Lin, L Genestine, M DiCicco-Bloom, E Lai, JKY Foster, JA Penagarikano, O Geschwind, DH Pacey, LK Hampson, DR Laliberte, CL Mills, AA Tam, E Osborne, LR Kouser, M Espinosa-Becerra, F Xuan, Z Powell, CM Raznahan, A Robins, DM Nakai, N Nakatani, J Takumi, T van Eede, MC Kerr, TM Muller, C Blakely, RD Veenstra-VanderWeele, J Henkelman, RM Lerch, JP AF Ellegood, J. Anagnostou, E. Babineau, B. A. Crawley, J. N. Lin, L. Genestine, M. DiCicco-Bloom, E. Lai, J. K. Y. Foster, J. A. Penagarikano, O. Geschwind, D. H. Pacey, L. K. Hampson, D. R. Laliberte, C. L. Mills, A. A. Tam, E. Osborne, L. R. Kouser, M. Espinosa-Becerra, F. Xuan, Z. Powell, C. M. Raznahan, A. Robins, D. M. Nakai, N. Nakatani, J. Takumi, T. van Eede, M. C. Kerr, T. M. Muller, C. Blakely, R. D. Veenstra-VanderWeele, J. Henkelman, R. M. Lerch, J. P. TI Clustering autism: using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity SO MOLECULAR PSYCHIATRY LA English DT Article ID SPECTRUM DISORDERS; BEHAVIORAL PHENOTYPES; STRUCTURAL MRI; BRAIN; MICE; ABNORMALITIES; REGISTRATION; RELEVANT; SUBTYPES AB Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for > 1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1a, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response. C1 [Ellegood, J.; Laliberte, C. L.; van Eede, M. C.; Henkelman, R. M.; Lerch, J. P.] Hosp Sick Children, Mouse Imaging Ctr, Toronto, ON M5T 3H7, Canada. [Anagnostou, E.] Holland Bloorview Kids Rehabil Hosp, Toronto, ON, Canada. [Babineau, B. A.; Crawley, J. N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. [Crawley, J. N.] Univ Calif Davis, Sch Med, MIND Inst, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. [Lin, L.; Genestine, M.; DiCicco-Bloom, E.] UMDNJ Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ USA. [Lai, J. K. Y.; Foster, J. A.] McMaster Univ, Brain Body Inst, Hamilton, ON, Canada. [Penagarikano, O.; Geschwind, D. H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Pacey, L. K.; Hampson, D. R.] Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON, Canada. [Mills, A. A.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Tam, E.; Osborne, L. R.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Tam, E.; Osborne, L. R.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Kouser, M.; Espinosa-Becerra, F.; Xuan, Z.; Powell, C. M.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Kouser, M.; Espinosa-Becerra, F.; Xuan, Z.; Powell, C. M.] Univ Texas SW Med Ctr Dallas, Dept Neurotherapeut Psychiat, Dallas, TX 75390 USA. [Raznahan, A.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Robins, D. M.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI USA. [Nakai, N.; Nakatani, J.; Takumi, T.] RIKEN, Brain Sci Inst, Dept Mental Biol, Wako, Saitama, Japan. [Kerr, T. M.; Muller, C.; Blakely, R. D.; Veenstra-VanderWeele, J.] Vanderbilt Brain Inst, Vanderbilt Kennedy Ctr, Dept Pharmacol, Nashville, TN USA. [Henkelman, R. M.; Lerch, J. P.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. RP Ellegood, J (reprint author), Hosp Sick Children, Mouse Imaging Ctr, 25 Orde St, Toronto, ON M5T 3H7, Canada. EM jacob@mouseimaging.ca; jason.lerch@utoronto.ca RI Veenstra-VanderWeele, Jeremy/K-1935-2015; Henkelman, Mark/F-3662-2011; OI Veenstra-VanderWeele, Jeremy/0000-0002-6349-1076; Penagarikano, Olga/0000-0001-8153-8221; Robins, Diane M./0000-0001-6727-6309; Lai, Jonathan/0000-0002-3060-1232 FU Canadian Institute for Health Research (CIHR); Ontario Brain Institute (OBI); Ontario Mental Health Foundation (OHMF) FX This work was primarily funded by the Canadian Institute for Health Research (CIHR) and the Ontario Brain Institute (OBI). JE received salary support from the Ontario Mental Health Foundation (OHMF) and RMH holds a Canada Research Chair. NR 51 TC 35 Z9 36 U1 1 U2 19 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 FEB PY 2015 VL 20 IS 1 BP 118 EP 125 DI 10.1038/mp.2014.98 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CB1QR UT WOS:000349403400012 PM 25199916 ER PT J AU Chuang, YF Tanaka, T Beason-Held, LL An, Y Terracciano, A Sutin, AR Kraut, M Singleton, AB Resnick, SM Thambisetty, M AF Chuang, Y-F Tanaka, T. Beason-Held, L. L. An, Y. Terracciano, A. Sutin, A. R. Kraut, M. Singleton, A. B. Resnick, S. M. Thambisetty, M. TI FTO genotype and aging: pleiotropic longitudinal effects on adiposity, brain function, impulsivity and diet SO MOLECULAR PSYCHIATRY LA English DT Article ID BODY-MASS INDEX; ALZHEIMERS-DISEASE; OLDER-ADULTS; PERSONALITY-TRAITS; CHILDHOOD OBESITY; FAT MASS; GENE; CORTEX; RISK; MEN AB Although overweight and obesity are associated with poor health outcomes in the elderly, the biological bases of obesity-related behaviors during aging are poorly understood. Common variants in the FTO gene are associated with adiposity in children and younger adults as well as with adverse mental health in older individuals. However, it is unclear whether FTO influences longitudinal trajectories of adiposity and other intermediate phenotypes relevant to mental health during aging. We examined whether a commonly carried obesity-risk variant in the FTO gene (rs1421085 single-nucleotide polymorphism) influences adiposity and is associated with changes in brain function in participants within the Baltimore Longitudinal Study of Aging, one of the longest-running longitudinal aging studies in the United States. Our results show that obesity-related risk allele carriers of FTO gene show dose-dependent increments in body mass index during aging. Moreover, the obesity-related risk allele is associated with reduced medial prefrontal cortical function during aging. Consistent with reduced brain function in regions intrinsic to impulse control and taste responsiveness, risk allele carriers of FTO exhibit dose-dependent increments in both impulsivity and intake of fatty foods. We propose that a common neural mechanism may underlie obesity-associated impulsivity and increased consumption of high-calorie foods during aging. C1 [Chuang, Y-F; Thambisetty, M.] NIA, Clin & Translat Neurosci Unit, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Tanaka, T.] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Beason-Held, L. L.; An, Y.; Resnick, S. M.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Terracciano, A.; Sutin, A. R.] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA. [Kraut, M.] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21205 USA. [Singleton, A. B.] NIA, Neurogenet Lab, Baltimore, MD 21224 USA. RP Thambisetty, M (reprint author), NIA, Clin & Translat Neurosci Unit, Lab Behav Neurosci, Baltimore, MD 21224 USA. EM thambisettym@mail.nih.gov RI Singleton, Andrew/C-3010-2009 FU Intramural Research Program, National Institute on Aging, National Institutes of Health [N01-AG-3-2124] FX We are grateful to the Baltimore Longitudinal Study of Aging participants and neuroimaging staff for their dedication to these studies and the staff of the Johns Hopkins University PET facility for their assistance. This work was supported in part by research and development contract N01-AG-3-2124 from the Intramural Research Program, National Institute on Aging, National Institutes of Health. NR 43 TC 6 Z9 6 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD FEB PY 2015 VL 20 IS 1 BP 133 EP 139 DI 10.1038/mp.2014.49 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CB1QR UT WOS:000349403400014 PM 24863145 ER PT J AU Klinman, DM AF Klinman, Dennis M. TI Therapeutic Implications of Orally Delivered Immunomodulatory Oligonucleotides SO MOLECULAR THERAPY LA English DT Editorial Material ID CPG OLIGONUCLEOTIDES; OLIGODEOXYNUCLEOTIDES; ACTIVATION; ADJUVANTS; IMMUNITY; CELLS C1 NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Klinman, DM (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Bldg 567,Room 205, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov NR 14 TC 1 Z9 1 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD FEB PY 2015 VL 23 IS 2 BP 222 EP 223 DI 10.1038/mt.2014.251 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CA2PT UT WOS:000348750700002 PM 25633172 ER PT J AU Fehrmann, RSN Karjalainen, JM Krajewska, M Westra, HJ Maloney, D Simeonov, A Pers, TH Hirschhorn, JN Jansen, RC Schultes, EA van Haagenl, HHHBM de Vries, EGE Meerman, GJT Wijmenga, C van Vugt, MATM Franke, L AF Fehrmann, Rudolf S. N. Karjalainen, Juha M. Krajewska, Malgorzata Westra, Harm-Jan Maloney, David Simeonov, Anton Pers, Tune H. Hirschhorn, Joel N. Jansen, Ritsert C. Schultes, Erik A. van Haagenl, Herman H. H. B. M. de Vries, Elisabeth G. E. Meerman, Gerard J. te Wijmenga, Cisca van Vugt, Marcel A. T. M. Franke, Lude TI Gene expression analysis identifies global gene dosage sensitivity in cancer SO NATURE GENETICS LA English DT Article ID HOMOLOGOUS RECOMBINATION; HUMAN-BREAST; MUTATIONS; LANDSCAPE; REPAIR; TUMORS; CELLS AB Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gene expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying this method to 16,172 patient-derived tumor samples, we replicated many loci with aberrant copy numbers and identified recurrently disrupted genes in genomically unstable cancers. C1 [Fehrmann, Rudolf S. N.; Krajewska, Malgorzata; de Vries, Elisabeth G. E.; van Vugt, Marcel A. T. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, Netherlands. [Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Westra, Harm-Jan; Meerman, Gerard J. te; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Maloney, David; Simeonov, Anton] US Natl Inst Hlth, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Pers, Tune H.; Hirschhorn, Joel N.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Pers, Tune H.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Pers, Tune H.; Hirschhorn, Joel N.] Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Pers, Tune H.] Tech Univ Denmark, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Jansen, Ritsert C.] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Groningen Bioinformat Ctr, Haren, Netherlands. [Schultes, Erik A.; van Haagenl, Herman H. H. B. M.] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Schultes, Erik A.] Leiden Univ, Leiden Inst Adv Comp Sci, BioSemant Grp, Leiden, Netherlands. RP Fehrmann, RSN (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, Netherlands. EM r.s.n.fehrmann@umcg.nl; lude@ludesign.nl RI Karjalainen, Juha/P-8624-2016; Fehrmann, Rudolf/E-2551-2011; Franke, Lude/P-7036-2016 OI Fehrmann, Rudolf/0000-0002-7516-315X; Franke, Lude/0000-0002-5159-8802 FU Netherlands Organization for Scientific Research [916-10135, 916-76062, 917-14374]; Horizon Breakthrough grant from the Netherlands Genomics Initiative [92519031]; Van der Meer-Boerema Foundation; Dutch Cancer Society [RUG 2011-5093, RUG 2013-5960]; SIA-raakPRO subsidy for project BioCOMP; European Community's Health Seventh Framework Programme (FP7) [259867]; John Templeton Foundation; Leiden Centre for Data Sciences FX We thank J.L. Senior for editing the manuscript. This work was financially supported by grants from the Netherlands Organization for Scientific Research (NWO-VENI grant 916-10135 to L.F., NWO VIDI grant 916-76062 to M.A.T.M.v.V. and NWO VIDI grant 917-14374 to L.F.), a Horizon Breakthrough grant from the Netherlands Genomics Initiative (grant 92519031 to L.F.), a grant from the Van der Meer-Boerema Foundation to M.K. and grants from the Dutch Cancer Society (RUG 2011-5093 to M.A.T.M.v.V. and RUG 2013-5960 to R.S.N.F.). In addition, this study was financed in part by the SIA-raakPRO subsidy for project BioCOMP. The research leading to these results has received funding from the European Community's Health Seventh Framework Programme (FP7/2007-2013) under grant agreement 259867. This publication was made possible through the support of a grant from the John Templeton Foundation. Additional support for E.A.S. was provided by the Leiden Centre for Data Sciences. NR 31 TC 56 Z9 58 U1 0 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD FEB PY 2015 VL 47 IS 2 BP 115 EP 125 DI 10.1038/ng.3173 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA CA1TQ UT WOS:000348694700006 PM 25581432 ER PT J AU Kuchenbaecker, KB Ramus, SJ Tyrer, J Lee, A Shen, HC Beesley, J Lawrenson, K McGuffog, L Healey, S Lee, JM Spindler, TJ Lin, YG Pejovic, T Bean, Y Li, Q Coetzee, S Hazelett, D Miron, A Southey, M Terry, MB Goldgar, DE Buys, SS Janavicius, R Dorfling, CM van Rensburg, EJ Neuhausen, SL Ding, YC Hansen, TVO Jonson, L Gerdes, AM Ejlertsen, B Barrowdale, D Dennis, J Benitez, J Osorio, A Garcia, MJ Komenaka, I Weitzel, JN Ganschow, P Peterlongo, P Bernard, L Viel, A Bonanni, B Peissel, B Manoukian, S Radice, P Papi, L Ottini, L Fostira, F Konstantopoulou, I Garber, J Frost, D Perkins, J Platte, R Ellis, S Godwin, AK Schmutzler, RK Meindl, A Engel, C Sutter, C Sinilnikova, OM Damiola, F Mazoyer, S Stoppa-Lyonnet, D Claes, K De Leeneer, K Kirk, J Rodriguez, GC Piedmonte, M O'Malley, DM de la Hoya, M Caldes, T Aittomaki, K Nevanlinna, H Collee, JM Rookus, MA Oosterwijk, JC Tihomirova, L Tung, N Hamann, U Isaccs, C Tischkowitz, M Imyanitov, EN Caligo, MA Campbe, IG Hogervorst, FBL Olah, E Diez, O Blanco, I Brunet, J Lazaroso, C Pujana, MA Jakubowska, A Gronwald, J Lubinski, J Sukiennicki, G Barkardottir, RB Plante, M Simard, J Soucy, P Montagna, M Tognazzo, S Teixeira, MR Pankratz, VS Wang, XS Lindor, N Szabo, CI Kauff, N Vijai, J Aghajanian, CA Pfeiler, G Berger, A Singer, CF Tea, MK Phelan, CM Greene, MH Mai, PL Rennert, G Mulligan, AM Tchatchou, S Andrulis, IL Glendon, G Toland, AE Jensen, UB Kruse, TA Thomassen, M Bojesen, A Zidan, J Friedman, E Laitman, Y Soller, M Liljegren, A Arver, B Einbeigi, Z Stenmark-Askmalm, M Olopade, OI Nussbaum, RL Rebbeck, TR Nathanson, KL Domchek, SM Lu, KH Karlan, BY Walsh, C Lester, J Hein, A Ekici, AB Beckmann, MW Fasching, PA Lambrechts, D Van Nieuwenhuysen, E Vergote, I Lambrechts, S Dicks, E Doherty, JA Wicklund, KG Rossing, MA Rudolph, A Chang-Claude, J Wang-Gohrke, S Eilber, U Moysich, KB Odunsi, K Sucheston, L Lele, S Wilkens, LR Goodman, MT Thompson, PJ Shvetsov, YB Runnebaum, IB Durst, M Hillemanns, P Dork, T Antonenkova, N Bogdanova, N Leminen, A Pelttari, LM Butzow, R Modugno, F Kelley, JL Edwards, RP Ness, RB du Bois, A Heitz, F Schwaab, I Harter, P Matsuo, K Hosono, S Orsulic, S Jensen, A Kjaer, SK Hogdall, E Hasmad, HN Azmi, MAN Teo, SH Woo, YL Fridley, BL Goode, EL Cunningham, JM Vierkant, RA Bruinsma, F Giles, GG Liang, D Hildebrandt, MAT Wu, XF Levine, DA Bisogna, M Berchuck, A Iversen, ES Schildkraut, JM Concannon, P Weber, RP Cramer, DW Terry, KL Poole, EM Tworoger, SS Bandera, EV Orlow, I Olson, SH Krakstad, C Salvesen, HB Tangen, IL Bjorge, L van Altena, AM Aben, KKH Kiemeney, LA Massuger, LFAG Kellar, M Brooks-Wilson, A Kelemen, LE Cook, LS Le, ND Cybulski, C Yang, H Lissowska, J Brinton, LA Wentzensen, N Hogdall, C Lundvall, L Nedergaard, L Baker, H Song, HL Eccles, D McNeish, I Paul, J Carty, K Siddiqui, N Glasspool, R Whittemore, AS Rothstein, JH McGuire, V Sieh, W Ji, BT Zheng, W Shu, XO Gao, YT Rosen, B Risch, HA McLaughlin, JR Narod, SA Monteiro, AN Chen, A Lin, HY Permuth-Wey, J Sellers, TA Tsai, YY Chen, Z Ziogas, A Anton-Culver, H Gentry-Maharaj, A Menon, U Harrington, P Lee, AW Wu, AH Pearce, CL Coetzee, G Pike, MC Dansonka-Mieszkowska, A Timorek, A Rzepecka, IK Kupryjanczyk, J Freedman, M Noushmehr, H Easton, DF Offit, K Couch, FJ Gayther, S Pharoah, PP Antoniou, AC Chenevix-Trench, G AF Kuchenbaecker, Karoline B. Ramus, Susan J. Tyrer, Jonathan Lee, Andrew Shen, Howard C. Beesley, Jonathan Lawrenson, Kate McGuffog, Lesley Healey, Sue Lee, Janet M. Spindler, Tassja J. Lin, Yvonne G. Pejovic, Tanja Bean, Yukie Li, Qiyuan Coetzee, Simon Hazelett, Dennis Miron, Alexander Southey, Melissa Terry, Mary Beth Goldgar, David E. Buys, Saundra S. Janavicius, Ramunas Dorfling, Cecilia M. van Rensburg, Elizabeth J. Neuhausen, Susan L. Ding, Yuan Chun Hansen, Thomas V. O. Jonson, Lars Gerdes, Anne-Marie Ejlertsen, Bent Barrowdale, Daniel Dennis, Joe Benitez, Javier Osorio, Ana Garcia, Maria Jose Komenaka, Ian Weitzel, Jeffrey N. Ganschow, Pamela Peterlongo, Paolo Bernard, Loris Viel, Alessandra Bonanni, Bernardo Peissel, Bernard Manoukian, Siranoush Radice, Paolo Papi, Laura Ottini, Laura Fostira, Florentia Konstantopoulou, Irene Garber, Judy Frost, Debra Perkins, Jo Platte, Radka Ellis, Steve Godwin, Andrew K. Schmutzler, Rita Katharina Meindl, Alfons Engel, Christoph Sutter, Christian Sinilnikova, Olga M. Damiola, Francesca Mazoyer, Sylvie Stoppa-Lyonnet, Dominique Claes, Kathleen De Leeneer, Kim Kirk, Judy Rodriguez, Gustavo C. Piedmonte, Marion O'Malley, David M. de la Hoya, Miguel Caldes, Trinidad Aittomaeki, Kristiina Nevanlinna, Heli Collee, J. Margriet Rookus, Matti A. Oosterwijk, Jan C. Tihomirova, Laima Tung, Nadine Hamann, Ute Isaccs, Claudine Tischkowitz, Marc Imyanitov, Evgeny N. Caligo, Maria A. Campbell, Ian G. Hogervorst, Frans B. L. Olah, Edith Diez, Orland Blanco, Ignacio Brunet, Joan Lazaroso, Conxi Angel Pujana, Miguel Jakubowska, Anna Gronwald, Jacek Lubinski, Jan Sukiennicki, Grzegorz Barkardottir, Rosa B. Plante, Marie Simard, Jacques Soucy, Penny Montagna, Marco Tognazzo, Silvia Teixeira, Manuel R. Pankratz, Vernon S. Wang, Xianshu Lindor, Noralane Szabo, Csilla I. Kauff, Noah Vijai, Joseph Aghajanian, Carol A. Pfeiler, Georg Berger, Andreas Singer, Christian F. Tea, Muy-Kheng Phelan, Catherine M. Greene, Mark H. Mai, Phuong L. Rennert, Gad Mulligan, Anna Marie Tchatchou, Sandrine Andrulis, Irene L. Glendon, Gord Toland, Amanda Ewart Jensen, Uffe Birk Kruse, Torben A. Thomassen, Mads Bojesen, Anders Zidan, Jamal Friedman, Eitan Laitman, Yael Soller, Maria Liljegren, Annelie Arver, Brita Einbeigi, Zakaria Stenmark-Askmalm, Marie Olopade, Olufunmilayo I. Nussbaum, Robert L. Rebbeck, Timothy R. Nathanson, Katherine L. Domchek, Susan M. Lu, Karen H. Karlan, Beth Y. Walsh, Christine Lester, Jenny Hein, Alexander Ekici, Arif B. Beckmann, Matthias W. Fasching, Peter A. Lambrechts, Diether Van Nieuwenhuysen, Els Vergote, Ignace Lambrechts, Sandrina Dicks, Ed Doherty, Jennifer A. Wicklund, Kristine G. Rossing, Mary Anne Rudolph, Anja Chang-Claude, Jenny Wang-Gohrke, Shan Eilber, Ursula Moysich, Kirsten B. Odunsi, Kunle Sucheston, Lara Lele, Shashi Wilkens, Lynne R. Goodman, Marc T. Thompson, Pamela J. Shvetsov, Yurii B. Runnebaum, Ingo B. Duerst, Matthias Hillemanns, Peter Doerk, Thilo Antonenkova, Natalia Bogdanova, Natalia Leminen, Arto Pelttari, Liisa M. Butzow, Ralf Modugno, Francesmary Kelley, Joseph L. Edwards, Robert P. Ness, Roberta B. du Bois, Andreas Heitz, Florian Schwaab, Ira Harter, Philipp Matsuo, Keitaro Hosono, Satoyo Orsulic, Sandra Jensen, Allan Kjaer, Susanne Kruger Hogdall, Estrid Hasmad, Hanis Nazihah Azmi, Mat Adenan Noor Teo, Soo-Hwang Woo, Yin-Ling Fridley, Brooke L. Goode, Ellen L. Cunningham, Julie M. Vierkant, Robert A. Bruinsma, Fiona Giles, Graham G. Liang, Dong Hildebrandt, Michelle A. T. Wu, Xifeng Levine, Douglas A. Bisogna, Maria Berchuck, Andrew Iversen, Edwin S. Schildkraut, Joellen M. Concannon, Patrick Weber, Rachel Palmieri Cramer, Daniel W. Terry, Kathryn L. Poole, Elizabeth M. Tworoger, Shelley S. Bandera, Elisa V. Orlow, Irene Olson, Sara H. Krakstad, Camilla Salvesen, Helga B. Tangen, Ingvild L. Bjorge, Line van Altena, Anne M. Aben, Katja K. H. Kiemeney, Lambertus A. Massuger, Leon F. A. G. Kellar, Melissa Brooks-Wilson, Angela Kelemen, Linda E. Cook, Linda S. Le, Nhu D. Cybulski, Cezary Yang, Hannah Lissowska, Jolanta Brinton, Louise A. Wentzensen, Nicolas Hogdall, Claus Lundvall, Lene Nedergaard, Lotte Baker, Helen Song, Honglin Eccles, Diana McNeish, Ian Paul, James Carty, Karen Siddiqui, Nadeem Glasspool, Rosalind Whittemore, Alice S. Rothstein, Joseph H. McGuire, Valerie Sieh, Weiva Ji, Bu-Tian Zheng, Wei Shu, Xiao-Ou Gao, Yu-Tang Rosen, Barry Risch, Harvey A. McLaughlin, John R. Narod, Steven A. Monteiro, Alvaro N. Chen, Ann Lin, Hui-Yi Permuth-Wey, Jenny Sellers, Thomas A. Tsai, Ya-Yu Chen, Zhihua Ziogas, Argyrios Anton-Culver, Hoda Gentry-Maharaj, Aleksandra Menon, Usha Harrington, Patricia Lee, Alice W. Wu, Anna H. Pearce, Celeste L. Coetzee, Gerry Pike, Malcolm C. Dansonka-Mieszkowska, Agnieszka Timorek, Agnieszka Rzepecka, Iwona K. Kupryjanczyk, Jolanta Freedman, Matt Noushmehr, Houtan Easton, Douglas F. Offit, Kenneth Couch, Fergus J. Gayther, Simon Pharoah, Paul P. Antoniou, Antonis C. Chenevix-Trench, Georgia CA EMBRACE GEMO Study Collaborators Breast Cancer Family Registry HEBON KConFab Investigators Australian Canc Study Ovarian Canc Australian Ovarian Canc Study Grp Consortium Invest Modifiers BRCA1 TI Identification of six new susceptibility loci for invasive epithelial ovarian cancer SO NATURE GENETICS LA English DT Article ID BRCA2 MUTATION CARRIERS; GENOME-WIDE ASSOCIATION; ABO BLOOD-GROUP; BREAST-CANCER; GENETIC-VARIATION; COMMON VARIANTS; HUMAN ELG1; RISK; MYOPODIN; METAANALYSIS AB Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 x 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers. C1 [Kuchenbaecker, Karoline B.; Lee, Andrew; McGuffog, Lesley; Barrowdale, Daniel; Dennis, Joe; Frost, Debra; Perkins, Jo; Platte, Radka; Ellis, Steve; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Ramus, Susan J.; Shen, Howard C.; Lawrenson, Kate; Lee, Janet M.; Spindler, Tassja J.; Hazelett, Dennis; Lee, Alice W.; Wu, Anna H.; Pearce, Celeste L.; Coetzee, Gerry; Pike, Malcolm C.; Gayther, Simon] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Tyrer, Jonathan; Dennis, Joe; Dicks, Ed; Baker, Helen; Song, Honglin; Harrington, Patricia; Pharoah, Paul P.] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge, England. [Beesley, Jonathan; Healey, Sue; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Cancer Div, Brisbane, Qld, Australia. [Lin, Yvonne G.] Univ So Calif, Dept Obstet & Gynaecol, Los Angeles, CA USA. [Pejovic, Tanja; Bean, Yukie; Kellar, Melissa] Oregon Hlth & Sci Univ, Dept Obstet & Gynaecol, Portland, OR 97201 USA. [Pejovic, Tanja; Bean, Yukie; Kellar, Melissa] Knight Canc Inst, Portland, OR USA. [Li, Qiyuan; Freedman, Matt] Ctr Funct Canc Epigenet, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Coetzee, Simon; Noushmehr, Houtan] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049 Ribeirao Preto, Brazil. Ctr Cell Based Therapy, Ribeirao Preto, Brazil. [Coetzee, Simon] Ctr Integrat Syst Biol, Ribeirao Preto, Brazil. [Hazelett, Dennis; Coetzee, Gerry] Univ So Calif, Dept Urol, Los Angeles, CA USA. [Miron, Alexander] Case Western Reserve Univ, Sch Med, Dept Genom & Genome Sci, Cleveland, OH 44106 USA. [Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia. [Terry, Mary Beth] Columbia Univ, Dept Epidemiol, New York, NY USA. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. 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[Blanco, Ignacio] Catalan Inst Oncol, IDIBELL Bellvitge Biomed Res Inst, Hereditary Canc Program, Genet Counseling Unit, Barcelona, Spain. [Brunet, Joan] Catalan Inst Oncol, IDIBGI Institut dInvestigacie Biomed Girona, Hereditary Canc Program, Genet Counseling Unit, Girona, Spain. [Lazaroso, Conxi; Angel Pujana, Miguel] Catalan Inst Oncol, IDIBELL, Hereditary Canc Program, Molecular Diagnost Unit, Barcelona, Spain. [Jakubowska, Anna; Gronwald, Jacek; Lubinski, Jan; Sukiennicki, Grzegorz] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Barkardottir, Rosa B.] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Barkardottir, Rosa B.] Univ Iceland, Fac Med, Biomed Ctr, Reykjavik, Iceland. [Plante, Marie] CHUQ, Gynaecol Oncol Serv, Quebec City, PQ, Canada. [Simard, Jacques; Soucy, Penny] Univ Laval, CHUQ, Res Ctr, Quebec City, PQ, Canada. [Montagna, Marco; Tognazzo, Silvia] IRCCS, IOV, Immunol & Mol Oncol Unit, Padua, Italy. [Teixeira, Manuel R.; McNeish, Ian] Univ Porto, Inst Biomed Sci ICBAS, P-4100 Oporto, Portugal. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Pankratz, Vernon S.; Lindor, Noralane; Goode, Ellen L.; Couch, Fergus J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Wang, Xianshu; Cunningham, Julie M.; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Szabo, Csilla I.] NHGRI, NIH, Bethesda, MD 20892 USA. [Kauff, Noah; Vijai, Joseph; Aghajanian, Carol A.; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Pfeiler, Georg; Berger, Andreas; Singer, Christian F.; Tea, Muy-Kheng] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Ginecol, Vienna, Austria. [Phelan, Catherine M.; Monteiro, Alvaro N.; Permuth-Wey, Jenny; Sellers, Thomas A.; Tsai, Ya-Yu] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA. [Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Mulligan, Anna Marie; Andrulis, Irene L.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada. [Tchatchou, Sandrine; Glendon, Gord] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Toland, Amanda Ewart] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Kruse, Torben A.; Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Bojesen, Anders] Vejle Hosp, Dept Clin Genet, Vejle, Denmark. [Zidan, Jamal] Rivka Ziv Med Ctr, Inst Oncol, Safed, Israel. 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[Runnebaum, Ingo B.; Duerst, Matthias] Univ Jena, Jena Univ Hosp, Dept Gynecol, Jena, Germany. [Hillemanns, Peter] Hannover Med Sch, Clin Obstet & Gynaecol, Hannover, Germany. [Doerk, Thilo; Bogdanova, Natalia] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany. [Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandrov, Minsk, Byelarus. [Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland. [Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Kelley, Joseph L.; Edwards, Robert P.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Edwards, Robert P.] Univ Pittsburgh, Ovarian Canc Ctr Excellence, Pittsburgh, PA USA. [Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res ProgramInst Canc, Pittsburgh, PA USA. [Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [du Bois, Andreas; Heitz, Florian; Harter, Philipp] Dr Horst Schmidt Klin Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany. [du Bois, Andreas; Heitz, Florian; Harter, Philipp] Klin Essen Mitte, Dept Gynecol & Gynecol Oncol, Essen, Germany. [Schwaab, Ira] Inst Humangenetik Wiesbaden, Wiesbaden, Germany. [Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 812, Japan. [Hosono, Satoyo] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan. [Jensen, Allan; Kjaer, Susanne Kruger; Hogdall, Estrid] Danish Canc Soc, Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark. [Kjaer, Susanne Kruger; Hogdall, Claus; Lundvall, Lene] Univ Copenhagen, Dept Gynaecol, Copenhagen, Denmark. [Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark. [Hasmad, Hanis Nazihah; Teo, Soo-Hwang] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya, Malaysia. [Azmi, Mat Adenan Noor; Woo, Yin-Ling] Univ Malaya, Med Ctr, Dept Obstet & Gynaecol, Kuala Lumpur, Malaysia. [Teo, Soo-Hwang; Woo, Yin-Ling] Univ Malaya, Fac Med, Med Ctr, Canc Res Inst, Kuala Lumpur, Malaysia. [Fridley, Brooke L.] Univ Kansas, Med Ctr, Biostat & Informat Shared Resource, Kansas City, KS 66103 USA. [Vierkant, Robert A.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA. [Bruinsma, Fiona; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA. [Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Levine, Douglas A.; Bisogna, Maria] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA. [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA. [Schildkraut, Joellen M.] Duke Canc Inst, Canc Control & Populat Sci, Durham, NC USA. [Schildkraut, Joellen M.; Weber, Rachel Palmieri] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Concannon, Patrick] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. [Concannon, Patrick] Univ Florida, Genet Inst, Gainesville, FL USA. [Cramer, Daniel W.; Terry, Kathryn L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Cramer, Daniel W.; Terry, Kathryn L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Obstetr & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bandera, Elisa V.] Rutgers Canc Inst New Jersey, Cancer Prevent & Control, New Brunswick, NJ USA. [Orlow, Irene; Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Epidemiol Serv, New York, NY 10021 USA. [Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.; Bjorge, Line] Univ Bergen, Dept Clin Med, Ctr Canc Biomarkers, Bergen, Norway. [Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.; Bjorge, Line] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway. [van Altena, Anne M.; Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Dept Gynaecol, Nijmegen, Netherlands. [Aben, Katja K. H.] Ctr Comprehens Canc, Utrecht, Netherlands. [Aben, Katja K. H.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, Nijmegen, Netherlands. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, Nijmegen, Netherlands. [Brooks-Wilson, Angela] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. [Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada. [Kelemen, Linda E.] Med Univ S Carolina, Coll Med, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA. [Le, Nhu D.] British Columbia Canc Agcy, Canc Control Res, Vancouver, BC V5Z 4E6, Canada. [Cybulski, Cezary] Pomeranian Med Univ, Internat Hereditary Canc Ctr, Dept Genet & Pathol, Clin Opthalmol, Szczecin, Poland. [Yang, Hannah; Brinton, Louise A.; Wentzensen, Nicolas; Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Nedergaard, Lotte; Paul, James; Carty, Karen] Univ Copenhagen, Dept Pathol, Copenhagen, Denmark. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [McNeish, Ian] Univ Glasgow, Wolfson Wohl Canc Res Ctr, Beatson Inst Canc Res, Inst Canc Sci, Glasgow, Lanark, Scotland. [Glasspool, Rosalind] Beatson West Scotland, Ctr Canc, Canc Res UK Clin, Trials Unit, Glasgow, Lanark, Scotland. [Siddiqui, Nadeem] Glasgow Royal Infirm, Dept Gynecol Oncol, Glasgow G4 0SF, Lanark, Scotland. [Whittemore, Alice S.; Rothstein, Joseph H.; McGuire, Valerie; Sieh, Weiva] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. [Rosen, Barry] Univ Toronto, Fac Med, Dept Obstet & Gynaecol, Toronto, ON, Canada. [Rosen, Barry] Princess Margaret Hosp, Dept Gynecol Oncol, Toronto, ON M4X 1K9, Canada. [Risch, Harvey A.] Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. [McLaughlin, John R.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada. [Chen, Ann; Lin, Hui-Yi; Chen, Zhihua] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, Tampa, FL USA. [Ziogas, Argyrios; Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Elizabeth Garrett Anderson EGA Inst Womens Hlth, London, England. [Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K.; Kupryjanczyk, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Inst Oncol, Dept Pathol, Warsaw, Poland. [Timorek, Agnieszka] Med Univ Warsaw, Fac Med 2, Dept Obstet Gynecol & Oncol, Warsaw, Poland. [Timorek, Agnieszka] Brodnowski Hosp, Warsaw, Poland. RP Chenevix-Trench, G (reprint author), QIMR Berghofer Med Res Inst, Cancer Div, Brisbane, Qld, Australia. EM georgia.trench@qimrberghofer.edu.au RI Brooks-Wilson, Angela/E-9399-2012; Bandera, Elisa/M-4169-2014; montagna, marco/E-2225-2012; Hein, Alexander/F-6999-2010; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Kiemeney, Lambertus/D-3357-2009; Teo, Soo-hwang/H-2353-2014; Fridley, Brooke/D-8315-2015; BYRSKI, Tomasz/I-2844-2014; Ehrencrona, Hans/M-5619-2014; Brinton, Louise/G-7486-2015; Woo, Yin Ling/B-5198-2010; Massuger, Leon/H-8072-2014; Gronwald, Jacek/A-4576-2017; Bjorge, Line/C-1307-2017; salvesen, Helga/C-1187-2017; manoukian, siranoush/E-7132-2017; Coetzee, Simon/C-1218-2014; Peissel, Bernard/E-8187-2017; Ligtenberg, Marjolijn/N-9666-2013; Mensenkamp, A.R./L-4520-2015; Osorio, Ana/I-4324-2014; van Altena, Anne/B-9824-2016; Dork, Thilo/J-8620-2012; Arnold, Norbert/E-3012-2010; Teixeira, Manuel/E-4885-2011; Garcia, Maria/G-1361-2016; Aben, Katja/G-9686-2016; Bowtell, David/H-1007-2016; Andrulis, Irene/E-7267-2013; OMalley, David/E-3789-2011; Menkiszak, Janusz/I-4036-2014 OI Orlow, Irene/0000-0001-6234-6961; Dunning, Alison Margaret/0000-0001-6651-7166; Krakstad, Camilla/0000-0002-0174-8139; ROMERO, ATOCHA/0000-0002-1634-7397; Giles, Graham/0000-0003-4946-9099; Matsuo, Keitaro/0000-0003-1761-6314; Dobrovic, Alexander/0000-0003-3414-112X; Evans, Gareth/0000-0002-8482-5784; Brooks-Wilson, Angela/0000-0003-1009-6408; Bandera, Elisa/0000-0002-8789-2755; montagna, marco/0000-0002-4929-2150; Hein, Alexander/0000-0003-2601-3398; Kiemeney, Lambertus/0000-0002-2368-1326; Fridley, Brooke/0000-0001-7739-7956; Ehrencrona, Hans/0000-0002-5589-3622; Brinton, Louise/0000-0003-3853-8562; Woo, Yin Ling/0000-0003-1742-1066; Eeles, Rosalind/0000-0002-3698-6241; Blanco, Ignacio/0000-0002-7414-7481; Kjaer, Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798; Sunde, Lone/0000-0002-8479-165X; Khan, Sofia/0000-0003-4185-8882; Brunet, Joan/0000-0003-1945-3512; Kauff, Noah/0000-0001-7242-6156; Joseph, Vijai/0000-0002-7933-151X; Tommasi, Stefania/0000-0002-2157-2978; McNeish, Iain/0000-0002-9387-7586; Gronwald, Jacek/0000-0002-3643-2871; Bjorge, Line/0000-0002-0240-2770; salvesen, Helga/0000-0002-4438-8831; manoukian, siranoush/0000-0002-6034-7562; Coetzee, Simon/0000-0003-4267-5930; Peissel, Bernard/0000-0001-9233-3571; Peixoto, Ana/0000-0002-1404-5897; Glasspool, Rosalind/0000-0002-5000-1680; Barrowdale, Daniel/0000-0003-1661-3939; Dolcetti, Riccardo/0000-0003-1625-9853; Ligtenberg, Marjolijn/0000-0003-1290-1474; Osorio, Ana/0000-0001-8124-3984; Arnold, Norbert/0000-0003-4523-8808; Teixeira, Manuel/0000-0002-4896-5982; Garcia, Maria/0000-0002-2236-9912; Aben, Katja/0000-0002-0214-2147; Bowtell, David/0000-0001-9089-7525; FU European Commission Seventh Framework Programme [223175-HEALTH-F2-2009-223175]; Cancer Research UK [C12292/A11174, C1287/A10118]; Ovarian Cancer Research Fund; US National Cancer Institute GAME-ON Post-GWAS Initiative [U19-CA148112]; Wellcome Trust [076113]; National Health and Medical Research Council of Australia Program Grant; Associazione Italiana per la Ricerca sul Cancro FX We thank all the individuals who took part in this study and all the researchers, clinicians, and technical and administrative staff who made possible the many studies contributing to this work (a full list is provided in the Supplementary Note), including X.Q. Chen for iPLEX genotyping. The COGS project is funded through a European Commission Seventh Framework Programme grant (agreement number 223175-HEALTH-F2-2009-223175). CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The Ovarian Cancer Association Consortium (OCAC) is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). Scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control Consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based on data generated by The Cancer Genome Atlas (TCGA) Pilot Project established by the US National Cancer Institute and US National Human Genome Research Institute (database of Genotypes and Phenotypes (dbGaP) accession phs000178.v8.p7). The cBio Portal is developed and maintained by the Computational Biology Center at the Memorial Sloan-Kettering Cancer Center. S. Healey is supported by a National Health and Medical Research Council of Australia Program Grant to G.C.-T. Details of the funding of individual investigators and studies are provided in the Supplementary Note. A full list of the investigators who contributed to the generation of the data is available on the CIMBA website (see URLs). NR 38 TC 51 Z9 52 U1 6 U2 53 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD FEB PY 2015 VL 47 IS 2 BP 164 EP 171 DI 10.1038/ng.3185 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CA1TQ UT WOS:000348694700012 PM 25581431 ER PT J AU Goyette, P Boucher, G Mallon, D Ellinghaust, E Jostins, L Huang, HL Ripke, S Gusareva, ES Annese, V Hauser, SL Oksenberg, JR Thomsent, I Leslie, S Daly, MJ Van Steen, K Duerr, RH Barrett, JC McGovern, DPB Schumm, LP Traherne, JA Carrington, MN Kosmoliaptsis, V Karsen, TH Franke, A Rioux, JD AF Goyette, Philippe Boucher, Gabrielle Mallon, Dermot Ellinghaust, Eva Jostins, Luke Huang, Hailiang Ripke, Stephan Gusareva, Elena S. Annese, Vito Hauser, Stephen L. Oksenberg, Jorge R. Thomsent, Ingo Leslie, Stephen Daly, Mark J. Van Steen, Kristel Duerr, Richard H. Barrett, Jeffrey C. McGovern, Dermot P. B. Schumm, L. Philip Traherne, James A. Carrington, Mary N. Kosmoliaptsis, Vasilis Karsen, Tom H. Franke, Andre Rioux, John D. CA Int Inflammatory Bowel Dis Genetic TI High-density mapping of the MHC identifies a shared role for HLA-DRB1(star)01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis SO NATURE GENETICS LA English DT Article ID PRIMARY SCLEROSING CHOLANGITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; HLA-DR; SUSCEPTIBILITY; ALLELES; HAPLOTYPES; REGION AB Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules(1). Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles2,3. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD. C1 [Goyette, Philippe; Boucher, Gabrielle; Rioux, John D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Mallon, Dermot; Kosmoliaptsis, Vasilis] Univ Cambridge, Dept Surg, Cambridge, England. [Mallon, Dermot; Kosmoliaptsis, Vasilis] Cambridge Biomed Res Ctr, NIHR, Cambridge, England. [Ellinghaust, Eva; Thomsent, Ingo; Franke, Andre] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Huang, Hailiang; Ripke, Stephan; Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit, Boston, MA 02115 USA. [Huang, Hailiang; Ripke, Stephan; Daly, Mark J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Gusareva, Elena S.; Van Steen, Kristel] Univ Liege, Inst Montefiore, Syst & Modeling Unit, B-4000 Liege, Belgium. [Gusareva, Elena S.; Van Steen, Kristel] Univ Liege, GIGA R Grp Interdisciplinaire Genoproteom Appl Re, Liege, Belgium. [Annese, Vito] IRCCS CSS Hosp, Gastroenterol Unit, San Giovanni Rotondo, Italy. [Annese, Vito] Azienda Osped Univ AOU Careggi, Strut Org Dipartimentali, Unit Gastroenterol SOD2, Florence, Italy. [Hauser, Stephen L.; Oksenberg, Jorge R.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Thomsent, Ingo; Leslie, Stephen] Murdoch Childrens Res Inst, Parkville, Vic, Australia. [Leslie, Stephen] Univ Melbourne, Dept Math & Stat, Melbourne, Vic, Australia. [Duerr, Richard H.] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [McGovern, Dermot P. B.] Cedars Sinai Med Ctr, F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, Los Angeles, CA 90048 USA. [Schumm, L. Philip] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA. [Traherne, James A.] Cambridge Inst Med Res, Cambridge, England. [Traherne, James A.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Carrington, Mary N.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. [Carrington, Mary N.] Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA USA. [Karsen, Tom H.] Oslo Univ Hosp, Rikshosp, Res Inst Internal Med, Dept Transplantat Med,Div Canc Surg & Transplanta, N-0450 Oslo, Norway. [Karsen, Tom H.] Oslo Univ Hosp, Rikshosp, Norwegian Primary Sclerosing Cholangitis Res Ctr, Dept Transplantat Med,Div Canc Surg & Transplanta, N-0450 Oslo, Norway. [Karsen, Tom H.] Univ Oslo, Inst Clin Med, KG Jebsen Inflammat Res Ctr, Oslo, Norway. [Rioux, John D.] Univ Montreal, Fac Med, Montreal, PQ H3C 3J7, Canada. RP Rioux, JD (reprint author), Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. EM john.david.rioux@umontreal.ca RI Prescott, Natalie/F-6490-2011; Zeissig, Sebastian/B-6297-2012; Rioux, John/A-9599-2015; Ellinghaus, Eva/E-6490-2012; Palmieri, Orazio/J-7697-2012; Silverberg, Mark/B-4183-2008; Whiteman, David/P-2728-2014; Franke, Andre/B-2151-2010; OI Laukens, Debby/0000-0002-1984-5850; Winkelmann, Juliane/0000-0003-2667-9691; Kennedy, Nicholas/0000-0003-4368-1961; Barrett, Jeffrey/0000-0002-1152-370X; D'Amato, Mauro/0000-0003-2743-5197; Nothen, Markus/0000-0002-8770-2464; Kosmoliaptsis, Vasilis/0000-0001-7298-1387; Andersen, Vibeke/0000-0002-0127-2863; Newman, William/0000-0002-6382-4678; Prescott, Natalie/0000-0002-5901-7371; Rioux, John/0000-0001-7560-8326; Ellinghaus, Eva/0000-0003-2914-3382; Palmieri, Orazio/0000-0002-0019-7929; Whiteman, David/0000-0003-2563-9559; Franke, Andre/0000-0003-1530-5811; Duerr, Richard/0000-0001-6586-3905; Potocnik, Uros/0000-0003-1624-9428; Mallon, Dermot/0000-0001-7434-1201 FU Canada Research Chair; US National Institute of Diabetes and Digestive and Kidney Diseases grant (NIDDK) [R01 DK064869, U01 DK062432]; German Ministry of Education and Research (BMBF) grant programe: Med (sysINFLAME); Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence 'Inflammation at Interfaces'; Foundation for Experimental Biomedicine (Zurich, Switzerland); European Union Seventh Framework Programme (FP7) [262055]; Intramural Research Program of the US National Institutes of Health (NIH); Frederick National Laboratory; Center for Cancer Research; Frederick National Laboratory for Cancer Research [HHSN261200800001E]; Wellcome Trust [WT098051]; NIHR Cambridge Biomedical Research Centre; NIDDK [U01 DK062429-14, U01 DK062413, P01 DK046763-19, U54 DE023789-01, U01 DK062420]; UK Medical Research Council; Leona M. and Harry B. Helmsley Charitable Trust; European Union [305479]; National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI067068]; Agency for Healthcare Research and Quality (AHRQ) [HS021747]; Inflammatory Bowel Disease Genetic Research endowed chair at the University of Pittsburgh; US National Cancer Institute grant [CA141743]; US NIH [R01 NSO49477, 1U19 A1067152]; National Multiple Sclerosis Society [RG 2899-D11]; Australian National Health and Medical Research Council (R.D. Wright Career Development Fellowship) [APP1053756] FX We would like to thank the International PSC study group (http://www.ipscsg.org/) for sharing data. We are grateful to B.A. Lie and K. Holm for helpful discussions. J.D.R. holds a Canada Research Chair, and this work was supported by a US National Institute of Diabetes and Digestive and Kidney Diseases grant (NIDDK; R01 DK064869 and U01 DK062432). The laboratory of A.F. is supported by the German Ministry of Education and Research (BMBF) grant programe: Med (sysINFLAME). A.F. receives infrastructure support from the Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence 'Inflammation at Interfaces' and holds an endowment professorship (Peter Hans Hofschneider Professorship) of the Foundation for Experimental Biomedicine (Zurich, Switzerland). Grant support for T.H.K. and A.F. was received from the European Union Seventh Framework Programme (FP7/2007-2013, grant number 262055, ESGI). M.N.C. is supported by the Intramural Research Program of the US National Institutes of Health (NIH), Frederick National Laboratory, Center for Cancer Research. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US government. J.C.B. was supported by a Wellcome Trust grant (WT098051). D.M. and V.K. are supported by the NIHR Cambridge Biomedical Research Centre. L.P.S. is supported by an NIDDK grant (U01 DK062429-14). J.A.T. is supported by the UK Medical Research Council. D.P.B.M. is supported by the Leona M. and Harry B. Helmsley Charitable Trust, the European Union (305479) and by grants from the NIDDK (U01 DK062413, P01 DK046763-19, U54 DE023789-01), the National Institute of Allergy and Infectious Diseases (NIAID; U01 AI067068) and the Agency for Healthcare Research and Quality (AHRQ; HS021747). R.H.D. holds the Inflammatory Bowel Disease Genetic Research endowed chair at the University of Pittsburgh and was supported by an NIDDK grant (U01 DK062420) and a US National Cancer Institute grant (CA141743). S.L.H. and J.R.O. would like to also acknowledge the support of the US NIH (R01 NSO49477 and 1U19 A1067152) and the National Multiple Sclerosis Society (RG 2899-D11). S.L. wishes to acknowledge support from the Australian National Health and Medical Research Council (R.D. Wright Career Development Fellowship, APP1053756). NR 16 TC 49 Z9 50 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD FEB PY 2015 VL 47 IS 2 BP 172 EP 179 DI 10.1038/ng.3176 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CA1TQ UT WOS:000348694700013 PM 25559196 ER PT J AU Fukazawa, Y Lum, R Okoye, AA Park, H Matsuda, K Bae, JY Hagen, SI Shoemaker, R Deleage, C Lucero, C Morcock, D Swanson, T Legasse, AW Axthelm, MK Hesselgesser, J Geleziunas, R Hirsch, VM Edlefsen, PT Piatak, M Estes, JD Lifson, JD Picker, LJ AF Fukazawa, Yoshinori Lum, Richard Okoye, Afam A. Park, Haesun Matsuda, Kenta Bae, Jin Young Hagen, Shoko I. Shoemaker, Rebecca Deleage, Claire Lucero, Carissa Morcock, David Swanson, Tonya Legasse, Alfred W. Axthelm, Michael K. Hesselgesser, Joseph Geleziunas, Romas Hirsch, Vanessa M. Edlefsen, Paul T. Piatak, Michael, Jr. Estes, Jacob D. Lifson, Jeffrey D. Picker, Louis J. TI B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers SO NATURE MEDICINE LA English DT Article ID LOW-LEVEL VIREMIA; CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; SIV INFECTION; HIV-INFECTION; LYMPHOID-TISSUE; DURABLE CONTROL; HELPER-CELLS; REPLICATION; RESPONSES AB Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (T-FH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected T-FH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-T-FH cells, with restriction of productive infection to T-FH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy. C1 [Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam A.; Park, Haesun; Bae, Jin Young; Hagen, Shoko I.; Swanson, Tonya; Legasse, Alfred W.; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. [Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam A.; Park, Haesun; Bae, Jin Young; Hagen, Shoko I.; Swanson, Tonya; Legasse, Alfred W.; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Matsuda, Kenta] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Shoemaker, Rebecca; Deleage, Claire; Lucero, Carissa; Morcock, David; Piatak, Michael, Jr.; Estes, Jacob D.; Lifson, Jeffrey D.] Leidos Biomed Res Inc, Frederick Natl Lab, AIDS & Canc Virus Program, Frederick, MD USA. [Hesselgesser, Joseph; Geleziunas, Romas] Gilead Sci Inc, Foster City, CA USA. [Edlefsen, Paul T.] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. RP Picker, LJ (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. EM pickerl@ohsu.edu FU US National Institutes of Health [5R37A1054292, 5U19AI096109, 8P51OD01109255, HHSN261200800001E]; Intramural Program of the US National Institute of Allergy and Infectious Diseases; Bill and Melinda Gates Foundation [41185] FX The authors dedicate this paper to the memory of Michael Piatak, Jr., in recognition of his key enabling contributions to this study and so many others. This work was supported by the US National Institutes of Health; grants 5R37A1054292 (L.J.P.), 5U19AI096109 (L.J.P. and A.A.O.), and 8P51OD01109255, contract HHSN261200800001E (R.S., M.P., J.D.E. and J.D.L.) and Intramural Program of the US National Institute of Allergy and Infectious Diseases, and the Bill and Melinda Gates Foundation (grant no. 41185; L.J.P.). The authors thank R. Wiseman and D. Watkins for MHC typing; Dr. K. Reimann and the US National Institutes of Health Nonhuman Primate Reagent Resource Program for provision of the CD8 alpha-specific monoclonal antibody M-T807R1; D. Hazuda (Merck Research Labs) for providing cART drugs for cohort 1; Cytheris SA (Issy Les Moulineaux, France) for recombinant rhesus IL-7; S. Hansen for animal study management; A. Sylwester, L. Koo, J. Clock, A. Konfe, H.W. Kim, M. Rohankhedkar, M. Reyes, N. Coombes, B. Assaf, K. Oswald, R. Fast, Y. Li, C. Trubey, J. Turner, S. Planer and L. Boshears for technical or administrative assistance. NR 45 TC 52 Z9 52 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD FEB PY 2015 VL 21 IS 2 BP 44 EP 51 DI 10.1038/nm.3781 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CA5VB UT WOS:000348974800015 ER PT J AU Huber, W Carey, VJ Gentleman, R Anders, S Carlson, M Carvalho, BS Bravo, HC Davis, S Gatto, L Girke, T Gottardo, R Hahne, F Hansen, KD Irizarry, RA Lawrence, M Love, MI MacDonald, J Obenchain, V Oles, AK Pages, H Reyes, A Shannon, P Smyth, GK Tenenbaum, D Waldron, L Morgan, M AF Huber, Wolfgang Carey, Vincent J. Gentleman, Robert Anders, Simon Carlson, Marc Carvalho, Benilton S. Bravo, Hector Corrada Davis, Sean Gatto, Laurent Girke, Thomas Gottardo, Raphael Hahne, Florian Hansen, Kasper D. Irizarry, Rafael A. Lawrence, Michael Love, Michael I. MacDonald, James Obenchain, Valerie Oles, Andrzej K. Pages, Herve Reyes, Alejandro Shannon, Paul Smyth, Gordon K. Tenenbaum, Dan Waldron, Levi Morgan, Martin TI Orchestrating high-throughput genomic analysis with Bioconductor SO NATURE METHODS LA English DT Article ID COMPUTATIONAL BIOLOGY; BIOINFORMATICS; SOFTWARE AB Bioconductor is an open-source, open-development software project for the analysis and comprehension of high-throughput data in genomics and molecular biology. The project aims to enable interdisciplinary research, collaboration and rapid development of scientific software. Based on the statistical programming language R, Bioconductor comprises 934 interoperable packages contributed by a large, diverse community of scientists. Packages cover a range of bioinformatic and statistical applications. They undergo formal initial review and continuous automated testing. We present an overview for prospective users and contributors. C1 [Huber, Wolfgang; Anders, Simon; Oles, Andrzej K.] European Mol Biol Lab, Heidelberg, Germany. [Carey, Vincent J.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Carey, Vincent J.] Harvard Univ, Sch Med, Boston, MA USA. [Carey, Vincent J.; Irizarry, Rafael A.; Love, Michael I.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gentleman, Robert; Lawrence, Michael] Genentech Inc, San Francisco, CA USA. [Carlson, Marc; Obenchain, Valerie; Pages, Herve; Shannon, Paul; Tenenbaum, Dan; Morgan, Martin] Fred Hutchinson Canc Res Ctr, Computat Biol Program, Seattle, WA 98104 USA. [Carvalho, Benilton S.] Univ Estadual Campinas, Sch Med Sci, Dept Med Genet, Campinas, Brazil. [Bravo, Hector Corrada] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. [Davis, Sean] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Gatto, Laurent] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. [Girke, Thomas] Univ Calif Riverside, Inst Integrat Genome Biol, Riverside, CA 92521 USA. [Gottardo, Raphael] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Hahne, Florian] Novartis Inst Biomed Res, Basel, Switzerland. [Hansen, Kasper D.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Hansen, Kasper D.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD USA. [Irizarry, Rafael A.; Love, Michael I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [MacDonald, James] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Smyth, Gordon K.] Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia. [Smyth, Gordon K.] Univ Melbourne, Dept Math & Stat, Parkville, Vic 3052, Australia. [Waldron, Levi] CUNY, Hunter Coll, Sch Urban Publ Hlth, New York, NY 10021 USA. RP Huber, W (reprint author), European Mol Biol Lab, Heidelberg, Germany. EM whuber@embl.de RI Carvalho, Benilton/G-1868-2012; Anders, Simon/D-4087-2011; Smyth, Gordon/B-5276-2008; Reyes, Alejandro/D-8258-2017; OI Hansen, Kasper/0000-0003-0086-0687; Waldron, Levi/0000-0003-2725-0694; Carvalho, Benilton/0000-0001-5122-5646; Anders, Simon/0000-0003-4868-1805; Smyth, Gordon/0000-0001-9221-2892; Reyes, Alejandro/0000-0001-8717-6612; Gatto, Laurent/0000-0002-1520-2268; Huber, Wolfgang/0000-0002-0474-2218; Corrada Bravo, Hector/0000-0002-1255-4444; Davis, Sean/0000-0002-8991-6458; Love, Michael/0000-0001-8401-0545 FU National Human Genome Research Institute of the US National Institutes of Health [U41HG004059]; US National Science Foundation [1247813]; European Commission FP7 project RADIANT FX We thank all contributors to the Bioconductor and R projects. Bioconductor is supported by the National Human Genome Research Institute of the US National Institutes of Health (U41HG004059 to M.M.). Additional support is from the US National Science Foundation (1247813 to M.M.) and the European Commission FP7 project RADIANT (to W.H.). A. Bruce provided graphics support for Figure 2. NR 24 TC 188 Z9 189 U1 11 U2 53 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD FEB PY 2015 VL 12 IS 2 BP 115 EP 121 DI 10.1038/NMETH.3252 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CA4GL UT WOS:000348862500011 PM 25633503 ER PT J AU McNab, F Mayer-Barber, K Sher, A Wack, A O'Garra, A AF McNab, Finlay Mayer-Barber, Katrin Sher, Alan Wack, Andreas O'Garra, Anne TI Type I interferons in infectious disease SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID CD8 T-CELLS; IFN-ALPHA-BETA; INFLUENZA-VIRUS INFECTION; NATURAL-KILLER-CELLS; INNATE IMMUNE-RESPONSE; NITRIC-OXIDE SYNTHASE; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; INTRACELLULAR BACTERIAL-INFECTION; CHRONIC MUCOCUTANEOUS CANDIDIASIS; EXPERIMENTAL VIRAL-INFECTIONS AB Type I interferons (IFNs) have diverse effects on innate and adaptive immune cells during infection with viruses, bacteria, parasites and fungi, directly and/or indirectly through the induction of other mediators. Type I IFNs are important for host defence against viruses. However, recently, they have been shown to cause immunopathology in some acute viral infections, such as influenza virus infection. Conversely, they can lead to immunosuppression during chronic viral infections, such as lymphocytic choriomeningitis virus infection. During bacterial infections, low levels of type I IFNs may be required at an early stage, to initiate cell-mediated immune responses. High concentrations of type I IFNs may block B cell responses or lead to the production of immunosuppressive molecules, and such concentrations also reduce the responsiveness of macrophages to activation by IFN gamma, as has been shown for infections with Listeria monocytogenes and Mycobacterium tuberculosis. Recent studies in experimental models of tuberculosis have demonstrated that prostaglandin E2 and interleukin-1 inhibit type I IFN expression and its downstream effects, demonstrating that a cross-regulatory network of cytokines operates during infectious diseases to provide protection with minimum damage to the host. C1 [Mayer-Barber, Katrin; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [McNab, Finlay; Wack, Andreas; O'Garra, Anne] Natl Inst Med Res, MRC, London NW7 1AA, England. [O'Garra, Anne] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Fac Med, London, England. RP O'Garra, A (reprint author), Natl Inst Med Res, MRC, Mill Hill, London NW7 1AA, England. EM aogarra@nimr.mrc.ac.uk OI Wack, Andreas/0000-0001-5226-2991; O'Garra, Anne/0000-0001-9845-6134 FU Medical Research Council, UK [U117565642, U117597139]; European Research Council [294682-TB-PATH]; National Institute of Allergy and Infectious Diseases, US National Institutes of Health FX The authors' work was supported by the Medical Research Council, UK (grants U117565642 to A. O. G. and U117597139 to A.W.), the European Research Council (grant 294682-TB-PATH to A.O.G.) and the National Institute of Allergy and Infectious Diseases, US National Institutes of Health (grants to K.M.-B. and A.S.). NR 237 TC 153 Z9 157 U1 17 U2 72 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 EI 1474-1741 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD FEB PY 2015 VL 15 IS 2 BP 87 EP 103 DI 10.1038/nri3787 PG 17 WC Immunology SC Immunology GA CA0ZQ UT WOS:000348642400008 PM 25614319 ER PT J AU Andres, SN Appel, CD Westmoreland, JW Williams, JS Nguyen, Y Robertson, PD Resnick, MA Williams, RS AF Andres, Sara N. Appel, C. Denise Westmoreland, James W. Williams, Jessica S. Nguyen, Yvonne Robertson, Patrick D. Resnick, Michael A. Williams, R. Scott TI Tetrameric Ctp1 coordinates DNA binding and DNA bridging in DNA double-strand-break repair SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID END RESECTION; MRE11 COMPLEX; HOMOLOGOUS RECOMBINATION; TOPOISOMERASE-I; EXONUCLEASE 1; CTIP; PROTEIN; SAE2; NBS1; MRE11-RAD50-NBS1 AB Ctp1 (also known as CtIP or Sae2) collaborates with Mre11-Rad50-Nbs1 to initiate repair of DNA double-strand breaks (DSBs), but its functions remain enigmatic. We report that tetrameric Schizosaccharomyces pombe Ctp1 contains multivalent DNA-binding and DNA-bridging activities. Through structural and biophysical analyses of the Ctp1 tetramer, we define the salient features of Ctp1 architecture: an N-terminal interlocking tetrameric helical dimer-of-dimers (THDD) domain and a central intrinsically disordered region (IDR) linked to C-terminal 'RHR' DNA-interaction motifs. The THDD, IDR and RHR are required for Ctp1 DNA-bridging activity in vitro, and both the THDD and RHR are required for efficient DSB repair in S. pombe. Our results establish non-nucleolytic roles of Ctp1 in binding and coordination of DSB-repair intermediates and suggest that ablation of human CtIP DNA binding by truncating mutations underlie the CtIP-linked Seckel and Jawad syndromes. C1 [Andres, Sara N.; Appel, C. Denise; Westmoreland, James W.; Williams, Jessica S.; Nguyen, Yvonne; Robertson, Patrick D.; Resnick, Michael A.; Williams, R. Scott] NIEHS, Genome Integr & Struct Biol Lab, US Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Williams, RS (reprint author), NIEHS, Genome Integr & Struct Biol Lab, US Natl Inst Hlth, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM williamsrs@niehs.nih.gov RI Williams, Robert/A-6059-2015 FU US National Institute of Health Intramural Program, US National Institute of Environmental Health Sciences (NIEHS) [1Z01ES102765, 1Z01ES021016]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX Our studies are supported by the US National Institute of Health Intramural Program, US National Institute of Environmental Health Sciences (NIEHS) grants 1Z01ES102765 (R.S.W.) and 1Z01ES021016 (M.A.R.). We thank L. Pedersen of the NIEHS Collaborative crystallography group and the Advanced Photon Source (APS) Southeast Regional Collaborative Access Team (SER-CAT) for beamline access. Use of the APS was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. W-31-109-Eng-38. We thank M. Junop (University of Western Ontario) for nicked plasmid substrate, J. Williams of the NIEHS protein microcharacterization core for MS analysis, R. Dutcher (NIEHS) for help with MALS analysis and G. Mueller (NIEHS) and B. Wallace (NIEHS) for comments on the manuscript. NR 44 TC 14 Z9 14 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD FEB PY 2015 VL 22 IS 2 BP 158 EP 166 DI 10.1038/nsmb.2945 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CA5SF UT WOS:000348967400012 PM 25580577 ER PT J AU Liu, JM Pattanaik, S Yao, JH Dwyer, AJ Pickhardt, PJ Choi, JR Summers, RM AF Liu, Jiamin Pattanaik, Sanket Yao, Jianhua Dwyer, Andrew J. Pickhardt, Perry J. Choi, J. Richard Summers, Ronald M. TI Associations Among Pericolonic Fat, Visceral Fat, and Colorectal Polyps on CT Colonography SO OBESITY LA English DT Article DE colonic polyps; CT; colon; CT; virtual imaging; pericolonic fat measurement; visceral fat measurement ID ADIPOSE-TISSUE; CANCER; COLONOSCOPY; OBESITY; COLON; RISK AB ObjectiveTo determine the association between pericolonic fat and colorectal polyps using CT colonography (CTC). MethodsA total of 1169 patients who underwent CTC and optical colonoscopy on the same day were assessed. Pericolonic fat was measured on CTC in a band surrounding the colon. Visceral adipose tissue volume was measured at the L2-L3 levels. Student's t-tests, odds ratio, logistic regression, binomial statistics, and weighted kappa were performed to ascertain associations with the incidence of colorectal polyps. ResultsPericolonic fat volume fractions (PFVF) were 61.511.0% versus 58.1 +/- 11.5%, 61.6 +/- 11.1% versus 58.7 +/- 11.5%, and 62.4 +/- 10.6% versus 58.8 +/- 11.5% for patients with and without any polyps, adenomatous polyps, and hyperplastic polyps, respectively (P<0.0001). Similar trends were observed when examining visceral fat volume fractions (VFVF). When patients were ordered by quintiles of PFVF or VFVF, there were 2.49-, 2.19-, and 2.39-fold increases in odds ratio for the presence of any polyp, adenomatous polyps, or hyperplastic polyps from the first to the fifth quintile for PFVF and 1.92-, 2.00-, and 1.71-fold increases in odds ratio for VFVF. Polyps tended to occur more commonly in parts of the colon that had more PFVF than the spatially adjusted average for patients in the highest quintile of VFVF. ConclusionsPericolonic fat accumulations, like visceral fat, are correlated with an increased risk of adenomatous and hyperplastic polyps. C1 [Liu, Jiamin; Pattanaik, Sanket; Yao, Jianhua; Dwyer, Andrew J.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. [Pickhardt, Perry J.] Univ Wisconsin, Dept Radiol, Sch Med, Clin Sci Ctr E3 311, Madison, WI 53706 USA. [Choi, J. Richard] Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural Research Program of the National Institutes of Health, Clinical Center FX Intramural Research Program of the National Institutes of Health, Clinical Center. NR 25 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD FEB PY 2015 VL 23 IS 2 BP 408 EP 414 DI 10.1002/oby.20987 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CA6QN UT WOS:000349040400024 PM 25558027 ER PT J AU Huh, WK Ault, KA Chelmow, D Davey, DD Goulart, RA Garcia, FAR Kinney, WK Massad, LS Mayeaux, EJ Saslow, D Schiffman, M Wentzensen, N Lawson, HW Einstein, MH AF Huh, Warner K. Ault, Kevin A. Chelmow, David Davey, Diane D. Goulart, Robert A. Garcia, Francisco A. R. Kinney, Walter K. Massad, L. Stewart Mayeaux, Edward J. Saslow, Debbie Schiffman, Mark Wentzensen, Nicolas Lawson, Herschel W. Einstein, Mark H. TI Use of Primary High-Risk Human Papillomavirus Testing for Cervical Cancer Screening Interim Clinical Guidance SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LIQUID-BASED CYTOLOGY; FOLLOW-UP; WOMEN; TRIAL; COLPOSCOPY; PREVENTION; SERVICES; FINLAND AB In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U. S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U. S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation. C1 Univ Alabama Birmingham, Birmingham, AL USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. Univ Cent Florida, Orlando, FL 32816 USA. New England Pathol Associates, Springfield, MA USA. Pima Cty Hlth Dept, Tucson, AZ USA. Kaiser Permanente, Sacramento, CA USA. Washington Univ, Sch Med, St Louis, MO USA. Univ S Carolina, Sch Med, Columbia, SC USA. Amer Canc Soc, Atlanta, GA 30329 USA. NCI, Bethesda, MD 20892 USA. Amer Soc Colposcopy & Cerv Pathol, Frederick, MD USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Huh, WK (reprint author), Div Gynecol Oncol, 1700 6th Ave South,WIC Room 10250, Birmingham, AL 35233 USA. EM whuh@uabmc.edu RI Schiffman, Mark/B-9766-2015; OI Zucker-Scharff, Thomas/0000-0002-1790-7405 FU Merck; Hologic; Roche; Gen Probe; GSK; Bristol-Myers Squibb; Photocure; Cepheid; PDS Biotechnologies; Inovio; Endocyte; Fujiboro; Eli Lilly; Becton-Dickinson FX Dr. Huh is on the scientific advisory board of Merck. While at Emory University, Dr. Ault was the site principle investigator for clinical trials sponsored by Merck, Hologic, Roche, and Gen Probe; all payments for the research went to the university. Dr. Ault also has been a consultant to the National Cancer Institute and the American College of Obstetricians and Gynecologists but has not received any payment for these activities. Dr. Garcia was the principle investigator for the 2012 contract between the University of Arizona and Ventana Medical. The contract had a $100,000 value, but Dr. Garcia received no personal compensation. Dr. Schiffman has received assays at no cost from Roche and BD for National Cancer Institute research under his control. Dr. Einstein has advised or participated in educational speaking activities but does not receive an honorarium from any companies. In specific cases, his hospital, Montefiore Medical Center, has received payment for time spent for these activities from Merck, GSK, Roche, Bristol-Myers Squibb, Photocure, Hologic, Cepheid, and PDS Biotechnologies. If travel is required for meetings with any industry, the company pays for Dr. Einstein's travel-related expenses. Also, Montefiore Medical Center has received grant funding for research-related costs of clinical trials for which Dr. Einstein has been the overall principle investigator or the Montefiore principle investigator from Merck, GSK, Roche, Photocure, Inovio, Endocyte, Fujiboro, Eli Lilly, PDS Biotechnologies, Becton-Dickinson, Cepheid, and Hologic. The other authors did not report any potential conflicts of interest. NR 25 TC 24 Z9 27 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2015 VL 125 IS 2 BP 330 EP 337 DI 10.1097/AOG.0000000000000669 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CA0GR UT WOS:000348595500008 PM 25569009 ER PT J AU Azim, S Nicholson, J Rebecchi, MJ Galbavy, W Feng, T Reinsel, R Volkow, ND Benveniste, H Kaczoche, M AF Azim, Syed Nicholson, James Rebecchi, Mario J. Galbavy, William Feng, Tian Reinsel, Ruth Volkow, Nora D. Benveniste, Helene Kaczoche, Martin TI Endocannabinoids and acute pain after total knee arthroplasty SO PAIN LA English DT Article DE Total knee arthroplasty; Pain; Endocannabinoid; 2-AG; Opioid; Osteoarthritis ID ACTIVATED-RECEPTOR-ALPHA; DISABILITY QUESTIONNAIRE; CANNABINOID RECEPTORS; POSTOPERATIVE PAIN; OSTEOARTHRITIS; ANALGESIA; SYSTEM; INHIBITOR; 2-ARACHIDONYLGLYCEROL; PALMITOYLETHANOLAMIDE AB Osteoarthritis (OA) of the knee is a progressive disease that is associated with inflammation of the joints and lower extremity pain. Total knee arthroplasty (TKA) is a surgical procedure that aims to reduce pain and restore motor function in patients suffering from OA. The immediate postoperative period can be intensely painful leading to extended recovery times including persistent pain. The endocannabinoid system regulates nociception, and the activation of cannabinoid receptors produces antinociceptive effects in preclinical models of OA. To date, the influence of the endocannabinoid tone on pain and disability in OA patients and on acute postoperative pain in humans has not been explored. In this study, we provide the first comprehensive profile of endocannabinoids in serum, cerebrospinal fluid, and synovial fluid of patients with painful end-stage OA undergoing TKA and examine correlations between endocannabinoid levels, interleukin 6, functional disability, acute postoperative pain, and postoperative opioid use. Our results reveal that central (cerebrospinal fluid) and peripheral (synovial fluid) levels of the endocannabinoid 2-arachidonoyl glycerol were significantly elevated in patients who developed higher postoperative pain after TKA. In addition, synovial fluid 2-arachidonoyl glycerol levels were positively correlated with postoperative opioid use. Similarly, synovial fluid levels of the anti-inflammatory lipid palmitoylethanolamide correlated with functional disability in OA. Taken together, our results are the first to reveal associations between central and peripheral endocannabinoid levels and postoperative pain. This suggests that endocannabinoid metabolism may serve as a target for the development of novel analgesics both for systemic or local delivery into the joint. C1 [Azim, Syed; Rebecchi, Mario J.; Galbavy, William; Reinsel, Ruth; Benveniste, Helene; Kaczoche, Martin] SUNY Stony Brook, Dept Anesthesiol, Stony Brook, NY 11794 USA. [Nicholson, James] SUNY Stony Brook, Dept Orthoped Surg, Stony Brook, NY 11794 USA. [Feng, Tian] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [Volkow, Nora D.] Natl Inst Alcohol Abuse & Alcoholism, Bethesda, MD USA. RP Kaczoche, M (reprint author), SUNY Stony Brook, Hlth Sci Ctr L4 077, Dept Anesthesiol, Stony Brook, NY 11794 USA. EM martin.kaczocha@stonybrook.edu OI Kaczocha, Martin/0000-0002-2527-1398 FU Department of Anesthesiology; National Institutes of Health [DA035923, DA035949] FX We would like to thank Robert Rieger at the Stony Brook Proteomics Facility for help with mass spectrometry. This work was supported by the Department of Anesthesiology and by National Institutes of Health grants DA035923 and DA035949. NR 52 TC 6 Z9 6 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD FEB PY 2015 VL 156 IS 2 BP 341 EP 347 DI 10.1097/01.j.pain.0000460315.80981.59 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA CA5UQ UT WOS:000348973700019 PM 25599456 ER PT J AU Wiener, L Viola, A Koretski, J Perper, ED Patenaude, AF AF Wiener, Lori Viola, Adrienne Koretski, Julia Perper, Emily Diana Patenaude, Andrea Farkas TI Pediatric psycho-oncology care: standards, guidelines, and consensus reports SO PSYCHO-ONCOLOGY LA English DT Article DE pediatric; psychosocial; standards; guidelines; consensus reports ID SIOP WORKING COMMITTEE; QUALITY CANCER CARE; CHILDHOOD-CANCER; ISSUES; CHILDREN; ADOLESCENT; DIAGNOSIS; SURVIVORS; SUPPORT; ASSISTANCE AB ObjectiveThe aim of this study was to identify existing guidelines, standards, or consensus-based reports for psychosocial care of children with cancer and their families. PurposePsychosocial standards of care for children with cancer can systematize the approach to care and create a replicable model that can be utilized in pediatric hospitals around the world. Determining gaps in existing standards in pediatric psycho-oncology can guide development of useful evidence-based and consensus-based standards. MethodsThe MEDLINE and PubMed databases were searched by investigators at two major pediatric oncology centers for existing guidelines, consensus-based reports, or standards for psychosocial care of patients with pediatric cancer and their families published in peer-reviewed journals in English between 1980 and 2013. ResultsWe located 27 articles about psychosocial care that met inclusion criteria: 5 set forth standards, 19 were guidelines, and 3 were consensus-based reports. None was sufficiently up to date, comprehensive, specific enough, or evidence- or consensus-based to serve as a current standard for psychosocial care for children with cancer and their families. ConclusionDespite calls by a number of international pediatric oncology and psycho-oncology professional organizations about the urgency of addressing the psychosocial needs of the child with cancer to reduce suffering, there remains a need for development of a widely acceptable, evidence-based and consensus-based, comprehensive standard of care to guide provision of essential psychosocial services to all patients with pediatric cancer. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. C1 [Wiener, Lori] NCI, NIH, Bethesda, MD 20892 USA. [Viola, Adrienne] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Koretski, Julia; Patenaude, Andrea Farkas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Perper, Emily Diana] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Patenaude, Andrea Farkas] Childrens Hosp, Boston, MA 02115 USA. [Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wiener, L (reprint author), NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 47 TC 7 Z9 7 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD FEB PY 2015 VL 24 IS 2 BP 204 EP 211 DI 10.1002/pon.3589 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CA2TN UT WOS:000348760800012 PM 24906202 ER PT J AU Stevenson, MC Salerno, JM Bottoms, BL Najdowski, CJ Wiley, TRA Farnum, KS AF Stevenson, Margaret C. Salerno, Jessica M. Bottoms, Bette L. Najdowski, Cynthia J. Wiley, Tisha R. A. Farnum, Katlyn S. TI The Influence of a Juvenile's Abuse History on Support for Sex Offender Registration SO PSYCHOLOGY PUBLIC POLICY AND LAW LA English DT Article DE child sexual abuse; juvenile sex offending; legal decision making; attributions; public policy ID INTELLECTUAL DISABILITY; CONFESSION EVIDENCE; CAPITAL-PUNISHMENT; RECIDIVISM RISK; PUBLIC SUPPORT; CHILD-ABUSE; MEGANS LAW; PERCEPTIONS; DEFENDANTS; JUDGMENTS AB We investigated whether and how a juvenile's history of experiencing sexual abuse affects public perceptions of juvenile sex offenders in a series of 5 studies. When asked about juvenile sex offenders in an abstract manner (Studies 1 and 2), the more participants (community members and undergraduates) believed that a history of being sexually abused as a child causes later sexually abusive behavior, the less likely they were to support sex offender registration for juveniles. Yet when participants considered specific sexual offenses, a juvenile's history of sexual abuse was not considered to be a mitigating factor. This was true when participants considered a severe sexual offense (forced rape; Study 3 and Study 4) and a case involving less severe sexual offenses (i.e., statutory rape), when a juvenile's history of sexual abuse backfired and was used as an aggravating factor, increasing support for registering the offender (Study 3 and Study 5). Theoretical and practical implications of these results are discussed. C1 [Stevenson, Margaret C.] Univ Evansville, Dept Psychol, Evansville, IN 47722 USA. [Najdowski, Cynthia J.] SUNY Albany, Dept Criminal Justice, Albany, NY 12222 USA. [Salerno, Jessica M.] Arizona State Univ, Dept Social & Behav Sci, Tempe, AZ 85287 USA. [Wiley, Tisha R. A.] NIDA, Rockville, MD USA. [Bottoms, Bette L.] Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. [Farnum, Katlyn S.] Univ Nebraska, Dept Psychol, Lincoln, NE 68583 USA. RP Stevenson, MC (reprint author), Univ Evansville, Dept Psychol, 1800 Lincoln Ave, Evansville, IN 47722 USA. EM ms446@evansville.edu NR 73 TC 1 Z9 1 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1076-8971 EI 1939-1528 J9 PSYCHOL PUBLIC POL L JI Psychol. Public Policy Law PD FEB PY 2015 VL 21 IS 1 BP 35 EP 49 DI 10.1037/law0000028 PG 15 WC Health Policy & Services; Law; Psychology, Multidisciplinary SC Health Care Sciences & Services; Government & Law; Psychology GA CA6KH UT WOS:000349021500004 ER PT J AU Strang, NM Claus, ED Ramchandani, VA Graff-Guerrero, A Boileau, I Hendershot, CS AF Strang, Nicole M. Claus, Eric D. Ramchandani, Vijay A. Graff-Guerrero, Ariel Boileau, Isabelle Hendershot, Christian S. TI Dose-dependent effects of intravenous alcohol administration on cerebral blood flow in young adults SO PSYCHOPHARMACOLOGY LA English DT Article DE Alcohol intoxication; Alcohol clamp; Alcohol sensitivity; Cerebral perfusion; FMRI; Self-rating of the effects of alcohol ID HUMAN BRAIN; PERFUSION; INTOXICATION; RESPONSES; ETHANOL; FMRI; STIMULATION; TOLERANCE; INGESTION; DRINKING AB Functional magnetic resonance imaging (fMRI) studies involving alcohol challenge are important for identifying neural correlates of alcohol's psychopharmacological effects. However, evaluating acute alcohol effects on blood oxygen level-dependent (BOLD) signal change is complicated by alcohol-related increases in cerebral blood flow (CBF). The present study aimed to further characterize acute alcohol effects on CBF using intravenous alcohol administration to maximize control over brain alcohol exposure. Twenty heavy-drinking young adults (M = 19.95 years old, SD = 0.76) completed alcohol and placebo imaging sessions in a within-subject, counter-balanced, placebo-controlled design. Arterial spin labeling (ASL) provided estimates of perfusion change at two target blood alcohol concentrations (40 and 80 mg%) relative to baseline and relative to a saline control infusion. Voxel-wise analyses showed widespread and dose-dependent effects of alcohol on CBF increase. Region-of-interest analyses confirmed these findings, also indicating regional variation in the magnitude of perfusion change. Additional findings indicated that lower self-reported sensitivity to alcohol corresponded with reduced perfusion change during alcohol administration. This study provides further evidence for widespread effects of acute alcohol on cerebral perfusion, also demonstrating regional, dose-dependent, and inter-individual variation. Further research is needed to evaluate implications of these effects for the design and interpretation of pharmacological fMRI studies involving alcohol challenge. C1 [Strang, Nicole M.; Graff-Guerrero, Ariel; Boileau, Isabelle; Hendershot, Christian S.] Campbell Family Mental Hlth Res Inst, Ctr Addict & Mental Hlth, Toronto, ON M6J 1H4, Canada. [Claus, Eric D.] Mind Res Network, Albuquerque, NM USA. [Claus, Eric D.] Lovelace Biomed & Environm Res Inst, Albuquerque, NM USA. [Ramchandani, Vijay A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Graff-Guerrero, Ariel; Boileau, Isabelle; Hendershot, Christian S.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. RP Hendershot, CS (reprint author), Campbell Family Mental Hlth Res Inst, Ctr Addict & Mental Hlth, 100 Stokes St, Toronto, ON M6J 1H4, Canada. EM christian.hendershot@utoronto.ca RI Hendershot, Christian/C-1638-2009; boileau, isabelle/L-5153-2016; OI boileau, isabelle/0000-0002-9901-1484; Hendershot, Christian/0000-0002-5328-2035 FU Canadian Institutes of Health Research (CIHR) [260418, 288905/307742]; ABMRF/The Foundation for Alcohol Research; Canada Foundation for Innovation; NIH [R21 AA020304, P60AA 007611]; NIAAA Division of Intramural Clinical and Biological Research FX This study was supported by Canadian Institutes of Health Research (CIHR) grant 260418 (CH). The authors also acknowledge the support from CIHR grants 288905/307742; ABMRF/The Foundation for Alcohol Research; and the Canada Foundation for Innovation (CH), NIH R21 AA020304 (EC, CH), the NIAAA Division of Intramural Clinical and Biological Research (VAR), and NIH P60AA 007611. The authors declare no conflicts of interest. NR 49 TC 7 Z9 8 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2015 VL 232 IS 4 BP 733 EP 744 DI 10.1007/s00213-014-3706-z PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CA5XX UT WOS:000348982800007 PM 25110231 ER PT J AU Bluemke, DA Meltzer, CC AF Bluemke, David A. Meltzer, Carolyn C. TI Ebola Virus Disease: Radiology Preparedness SO RADIOLOGY LA English DT Article AB At present, there is a major emphasis on Ebola virus disease (EVD) preparedness training at medical facilities throughout the United States. Failure to have proper EVD procedures in place was cited as a major reason for infection of medical personnel in the United States. Medical imaging does not provide diagnosis of EVD, but patient assessment in the emergency department and treatment isolation care unit is likely to require imaging services. The purpose of this article is to present an overview of relevant aspects of EVD disease and preparedness relevant to the radiologic community. (C) RSNA, 2014 C1 [Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Meltzer, Carolyn C.] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Atlanta, GA USA. [Meltzer, Carolyn C.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Meltzer, Carolyn C.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA USA. RP Bluemke, DA (reprint author), NIH, Dept Radiol & Imaging Sci, 10 Ctr Dr,Room 1C355, Bethesda, MD 20892 USA. EM bluemked@nih.gov OI Bluemke, David/0000-0002-8323-8086 NR 4 TC 5 Z9 5 U1 0 U2 3 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 FEB PY 2015 VL 274 IS 2 BP 527 EP 531 DI 10.1148/radiol.14142502 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CA1WS UT WOS:000348700300025 PM 25405643 ER PT J AU Marras, TK Prevots, DR Jamieson, FB Winthrop, KL AF Marras, Theodore K. Prevots, D. Rebecca Jamieson, Frances B. Winthrop, Kevin L. CA Pulm MAC Outcomes Grp TI Variable agreement among experts regarding Mycobacterium avium complex lung disease SO RESPIROLOGY LA English DT Article DE Delphi technique; Mycobacterium avium-intracellulare infection; mycobacterium infection; non-tuberculous mycobacterium; practice guideline ID PREVALENCE; ONTARIO; MANAGEMENT; INFECTION; CANADA; COSTS AB Data regarding many clinical aspects of pulmonary Mycobacterium avium complex (pMAC) are lacking. Guidelines rely substantially upon expert opinion, integrated through face-to-face meetings, variably weighting individual opinions. We surveyed North American non-tuberculous mycobacteria experts regarding clinical aspects of pMAC using Delphi methods. Nineteen of 26 invited experts (73%) responded, with extensive variability. Convergence could not be reached for most questions. Respondents described extensive uncertainty around specific issues. Findings underscore urgent need for more research. C1 [Marras, Theodore K.] Univ Hlth Network & Mt Sinai Hosp, Joint Div Respirol, Toronto, ON, Canada. [Marras, Theodore K.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Jamieson, Frances B.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Jamieson, Frances B.] Ontario Agcy Hlth Protect & Promot, Publ Hlth Labs, Toronto, ON, Canada. [Prevots, D. Rebecca] NIAID, NIH, Bethesda, MD 20892 USA. [Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Marras, TK (reprint author), Toronto Western Hosp, 7E-452,399 Bathurst St, Toronto, ON M5T 2S8, Canada. EM ted.marras@uhn.ca NR 15 TC 7 Z9 7 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-7799 EI 1440-1843 J9 RESPIROLOGY JI Respirology PD FEB PY 2015 VL 20 IS 2 BP 348 EP 351 DI 10.1111/resp.12440 PG 4 WC Respiratory System SC Respiratory System GA AZ3EK UT WOS:000348110300026 PM 25430584 ER PT J AU Munk, MR Jung, JJ Biggee, K Tucker, WR Sen, HN Schmidt-Erfurth, U Fawzi, AA Jampol, LM AF Munk, Marion R. Jung, Jesse J. Biggee, Kristin Tucker, William R. Sen, H. Nida Schmidt-Erfurth, Ursula Fawzi, Amani A. Jampol, Lee M. TI IDIOPATHIC MULTIFOCAL CHOROIDITIS/PUNCTATE INNER CHOROIDOPATHY WITH ACUTE PHOTORECEPTOR LOSS OR DYSFUNCTION OUT OF PROPORTION TO CLINICALLY VISIBLE LESIONS SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE multifocal choroiditis; punctate inner choroidopathy; acute zonal occult outer retinopathy; optical coherence tomography; acute vision loss; autofluorescence; photoreceptor loss ID OCCULT OUTER RETINOPATHY; INDOCYANINE GREEN ANGIOGRAPHY; PERSISTENT PLACOID MACULOPATHY; CENTRAL SEROUS RETINOPATHY; BLIND SPOT ENLARGEMENT; PANUVEITIS AB Purpose: To report acute/subacute vision loss and paracentral scotomata in patients with idiopathic multifocal choroiditis/punctate inner choroidopathy due to large zones of acute photoreceptor attenuation surrounding the chorioretinal lesions. Methods: Multimodal imaging case series. Results: Six women and 2 men were included (mean age, 31.5 +/- 5.8 years). Vision ranged from 20/20-1 to hand motion (mean, 20/364). Spectral domain optical coherence tomography demonstrated extensive attenuation of the external limiting membrane, ellipsoid and interdigitation zones, adjacent to the visible multifocal choroiditis/punctate inner choroidopathy lesions. The corresponding areas were hyperautofluorescent on fundus autofluorescence and were associated with corresponding visual field defects. Full-field electroretinogram (available in three cases) showed markedly decreased cone/rod response, and multifocal electroretinogram revealed reduced amplitudes and increased implicit times in two cases. Three patients received no treatment, the remaining were treated with oral corticosteroids (n = 4), oral acyclovir/valacyclovir (n = 2), intravitreal/posterior subtenon triamcinolone acetate (n = 3), and anti-vascular endothelial growth factor (n = 2). Visual recovery occurred in only three cases of whom two were treated. Varying morphological recovery was found in six cases, associated with decrease in hyperauto-fluorescence on fundus autofluorescence. Conclusion: Multifocal choroiditis/punctate inner choroidopathy can present with transient or permanent central photoreceptor attenuation/loss. This presentation is likely a variant of multifocal choroiditis/punctate inner choroidopathy with chorioretinal atrophy. Associated changes are best evaluated using multimodal imaging. C1 [Munk, Marion R.; Fawzi, Amani A.; Jampol, Lee M.] Northwestern Univ, Feinberg Sch Med, Dept Ophthalmol, Chicago, IL 60611 USA. [Munk, Marion R.; Schmidt-Erfurth, Ursula] Med Univ Vienna, Dept Ophthalmol, Vienna, Austria. [Jung, Jesse J.] NYU, Dept Ophthalmol, Sch Med, New York, NY 10016 USA. [Jung, Jesse J.] Vitreous Retina Macula Consultants New York, New York, NY USA. [Jung, Jesse J.] Columbia Coll Phys & Surg, Edward S Harkness Eye Inst, Dept Ophthalmol, New York, NY USA. [Biggee, Kristin] Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, Portland, OR 97201 USA. [Tucker, William R.; Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA. RP Jampol, LM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Ophthalmol, 645 N Michigan Ave,Suite 440, Chicago, IL 60611 USA. EM l-jampol@northwestern.edu OI fawzi, amani/0000-0002-9568-3558 FU Research to Prevent Blindness, Inc, New York, NY FX Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc, New York, NY and by Kevin Hitzeman and Mary Demsey. NR 28 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD FEB PY 2015 VL 35 IS 2 BP 334 EP 343 PG 10 WC Ophthalmology SC Ophthalmology GA CA2UU UT WOS:000348764200024 PM 25322466 ER PT J AU Hall, MH Smagula, SF Boudreau, RM Ayonayon, HN Goldman, SE Harris, TB Naydeck, BL Rubin, SM Samuelsson, L Satterfield, S Stone, KL Visser, M Newman, AB AF Hall, Martica H. Smagula, Stephen F. Boudreau, Robert M. Ayonayon, Hilsa N. Goldman, Suzanne E. Harris, Tamara B. Naydeck, Barbara L. Rubin, Susan M. Samuelsson, Laura Satterfield, Suzanne Stone, Katie L. Visser, Marjolein Newman, Anne B. TI Association between Sleep Duration and Mortality Is Mediated by Markers of Inflammation and Health in Older Adults: The Health, Aging and Body Composition Study SO SLEEP LA English DT Article DE epidemiology; sleep; inflammation; mortality; aging ID C-REACTIVE PROTEIN; ALL-CAUSE MORTALITY; CARDIOVASCULAR RISK; LEPTIN LEVELS; WHITEHALL-II; YOUNG-WOMEN; MASS INDEX; LONG-SLEEP; RESTRICTION; DEPRIVATION AB Study Objective: Inflammation may represent a common physiological pathway linking both short and long sleep duration to mortality. We evaluated inflammatory markers as mediators of the relationship between sleep duration and mortality in community-dwelling older adults. Design: Prospective cohort with longitudinal follow-up for mortality outcomes. Setting: Pittsburgh, Pennsylvania, and Memphis, Tennessee. Participants: Participants in the Health, Aging and Body Composition (Health ABC) Study (mean age 73.6 +/- 2.9 years at baseline) were sampled and recruited from Medicare listings. Measurements and Results: Baseline measures of subjective sleep duration, markers of inflammation (serum interleukin-6, tumor necrosis factor-a, and C-reactive protein) and health status were evaluated as predictors of all-cause mortality (average follow-up = 8.2 +/- 2.3 years). Sleep duration was related to mortality, and age-, sex-, and race-adjusted hazard ratios (HR) were highest for those with the shortest (< 6 h HR: 1.30, CI: 1.05-1.61) and longest (> 8 h HR: 1.49, CI: 1.15-1.93) sleep durations. Adjustment for inflammatory markers and health status attenuated the HR for short (< 6 h) sleepers (HR = 1.06, 95% CI = 0.83-1.34). Age-, sex-, and race-adjusted HRs for the > 8-h sleeper group were less strongly attenuated by adjustment for inflammatory markers than by other health factors associated with poor sleep with adjusted HR = 1.23, 95% CI = 0.93-1.63. Inflammatory markers remained significantly associated with mortality. Conclusions: Inflammatory markers, lifestyle, and health status explained mortality risk associated with short sleep, while the mortality risk associated with long sleep was explained predominantly by lifestyle and health status. C1 [Hall, Martica H.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15261 USA. [Smagula, Stephen F.; Boudreau, Robert M.; Goldman, Suzanne E.; Naydeck, Barbara L.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Ayonayon, Hilsa N.; Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Ayonayon, Hilsa N.; Rubin, Susan M.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Samuelsson, Laura] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15261 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Stone, Katie L.] Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA USA. [Visser, Marjolein] Vrije Univ Amsterdam Med Ctr, Inst Hlth Sci, Amsterdam, Netherlands. [Visser, Marjolein] Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Med, Pittsburgh, PA 15261 USA. RP Newman, AB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, 130 Desoto St,A527 Crabtree Hall, Pittsburgh, PA 15261 USA. EM NewmanA@edc.pitt.edu RI Newman, Anne/C-6408-2013; Hall, Martica/D-2809-2012; OI Newman, Anne/0000-0002-0106-1150; Hall, Martica/0000-0003-0642-2098; Samuelsson, Laura B./0000-0002-4632-2027; Boudreau, Robert/0000-0003-0162-5187 FU National Institute on Aging (NIA) [N 01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR [R01-NR012459] FX This was not an industry supported study. This research was supported by National Institute on Aging (NIA) Contracts N 01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, and NINR grant R01-NR012459. The authors have indicated no financial conflicts of interest. Dr. Goldman, is currently with the Vanderbilt University Medical Center, Department of Neurology, Sleep Disorders Center, Nashville, Tennessee, USA; Ms. Naydeck is currently with HM Insurance, Pittsburgh, PA, USA. NR 47 TC 14 Z9 14 U1 2 U2 5 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD FEB 1 PY 2015 VL 38 IS 2 BP 189 EP 195 DI 10.5665/sleep.4394 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CA2SO UT WOS:000348757800006 PM 25348127 ER PT J AU Blank, M Zhang, JH Lamers, F Taylor, AD Hickie, IB Merikangas, KR AF Blank, Madeleine Zhang, Jihui Lamers, Femke Taylor, Adrienne D. Hickie, Ian B. Merikangas, Kathleen R. TI Health Correlates of Insomnia Symptoms and Comorbid Mental Disorders in a Nationally Representative Sample of US Adolescents SO SLEEP LA English DT Article DE adolescent; chronic medical conditions; insomnia; mental disorders; suicidality ID QUALITY-OF-LIFE; SLEEP PROBLEMS; SURVEY-REPLICATION; BEHAVIORAL-PROBLEMS; GENERAL-POPULATION; PERCEIVED HEALTH; SUICIDE ATTEMPTS; SUBSTANCE USE; PREVALENCE; DEPRESSION AB Study Objectives: To estimate the prevalence and health correlates of insomnia symptoms and their association with comorbid mental disorders in a nationally representative sample of adolescents in the United States. Design: National representative cross-sectional study. Setting: Population-based sample from the US adolescents. Measurements and Results: A total of 6,483 individuals aged between 13-18 y in the National Comorbidity Survey-Adolescent Supplement (NCS-A) with both individual and parental reports of mental health were included in this study. Participants were classified with insomnia symptoms if they reported difficulty initiating sleep, difficulty maintaining sleep, and/or early morning awakening, nearly every day for at least 2 w in the past year. Nearly one-third of adolescents reported insomnia symptoms for at least 2 w during the previous year. Hispanic and black youth were significantly more likely to report insomnia symptoms (42.0% and 41.3%, respectively) than non-Hispanic white youth (30.4%). Adolescents with insomnia symptoms were at a higher risk for all classes of mental disorders {odds ratio [OR] (95% confidence interval [CI]: 3.4 (2.9-4.0)} including mood, anxiety, behavioral, substance use, and eating disorders, suicidality [OR (95% CI): 2.63 (1.34-5.16)], poor perceived mental health [OR (95% CI): 2.01 (1.02-3.96)], chronic medical conditions [OR (95% CI): 1.94 (1.55-2.43)], smoking [OR (95% CI: 2.60 (1.00-6.72)], and obesity [OR (95% CI: 1.46 (1.10-1.93)] than those without insomnia symptoms. Adolescents with insomnia symptoms and comorbid mental disorders manifested even greater rates of these indicators of negative health behaviors and disorders than those with mental disorders alone (P < 0.05). Conclusions: Insomnia symptoms are reported by one-third of adolescents in the general population. Insomnia symptoms, even in the absence of concomitant depression or other mental disorders, are associated with serious health conditions, risk factors, and suicidality. Comorbid mental disorders potentiate the effect of insomnia symptoms on both physical and mental health. Further evaluation of the causes and effective interventions to reduce insomnia symptoms may have a significant effect on public health. C1 [Blank, Madeleine; Zhang, Jihui; Lamers, Femke; Taylor, Adrienne D.; Merikangas, Kathleen R.] NIMH, Genet Epidemiol Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Zhang, Jihui] Chinese Univ Hong Kong, Fac Med, Dept Psychiat, Shatin, Hong Kong, Peoples R China. [Lamers, Femke] GGZ Geest VUmc, Dept Psychiat, Amsterdam, Netherlands. [Taylor, Adrienne D.] Duke Univ, Sch Med, Durham, NC USA. [Hickie, Ian B.] Univ Sydney Camperdown, Brain & Mind Res Inst, Sydney, NSW, Australia. RP Merikangas, KR (reprint author), NIMH, Intramural Res Program, Genet Epidemiol Branch, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM Kathleen.merikangas@nih.gov FU National Institute of Mental Health [U01-MH60220, ZIA MH 002808]; National Institute of Drug Abuse [R01DA016558]; Intramural Research Program of the National Institute of Mental Health FX This was not an industry supported study. The National Comorbidity Survey-Adolescent Supplement (NCS-A) was supported by the National Institute of Mental Health (U01-MH60220) and (ZIA MH 002808), and the National Institute of Drug Abuse (R01DA016558). The NCS-A was carried out in conjunction with the World Health Organization World Mental Health (WMH) Survey Initiative. This work was supported by the Intramural Research Program of the National Institute of Mental Health. The views and opinions expressed in this article are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies, or the U.S. government. The authors have indicated no financial conflicts of interest. NR 47 TC 11 Z9 11 U1 4 U2 22 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD FEB 1 PY 2015 VL 38 IS 2 BP 197 EP + DI 10.5665/sleep.4396 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CA2SO UT WOS:000348757800007 PM 25325502 ER PT J AU Lomax, GP Hull, SC Isasi, R AF Lomax, Geoffrey P. Hull, Sara Chandros Isasi, Rosario TI The DISCUSS Project: Revised Points to Consider for the Derivation of Induced Pluripotent Stem Cell Lines From Previously Collected Research Specimens SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Article AB Human somatic cell reprogramming is a leading technology for accelerating disease modeling and drug discovery. The Deriving Induced Stem Cells Using Stored Specimens (DISCUSS) project is a consensus-building initiative designed to consider how human somatic cells obtained under general biomedical research protocols can be used in induced pluripotent stem cell (iPSC) derivation. We previously published a draft list of points to consider for the use of previously collected specimens in iPSC research and then initiated a structured feedback and comment process. Here, we present a summary of this feedback and revised list of points to consider. C1 [Lomax, Geoffrey P.] Calif Inst Regenerat Med, San Francisco, CA 94107 USA. [Hull, Sara Chandros] NHGRI, Off Clin Director, Bethesda, MD 20892 USA. [Hull, Sara Chandros] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Isasi, Rosario] McGill Univ, Fac Med, Dept Human Genet, Ctr Genom & Policy, Montreal, PQ, Canada. RP Lomax, GP (reprint author), Calif Inst Regenerat Med, 210 King St,3rd Floor, San Francisco, CA 94107 USA. EM glomax@cirm.ca.gov FU International Stem Cell Forum; Stem Cell Network of Canada FX The opinions expressed above are those of the authors alone and do not necessarily reflect the policies or positions of the NIH, the U.S. Public Health Service, or the U.S. Department of Health and Human Services. The points to consider do not form policy of a U.S. federal agency or the International Stem Cell Forum. We acknowledge the International Stem Cell Forum and the Stem Cell Network of Canada for funding support and Justin Lowenthal, Mahendra Rao, and the DISCUSS Workshop participants for their intellectual contribution to this work. NR 16 TC 2 Z9 2 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 EI 2157-6580 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD FEB PY 2015 VL 4 IS 2 BP 123 EP 129 DI 10.5966/sctm.2014-0192 PG 7 WC Cell & Tissue Engineering SC Cell Biology GA CA5SK UT WOS:000348967900002 PM 25561681 ER PT J AU Leung, AM Avram, AM Brenner, AV Duntas, LH Ehrenkranz, J Hennessey, JV Lee, SL Pearce, EN Roman, SA Stagnaro-Green, A Sturgis, EM Sundaram, K Thomas, MJ Wexler, JA AF Leung, Angela M. Avram, Anca M. Brenner, Alina V. Duntas, Leonidas H. Ehrenkranz, Joel Hennessey, James V. Lee, Stephanie L. Pearce, Elizabeth N. Roman, Sanziana A. Stagnaro-Green, Alex Sturgis, Erich M. Sundaram, Krishnamurthi Thomas, Michael J. Wexler, Jason A. CA Amer Thyroid Assoc Public Hlth TI Potential Risks of Excess Iodine Ingestion and Exposure: Statement by the American Thyroid Association Public Health Committee SO THYROID LA English DT Article ID POSTPARTUM; MANAGEMENT; PREGNANCY; DISEASE C1 [Leung, Angela M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol, Los Angeles, CA 90073 USA. [Avram, Anca M.] Univ Michigan, Med Ctr, Div Nucl Med Radiol, Ann Arbor, MI USA. [Brenner, Alina V.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Duntas, Leonidas H.] Univ Athens, Evgenid Hosp, Unit Endocrinol Metab & Diabet, Athens, Greece. [Ehrenkranz, Joel] Intermt Healthcare, Dept Med, Salt Lake City, UT USA. [Hennessey, James V.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol,Dept Med, Boston, MA 02215 USA. [Lee, Stephanie L.; Pearce, Elizabeth N.] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Roman, Sanziana A.] Duke Univ, Sch Med, Dept Surg, Durham, NC USA. [Stagnaro-Green, Alex] Univ Illinois, Coll Med Rockford, Rockford, IL USA. [Sturgis, Erich M.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. [Sundaram, Krishnamurthi] Suny Downstate Med Ctr, Dept Otolaryngol, Brooklyn, NY 11203 USA. [Thomas, Michael J.] Carolina Endocrine PA, Raleigh, NC USA. [Wexler, Jason A.] Georgetown Univ, Sch Med, Div Endocrinol & Metab, Washington, DC USA. RP Leung, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM amleung@mednet.ucla.edu NR 6 TC 4 Z9 4 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD FEB 1 PY 2015 VL 25 IS 2 BP 145 EP 146 DI 10.1089/thy.2014.0331 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CA6HQ UT WOS:000349012300001 PM 25275241 ER PT J AU George, AK Pinto, PA AF George, Arvin K. Pinto, Peter A. TI Multiparametric Magnetic Resonance Imaging Enhances Detection of Significant Tumor in Patients on Active Surveillance for Prostate Cancer COMMENT SO UROLOGY LA English DT Editorial Material C1 [George, Arvin K.; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP George, AK (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 BC011023-01]; NCI NIH HHS [Z01 BC011081-01, Z01 BC011023-01] NR 4 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD FEB PY 2015 VL 85 IS 2 BP 429 EP 429 DI 10.1016/j.urology.2014.09.063 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AZ9UN UT WOS:000348562200041 PM 25623711 ER PT J AU Langan, RC Lagisetty, KH Atay, S Pandalai, P Stojadinovic, A Rudloff, U Avital, I AF Langan, Russell C. Lagisetty, Kiran H. Atay, Scott Pandalai, Prakash Stojadinovic, Alexander Rudloff, Udo Avital, Itzhak TI Surgery for Li Fraumeni Syndrome Pushing the Limits of Surgical Oncology SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE Li Fraumeni syndrome; metastasectomy; simultaneous pancreaticoduodenectomy and hepatectomy ID GERMLINE MUTATION; BREAST-CANCER; PATIENT; TUMORS; RADIOTHERAPY; PANCREATICODUODENECTOMY; MALIGNANCIES; MANAGEMENT; MORBIDITY; MORTALITY AB Objectives: Li Fraumeni syndrome is an autosomal dominant cancer syndrome due to a germline mutation in the p53 tumor suppressor gene. It results in multiple primary neoplasms in children and adults. A common question when faced with a Li Fraumeni patient who develops multiple primary cancers and/or recurrences is what is the proper treatment? Data suggests that ionizing radiation exposure increases the incidence of second malignancies in the Li Fraumeni population. Therefore, how much surgery can a cancer patient tolerate and still derive benefit from it? Methods: We describe a representative case of a 54-year-old female with Li Fraumeni syndrome with an enlarging adrenocortical hepatic metastasis, a new primary ampullary cancer, and an extensive surgical history. Results: We performed a simultaneous pancreaticoduodenectomy and repeat partial hepatectomy. Conclusions: We propose that surgery is underutilized in metastatic solid organ familial cancers in general, and argue that an aggressive surgical approach should be considered in a multidisciplinary manner for patients with Li Fraumeni syndrome and recurrent tumors. However, because of the rarity of this familial cancer there is a paucity of evidence to support this approach, therefore a review of the literature is presented. C1 [Langan, Russell C.] Georgetown Univ Hosp, Dept Surg, Washington, DC 20037 USA. [Lagisetty, Kiran H.; Atay, Scott] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Langan, Russell C.; Lagisetty, Kiran H.; Atay, Scott; Pandalai, Prakash; Rudloff, Udo] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Stojadinovic, Alexander] Walter Reed Natl Mil, Med Ctr, Dept Surg, Div Surg Oncol, Bethesda, MD USA. [Stojadinovic, Alexander] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. [Avital, Itzhak] Bon Secours Canc Inst, Richmond, VA USA. RP Langan, RC (reprint author), Georgetown Univ Hosp, Dept Surg, 3800 Reservoir Rd, Washington, DC 20037 USA. EM russell.c.langan@gunet.georgetown.edu FU NIH FX Supported by the NIH intramural grant. NR 24 TC 1 Z9 1 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD FEB PY 2015 VL 38 IS 1 BP 98 EP 102 DI 10.1097/COC.0b013e3182880bc5 PG 5 WC Oncology SC Oncology GA AZ5WK UT WOS:000348288900018 PM 23563208 ER PT J AU Horger, KS Liu, HY Rao, DK Shulda, S Sept, D Ambudkar, SV Mayer, M AF Horger, Kim S. Liu, Haiyan Rao, Divya K. Shulda, Suneet Sept, David Ambudkar, Suresh V. Mayer, Michael TI Hydrogel-assisted functional reconstitution of human P-glycoprotein (ABCB1) in giant liposomes SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE Liposome; Proteoliposome; P-glycoprotein; Chloride ion channel; Transport rate constant; Permeability ID ACTIVATED CHLORIDE CHANNELS; UNILAMELLAR VESICLES; MULTIDRUG-RESISTANCE; MEMBRANE-PROTEINS; ATP HYDROLYSIS; CELL-VOLUME; PHYSIOLOGICAL CONDITIONS; LIPID-MEMBRANES; TRANSPORT; PROTEOLIPOSOMES AB This paper describes the formation of giant proteoliposomes containing P-glycoprotein (P-gp) from a solution of small proteoliposomes that had been deposited and partially dried on a film of agarose. This preparation method generated a significant fraction of giant proteoliposomes that were free of internalized vesicles, making it possible to determine the accessible liposome volume. Measuring the intensity of the fluorescent substrate rhodamine 123 (Rho123) inside and outside these giant proteoliposomes determined the concentration of transported substrates of P-gp. Fitting a kinetic model to the fluorescence data revealed the rate of passive diffusion as well as active transport by reconstituted P-gp in the membrane. This approach determined estimates for the membrane permeability coefficient (P-s) of passive diffusion and rate constants of active transport (k(T)) by P-gp as a result of different experimental conditions. The P-s value for Rho123 was larger in membranes containing P-gp under all assay conditions than in membranes without P-gp indicating increased leakiness in the presence of reconstituted transmembrane proteins. For P-gp liposomes, the k(T) value was significantly higher in the presence of ATP than in its absence or in the presence of ATP and the competitive inhibitor verapamil. This difference in k(T) values verified that P-gp was functionally active after reconstitution and quantified the rate of active transport. Lastly, patch clamp experiments on giant proteoliposomes showed ion channel activity consistent with a chloride ion channel protein that co-purified with P-gp. Together, these results demonstrate several advantages of using giant rather than small proteoliposomes to characterize transport properties of transport proteins and ion channels. (C) 2014 Elsevier B.V. All rights reserved. C1 [Horger, Kim S.; Mayer, Michael] Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. [Liu, Haiyan; Rao, Divya K.; Sept, David; Mayer, Michael] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. [Shulda, Suneet; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20814 USA. [Sept, David] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. RP Mayer, M (reprint author), Univ Michigan, Dept Chem Engn, 1101 Beal Ave, Ann Arbor, MI 48109 USA. EM mimayer@umich.edu RI Mayer, Michael/C-1299-2010; OI Mayer, Michael/0000-0002-6148-5756; Sept, David/0000-0003-3719-2483 FU National Institutes of Health [1R01GM081705]; Air Force Office of Scientific Research (AFOSR) [FA9550-12-1-0435]; NIH, National Cancer Institute, Center for Cancer Research; NIH from the National Institute of Biomedical Imaging and Bioengineering at NIH [T32EB005582]; Rackham Engineering Award Fellowship FX This work was supported by the National Institutes of Health (M.M., grant no. 1R01GM081705) and the Air Force Office of Scientific Research (AFOSR) (M.M. and D.S. grant no. FA9550-12-1-0435). Drs. S. Shukla and S.V. Ambudkar were supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. K.S.H. acknowledges a Microfluidics in Biomedical Sciences Training Program fellowship from NIH (grant no. T32EB005582 from the National Institute of Biomedical Imaging and Bioengineering at NIH) and a Rackham Engineering Award Fellowship. NR 70 TC 6 Z9 6 U1 3 U2 33 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 EI 0006-3002 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD FEB PY 2015 VL 1848 IS 2 BP 643 EP 653 DI 10.1016/j.bbamem.2014.10.023 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CA1QT UT WOS:000348687500030 PM 25450342 ER PT J AU Saxman, SB AF Saxman, Scott Brian TI ETHICAL CONSIDERATIONS FOR OUTCOME-ADAPTIVE TRIAL DESIGNS: A CLINICAL RESEARCHER'S PERSPECTIVE SO BIOETHICS LA English DT Article DE outcome-adaptive trial design; clinical research ethics ID EQUIPOISE AB In a typical comparative clinical trial the randomization scheme is fixed at the beginning of the study, and maintained throughout the course of the trial. A number of researchers have championed a randomized trial design referred to as outcome-adaptive randomization.' In this type of trial, the likelihood of a patient being enrolled to a particular arm of the study increases or decreases as preliminary information becomes available suggesting that treatment may be superior or inferior. While the design merits of outcome-adaptive trials have been debated, little attention has been paid to significant ethical concerns that arise in the conduct of such studies. These include loss of equipoise, lack of processes for adequate informed consent, and inequalities inherent in the research design which could lead to perceptions of injustice that may have negative implications for patients and the research enterprise. This article examines the ethical difficulties inherent in outcome-adaptive trials. C1 [Saxman, Scott Brian] Eli Lilly, Indianapolis, IN USA. [Saxman, Scott Brian] Univ Oklahoma, Norman, OK 73019 USA. [Saxman, Scott Brian] Indiana Univ, Bloomington, IN 47405 USA. [Saxman, Scott Brian] NCI, Bethesda, MD 20892 USA. [Saxman, Scott Brian] Off Med Serv Peace Corps, Washington, DC USA. RP Saxman, SB (reprint author), Lilly Corp Ctr, Indianapolis, IN 46285 USA. EM saxmansc@lilly.com NR 13 TC 7 Z9 7 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-9702 EI 1467-8519 J9 BIOETHICS JI Bioethics PD FEB PY 2015 VL 29 IS 2 BP 59 EP 65 DI 10.1111/bioe.12084 PG 7 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA AZ8BX UT WOS:000348440700002 PM 24547903 ER PT J AU Arai, S Arora, M Wang, T Spellman, SR He, W Courie, DR Urbano-Ispizua, A Cutler, CS Bacigalupo, AA Battiwallaw, M Flowers, ME Juckett, MB Lee, SJ Loren, AW Klumpp, TR Prockup, SE Ringden, OETH Savani, BN Socie, G Schultz, KR Spitzer, T Teshima, T Bredeson, CN Jacobsohn, DA Hayashi, RJ Drobyski, WR Frangoul, HA Akpek, G Ho, VT Lewis, VA Gale, RP Koreth, J Chao, NJ Aljurf, MD Cooper, BW Laughlin, MJ Hsu, JW Hematti, P Verdonck, LF Solh, MM Norkin, M Reddy, V Perez-Simon, JA Khera, N Lewis, ID Atsuta, Y Olsson, RF Saber, W Waller, EK Blaise, D Pidala, JA Martin, PJ Satwani, P Bornhauser, M Inamoto, Y Weisdorf, DJ Horowitz, MM Pavletic, SZ AF Arai, Sally Arora, Mukta Wang, Tao Spellman, Stephen R. He, Wensheng Courie, Daniel R. Urbano-Ispizua, Alvaro Cutler, Corey S. Bacigalupo, Andrea A. Battiwallaw, Minoo Flowers, Mary E. Juckett, Mark B. Lee, Stephanie J. Loren, Alison W. Klumpp, Thomas R. Prockup, Susan E. Ringden, Olle E. T. H. Savani, Bipin N. Socie, Gerard Schultz, Kirk R. Spitzer, Thomas Teshima, Takanori Bredeson, Christopher N. Jacobsohn, David A. Hayashi, Robert J. Drobyski, William R. Frangoul, Haydar A. Akpek, Gorgiin Ho, Vincent T. Lewis, Victor A. Gale, Robert Peter Koreth, John Chao, Nelson J. Aljurf, Mahmoud D. Cooper, Brenda W. Laughlin, Mary J. Hsu, Jack W. Hematti, Peiman Verdonck, Leo F. Solh, Melhelm M. Norkin, Maxim Reddy, Vijay Perez-Simon, Jose A. Khera, Nandita Lewis, Ian D. Atsuta, Yoshiko Olsson, Richard F. Saber, Wael Waller, Edmund K. Blaise, Didier Pidala, Joseph A. Martin, Paul J. Satwani, Prakash Bornhauser, Martin Inamoto, Yoshihiro Weisdorf, Daniel J. Horowitz, Mary M. Pavletic, Steven Z. CA Graft-Vs-Host Dis Working Comm CIB TI Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic Transplantation: A Report from the Center for International Blood and Marrow Transplant Research SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Incidence; cGVHD; Allogeneic transplant; Nonrelapse mortality ID HEMATOPOIETIC-CELL TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; BONE-MARROW; UNRELATED DONORS; STEM-CELL; REDUCED-INTENSITY; CLINICAL-TRIALS; COMPETING RISKS; SINGLE-CENTER AB Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P <.0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Arai, Sally; Arora, Mukta; Wang, Tao] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. [Arora, Mukta] Univ Minnesota, Med Ctr, Div Hematol Oncol & Transplant, Minneapolis, MN 55455 USA. [Wang, Tao] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA. [Wang, Tao] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Natl Marrow Donor Program, Minneapolis, MN USA. [He, Wensheng; Loren, Alison W.] Univ Michigan, Div Hematol Oncol, Ann Arbor, MI USA. [Loren, Alison W.; Spitzer, Thomas] Hosp Clin Barcelona, Div Hematol Oncol, Barcelona, Spain. [Socie, Gerard; Bredeson, Christopher N.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Teshima, Takanori; Waller, Edmund K.] IRCCS AOU San Martino IST, Dept Hematol, Genoa, Italy. [Loren, Alison W.; Hematti, Peiman; Satwani, Prakash] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Koreth, John; Norkin, Maxim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Koreth, John; Perez-Simon, Jose A.] Univ Washington, Seattle, WA 98195 USA. [Aljurf, Mahmoud D.; Cooper, Brenda W.; Laughlin, Mary J.] Univ Wisconsin, Hosp & Clin, Dept Med, Div Hematol Oncol Bone Marrow Transplantat, Madison, WI 53792 USA. [Hematti, Peiman; Verdonck, Leo F.; Solh, Melhelm M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Hematti, Peiman; Solh, Melhelm M.; Norkin, Maxim] Univ Penn, Med Ctr, Abramson Canc Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Reddy, Vijay; Perez-Simon, Jose A.; Khera, Nandita] Temple Bone Marrow Transplant Program, Div Bone Marrow Transplantat, Philadelphia, PA USA. [Lewis, Ian D.; Atsuta, Yoshiko; Olsson, Richard F.] Mem Sloan Kettering Canc Ctr, Dept Pediat, Div Bone Marrow Transplant, New York, NY 10021 USA. [Saber, Wael; Waller, Edmund K.; Blaise, Didier] Karolinska Univ Hosp, Div Clin Immunol, Stockholm, Sweden. [Saber, Wael; Waller, Edmund K.; Blaise, Didier] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. [Pidala, Joseph A.; Martin, Paul J.; Satwani, Prakash] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN 37235 USA. [Martin, Paul J.] Hop St Louis, Div Hematol, Paris, France. [Satwani, Prakash; Bornhauser, Martin] Univ British Columbia, British Columbias Childrens Hosp, Dept Pediat Hematol Oncol BMT, Vancouver, BC V5Z 1M9, Canada. [Bornhauser, Martin; Inamoto, Yoshihiro] Massachusetts Gen Hosp, Dept Bone Marrow Transplant Oncol, Boston, MA 02114 USA. [Inamoto, Yoshihiro; Weisdorf, Daniel J.] Kyushu Univ Hosp, Fukuoka 812, Japan. [Horowitz, Mary M.] Ottawa Hosp, Dept Med, Ottawa, ON, Canada. [Horowitz, Mary M.; Pavletic, Steven Z.] Childrens Natl Hlth Syst, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC USA. [Pavletic, Steven Z.; Graft-Vs-Host Dis Working Comm CIB] Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO USA. RP Pavletic, SZ (reprint author), NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, 9000 Rockville Pike,Bldg 10 CRC,Room 3E-3330, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov RI IBIS, ONCOHEMATOLOGI/P-3457-2015; OI Olsson, Richard/0000-0001-5970-2128 FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung, and Blood Institute (NHLBI) [U24-CA76518]; National Institute of Allergy and Infectious Diseases (NIAID) [U24-CA76518]; NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be The Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; Medical College of Wisconsin; Merck 82 Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; Therakos; WellPoint The views expressed in this article do not reflect the official policy or position of the NIH; Department of the Navy; Department of Defense, or any other agency of the U.S. Government FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) (U24-CA76518), and the National Institute of Allergy and Infectious Diseases (NIAID) (U24-CA76518); Grant/Cooperative Agreement 5U01HL069294 from the NHLBI and NCI; contract HHSH234200637015C with Health Resources and Services Administration; 2 grants (N00014-06-1-0704 and N00014-08-1-0058) from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be The Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Medical College of Wisconsin; Merck 82 Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; Therakos; and WellPoint The views expressed in this article do not reflect the official policy or position of the NIH, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government. NR 32 TC 41 Z9 44 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2015 VL 21 IS 2 BP 266 EP 274 DI 10.1016/j.bbmt.2014.10.021 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CA0UW UT WOS:000348632700009 PM 25445023 ER PT J AU Blair, RJR AF Blair, R. J. R. TI Psychopathic traits from an RDoC perspective SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID CALLOUS-UNEMOTIONAL TRAITS; DISRUPTIVE BEHAVIOR DISORDERS; AMYGDALA RESPONSE; CONDUCT PROBLEMS; METAANALYTIC EVIDENCE; ANTISOCIAL-BEHAVIOR; FACIAL EXPRESSIONS; PREFRONTAL CORTEX; PREDICTION ERROR; REWARD SYSTEM AB In this review an RDoC approach is applied to psychopathic traits. Two core neuro-cognitive systems relevant to the emergence of psychopathic traits are considered. These are the response to other individuals' emotional displays and reinforcement-based decision-making. C1 NIMH, Sect Affect Cognit Neurosci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Sect Affect Cognit Neurosci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM jamesblair@mail.nih.gov FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health [1-ZIA-MH002860-08] FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health under grant number 1-ZIA-MH002860-08. NR 48 TC 4 Z9 4 U1 3 U2 12 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD FEB PY 2015 VL 30 BP 79 EP 84 DI 10.1016/j.conb.2014.09.011 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AZ6OA UT WOS:000348337600012 PM 25464372 ER PT J AU Friedman, LA Rapoport, JL AF Friedman, Lisa A. Rapoport, Judith L. TI Brain development in ADHD SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; PREFRONTAL CORTEX; FOLLOW-UP; METAANALYSIS; CHILDHOOD; CHILDREN; ADULTS; AGE; ADOLESCENTS AB Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with underlying brain anatomical and functional measures, as well as familial/genetic factors that are major foci of neuropsychiatric research. Advances in imaging technology have shown structural and functional brain differences between individuals with and without ADHD. Longitudinal studies have enabled the elucidation of differences in developmental course. Studies comparing persisting and remitting cases of ADHD are particularly promising. Therapeutic doses of psychostimulants normalize many measures of brain anatomy and function. C1 [Friedman, Lisa A.; Rapoport, Judith L.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Friedman, LA (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM Lisa.Friedman@nih.gov; Judy.Rapoport@nih.gov NR 53 TC 10 Z9 12 U1 5 U2 39 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD FEB PY 2015 VL 30 BP 106 EP 111 DI 10.1016/j.conb.2014.11.007 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AZ6OA UT WOS:000348337600016 PM 25500059 ER PT J AU Monteggia, LM Zarate, C AF Monteggia, Lisa M. Zarate, Carlos, Jr. TI Antidepressant actions of ketamine: from molecular mechanisms to clinical practice SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID TREATMENT-RESISTANT DEPRESSION; NEUROTROPHIC FACTOR; MAJOR DEPRESSION; DOUBLE-BLIND; ANTAGONIST; TRIAL AB In the past decade the emergence of glutamate N-methyl-D-aspartate (NMDA) receptor blockers such as ketamine as fast-acting antidepressants fostered a major conceptual advance by demonstrating the possibility of a rapid antidepressant response. This discovery brings unique mechanistic insight into antidepressant action, as there is a substantial amount of basic knowledge on glutamatergic neurotransmission and how blockade of NMDA receptors may elicit plasticity. The combination of this basic knowledge base and the growing clinical findings will facilitate the development of novel fast acting antidepressants. C1 [Monteggia, Lisa M.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA. [Zarate, Carlos, Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Zarate, Carlos, Jr.] Dept Hlth & Human Serv, Bethesda, MD USA. RP Monteggia, LM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Neurosci, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM lisa.monteggia@utsouthwestern.edu FU National Institutes of Health [MH070727]; Intramural Research Program of the National Institute of Mental Health/National Institutes of Health; National Alliance for Research on Schizophrenia and Depression Independent Investigator Award; Brain and Behavior Foundation Award; International Mental Health Research Organization FX This work was supported by National Institutes of Health Grant MH070727 (to L.M.M.), the Intramural Research Program of the National Institute of Mental Health/National Institutes of Health (to C.A.Z.), by a National Alliance for Research on Schizophrenia and Depression Independent Investigator Award (to C.A.Z), by a Brain and Behavior Foundation Award (to C.A.Z. and to L.M.M) and the International Mental Health Research Organization (to L.M.M.). NR 43 TC 34 Z9 34 U1 8 U2 37 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD FEB PY 2015 VL 30 BP 139 EP 143 DI 10.1016/j.conb.2014.12.004 PG 5 WC Neurosciences SC Neurosciences & Neurology GA AZ6OA UT WOS:000348337600020 PM 25562451 ER PT J AU Sumner, AE Thoreson, CK O'Connor, MY Ricks, M Chung, ST Tulloch-Reid, MK Lozier, JN Sacks, DB AF Sumner, Anne E. Thoreson, Caroline K. O'Connor, Michelle Y. Ricks, Madia Chung, Stephanie T. Tulloch-Reid, Marshall K. Lozier, Jay N. Sacks, David B. TI Detection of Abnormal Glucose Tolerance in Africans Is Improved by Combining A1C With Fasting Glucose: The Africans in America Study SO DIABETES CARE LA English DT Article ID LIFE-STYLE INTERVENTION; CARDIOVASCULAR RISK-FACTORS; SICKLE-CELL TRAIT; DIABETES PREVENTION; US POPULATION; HEMOGLOBIN-C; FOLLOW-UP; PREVALENCE; CRITERIA; MEN AB OBJECTIVEAbnormal glucose tolerance is rising in sub-Saharan Africa. Hemoglobin A(1c) by itself and in combination with fasting plasma glucose (FPG) is used to diagnose abnormal glucose tolerance. The diagnostic ability of A1C in Africans with heterozygous variant hemoglobin, such as sickle cell trait or hemoglobin C trait, has not been rigorously evaluated. In U.S.-based Africans, we determined by hemoglobin status the sensitivities of 1) FPG 5.6 mmol/L, 2) A1C 5.7% (39 mmol/mol), and 3) FPG combined with A1C (FPG 5.6 mmol/L and/or A1C 5.7% [39 mmol/mol]) for the detection of abnormal glucose tolerance.RESEARCH DESIGN AND METHODSAn oral glucose tolerance test (OGTT) was performed in 216 African immigrants (68% male, age 37 10 years [mean SD], range 20-64 years). Abnormal glucose tolerance was defined as 2-h glucose 7.8 mmol/L.RESULTSVariant hemoglobin was identified in 21% (46 of 216). Abnormal glucose tolerance occurred in 33% (72 of 216). When determining abnormal glucose tolerance from the OGTT (2-h glucose 7.8 mmol/L), sensitivities of FPG for the total, normal, and variant hemoglobin groups were 32%, 32%, and 33%, respectively. Sensitivities for A1C were 53%, 54%, and 47%. For FPG and A1C combined, sensitivities were 64%, 63%, and 67%. Sensitivities for FPG and A1C and the combination did not vary by hemoglobin status (all P > 0.6). For the entire cohort, sensitivity was higher for A1C than FPG and for both tests combined than for either test alone (all P values 0.01).CONCLUSIONSNo significant difference in sensitivity of A1C by variant hemoglobin status was detected. For the diagnosis of abnormal glucose tolerance in Africans, the sensitivity of A1C combined with FPG is significantly superior to either test alone. C1 [Sumner, Anne E.; Thoreson, Caroline K.; O'Connor, Michelle Y.; Ricks, Madia; Chung, Stephanie T.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Tulloch-Reid, Marshall K.] Univ W Indies, Res Inst Trop Med, Kingston 7, Jamaica. [Lozier, Jay N.; Sacks, David B.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Sumner, AE (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. EM annes@intra.niddk.nih.gov OI Sacks, David/0000-0003-3100-0735 FU NIH/National Institute of Diabetes and Digestive and Kidney Diseases/Clinical Center Intramural Program; intramural program of National Institute of Diabetes and Digestive and Kidney Diseases, NIH; Intramural Research Program of the NIH Clinical Center FX Support was received from the NIH/National Institute of Diabetes and Digestive and Kidney Diseases/Clinical Center Intramural Program. A.E.S., C.K.T., M.Y.O'C., M.R., and S.T.C. were supported by the intramural program of National Institute of Diabetes and Digestive and Kidney Diseases, NIH. J.N.L. and D.B.S. were supported by the Intramural Research Program of the NIH Clinical Center. NR 34 TC 7 Z9 7 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2015 VL 38 IS 2 BP 213 EP 219 DI 10.2337/dc14-1179 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AZ8JK UT WOS:000348461400019 PM 25338926 ER PT J AU Kemppainen, KM Ardissone, AN Davis-Richardson, AG Fagen, JR Gano, KA Leon-Novelo, LG Vehik, K Casella, G Simell, O Ziegler, AG Rewers, MJ Lernmark, A Hagopian, W She, JX Krischer, JP Akolkar, B Schatz, DA Atkinson, MA Triplett, EW AF Kemppainen, Kaisa M. Ardissone, Alexandria N. Davis-Richardson, Austin G. Fagen, Jennie R. Gano, Kelsey A. Leon-Novelo, Luis G. Vehik, Kendra Casella, George Simell, Olli Ziegler, Anette G. Rewers, Marian J. Lernmark, Ake Hagopian, William She, Jin-Xiong Krischer, Jeffrey P. Akolkar, Beena Schatz, Desmond A. Atkinson, Mark A. Triplett, Eric W. CA TEDDY Study Grp TI Early Childhood Gut Microbiomes Show Strong Geographic Differences Among Subjects at High Risk for Type 1 Diabetes SO DIABETES CARE LA English DT Article ID INTESTINAL MICROBIOTA; CELL AUTOIMMUNITY; CHILDREN; INFANTS; EUROPE AB OBJECTIVEGut microbiome dysbiosis is associated with numerous diseases, including type 1 diabetes. This pilot study determines how geographical location affects the microbiome of infants at high risk for type 1 diabetes in a population of homogenous HLA class II genotypes.RESEARCH DESIGN AND METHODSHigh-throughput 16S rRNA sequencing was performed on stool samples collected from 90 high-risk, nonautoimmune infants participating in The Environmental Determinants of Diabetes in the Young (TEDDY) study in the U.S., Germany, Sweden, and Finland.RESULTSStudy site-specific patterns of gut colonization share characteristics across continents. Finland and Colorado have a significantly lower bacterial diversity, while Sweden and Washington state are dominated by Bifidobacterium in early life. Bacterial community diversity over time is significantly different by geographical location.CONCLUSIONSThe microbiome of high-risk infants is associated with geographical location. Future studies aiming to identify the microbiome disease phenotype need to carefully consider the geographical origin of subjects. C1 [Kemppainen, Kaisa M.; Ardissone, Alexandria N.; Davis-Richardson, Austin G.; Fagen, Jennie R.; Gano, Kelsey A.; Triplett, Eric W.] Univ Florida, Inst Food & Agr Sci, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA. [Leon-Novelo, Luis G.] Univ Louisiana Lafayette, Dept Math, Lafayette, LA 70504 USA. [Vehik, Kendra; Krischer, Jeffrey P.] Univ S Florida, Hlth Informat Inst, Tampa, FL USA. [Casella, George] Univ Florida, Dept Stat, Gainesville, FL 32611 USA. [Simell, Olli] Univ Turku, Dept Pediat, Turku Univ Hosp, Turku, Finland. [Ziegler, Anette G.] Tech Univ Munich, Diabet Res Inst, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Ziegler, Anette G.] Tech Univ Munich, Klinikum Rechts Isar, Neuherberg, Germany. [Ziegler, Anette G.] Forschergrp Diabet eV, Neuherberg, Germany. [Rewers, Marian J.] Univ Colorado, Sch Med, Barbara Davis Ctr Diabet, Aurora, CO USA. [Lernmark, Ake] Lund Univ, Dept Clin Sci, Clin Res Ctr, Skane Univ Hosp, Malmo, Sweden. [Hagopian, William] Pacific Northwest Diabet Res Inst, Seattle, WA USA. [She, Jin-Xiong] Georgia Regents Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA USA. [Akolkar, Beena] NIDDK, NIH, Bethesda, MD 20892 USA. [Schatz, Desmond A.] Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. [Atkinson, Mark A.] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. RP Triplett, EW (reprint author), Univ Florida, Inst Food & Agr Sci, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA. EM ewt@ufl.edu RI Ziegler, Anette-Gabriele/M-4614-2014; Bonifacio, Ezio/E-7700-2010 OI Ziegler, Anette-Gabriele/0000-0002-6290-5548; Bonifacio, Ezio/0000-0002-8704-4713 FU National Institute of Diabetes and Digestive and Kidney Diseases [HHSN267200700014C]; National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development; National Institute of Environmental Health Sciences; JDRF; Centers for Disease Control and Prevention; National Institutes of Health/National Center for Advancing Translational Sciences Clinical and Translational Science Awards [UL1-TR-000064]; University of Colorado [UL1-TR-001082]; [U01-DK-63829]; [U01-DK-63861]; [U01-DK-63821]; [U01-DK-63865]; [U01-DK-63863]; [U01-DK-63836]; [U01-DK-63790]; [UC4-DK-63829]; [UC4-DK-63861]; [UC4-DK-63821]; [UC4-DK-63865]; [UC4-DK-63863]; [UC4-DK-63836]; [UC4-DK-95300] FX This study was funded by grants U01-DK-63829, U01-DK-63861, U01-DK-63821, U01-DK-63865, U01-DK-63863, U01-DK-63836, U01-DK-63790, UC4-DK-63829, UC4-DK-63861, UC4-DK-63821, UC4-DK-63865, UC4-DK-63863, UC4-DK-63836, and UC4-DK-95300, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute of Allergy and Infectious Diseases; the National Institute of Child Health and Human Development; the National Institute of Environmental Health Sciences; JDRF; and the Centers for Disease Control and Prevention. This work was supported in part by National Institutes of Health/National Center for Advancing Translational Sciences Clinical and Translational Science Awards to the University of Florida (UL1-TR-000064) and the University of Colorado (UL1-TR-001082). NR 18 TC 18 Z9 18 U1 1 U2 21 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 FEB PY 2015 VL 38 IS 2 BP 329 EP 332 DI 10.2337/dc14-0850 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AZ8JK UT WOS:000348461400035 PM 25519450 ER PT J AU Dize, L West, SK Mkocha, H Quinn, TC Gaydos, CA AF Dize, L. West, S. K. Mkocha, H. Quinn, T. C. Gaydos, C. A. TI Evaluation of pooled ocular and vaginal swabs by the Cepheid GeneXpert CT/NG assay for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae compared to the GenProbe Aptima Combo 2 Assay SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Trachoma; Chlamydia trachomatis; Neisseria gonorrhoeae; Pooling ID SEXUALLY-TRANSMITTED INFECTIONS; ACID AMPLIFICATION TESTS; LIGASE CHAIN-REACTION; COST-SAVING STRATEGY; SCREENING-PROGRAM; URINE SPECIMENS; PCR; SAMPLES; WOMEN; PERFORMANCE AB Ocular swabs from Tanzania were tested for Chlamydia trachomatis (Cr), and self-collected vaginal swabs collected through a home collection program, iwantthekit.org, were tested for Neisseria gonorrhoeae and CT to evaluate Cepheid GeneXpert for the use of pooling multiple specimens before testing. GeneXpert shows to be a promising test for pooling. (C) 2015 Elsevier Inc. All rights reserved. C1 [Dize, L.; Quinn, T. C.; Gaydos, C. A.] Johns Hopkins Univ, Int Sexually Transmitted Dis Res Lab, Div Infect Dis, Baltimore, MD 21218 USA. [West, S. K.] Johns Hopkins Univ, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21218 USA. [Mkocha, H.] Kongwa Trachoma Project, Kongwa, Tanzania. [Quinn, T. C.] NIH, Natl Inst Allergy & Infect Dis, Div Intramural Res, Bethesda, MD 20892 USA. RP Dize, L (reprint author), Johns Hopkins Univ, Int Sexually Transmitted Dis Res Lab, Div Infect Dis, Baltimore, MD 21218 USA. EM Ldize2@jhmi.edu FU NEI NIH HHS [U10 EY022584]; NIAID NIH HHS [UM1 AI068613, U01 AI068613]; NIBIB NIH HHS [U54 EB007958] NR 22 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 EI 1879-0070 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD FEB PY 2015 VL 81 IS 2 BP 102 EP 104 DI 10.1016/j.diagmicrobio.2014.11.010 PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA AZ8WD UT WOS:000348491500006 PM 25497459 ER PT J AU Christensen, J Fischer, RJ McCoy, BN Raffel, SJ Schwan, TG AF Christensen, Joshua Fischer, Robert J. McCoy, Brandi N. Raffel, Sandra J. Schwan, Tom G. TI Tickborne Relapsing Fever, Bitterroot Valley, Montana, USA SO EMERGING INFECTIOUS DISEASES LA English DT Article ID SPIROCHETE BORRELIA-HERMSII; MOUNTAIN-SPOTTED-FEVER; NORTH-AMERICA; MONOCLONAL-ANTIBODY; LYME BORRELIOSIS; UNITED-STATES; TICK; CALIFORNIA; TRANSMISSION; UVEITIS AB In July 2013, a resident of the Bitterroot Valley in western Montana, USA, contracted tickborne relapsing fever caused by an infection with the spirochete Borrelia hermsii. The patient's travel history and activities before onset of illness indicated a possible exposure on his residential property on the eastern side of the valley. An onsite investigation of the potential exposure site found the vector, Omithodoros hermsi ticks, and 1 chipmunk infected with spirochetes, which on the basis of multilocus sequence typing were identical to the spirochete isolated from the patient. Field studies in other locations found additional serologic evidence and an infected tick that demonstrated a wider distribution of spirochetes circulating among the small mammal populations. Our study demonstrates that this area of Montana represents a previously unrecognized focus of relapsing fever and poses a risk for persons of acquiring this tickborne disease. C1 [Christensen, Joshua] St Patricks Hosp, Missoula, MT USA. [Christensen, Joshua] Univ Montana, Coll Hlth Profess & Biomed Sci, Missoula, MT 59812 USA. [Fischer, Robert J.; McCoy, Brandi N.; Raffel, Sandra J.; Schwan, Tom G.] NIAID, Hamilton, MT 59840 USA. RP Schwan, TG (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM tschwan@niaid.nih.gov OI Fischer, Robert/0000-0002-1816-472X FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was supported in part by the Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 36 TC 3 Z9 3 U1 1 U2 5 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD FEB PY 2015 VL 21 IS 2 BP 217 EP 223 DI 10.3201/eid2102.141276 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AZ8WC UT WOS:000348491400004 PM 25625502 ER PT J AU Marzi, A Feldmann, F Geisbert, TW Feldmann, H Safronetz, D AF Marzi, Andrea Feldmann, Friederike Geisbert, Thomas W. Feldmann, Heinz Safronetz, David TI Vesicular Stomatitis Virus-Based Vaccines against Lassa and Ebola Viruses SO EMERGING INFECTIOUS DISEASES LA English DT Article ID PROTECTS NONHUMAN-PRIMATES; ANTIBODIES; GLYCOPROTEINS; CHALLENGE; DISEASE AB We demonstrated that previous vaccination with a vesicular stomatitis virus (VSV) based Lassa virus vaccine does not alter protective efficacy of subsequent vaccination with a VSV-based Ebola virus vaccine. These findings demonstrate the utility of VSV-based vaccines against divergent viral pathogens, even when preexisting immunity to the vaccine vector is present. C1 [Marzi, Andrea; Feldmann, Friederike; Feldmann, Heinz; Safronetz, David] NIH, Hamilton, MT 59840 USA. [Geisbert, Thomas W.] Univ Texas Med Branch, Galveston, TX 77555 USA. RP Safronetz, D (reprint author), NIH, Dis Modeling & Transmiss Sect, Virol Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM safronetzd@niaid.nih.gov FU Division of Intramural Research National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was supported by the Division of Intramural Research National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 12 TC 11 Z9 11 U1 3 U2 28 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD FEB PY 2015 VL 21 IS 2 BP 305 EP 307 DI 10.3201/eid2102.141649 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AZ8WC UT WOS:000348491400015 PM 25625358 ER PT J AU Cekartova, M Fernando, RI Siriwardhana, N Sukhthankar, M de la Parra, C Woraratphoka, J Malone, C Strom, A Baekd, SJ Wadef, PA Saxton, AM Donnell, RM Pestell, RG Dharmawardhane, S Wimalasena, J AF Cekartova, Maria Fernando, Romaine I. Siriwardhana, Nalin Sukhthankar, Mugdha de la Parra, Columba Woraratphoka, Jirayus Malone, Christine Stroem, Anders Baekd, Seung J. Wadef, Paul A. Saxton, Arnold M. Donnell, Robert M. Pestell, Richard G. Dharmawardhane, Suranganie Wimalasena, Jay TI BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE BAD; Extracellular matrix invasion; Breast cancer; Metastasis ID CYCLIN D1; MITOCHONDRIAL-MEMBRANES; ENDOPLASMIC-RETICULUM; MUTATIONAL ANALYSIS; PROGNOSTIC MARKER; PROAPOPTOTIC BAD; INDUCE APOPTOSIS; CARCINOMA-CELLS; COLON CANCERS; KAPPA-B AB We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of beta-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TIMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. (C) 2014 Elsevier Inc. All rights reserved. C1 [Cekartova, Maria] Univ Tennessee, Coll Vet Med, Dept Small Anim Clin Sci, Knoxville, TN 37996 USA. [Fernando, Romaine I.; Woraratphoka, Jirayus; Wimalasena, Jay] Univ Tennessee, Med Ctr, Grad Sch Med, Dept Obstet & Gynecol, Knoxville, TN USA. [Siriwardhana, Nalin; Saxton, Arnold M.] Univ Tennessee, Dept Anim Sci, Knoxville, TN 37901 USA. [Sukhthankar, Mugdha; Baekd, Seung J.; Donnell, Robert M.] Univ Tennessee, Coll Vet Med, Dept Biomed & Diagnost Sci, Knoxville, TN USA. [de la Parra, Columba; Dharmawardhane, Suranganie] Univ Puerto Rico, Sch Med, Dept Biochem, San Juan, PR 00936 USA. [Malone, Christine; Wadef, Paul A.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. [Stroem, Anders] Univ Houston, Ctr Nucl Receptors & Cell Signaling, Dept Biol & Biochem, Houston, TX USA. [Pestell, Richard G.] Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA. RP Cekartova, M (reprint author), Univ Tennessee, Coll Vet Med, Dept Small Anim Clin Sci, Knoxville, TN 37996 USA. EM mcekanov@utk.edu; jwimalas@gmail.com OI Cekanova, Maria/0000-0002-9651-1619; Donnell, Robert L./0000-0002-6778-954X FU NIH, USA Grant [R01CA84048]; University of Tennessee Graduate School of Medicine Physician's Medical Education and Research Foundation [R084025002, R181721242] FX This work was supported partially by NIH, USA Grant (R01CA84048, PI: Wimalasena), and two grants by the University of Tennessee Graduate School of Medicine Physician's Medical Education and Research Foundation (R084025002, PI: Wimalasena, and R181721242, PI: Cekanova). Dr. Jay Wimalasena is thankful to undergraduate students of UT: Erica Smith, Rhett Layman, and Blair Tatge for their technical assistance. NR 71 TC 8 Z9 10 U1 1 U2 15 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD FEB 1 PY 2015 VL 331 IS 1 BP 1 EP 10 DI 10.1016/j.yexcr.2014.11.016 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CA0UK UT WOS:000348631600001 PM 25499972 ER PT J AU Zhao, N Bell, DA Maity, A Staicu, AM Joubert, BR London, SJ Wu, MC AF Zhao, Ni Bell, Douglas A. Maity, Arnab Staicu, Ana-Maria Joubert, Bonnie R. London, Stephanie J. Wu, Michael C. TI Global Analysis of Methylation Profiles From High Resolution CpG Data SO GENETIC EPIDEMIOLOGY LA English DT Article DE density approximation; epigenome wide association study; global testing; spline smoothing; variance component testing ID EPIGENOME-WIDE ASSOCIATION; KERNEL MACHINE REGRESSION; DNA METHYLATION; RHEUMATOID-ARTHRITIS; GENE-EXPRESSION; MIXED MODELS; COMMON; METHYLOME; NEWBORNS; PATHWAY AB New high throughput technologies are now enabling simultaneous epigenetic profiling of DNA methylation at hundreds of thousands of CpGs across the genome. A problem of considerable practical interest is identification of large scale, global changes in methylation that are associated with environmental variables, clinical outcomes, or other experimental conditions. However, there has been little statistical research on methods for global methylation analysis using technologies with individual CpG resolution. To address this critical gap in the literature, we develop a new strategy for global analysis of methylation profiles using a functional regression approach wherein we approximate either the density or the cumulative distribution function (CDF) of the methylation values for each individual using B-spline basis functions. The spline coefficients for each individual are allowed to summarize the individual's overall methylation profile. We then test for association between the overall distribution and a continuous or dichotomous outcome variable using a variance component score test that naturally accommodates the correlation between spline coefficients. Simulations indicate that our proposed approach has desirable power while protecting type I error. The method was applied to detect methylation differences, both genome wide and at LINE1 elements, between the blood samples from rheumatoid arthritis patients and healthy controls and to detect the epigenetic changes of human hepatocarcinogenesis in the context of alcohol abuse and hepatitis C virus infection. A free implementation of our methods in the R language is available in the Global Analysis of Methylation Profiles (GAMP) package at . C1 [Zhao, Ni; Wu, Michael C.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Bell, Douglas A.] NIEHS, Environm Genom Grp, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Maity, Arnab; Staicu, Ana-Maria] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Joubert, Bonnie R.; London, Stephanie J.] NIEHS, Epidemiol Branch, Genet Environm & Resp Dis Grp, Res Triangle Pk, NC 27709 USA. RP Wu, MC (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Biostat & Biomath Program, 1100 Fairview Ave North,M3-C102 POB 19024, Seattle, WA 98109 USA. EM mcwu@fhcrc.org RI Zhao, Ni/P-9086-2014; MAITY, ARNAB/M-8142-2016; OI Zhao, Ni/0000-0002-7762-3949; MAITY, ARNAB/0000-0002-3364-8933; London, Stephanie/0000-0003-4911-5290; Wu, Michael C./0000-0002-3357-6570 FU Intramural Research Program of the National Institutes of Environmental Health Sciences, NIH [R00ES017744]; Hope Foundation FX This research was supported in part by the Intramural Research Program of the National Institutes of Environmental Health Sciences, NIH grant R00ES017744, and the Hope Foundation. NR 49 TC 1 Z9 2 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2015 VL 39 IS 2 BP 53 EP 64 DI 10.1002/gepi.21874 PG 12 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA AZ6DB UT WOS:000348307600001 PM 25537884 ER PT J AU Hsiung, CCS Morrissey, CS Udugama, M Frank, CL Keller, CA Baek, S Giardine, B Crawford, GE Sung, MH Hardison, RC Blobel, GA AF Hsiung, Chris C. -S. Morrissey, Christapher S. Udugama, Maheshi Frank, Christopher L. Keller, Cheryl A. Baek, Songjoon Giardine, Belinda Crawford, Gregory E. Sung, Myong-Hee Hardison, Ross C. Blobel, Gerd A. TI Genome accessibility is widely preserved and locally modulated during mitosis SO GENOME RESEARCH LA English DT Article ID INACTIVE X-CHROMOSOMES; TRANSCRIPTION FACTOR; MITOTIC CHROMOSOMES; CHROMATIN-STRUCTURE; ACTIVE GENES; CELL-CYCLE; CONDENSATION; EXPRESSION; LANDSCAPE; PROTEINS AB Mitosis entails global alterations to chromosome structure and nuclear architecture, concomitant with transient silencing of transcription. How cells transmit transcriptional states through mitosis remains incompletely understood. While many nuclear factors dissociate from mitotic chromosomes, the observation that certain nuclear factors and chromatin features remain associated with individual loci during mitosis originated the hypothesis that such mitotically retained molecular signatures could provide transcriptional memory through mitosis. To understand the role of chromatin structure in mitotic memory, we performed the first genome-wide comparison of DNase I sensitivity of chromatin in mitosis and interphase, using a murine erythroblast model. Despite chromosome condensation during mitosis visible by microscopy, the landscape of chromatin accessibility at the macromolecular level is largely unaltered. However, mitotic chromatin accessibility is locally dynamic, with individual loci maintaining none, some, or all of their interphase accessibility. Mitotic reduction in accessibility occurs primarily within narrow, highly DNase hypersensitive sites that frequently coincide with transcription factor binding sites, whereas broader domains of moderate accessibility tend to be more stable. In mitosis, proximal promoters generally maintain their accessibility more strongly, whereas distal regulatory elements tend to lose accessibility. Large domains of DNA hypomethylation mark a subset of promoters that retain accessibility during mitosis and across many cell types in interphase. Erythroid transcription factor GATA1 exerts site-specific changes in interphase accessibility that are most pronounced at distal regulatory elements, but has little influence on mitotic accessibility. We conclude that features of open chromatin are remarkably stable through mitosis, but are modulated at the level of individual genes and regulatory elements. C1 [Hsiung, Chris C. -S.; Udugama, Maheshi; Blobel, Gerd A.] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. [Hsiung, Chris C. -S.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Morrissey, Christapher S.; Keller, Cheryl A.; Giardine, Belinda; Hardison, Ross C.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Frank, Christopher L.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA. [Baek, Songjoon; Sung, Myong-Hee] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Crawford, Gregory E.] Duke Univ, Ctr Genom & Computat Biol, Durham, NC 27708 USA. [Crawford, Gregory E.] Duke Univ, Dept Pediat, Div Med Genet, Durham, NC 27708 USA. RP Blobel, GA (reprint author), Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. EM blobel@email.chop.edu FU NIH [T32GM008216, R01 DK065806, RC2 HG005573, RO1 DK054937]; Intramural Research Program of NCI at the National Institutes of Health FX We especially thank Gautham P. Nair for extensive advice on data analysis and comments on the manuscript. We also thank Jennifer E. Phillips-Cremins, Kenneth Zaret, Caleb Ng, and Caroline Barthian for comments on the manuscript, and Margaret Goodell, the Raj, Hardison, Weiss, Tong, and Blobel laboratories for discussions. This work was supported by NIH T32GM008216 to C.C.H., the Intramural Research Program of NCI at the National Institutes of Health (M.H.S. and S.B.), NIH R01 DK065806 and NIH RC2 HG005573 to R.C.H., and NIH RO1 DK054937 to G.A.B. NR 62 TC 12 Z9 12 U1 1 U2 24 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD FEB PY 2015 VL 25 IS 2 BP 213 EP 225 DI 10.1101/gr.180646.114 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CA5UY UT WOS:000348974500006 PM 25373146 ER PT J AU Parkinson, NJ Roddis, M Ferneyhough, B Zhang, G Marsden, AJ Maslau, S Sanchez-Pearson, Y Barthlott, T Humphreys, IR Ladell, K Price, DA Ponting, CP Hollander, G Fischer, MD AF Parkinson, Nicholas J. Roddis, Matthew Ferneyhough, Ben Zhang, Gang Marsden, Adam J. Maslau, Siarhei Sanchez-Pearson, Yasmin Barthlott, Thomas Humphreys, Ian R. Ladell, Kristin Price, David A. Ponting, Chris P. Hollander, Georg Fischer, Michael D. TI Violation of the 12/23 rule of genomic V(D)J recombination is common in lymphocytes SO GENOME RESEARCH LA English DT Article ID GENE REARRANGEMENT; CHAIN GENES; B-CELLS; MICE; PRODUCTS; SIGNAL; FREQUENCY; SEQUENCES; DNA; REGIONS AB V(D)J genomic recombination joins single gene segments to encode an extensive repertoire of antigen receptor specificities in T and B lymphocytes. This process initiates with double-stranded breaks adjacent to conserved recombination signal sequences that contain either 12- or 23-nucleotide spacer regions. Only recombination between signal sequences with unequal spacers results in productive coding genes, a phenomenon known as the "12/23 rule." Here we present two novel genomic tools that allow the capture and analysis of immune locus rearrangements from whole thymic and splenic tissues using second-generation sequencing. Further, we provide strong evidence that the 12/23 rule of genomic recombination is frequently violated under physiological conditions, resulting in unanticipated hybrid recombinations in -10% of Tcra excision circles. Hence, we demonstrate that strict adherence to the 12/23 rule is intrinsic neither to recombination signal sequences nor to the catalytic process of recombination and propose that nonclassical excision circles are liberated during the formation of antigen receptor diversity. C1 [Parkinson, Nicholas J.; Roddis, Matthew; Ferneyhough, Ben; Fischer, Michael D.] Syst Biol Lab UK, Abingdon OX14 4SA, Oxon, England. [Roddis, Matthew; Ponting, Chris P.] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford OX1 3PT, England. [Barthlott, Thomas; Hollander, Georg] Univ Basel, Dept Biomed, CH-4058 Basel, Switzerland. [Barthlott, Thomas; Hollander, Georg] Basel Univ Childrens Hosp, CH-4058 Basel, Switzerland. [Humphreys, Ian R.; Ladell, Kristin; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales. [Price, David A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hollander, Georg] Univ Oxford, Weatherall Inst Mol Med, Oxford OX3 9DS, England. [Hollander, Georg] Univ Oxford, Dept Paediat, Oxford OX3 9DS, England. [Fischer, Michael D.] St Georges Univ London, Dept Oncol, Div Cellular & Mol Med, London SW17 0QT, England. RP Parkinson, NJ (reprint author), Syst Biol Lab UK, Abingdon OX14 4SA, Oxon, England. EM nickp@sbl-uk.org RI Price, David/C-7876-2013; Ladell, Kristin/C-8301-2013; OI Price, David/0000-0001-9416-2737; Ladell, Kristin/0000-0002-9856-2938; Ponting, Chris/0000-0003-0202-7816; Humphreys, Ian/0000-0002-9512-5337 FU Fischer Family Trust; Medical Research Council; Wellcome Trust; Swiss National Science Foundation FX This work was made possible via Alamy grants administered by the Fischer Family Trust (N.J.P., M.R., B.F., G.Z., A.M., S.M., Y.S.P., and M.D.F.). Additional funding was provided by the Medical Research Council (C.P.P.), the Wellcome Trust (I.R.H., K.L., and D.A.P.), and the Swiss National Science Foundation (T.B. and G.H.). I.R.H. is a Wellcome Trust Senior Research Fellow in Basic Biomedical Science. D.A.P. is a Wellcome Trust Senior Investigator. NR 29 TC 0 Z9 0 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD FEB PY 2015 VL 25 IS 2 BP 226 EP 234 DI 10.1101/gr.179770.114 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CA5UY UT WOS:000348974500007 PM 25367293 ER PT J AU McLean, MH Dieguez, D Miller, LM Young, HA AF McLean, Mairi H. Dieguez, Dario, Jr. Miller, Lindsey M. Young, Howard A. TI Does the microbiota play a role in the pathogenesis of autoimmune diseases? SO GUT LA English DT Article ID ACTIVE RHEUMATOID-ARTHRITIS; INCREASED INTESTINAL PERMEABILITY; TREATMENT PARTIALLY PROTECTS; COLLAGEN-INDUCED ARTHRITIS; PEDIATRIC CELIAC-DISEASE; NONOBESE DIABETIC MICE; GUT MICROBIOTA; PORPHYROMONAS-GINGIVALIS; BACTEROIDES-FRAGILIS; ANKYLOSING-SPONDYLITIS AB The microbiota of the human metaorganism is not a mere bystander. These microbes have coevolved with us and are pivotal to normal development and homoeostasis. Dysbiosis of the GI microbiota is associated with many disease susceptibilities, including obesity, malignancy, liver disease and GI pathology such as IBD. It is clear that there is direct and indirect crosstalk between this microbial community and host immune response. However, the precise mechanism of this microbial influence in disease pathogenesis remains elusive and is now a major research focus. There is emerging literature on the role of the microbiota in the pathogenesis of autoimmune disease, with clear and increasing evidence that changes in the microbiota are associated with some of these diseases. Examples include type 1 diabetes, coeliac disease and rheumatoid arthritis, and these contribute significantly to global morbidity and mortality. Understanding the role of the microbiota in autoimmune diseases may offer novel insight into factors that initiate and drive disease progression, stratify patient risk for complications and ultimately deliver new therapeutic strategies. This review summarises the current status on the role of the microbiota in autoimmune diseases. C1 [McLean, Mairi H.; Young, Howard A.] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. [Dieguez, Dario, Jr.; Miller, Lindsey M.] Soc Womens Hlth Res, Washington, DC USA. RP McLean, MH (reprint author), NCI, Mol Immunoregulat Lab, Bldg 560,1050 Boyles St, Frederick, MD 21702 USA. EM mairi.mclean@nih.gov OI Dieguez Jr, Dario/0000-0002-8196-0534 FU Intramural Research Program of the NIH, National Cancer Institute; Crohn's and Colitis Foundation of America FX This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute. MHMcL-fellowship funded by Crohn's and Colitis Foundation of America. NR 159 TC 44 Z9 45 U1 10 U2 70 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 FEB PY 2015 VL 64 IS 2 BP 332 EP 341 DI 10.1136/gutjnl-2014-308514 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ8FG UT WOS:000348449800020 PM 25416067 ER PT J AU Kaphingst, KA Stafford, JD McGowan, LD Seo, J Lachance, CR Goodman, MS AF Kaphingst, Kimberly A. Stafford, Jewel D. McGowan, Lucy D'Agostino Seo, Joann Lachance, Christina R. Goodman, Melody S. TI Effects of Racial and Ethnic Group and Health Literacy on Responses to Genomic Risk Information in a Medically Underserved Population SO HEALTH PSYCHOLOGY LA English DT Article DE genetic communication; family history; genetic susceptibility testing; cultural competence; health literacy ID AFRICAN-AMERICAN WOMEN; FAMILY-HISTORY; CANCER-RISK; GENETIC INFORMATION; BEHAVIORAL-RESPONSE; HEREDITARY BREAST; OVARIAN-CANCER; DISEASE RISK; PRIMARY-CARE; COMMUNICATION AB Objective: Few studies have examined how individuals respond to genomic risk information for common, chronic diseases. This randomized study examined differences in responses by type of genomic information (genetic test/family history) and disease condition (diabetes/heart disease), and by race/ethnicity in a medically underserved population. Methods: 1,057 English-speaking adults completed a survey containing 1 of 4 vignettes (2-by-2 randomized design). Differences in dependent variables (i.e., interest in receiving genomic assessment, discussing with doctor or family, changing health habits) by experimental condition and race/ethnicity were examined using chi-squared tests and multivariable regression analysis. Results: No significant differences were found in dependent variables by type of genomic information or disease condition. In multivariable models, Hispanics were more interested in receiving a genomic assessment than Whites (OR = 1.93; p = .0001); respondents with marginal (OR = 1.54; p = .005) or limited (OR = 1.85; p = .009) health literacy had greater interest than those with adequate health literacy. Blacks (OR = 1.78; p = .001) and Hispanics (OR = 1.85; p = .001) had greater interest in discussing information with family than Whites. Non-Hispanic Blacks (OR = 1.45; p = .04) had greater interest in discussing genomic information with a doctor than Whites. Blacks (beta = -0.41; p < .001) and Hispanics (beta = -0.25; p = .033) intended to change fewer health habits than Whites; health literacy was negatively associated with number of health habits participants intended to change. Conclusions: Findings suggest that race/ethnicity may affect responses to genomic risk information. Additional research could examine how cognitive representations of this information differ across racial/ethnic groups. Health literacy is also critical to consider in developing approaches to communicating genomic information. C1 [Kaphingst, Kimberly A.; Stafford, Jewel D.; McGowan, Lucy D'Agostino; Seo, Joann; Goodman, Melody S.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63130 USA. [Lachance, Christina R.] NIH, Bethesda, MD 20892 USA. RP Kaphingst, KA (reprint author), Univ Utah, Dept Commun, 255 Cent Campus Dr, Salt Lake City, UT 84112 USA. EM kim.kaphingst@hci.utah.edu OI D'Agostino McGowan, Lucy/0000-0001-7297-9359; Goodman, Melody/0000-0001-8932-624X FU Intramural Research Program of the National Human Genome Research Institute at the National Institutes of Health; Alvin J. Siteman Cancer Center [P30CA91842]; Barnes Jewish Hospital Foundation FX This work was supported by the Intramural Research Program of the National Human Genome Research Institute at the National Institutes of Health, the Alvin J. Siteman Cancer Center (P30CA91842), and the Barnes Jewish Hospital Foundation. We thank the participants and team of data collectors. The authors have no conflicts of interest to disclose. NR 60 TC 7 Z9 7 U1 2 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD FEB PY 2015 VL 34 IS 2 BP 101 EP 110 DI 10.1037/hea0000177 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA AZ7AS UT WOS:000348371200002 PM 25622080 ER PT J AU Schaa, KL Roter, DL Biesecker, BB Cooper, LA Erby, LH AF Schaa, Kendra L. Roter, Debra L. Biesecker, Barbara B. Cooper, Lisa A. Erby, Lori H. TI Genetic Counselors' Implicit Racial Attitudes and Their Relationship to Communication SO HEALTH PSYCHOLOGY LA English DT Article DE implicit attitudes; race/ethnicity; genetic counseling; RIAS; patient-provider communication ID PRIMARY-CARE PHYSICIANS; ASSOCIATION TEST; HEALTH-CARE; EXPLICIT ATTITUDES; SOCIAL COGNITION; PATIENT; RACE; CANCER; STEREOTYPES; BIAS AB Objective: Implicit racial attitudes are thought to shape interpersonal interactions and may contribute to health-care disparities. This study explored the relationship between genetic counselors' implicit racial attitudes and their communication during simulated genetic counseling sessions. Method: A nationally representative sample of genetic counselors completed a web-based survey that included the Race Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998; Cooper et al., 2012). A subset of these counselors (n = 67) had participated in an earlier study in which they were video recorded counseling Black, Hispanic, and non-Hispanic White SCs about their prenatal or cancer risks. The counselors' IAT scores were related to their session communications through robust regression modeling. Results: Genetic counselors showed a moderate to strong pro-White bias on the Race IAT (M = 0.41, SD = 0.35). Counselors with stronger pro-White bias were rated as displaying lower levels of positive affect (p < .05) and tended to use less emotionally responsive communication (p < .10) when counseling minority SCs. When counseling White SCs, pro-White bias was associated with lower levels of verbal dominance during sessions (p < .10). Stronger pro-White bias was also associated with more positive ratings of counselors' nonverbal effectiveness by White SCs. Conclusion: Implicit racial bias is associated with negative markers of communication in minority client sessions and may contribute to racial disparities in processes of care related to genetic services. C1 [Schaa, Kendra L.; Roter, Debra L.; Erby, Lori H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Bethesda, MD USA. [Schaa, Kendra L.; Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Roter, Debra L.; Erby, Lori H.] Johns Hopkins Ctr Genom Literacy & Commun, Baltimore, MD USA. [Cooper, Lisa A.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21218 USA. RP Erby, LH (reprint author), 31 Ctr Dr,B1B36, Bethesda, MD 20892 USA. EM lori.erby@nih.gov FU United States Department of Health and Human Services, National Institutes of Health, National Human Genome Research Institute [1R01HG002688-01A1]; Department of Health, Behavior & Society of the Johns Hopkins Bloomberg School of Public Health; National Heart, Lung, and Blood Institute [K24 HL083113] FX This work was supported in part by the United States Department of Health and Human Services, National Institutes of Health, National Human Genome Research Institute, 1R01HG002688-01A1 and through the Department of Health, Behavior & Society of the Johns Hopkins Bloomberg School of Public Health.; Lisa A. Cooper is supported by a grant from the National Heart, Lung, and Blood Institute (K24 HL083113). NR 48 TC 10 Z9 10 U1 4 U2 19 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD FEB PY 2015 VL 34 IS 2 BP 111 EP 119 DI 10.1037/hea0000155 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA AZ7AS UT WOS:000348371200003 PM 25622081 ER PT J AU Rodriguez, SA Roter, DL Castillo-Salgado, C Hooker, GW Erby, LH AF Rodriguez, Sally Ann Roter, Debra L. Castillo-Salgado, Carlos Hooker, Gillian W. Erby, Lori H. TI Translation and Validation of a Spanish-Language Genetic Health Literacy Screening Tool SO HEALTH PSYCHOLOGY LA English DT Article DE genetic health literacy; health literacy; measure development; Spanish-language ID NUMERACY SKILLS; DISPARITIES; CARE; PERCEPTIONS; ACCESS; SCALE AB Objective: Literacy deficits and underutilization of medical services have been linked to health disparities among minorities, and this appears especially relevant for the Latino population. Given the increasing importance of genetics, assessment of genetic health literacy may direct future efforts to better serve this vulnerable population. The current study was designed to contribute to this area by translating and validating a Spanish-language genetic health literacy measure. Method: This was a cross-sectional study involving an interviewer-administered questionnaire. Eligible individuals were Latinos between the ages of 18 and 75 residing in Maryland, who self-reported Spanish as their primary language, recruited through convenience sampling. The genetic health literacy measure components were adapted from existing English-language measures [Erby, Roter, Larson, & Cho's (2008) Rapid Estimate of Adult Literacy in Genetics (REAL-G) and Hooker et al.' s (2014) Genetic Literacy and Comprehension]. An existing Spanish-language general health literacy measure was used to establish preliminary concurrent validity [Lee, Bender, Ruiz, & Cho's (2006) SAHLSA]. Results: 116 individuals completed the assessment. The Spanish-language REAL-G (REAL-G-Sp) was found to correlate well with the SAHLSA (Pearson's r = .77, p < .01). A cut-off score of 59 (out of 62) distinguished low versus high genetic health literacy with a sensitivity of 86% and specificity of 71%, identifying 28% of participants as having inadequate genetic health literacy. Conclusions: The REAL-G-Sp was found to have preliminary concurrent validity with an existing health literacy measure in the Latino population residing in Maryland. Significant proportions of this population are predicted to have limitations in genetic health literacy, even when information is provided in Spanish. C1 [Rodriguez, Sally Ann; Roter, Debra L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Bethesda, MD USA. [Rodriguez, Sally Ann; Hooker, Gillian W.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Roter, Debra L.; Hooker, Gillian W.; Erby, Lori H.] Johns Hopkins Ctr Genom Literacy & Commun, Baltimore, MD USA. [Castillo-Salgado, Carlos] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Bethesda, MD USA. [Erby, Lori H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Social & Behav Res Branch, Bethesda, MD USA. RP Erby, LH (reprint author), 31 Ctr Dr,B1B36, Bethesda, MD 20892 USA. EM lori.erby@nih.gov FU Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health FX This research was funded by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 32 TC 4 Z9 4 U1 0 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD FEB PY 2015 VL 34 IS 2 BP 120 EP 129 DI 10.1037/hea0000162 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA AZ7AS UT WOS:000348371200004 PM 25622082 ER PT J AU Jang, SI Ong, HL Gallo, A Liu, X Illei, G Alevizos, I AF Jang, S. I. Ong, H. L. Gallo, A. Liu, X. Illei, G. Alevizos, I. TI Establishment of Functional Acinar-like Cultures from Human Salivary Glands SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE acinar cells; calcium mobilization; primary epithelial cells; explant culture; primary cell culture; Sjogren's syndrome ID EPITHELIAL-CELLS; DIFFERENTIATION; GROWTH; MORPHOGENESIS; ACTIVATION; SECRETION; INVITRO; HSG AB Disorders of human salivary glands resulting from therapeutic radiation treatment for head and neck cancers or from the autoimmune disease Sjogren syndrome (SS) frequently result in the reduction or complete loss of saliva secretion. Such irreversible dysfunction of the salivary glands is due to the impairment of acinar cells, the major glandular cells of protein, salt secretion, and fluid movement. Availability of primary epithelial cells from human salivary gland tissue is critical for studying the underlying mechanisms of these irreversible disorders. We applied 2 culture system techniques on human minor salivary gland epithelial cells (phmSG) and optimized the growth conditions to achieve the maintenance of phmSG in an acinar-like phenotype. These phmSG cells exhibited progenitor cell markers (keratin 5 and nanog) as well as acinar-specific markersnamely, -amylase, cystatin C, TMEM16A, and NKCC1. Importantly, with an increase of the calcium concentration in the growth medium, these phmSG cells were further promoted to acinar-like cells in vitro, as indicated by an increase in AQP5 expression. In addition, these phmSG cells also demonstrated functional calcium mobilization, formation of epithelial monolayer with high transepithelial electrical resistance (TER), and polarized secretion of -amylase secretion after -adrenergic receptor stimulation. Taken together, suitable growth conditions have been established to isolate and support culture of acinar-like cells from the human salivary gland. These primary epithelial cells can be useful for study of molecular mechanisms involved in regulating the function of acinar cells and in the loss of salivary gland function in patients. C1 [Jang, S. I.; Gallo, A.; Illei, G.; Alevizos, I.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome & Salivary Gland Dysfunct Unit, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Ong, H. L.; Liu, X.] Natl Inst Dent & Craniofacial Res, Secretory & Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Alevizos, I (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome & Salivary Gland Dysfunct Unit, Mol Physiol & Therapeut Branch, NIH, 10 Ctr Dr,Rm 1N110, Bethesda, MD 20892 USA. EM alevizosi@nidcr.nih.gov FU Intramural Research Program of the National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR) FX We are grateful to all healthy volunteers and the individuals with Sjogren syndrome who participated in this project. We thank Paola Perez-Riveros and William D. Swaim for technical assistance and Indu Ambudkar for valuable suggestions on this study and critical review of the manuscript. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 25 TC 5 Z9 6 U1 1 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD FEB PY 2015 VL 94 IS 2 BP 304 EP 311 DI 10.1177/0022034514559251 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CA1BO UT WOS:000348647900009 PM 25416669 ER PT J AU Basile, BM Schroeder, GR Brown, EK Templer, VL Hampton, RR AF Basile, Benjamin M. Schroeder, Gabriel R. Brown, Emily Kathryn Templer, Victoria L. Hampton, Robert R. TI Evaluation of Seven Hypotheses for Metamemory Performance in Rhesus Monkeys SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL LA English DT Article DE metacognition; information seeking; explicit memory; memory monitoring; tubes ID MACACA-MULATTA; INFORMATION-SEEKING; MEMORY AWARENESS; CEBUS-APELLA; META-COGNITION; METACOGNITION; JUDGMENTS; ANIMALS; UNCERTAINTY; PIGEONS AB Knowing the extent to which nonhumans and humans share mechanisms for metacognition will advance our understanding of cognitive evolution and will improve selection of model systems for biomedical research. Some nonhuman species avoid difficult cognitive tests, seek information when ignorant, or otherwise behave in ways consistent with metacognition. There is agreement that some nonhuman animals "succeed" in these metacognitive tasks, but little consensus about the cognitive mechanisms underlying performance. In one paradigm, rhesus monkeys visually searched for hidden food when ignorant of the location of the food, but acted immediately when knowledgeable. This result has been interpreted as evidence that monkeys introspectively monitored their memory to adaptively control information seeking. However, convincing alternative hypotheses have been advanced that might also account for the adaptive pattern of visual searching. We evaluated seven hypotheses using a computerized task in which monkeys chose either to take memory tests immediately or to see the answer again before proceeding to the test. We found no evidence to support the hypotheses of behavioral cue association, rote response learning, expectancy violation, response competition, generalized search strategy, or postural mediation. In contrast, we repeatedly found evidence to support the memory monitoring hypothesis. Monkeys chose to see the answer when memory was poor, either from natural variation or experimental manipulation. We found limited evidence that monkeys also monitored the fluency of memory access. Overall, the evidence indicates that rhesus monkeys can use memory strength as a discriminative cue for information seeking, consistent with introspective monitoring of explicit memory. C1 [Basile, Benjamin M.; Brown, Emily Kathryn; Templer, Victoria L.; Hampton, Robert R.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Basile, Benjamin M.; Schroeder, Gabriel R.; Brown, Emily Kathryn; Templer, Victoria L.; Hampton, Robert R.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. RP Basile, BM (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr MSC 4415, Bethesda, MD 20892 USA. EM benjamin.basile@nih.gov FU National Science Foundation [0745573, 1146316]; National Center for Research Resources [P51RR000165]; Office of Research Infrastructure Programs/OD [P51OD011132]; Center for Behavioral Neuroscience under the Science and Technology Center Program of the National Science Foundation [IBN-9876754]; National Institute of Mental Health [R01M H082819] FX This work was supported by the National Science Foundation (Grants 0745573; 1146316), the National Center for Research Resources P51RR000165, the Office of Research Infrastructure Programs/OD P51OD011132, the Center for Behavioral Neuroscience under the Science and Technology Center Program of the National Science Foundation (under agreement IBN-9876754), and the National Institute of Mental Health (Grant R01M H082819). The authors declare no competing financial interests. We thank Steven L. Sherrin, Tara A. Dove-Van Wormer, and Jessica A. Joiner for help running subjects. NR 71 TC 12 Z9 12 U1 1 U2 18 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0096-3445 EI 1939-2222 J9 J EXP PSYCHOL GEN JI J. Exp. Psychol.-Gen. PD FEB PY 2015 VL 144 IS 1 BP 85 EP 102 DI 10.1037/xge0000031 PG 18 WC Psychology, Experimental SC Psychology GA AZ8XS UT WOS:000348495700011 PM 25365530 ER PT J AU Donovan, DM Daley, DC Brigham, GS Hodgkins, CC Perl, HI Garrett, SB Doyle, SR Floyd, AS Knox, PC Botero, C Kelly, TM Killeen, TK Hayes, C Baumhofer, NK Seamans, C Zammarelli, L AF Donovan, Dennis M. Daley, Dennis C. Brigham, Gregory S. Hodgkins, Candace C. Perl, Harold I. Garrett, Sharon B. Doyle, Suzanne R. Floyd, Anthony S. Knox, Patricia C. Botero, Christopher Kelly, Thomas M. Killeen, Therese K. Hayes, Carole Baumhofer, Nicole Kau'i Seamans, Cindy Zammarelli, Lucy TI Stimulant Abuser Groups to Engage in 12-Step: A Multisite Trial in the National Institute on Drug Abuse Clinical Trials Network (vol 44, pg 103, 2013) SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Correction C1 [Donovan, Dennis M.; Garrett, Sharon B.; Doyle, Suzanne R.] Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98195 USA. [Donovan, Dennis M.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Daley, Dennis C.; Kelly, Thomas M.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Daley, Dennis C.; Kelly, Thomas M.] Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Brigham, Gregory S.] Maryhaven, Columbus, OH USA. [Hodgkins, Candace C.] Gateway Community Serv Inc, Jacksonville, FL USA. [Perl, Harold I.] NIDA, Bethesda, MD 20892 USA. [Floyd, Anthony S.] Univ Washington, Human Subjects Div, Seattle, WA 98195 USA. [Knox, Patricia C.] Recovery Ctr King Cty, Seattle, WA USA. [Botero, Christopher] ChangePoint Inc, Portland, OR USA. [Kelly, Thomas M.] Ctr Psychiat & Chem Dependency Serv, Pittsburgh, PA USA. [Killeen, Therese K.] Dorchester Alcohol & Drug Commiss, Summerville, SC USA. [Killeen, Therese K.] Med Univ S Carolina, Inst Psychiat, Charleston, SC 29425 USA. [Hayes, Carole] Evergreen Manor, Everett, WA USA. [Baumhofer, Nicole Kau'i] Hina Mauka, Kaneohe, HI USA. [Seamans, Cindy] Nexus Recovery Ctr, Dallas, TX USA. [Zammarelli, Lucy] Willamette Family Treatment Serv, Eugene, OR USA. RP Donovan, DM (reprint author), Inst Alcohol & Drug Abuse, 1107 NE 45th St,Suite 120, Seattle, WA 98105 USA. EM ddonovan@u.washington.edu NR 1 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD FEB PY 2015 VL 49 BP 71 EP 71 DI 10.1016/j.jsat.2014.10.006 PG 1 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AZ5OC UT WOS:000348269000011 ER PT J AU Goldstein, SA Evangelista, A Abbara, S Arai, A Asch, FM Badano, LP Bolen, MA Connolly, HM Cuellar-Calabria, H Czerny, M Devereux, RB Erbel, RA Fattori, R Isselbacher, EM Lindsay, JM McCulloch, M Michelena, HI Nienaber, CA Oh, JK Pepi, M Taylor, AJ Weinsaft, JW Zamorano, JL Dietz, H Eagle, K Elefteriades, J Jondeau, G Rousseau, H Schepens, M AF Goldstein, Steven A. Evangelista, Arturo Abbara, Suhny Arai, Andrew Asch, Federico M. Badano, Luigi P. Bolen, Michael A. Connolly, Heidi M. Cuellar-Calabria, Hug Czerny, Martin Devereux, Richard B. Erbel, Raimund A. Fattori, Rossella Isselbacher, Eric M. Lindsay, Joseph M. McCulloch, Marti Michelena, Hector I. Nienaber, Christoph A. Oh, Jae K. Pepi, Mauro Taylor, Allen J. Weinsaft, Jonathan W. Zamorano, Jose Luis Dietz, Harry Eagle, Kim Elefteriades, John Jondeau, Guillaume Rousseau, Herve Schepens, Marc TI Multimodality Imaging of Diseases of the Thoracic Aorta in Adults: From the American Society of Echocardiography and the European Association of Cardiovascular Imaging Endorsed by the Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID PENETRATING ATHEROSCLEROTIC ULCERS; INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHY; STENT-GRAFT IMPLANTATION; CORONARY-ARTERY-DISEASE; MULTIDETECTOR ROW CT; GIANT-CELL ARTERITIS; ENDOVASCULAR ANEURYSM REPAIR; 3-DIMENSIONAL MR-ANGIOGRAPHY; CONTRAST-INDUCED NEPHROPATHY; EXPERT CONSENSUS DOCUMENT C1 [Goldstein, Steven A.; Asch, Federico M.; Lindsay, Joseph M.; Taylor, Allen J.] Washington Hosp Ctr, Medstar Heart Inst, Washington, DC 20010 USA. [Evangelista, Arturo; Cuellar-Calabria, Hug] Vall dHebron Univ Hosp, Barcelona, Spain. [Abbara, Suhny] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Arai, Andrew] Natl Inst Hlth, Bethesda, MD USA. [Badano, Luigi P.] Univ Padua, Padua, Italy. [Bolen, Michael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Connolly, Heidi M.; Michelena, Hector I.; Oh, Jae K.] Mayo Clin, Rochester, MN USA. [Czerny, Martin] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. [Devereux, Richard B.; Weinsaft, Jonathan W.] Weill Cornell Med Coll, New York, NY USA. [Erbel, Raimund A.] Univ Duisburg Essen, West German Heart Ctr, Essen, Germany. [Fattori, Rossella] San Salvatore Hosp, Pesaro, Italy. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nienaber, Christoph A.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [Nienaber, Christoph A.] Univ Rostock, D-18055 Rostock, Germany. [Pepi, Mauro] IRCCS, Ctr Cardiol Monzino, Milan, Italy. [Zamorano, Jose Luis] Univ Hosp Ramon y Cajal, Madrid, Spain. [Dietz, Harry] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Eagle, Kim] Univ Michigan, Ann Arbor, MI 48109 USA. [Elefteriades, John] Yale Univ, Sch Med, New Haven, CT USA. [Jondeau, Guillaume] Hop Bichat Claude Bernard, F-75877 Paris, France. [Rousseau, Herve] Hop Rangueil, Toulouse, France. [Schepens, Marc] AZ St Jan Brugge, Brugge, Belgium. RP Goldstein, SA (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. EM ase@asecho.org FU Siemens; GORE; Medtronic; Toshiba; Lantheus Medical Imaging FX The following authors reported relationships with one or more commercial interests: Suhny Abbara, MD, serves as a consultant for Perceptive Informatics. Andrew Arai, MD, receives research support from Siemens. Luigi P. Badano, MD, PhD, FESC, has received software and equipment from GE Healthcare, Siemens, and TomTec for research and testing purposes and is on the speakers' bureau of GE Healthcare. Kim Eagle, MD, received a research grant from GORE. John Elefteriades, MD, has a book published by CardioText and is a principal investigator on a grant and clinical trial from Medtronic. Jae K. Oh, MD, received a research grant from Toshiba and core laboratory support from Medtronic. Herve Rousseau, MD, serves as a consultant for GORE, Medtronic, and Bolton. Jonathan W. Weinsaft, MD, received a research grant from Lantheus Medical Imaging. NR 440 TC 45 Z9 46 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD FEB PY 2015 VL 28 IS 2 BP 119 EP 182 DI 10.1016/j.echo.2014.11.015 PG 64 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ8HU UT WOS:000348457200002 PM 25623219 ER PT J AU Kao, LY Lam, V Waldman, M Glassock, RJ Zhu, QS AF Kao, Liyo Lam, Vinson Waldman, Meryl Glassock, Richard J. Zhu, Quansheng TI Identification of the Immunodominant Epitope Region in Phospholipase A(2) Receptor-Mediating Autoantibody Binding in Idiopathic Membranous Nephropathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HEYMANN NEPHRITIS; MANNOSE RECEPTOR; ANTIBODIES; ANTIGEN; FAMILY; GLOMERULONEPHRITIS; PATHOGENESIS; EVOLUTION; RATS AB Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Recent clinical studies established that >70% of patients with idiopathic (also called primary) MN (IMN) possess circulating autoantibodies targeting the M-type phospholiPase A(2) receptor-1 (PLA(2)R) on the surface of glomerular visceral epithelial cells (podocytes). In situ, these autoantibodies trigger the formation of immune complexes, which are hypothesized to cause enhanced glonnerular permeability to plasma proteins. Indeed, the level of autoantibody in circulation correlates with the severity of proteinuria in patients. The autoantibody only recognizes the nonreduced form of PLA(2)R, suggesting that disulfide bonds determine the antigenic epitope conformation. Here, we identified the immunodonninant epitope region in PLA(2)R by probing isolated truncated PLA(2)R extracellular domains with sera from patients with IMN that contain anti-PLA(2)R autoantibodies. Patient sera specifically recognized a protein complex consisting of the cysteine-rich (CysR), fibronectin-like type II (FnII), and C-type lectin-like domain 1 (CTLD1) domains of PLA(2)R only under nonreducing conditions. Moreover, absence of either the CysR or CTLD1 domain prevented autoantibody recognition of the remaining domains. Additional analysis suggested that this three-domain complex contains at least one disulfide bond required for conformational configuration and autoantibody binding. Notably, the three-domain complex completely blocked the reactivity of autoantibodies from patient sera with the full-length PLA(2)R, and the reactivity of patient sera with the three-domain complex on immunoblots equaled the reactivity with full-length PLA(2)R. These results indicate that the immunodominant epitope in PLA(2)R is exclusively located in the CysR-FnII-CTLD1 region. C1 [Kao, Liyo; Lam, Vinson; Glassock, Richard J.; Zhu, Quansheng] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Waldman, Meryl] NIDDK, Clin Res Ctr, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Zhu, QS (reprint author), Univ Calif Los Angeles, Dept Med, 7-155 Factor Bldg,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM quzhu@mednet.ucla.edu FU Satellite Healthcare FX This work was supported by the Norman S. Coplon Grant from Satellite Healthcare (to Q.Z.). NR 29 TC 21 Z9 25 U1 0 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2015 VL 26 IS 2 BP 291 EP 301 DI 10.1681/ASN.2013121315 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA CA0RG UT WOS:000348623700009 PM 25205735 ER PT J AU Chowell, G Viboud, C AF Chowell, Gerardo Viboud, Cecile TI Controlling Ebola: key role of Ebola treatment centres SO LANCET INFECTIOUS DISEASES LA English DT Editorial Material ID TRANSMISSION DYNAMICS C1 [Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA. [Chowell, Gerardo; Viboud, Cecile] NIH, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, Bethesda, MD 20892 USA. [Viboud, Cecile] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ USA. RP Chowell, G (reprint author), Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA. EM gchowell@asu.edu NR 11 TC 3 Z9 3 U1 0 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD FEB PY 2015 VL 15 IS 2 BP 139 EP 141 DI 10.1016/S1473-3099(14)71086-2 PG 3 WC Infectious Diseases SC Infectious Diseases GA AZ7PJ UT WOS:000348410200007 PM 25575619 ER PT J AU Ford, N Meintjes, G Pozniak, A Bygrave, H Hill, A Peter, T Davies, MA Grinsztejn, B Calmy, A Kumarasamy, N Phanuphak, P deBeaudrap, P Vitoria, M Doherty, M Stevens, W Siberry, GK AF Ford, Nathan Meintjes, Graeme Pozniak, Anton Bygrave, Helen Hill, Andrew Peter, Trevor Davies, Mary-Ann Grinsztejn, Beatriz Calmy, Alexandra Kumarasamy, N. Phanuphak, Praphan deBeaudrap, Pierre Vitoria, Marco Doherty, Meg Stevens, Wendy Siberry, George K. TI The future role of CD4 cell count for monitoring antiretroviral therapy SO LANCET INFECTIOUS DISEASES LA English DT Editorial Material ID RESOURCE-LIMITED SETTINGS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HIGH-INCOME COUNTRIES; HIV-INFECTED PATIENTS; LIFE EXPECTANCY; SOUTH-AFRICA; VIRAL LOAD; COHORT ANALYSIS; HOMOSEXUAL-MEN; INDIVIDUALS AB For more than two decades, CD4 cell count measurements have been central to understanding HIV disease progression, making important clinical decisions, and monitoring the response to antiretroviral therapy (ART). In well resourced settings, the monitoring of patients on ART has been supported by routine virological monitoring. Viral load monitoring was recommended by WHO in 2013 guidelines as the preferred way to monitor people on ART, and efforts are underway to scale up access in resource-limited settings. Recent studies suggest that in situations where viral load is available and patients are virologically suppressed, long-term CD4 monitoring adds little value and stopping CD4 monitoring will have major cost savings. CD4 cell counts will continue to play an important part in initial decisions around ART initiation and clinical management, particularly for patients presenting late to care, and for treatment monitoring where viral load monitoring is restricted. However, in settings where both CD4 cell counts and viral load testing are routinely available, countries should consider reducing the frequency of CD4 cell counts or not doing routine CD4 monitoring for patients who are stable on ART. C1 [Ford, Nathan; Vitoria, Marco; Doherty, Meg] WHO, Dept HIV AIDS, CH-1211 Geneva, Switzerland. [Meintjes, Graeme] Univ Cape Town, Inst Infect Dis & Mol Med, Clin Infect Dis Res Initiat, ZA-7925 Cape Town, South Africa. [Pozniak, Anton] Chelsea & Westminster Hosp, London, England. [Bygrave, Helen] Med Sans Frontieres, Southern Africa Med Unit, Cape Town, South Africa. [Hill, Andrew] Univ Liverpool, Dept Pharmacol & Therapeut, Liverpool L69 3BX, Merseyside, England. [Peter, Trevor] Clinton Hlth Access Initiat, Boston, MA USA. [Ford, Nathan; Davies, Mary-Ann] Univ Cape Town, Ctr Infect Dis Epidemiol & Res, ZA-7925 Cape Town, South Africa. [Grinsztejn, Beatriz] Fundacao Oswaldo Cruz, Minist Hlth, Salvador, BA, Brazil. [Calmy, Alexandra] Univ Hosp Geneva, Infect Dis Serv, HIV AIDS Unit, Geneva, Switzerland. [Kumarasamy, N.] YRG Ctr AIDS Res & Educ, Madras, Tamil Nadu, India. [Phanuphak, Praphan] Thai Red Cross AIDS Res Ctr, Bangkok, Thailand. [deBeaudrap, Pierre] IRD, Montpellier, France. [Stevens, Wendy] Univ Witwatersrand, Dept Mol Med & Haematol, Johannesburg, South Africa. [Stevens, Wendy] Natl Hlth Lab Serv, Johannesburg, South Africa. [Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Rockville, MD USA. RP Ford, N (reprint author), WHO, Dept HIV AIDS, CH-1211 Geneva, Switzerland. EM fordn@who.int FU World Health Organization [001] NR 58 TC 26 Z9 29 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD FEB PY 2015 VL 15 IS 2 BP 241 EP 247 DI 10.1016/S1473-3099(14)70896-5 PG 7 WC Infectious Diseases SC Infectious Diseases GA AZ7PJ UT WOS:000348410200034 PM 25467647 ER PT J AU Kim, HY AF Kim, Hee-Yong TI A neuroinflammation emerging target SO NATURE CHEMICAL BIOLOGY LA English DT News Item ID LYSOPHOSPHATIDYLSERINE; INFLAMMATION C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Kim, HY (reprint author), NIAAA, NIH, Bethesda, MD 20892 USA. EM hykim@nih.gov NR 8 TC 1 Z9 1 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD FEB PY 2015 VL 11 IS 2 BP 99 EP 100 DI 10.1038/nchembio.1740 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ6WN UT WOS:000348358800003 PM 25602728 ER PT J AU O'Dushlaine, C Rossin, L Lee, PH Duncan, L Parikshak, NN Newhouse, S Ripke, S Neale, BM Purcell, SM Posthuma, D Nurnberger, JI Lee, SH Faraone, SV Perlis, RH Mowry, BJ Thapar, A Goddard, ME Witte, JS Absher, D Agartz, I Akil, H Amin, F Andreassen, OA Anjorin, A Anney, R Anttila, V Arking, DE Asherson, P Azevedo, MH Backlund, L Badner, JA Bailey, AJ Banaschewski, T Barchas, JD Barnes, MR Barrett, TB Bass, N Battaglia, A Bauer, M Bayes, M Bellivier, F Bergen, SE Berrettini, W Betancur, C Bettecken, T Biederman, J Binder, EB Black, DW Blackwood, DHR Bloss, CS Boehnke, M Boomsma, DI Breuer, R Bruggeman, R Cormican, P Buccola, NG Buitelaar, JK Bunney, WE Buxbaum, JD Byerley, WF Byrne, EM Caesar, S Cahn, W Cantor, RM Casas, M Chakravarti, A Chambert, K Choudhury, K Cichon, S Mattheisen, M Cloninger, CR Collier, DA Cook, EH Coon, H Cormand, B Corvin, A Coryell, WH Craig, DW Craig, IW Crosbie, J Cuccaro, ML Curtis, D Czamara, D Datta, S Dawson, G Day, R De Geus, EJ Degenhardt, F Djurovic, S Donohoe, GJ Doyle, AE Duan, J Dudbridge, F Duketis, E Ebstein, RP Edenberg, HJ Elia, J Ennis, S Etain, B Fanous, A Farmer, AE Ferrier, IN Flicldnger, M Fombonne, E Foroud, T Frank, J Franke, B Fraser, C Freedman, R Freimer, NB Freitag, CM Friedl, M Frisen, L Gailagher, L Gejman, PV Georgieva, L Gershon, ES Giegling, I Gill, M Gordon, SD Gordon-Smith, K Green, EK Greenwood, TA Grice, DE Gross, M Grozeva, D Guan, W Gurling, H De Haan, L Haines, JL Hakonarson, H Hallmayer, J Hamilton, SP Hamshere, ML Hansen, TF Hartmann, AM Hautzinger, M Heath, AC Henders, AK Herms, S Hickie, IB Hipolito, M Hoefels, S Holsboer, F Hoogendijk, WJ Hottenga, JJ Hultman, CM Hus, V Ingason, A Ising, M Jamain, S Jones, EG Jones, I Jones, L Tzeng, JY Kahler, AK Kahn, RS Kandaswamy, R Keller, MC Kennedy, JL Kenny, E Kent, L Kim, YJ Kirov, GK Klauck, SM Klei, L Knowles, JA Kohli, MA Koller, DL Konte, B Korszun, A Krabbendam, L Krasucki, R Kuntsi, J Kwan, P Landen, M Langstrom, N Lathrop, M Lawrence, J Lawson, WB Leboyer, M Ledbetter, DH Lencz, T Lesch, KP Levinson, DF Lewis, CM Li, J Lichtenstein, P Lieberman, JA Lin, DY Linszen, DH Liu, CY Lohoff, FW Loo, SK Lord, C Lowe, JK Lucae, S MacIntyre, DJ Madden, PAF Maestrini, E Magnusson, PKE Mahon, PB Maier, W Malhotra, AK Mane, SM Martin, CL Martin, NG Matthews, K Mattingsdal, M McCarroll, SA McGhee, KA McGough, JJ McGrath, PJ McGuffin, P McInnis, MG McIntosh, A McKinney, R McLean, AW McMahon, FJ McMahon, WM McQuillin, A Medeiros, H Medland, SE Meier, S Melle, I Meng, F Meyer, J Middeldorp, CM Middleton, L Milanova, V Miranda, A Monaco, AP Montgomery, GW Moran, JL Moreno-De-Luca, D Morken, G Morris, DW Morrow, EM Moskvina, V Muglia, P Muhleisen, TW Muir, WJ Muller-Myhsok, B Murtha, M Myers, RM Myin-Germeys, I Neale, MC Nelson, SF Nievergelt, CM Nikolov, I Nimgaonkar, V Nolen, WA Nothen, MM Nwulia, EA Nyholt, DR Oades, RD Olincy, A Oliveira, G Olsen, L Ophoff, RA Osby, U Owen, MJ Palotie, A Parr, JR Paterson, AD Pato, CN Pato, MT Penninx, BW Pergadia, ML Pericak-Vance, MA Pickard, BS Pimm, J Piven, J Potash, JB Poustka, F Propping, P Puri, V Quested, DJ Quinn, EM Ramos-Quiroga, JA Rasmussen, HB Raychaudhuri, S Rehnstrom, K Reif, A Ribases, M Rice, JP Rietschel, M Roeder, K Roeyers, H Rothenberger, A Rouleau, G Ruderfer, D Rujescu, D Sanders, AR Sanders, SJ Santangelo, SL Sergeant, JA Schachar, R Schalling, M Schatzberg, AF Scheftner, WA Schellenberg, GD Scherer, SW Schork, NJ Schulze, TG Schumacher, J Schwarz, M Scolnick, E Scott, LJ Shi, JX Shilling, PD Shyn, SI Silverman, JM Slager, SL Smalley, SL Smit, JH Smith, EN Sonuga-Barke, EJS Cair, DS State, M Steffens, M Steinhausen, HC Strauss, JS Strohmaier, J Stroup, TS Sutdiffe, JS Szatmari, P Szelinger, S Thirumalai, S Thompson, RC Todorov, AA Tozzi, F Treutlein, J Uhr, M Van den Oord, EJCG Van Grootheest, G Van Os, J Vicente, AM Vieland, VJ Vincent, JB Visscher, PM Walsh, CA Wassink, TH Watson, SJ Weissman, MM Werge, T Wienker, TF Wijsman, EM Willemsen, G Williams, N Willsey, AJ Witt, SH Xu, W Young, AH Yu, TW Zammit, S Zandi, PP Zhang, P Zitman, FG Zollner, S Devlin, B Kelsoe, JR Sklar, P Daly, MJ O'Donovan, MC Craddock, N Kendler, KS Weiss, LA Wray, NR Zhao, ZM Geschwind, DH Sullivan, PF Smoller, JW Holmans, PA Breen, G AF O'Dushlaine, Colm Rossin, Lizzy Lee, Phil H. Duncan, Laramie Parikshak, Neelroop N. Newhouse, Stephen Ripke, Stephan Neale, Benjamin M. Purcell, Shaun M. Posthuma, Danielle Nurnberger, John I. Lee, S. Hong Faraone, Stephen V. Perlis, Roy H. Mowry, Bryan J. Thapar, Anita Goddard, Michael E. Witte, John S. Absher, Devin Agartz, Ingrid Akil, Huda Amin, Farooq Andreassen, Ole A. Anjorin, Adebayo Anney, Richard Anttila, Verneri Arking, Dan E. Asherson, Philip Azevedo, Maria H. Backlund, Lena Badner, Judith A. Bailey, Anthony J. Banaschewski, Tobias Barchas, Jack D. Barnes, Michael R. Barrett, Thomas B. Bass, Nicholas Battaglia, Agatino Bauer, Michael Bayes, Monica Bellivier, Frank Bergen, Sarah E. Berrettini, Wade Betancur, Catalina Bettecken, Thomas Biederman, Joseph Binder, Elisabeth B. Black, Donald W. Blackwood, Douglas H. R. Bloss, Cinnamon S. Boehnke, Michael Boomsma, Dorret I. Breuer, Rene Bruggeman, Richard Cormican, Paul Buccola, Nancy G. Buitelaar, Jan K. Bunney, William E. Buxbaum, Joseph D. Byerley, William F. Byrne, Enda M. Caesar, Sian Cahn, Wiepke Cantor, Rita M. Casas, Miguel Chakravarti, Aravinda Chambert, Kimberly Choudhury, Khalid Cichon, Sven Mattheisen, Manuel Cloninger, C. Robert Collier, David A. Cook, Edwin H. Coon, Hilary Cormand, Bru Corvin, Aiden Coryell, William H. Craig, David W. Craig, Ian W. Crosbie, Jennifer Cuccaro, Michael L. Curtis, David Czamara, Darina Datta, Susmita Dawson, Geraldine Day, Richard De Geus, Eco J. Degenhardt, Franziska Djurovic, Srdjan Donohoe, Gary J. Doyle, Alysa E. Duan, Jubao Dudbridge, Frank Duketis, Eftichia Ebstein, Richard P. Edenberg, Howard J. Elia, Josephine Ennis, Sean Etain, Bruno Fanous, Ayman Farmer, Anne E. Ferrier, I. Nicol Flicldnger, Matthew Fombonne, Eric Foroud, Tatiana Frank, Josef Franke, Barbara Fraser, Christine Freedman, Robert Freimer, Nelson B. Freitag, Christine M. Friedl, Marion Frisen, Louise Gailagher, Louise Gejman, Pablo V. Georgieva, Lyudmila Gershon, Elliot S. Giegling, Ina Gill, Michael Gordon, Scott D. Gordon-Smith, Katherine Green, Elaine K. Greenwood, Tiffany A. Grice, Dorothy E. Gross, Magdalena Grozeva, Detelina Guan, Weihua Gurling, Hugh De Haan, Lieuwe Haines, Jonathan L. Hakonarson, Hakon Hallmayer, Joachim Hamilton, Steven P. Hamshere, Marian L. Hansen, Thomas F. Hartmann, Annette M. Hautzinger, Martin Heath, Andrew C. Henders, Anjali K. Herms, Stefan Hickie, Ian B. Hipolito, Maria Hoefels, Susanne Holsboer, Florian Hoogendijk, Witte J. Hottenga, Jouke-Jan Hultman, Christina M. Hus, Vanessa Ingason, Andres Ising, Marcus Jamain, Stephane Jones, Edward G. Jones, Ian Jones, Lisa Tzeng, Jung-Ying Kaehler, Anna K. Kahn, Rene S. Kandaswamy, Radhika Keller, Matthew C. Kennedy, James L. Kenny, Elaine Kent, Lindsey Kim, Yunjung Kirov, George K. Klauck, Sabine M. Klei, Lambertus Knowles, James A. Kohli, Martin A. Koller, Daniel L. Konte, Bettina Korszun, Ania Krabbendam, Lydia Krasucki, Robert Kuntsi, Jonna Kwan, Phoenix Landen, Mikael Laengstroem, Niklas Lathrop, Mark Lawrence, Jacob Lawson, William B. Leboyer, Marion Ledbetter, David H. Lencz, Todd Lesch, Klaus-Peter Levinson, Douglas F. Lewis, Cathryn M. Li, Jun Lichtenstein, Paul Lieberman, Jeffrey A. Lin, Dan-Yu Linszen, Don H. Liu, Chunyu Lohoff, Falk W. Loo, Sandra K. Lord, Catherine Lowe, Jennifer K. Lucae, Susanne MacIntyre, Donald J. Madden, Pamela A. F. Maestrini, Elena Magnusson, Patrik K. E. Mahon, Pamela B. Maier, Wolfgang Malhotra, Anil K. Mane, Shrikant M. Martin, Christa L. Martin, Nicholas G. Matthews, Keith Mattingsdal, Morten McCarroll, Steven A. McGhee, Kevin A. McGough, James J. McGrath, Patrick J. McGuffin, Peter McInnis, Melvin G. McIntosh, Andrew McKinney, Rebecca McLean, Alan W. McMahon, Francis J. McMahon, William M. McQuillin, Andrew Medeiros, Helena Medland, Sarah E. Meier, Sandra Melle, Ingrid Meng, Fan Meyer, Jobst Middeldorp, Christel M. Middleton, Lefkos Milanova, Vihra Miranda, Ana Monaco, Anthony P. Montgomery, Grant W. Moran, Jennifer L. Moreno-De-Luca, Daniel Morken, Gunnar Morris, Derek W. Morrow, Eric M. Moskvina, Valentina Muglia, Pierandrea Muehleisen, Thomas W. Muir, Walter J. Mueller-Myhsok, Bertram Murtha, Michael Myers, Richard M. Myin-Germeys, Inez Neale, Michael C. Nelson, Stan F. Nievergelt, Caroline M. Nikolov, Ivan Nimgaonkar, Vishwajit Nolen, Willem A. Noethen, Markus M. Nwulia, Evaristus A. Nyholt, Dale R. Oades, Robert D. Olincy, Ann Oliveira, Guiomar Olsen, Line Ophoff, Roel A. Osby, Urban Owen, Michael J. Palotie, Aarno Parr, Jeremy R. Paterson, Andrew D. Pato, Carlos N. Pato, Michele T. Penninx, Brenda W. Pergadia, Michele L. Pericak-Vance, Margaret A. Pickard, Benjamin S. Pimm, Jonathan Piven, Joseph Potash, James B. Poustka, Fritz Propping, Peter Puri, Vinay Quested, Digby J. Quinn, Emma M. Ramos-Quiroga, Josep Antoni Rasmussen, Henrik B. Raychaudhuri, Soumya Rehnstroem, Karola Reif, Andreas Ribases, Marta Rice, John P. Rietschel, Marcella Roeder, Kathryn Roeyers, Herbert Rothenberger, Aribert Rouleau, Guy Ruderfer, Douglas Rujescu, Dan Sanders, Alan R. Sanders, Stephan J. Santangelo, Susan L. Sergeant, Joseph A. Schachar, Russell Schalling, Martin Schatzberg, Alan F. Scheftner, William A. Schellenberg, Gerard D. Scherer, Stephen W. Schork, Nicholas J. Schulze, Thomas G. Schumacher, Johannes Schwarz, Markus Scolnick, Edward Scott, Laura J. Shi, Jianxin Shilling, Paul D. Shyn, Stanley I. Silverman, Jeremy M. Slager, Susan L. Smalley, Susan L. Smit, Johannes H. Smith, Erin N. Sonuga-Barke, Edmund J. S. Cair, David St. State, Matthew Steffens, Michael Steinhausen, Hans-Christoph Strauss, John S. Strohmaier, Jana Stroup, T. Scott Sutdiffe, James S. Szatmari, Peter Szelinger, Szabocls Thirumalai, Srinivasa Thompson, Robert C. Todorov, Alexandre A. Tozzi, Federica Treutlein, Jens Uhr, Manfred Van den Oord, Edwin J. C. G. Van Grootheest, Gerard Van Os, Jim Vicente, Astrid M. Vieland, Veronica J. Vincent, John B. Visscher, Peter M. Walsh, Christopher A. Wassink, Thomas H. Watson, Stanley J. Weissman, Myrna M. Werge, Thomas Wienker, Thomas F. Wijsman, Ellen M. Willemsen, Gonneke Williams, Nigel Willsey, A. Jeremy Witt, Stephanie H. Xu, Wei Young, Allan H. Yu, Timothy W. Zammit, Stanley Zandi, Peter P. Zhang, Peng Zitman, Frans G. Zoellner, Sebastian Devlin, Bernie Kelsoe, John R. Sklar, Pamela Daly, Mark J. O'Donovan, Michael C. Craddock, Nicholas Kendler, Kenneth S. Weiss, Lauren A. Wray, Naomi R. Zhao, Zhaoming Geschwind, Daniel H. Sullivan, Patrick F. Smoller, Jordan W. Holmans, Peter A. Breen, Gerome CA IIBDGC Network & Pathway Anal Subgrp Psyc TI Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways SO NATURE NEUROSCIENCE LA English DT Article ID DE-NOVO MUTATIONS; SCHIZOPHRENIA; METHYLATION; DISORDERS; AUTISM; BRAIN; PROMOTERS; BURDEN; LOCI AB Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders. C1 [O'Dushlaine, Colm] Regeneron Pharmaceut Inc, Regeneron Genet Ctr, Tarrytown, NY 10591 USA. [O'Dushlaine, Colm; Rossin, Lizzy; Duncan, Laramie; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Perlis, Roy H.; Anttila, Verneri; Raychaudhuri, Soumya; Daly, Mark J.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Lee, Phil H.; Perlis, Roy H.; Bergen, Sarah E.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodevelopmental Genet Unit, Boston, MA 02114 USA. [Duncan, Laramie; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Bergen, Sarah E.; Chambert, Kimberly; McCarroll, Steven A.; Moran, Jennifer L.; Raychaudhuri, Soumya; Scolnick, Edward; Daly, Mark J.; Smoller, Jordan W.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Duncan, Laramie; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Bergen, Sarah E.; Chambert, Kimberly; McCarroll, Steven A.; Moran, Jennifer L.; Raychaudhuri, Soumya; Scolnick, Edward; Daly, Mark J.; Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Parikshak, Neelroop N.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Program Neurobehav Genet, Los Angeles, CA 90095 USA. [Newhouse, Stephen; Asherson, Philip; Collier, David A.; Craig, Ian W.; Farmer, Anne E.; Kuntsi, Jonna; Lewis, Cathryn M.; McGuffin, Peter; Breen, Gerome] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, MRC, London, England. [Newhouse, Stephen; Breen, Gerome] NIHR, Biomed Res Ctr Mental Hlth, South London & Maudsley NHS Trust & Inst Psychiat, London, England. [Purcell, Shaun M.; Ruderfer, Douglas] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Gen, New York, NY USA. [Posthuma, Danielle] Vrije Univ Amsterdam, Dept Funct Gen, Amsterdam, Netherlands. Vrije Univ Amsterdam, Dept Clin Genet, Amsterdam, Netherlands. [Posthuma, Danielle] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Nurnberger, John I.] Indiana Univ, Sch Med, Inst Psychiat Res, Indianapolis, IN 46202 USA. [Nurnberger, John I.] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Lee, S. Hong; Mowry, Bryan J.; Byrne, Enda M.; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. [Mowry, Bryan J.] Queensland Ctr Mental Hlth Res, Wacol, Qld, Australia. [Thapar, Anita; Fraser, Christine; Georgieva, Lyudmila; Gordon-Smith, Katherine; Grozeva, Detelina; Jones, Ian; Kirov, George K.; Moskvina, Valentina; Nikolov, Ivan; Owen, Michael J.; Williams, Nigel; Zammit, Stanley; O'Donovan, Michael C.; Craddock, Nicholas; Holmans, Peter A.] Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Gen, Cardiff CF10 3AX, S Glam, Wales. [Thapar, Anita; Fraser, Christine; Georgieva, Lyudmila; Jones, Ian; Kirov, George K.; Nikolov, Ivan; Owen, Michael J.; Williams, Nigel; Zammit, Stanley; Sklar, Pamela; O'Donovan, Michael C.; Craddock, Nicholas] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales. [Goddard, Michael E.] Dept Environm & Primary Ind Victoria, Biosci Res Div, Melbourne, Vic, Australia. [Goddard, Michael E.] Univ Melbourne, Fac Land & Environm, Melbourne, Vic, Australia. [Witte, John S.; Foroud, Tatiana; Koller, Daniel L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Absher, Devin; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Agartz, Ingrid; Andreassen, Ole A.; Djurovic, Srdjan; Mattingsdal, Morten; Melle, Ingrid] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, Oslo, Norway. [Agartz, Ingrid] Diakonhjemmet Hosp Oslo, Dept Res, Oslo, Norway. [Akil, Huda; Meng, Fan; Thompson, Robert C.; Watson, Stanley J.] Univ Michigan, Mol & Behav Neurosci Inst, Mol Psychiat Lab, Ann Arbor, MI 48109 USA. [Amin, Farooq] Emory Univ, Atlanta Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Andreassen, Ole A.; Melle, Ingrid] Oslo Univ Hosp, Div Mental Hlth & Addict, N-0450 Oslo, Norway. [Anjorin, Adebayo; Bass, Nicholas; Choudhury, Khalid; Gurling, Hugh; Kandaswamy, Radhika; Krasucki, Robert; Lawrence, Jacob; McQuillin, Andrew; Pimm, Jonathan; Puri, Vinay] UCL, Mental Hlth Sci Unit, London, England. [Anney, Richard; Cormican, Paul; Corvin, Aiden; Donohoe, Gary J.; Gailagher, Louise; Gill, Michael; Kenny, Elaine; Morris, Derek W.; Quinn, Emma M.; Visscher, Peter M.] Trin Coll Dublin, Dept Psychiat, Dublin, Ireland. [Arking, Dan E.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Azevedo, Maria H.; Oliveira, Guiomar] Univ Coimbra, Fac Med, Coimbra, Portugal. [Backlund, Lena; Frisen, Louise; Osby, Urban; Schalling, Martin] Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden. [Badner, Judith A.; Gershon, Elliot S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Bailey, Anthony J.] Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada. [Banaschewski, Tobias] Heidelberg Univ, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherary, Mannheim, Germany. [Barchas, Jack D.] Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA. [Barnes, Michael R.] GlaxoSmithKline, London, England. [Barrett, Thomas B.] Portland VA Med Ctr, Portland, OR USA. [Battaglia, Agatino] Stella Maris Inst Child & Adolescent Neuropsychia, Pisa, Italy. [Bauer, Michael] Carl Gustav Carus Univ Hosp, Dept Psychiat & Psychotherapy, Dresden, Germany. [Bayes, Monica] CNAG, PCB, Barcelona, Spain. [Bellivier, Frank; Etain, Bruno; Jamain, Stephane; Leboyer, Marion] INSERM, U955, Creteil, France. 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[Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke-Jan; Middeldorp, Christel M.; Willemsen, Gonneke] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Penninx, Brenda W.; Smit, Johannes H.; Van Grootheest, Gerard; Willemsen, Gonneke] Inst Hlth & Care Res, EMGO, Amsterdam, Netherlands. [Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke-Jan; Middeldorp, Christel M.; Penninx, Brenda W.] Neurosci Campus Amsterdam, Amsterdam, Netherlands. [Breuer, Rene; Frank, Josef; Meier, Sandra; Strohmaier, Jana; Treutlein, Jens; Witt, Stephanie H.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany. [Bruggeman, Richard; Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Buccola, Nancy G.] Louisiana State Univ, Hlth Sci Ctr, Sch Nursing, New Orleans, LA USA. 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[Greenwood, Tiffany A.; McKinney, Rebecca; Nievergelt, Caroline M.; Shilling, Paul D.; Kelsoe, John R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Grice, Dorothy E.] Icahn Sch Med Mt Sinai, OCD & Related Disorders, Div Tics, New York, NY 10029 USA. [Grice, Dorothy E.; Silverman, Jeremy M.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Gross, Magdalena; Hoefels, Susanne; Maier, Wolfgang] Univ Bonn, Dept Psychiat, Bonn, Germany. [Guan, Weihua] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [De Haan, Lieuwe] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. [Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN 37235 USA. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Gen, Div Human, Philadelphia, PA 19104 USA. [Hakonarson, Hakon] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Hallmayer, Joachim] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. [Hamshere, Marian L.; Hautzinger, Martin] Univ Tubingen, Dept Clin & Dev Psychol, Tubingen, Germany. [Hansen, Thomas F.; Ingason, Andres; Jones, Edward G.; Olsen, Line; Rasmussen, Henrik B.; Werge, Thomas] Copenhagen Univ Hosp, Inst Biol Psychiat, Roskilde, Denmark. [Hickie, Ian B.] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2006, Australia. [Hipolito, Maria; Lawson, William B.; Nwulia, Evaristus A.] Howard Univ, Coll Med, Dept Psychiat & Behav Sci, Washington, DC 20059 USA. [Hoogendijk, Witte J.] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands. [Hus, Vanessa] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. [Tzeng, Jung-Ying] N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA. [Keller, Matthew C.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Kennedy, James L.] Ctr Addict & Mental Hlth, Psychiat Neurogenet Sect, Toronto, ON, Canada. [Kent, Lindsey] Univ St Andrews, Sch Med, St Andrews, Fife, Scotland. [Kim, Yunjung; Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Klauck, Sabine M.] German Canc Res Ctr, DKFZ, Div Mol Genome Anal, Heidelberg, Germany. [Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Knowles, James A.; Medeiros, Helena; Pato, Carlos N.; Pato, Michele T.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Psychiat, Los Angeles, CA 90033 USA. [Korszun, Ania] Queen Mary Univ London, Wolfson Inst Preventat Med, London, England. [Krabbendam, Lydia; Myin-Germeys, Inez; Van Os, Jim] Maastricht Univ Med Ctr, South Limburg Mental Hlth Res & Teaching Network, Dept Psychiat Neuropsychol, Maastricht, Netherlands. [Landen, Mikael] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden. [Lathrop, Mark] Ctr Natl Genotypage, Evry, France. [Ledbetter, David H.; Martin, Christa L.] Autism & Dev Med Inst, Geisinger Hlth Syst, Danville, PA USA. 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[Wijsman, Ellen M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Young, Allan H.] Kings Coll London, Inst Psychiat, Ctr Affect Disorders, London, England. [Yu, Timothy W.] Harvard Univ, Sch Med, Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Zandi, Peter P.] Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD USA. [Zitman, Frans G.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. [Kelsoe, John R.] Vet Affairs San Diego Healthcare Syst, STEP, Dept Psychiat, San Diego, CA USA. Virginia Commonwealth Univ, Dept Human Mol Genet, Richmond, VA USA. [Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Kendler, Kenneth S.] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA. [Zhao, Zhaoming] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. RP Breen, G (reprint author), Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, MRC, London, England. EM holmanspa@cardiff.ac.uk; gerome.breen@kcl.ac.uk RI Lee, Sang Hong/A-2569-2011; Lohoff, Falk/M-7951-2016; Lencz, Todd/J-3418-2014; BELLIVIER, FRANK/H-5197-2012; McQuillin, Andrew/C-1623-2008; Magnusson, Patrik/C-4458-2017; Lesch, Klaus-Peter/J-4906-2013; Schumacher, Johannes/F-4970-2015; Monaco, Anthony/A-4495-2010; Ruderfer, Douglas/M-5795-2016; Scherer, Stephen /B-3785-2013; Franke, Barbara/D-4836-2009; Hansen, Thomas/O-5965-2014; Holmans, Peter/F-4518-2015; Kuntsi, Jonna/G-9750-2011; Zhang, Peng/N-2920-2014; Mattheisen, Manuel/B-4949-2012; Breen, Gerome/A-5540-2010; Paterson, Andrew/A-4088-2011; Melle, Ingrid /B-4858-2011 OI Backlund, Lena/0000-0001-9399-5024; Zammit, Stanley/0000-0002-2647-9211; Myin-Germeys, Inez/0000-0002-3731-4930; Jamain, Stephane/0000-0002-4321-4100; Greenwood, Tiffany/0000-0002-6080-6503; Kent, Lindsey/0000-0002-5315-3399; Anney, Richard/0000-0002-6083-407X; Bruggeman, Richard/0000-0002-3238-8471; Nothen, Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; Oliveira, Guiomar/0000-0002-7049-1277; Thapar, Anita/0000-0002-3689-737X; Etain, Bruno/0000-0002-5377-1488; de Geus, Eco/0000-0001-6022-2666; Cormand, Bru/0000-0001-5318-4382; Betancur, Catalina/0000-0002-3327-4804; Yu, Timothy/0000-0003-2988-7701; Gallagher, Louise/0000-0001-9462-2836; Lee, Sang Hong/0000-0001-9701-2718; Lencz, Todd/0000-0001-8586-338X; McQuillin, Andrew/0000-0003-1567-2240; Lesch, Klaus-Peter/0000-0001-8348-153X; Hamilton, Steven/0000-0001-8106-6260; Bergen, Sarah/0000-0002-5888-0034; Anttila, Verneri/0000-0002-0073-4675; McMahon, Francis/0000-0002-9469-305X; Schumacher, Johannes/0000-0001-9217-6457; Monaco, Anthony/0000-0001-7480-3197; Ruderfer, Douglas/0000-0002-2365-386X; Scherer, Stephen /0000-0002-8326-1999; Franke, Barbara/0000-0003-4375-6572; Hansen, Thomas/0000-0001-6703-7762; Holmans, Peter/0000-0003-0870-9412; Zhang, Peng/0000-0003-1182-1392; Mattheisen, Manuel/0000-0002-8442-493X; Breen, Gerome/0000-0003-2053-1792; Paterson, Andrew/0000-0002-9169-118X; Melle, Ingrid /0000-0002-9783-548X FU National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London; Maudsley NHS Foundation Trust; King's College London; US National Institute of Mental Health (NIMH) [K99MH101367]; NIMH [U01 MH085520]; Netherlands Scientific Organization (NOW) [480-05-003]; Dutch Brain Foundation; VU University FX G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. The PGC Cross-Disorder Group is supported by NIMH grant U01 MH085520. Statistical analyses were carried out on the Genetic Cluster Computer, which is fmancially supported by the Netherlands Scientific Organization (NOW; 480-05-003; principal investigator D.P.) along with a supplement from the Dutch Brain Foundation and VU University. Numerous (> 100) grants from government agencies along with substantial private and foundation support worldwide enabled the collection of phenotype and genotype data, without which this research would not be possible. NR 39 TC 110 Z9 111 U1 19 U2 126 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 FEB PY 2015 VL 18 IS 2 BP 199 EP 209 DI 10.1038/nn.3922 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CA0UM UT WOS:000348631800010 ER PT J AU Hsu, T Steeg, PS Zollo, M Wieland, T AF Hsu, Tien Steeg, Patricia S. Zollo, Massimo Wieland, Thomas CA Steering Comm Nme-related Res TI Progress on Nme (NDP kinase/Nm23/Awd) gene family-related functions derived from animal model systems: studies on development, cardiovascular disease, and cancer metastasis exemplified SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Editorial Material ID NUCLEOSIDE-DIPHOSPHATE KINASE; HETEROTRIMERIC G-PROTEIN; BREAST-CARCINOMA CELLS; BETA-GAMMA DIMERS; GROWTH-FACTOR; MEDROXYPROGESTERONE ACETATE; HISTIDINE PHOSPHORYLATION; EXPRESSION PROFILE; SUPPRESSOR NM23-H2; COMPLEX-FORMATION C1 [Hsu, Tien] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Hsu, Tien] Natl Cent Univ, Inst Syst Biol & Bioinformat, Jhongli, Taiwan. [Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Zollo, Massimo] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy. [Zollo, Massimo] Univ Naples Federico II, Ctr Ingn Genet Biotecnol Avanzate, CEINGE, I-80131 Naples, Italy. [Wieland, Thomas] Heidelberg Univ, Mannheim Med Fac, Inst Expt & Clin Pharmacol & Toxicol, D-68169 Mannheim, Germany. [Wieland, Thomas] DZHK German Ctr Cardiovasc Res, Mannheim, Germany. RP Hsu, T (reprint author), Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. EM tienhsu@ncu.edu.tw; steegp@mail.nih.gov; massimo.zollo@unina.it; thomas.wieland@urz.uni-heidelberg.de RI Zollo, Massimo/K-5857-2016; Wieland, Thomas/G-1772-2012 OI Zollo, Massimo/0000-0002-0970-7243; NR 99 TC 3 Z9 3 U1 5 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1298 EI 1432-1912 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2015 VL 388 IS 2 BP 109 EP 117 DI 10.1007/s00210-014-1079-9 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CA0ZM UT WOS:000348642000001 PM 25585611 ER PT J AU Blair, A Ritz, B Wesseling, C Freeman, LB AF Blair, Aaron Ritz, Beate Wesseling, Catharina Freeman, Laura Beane TI Pesticides and human health SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Editorial Material ID ORGANOPHOSPHATE PESTICIDES; EXPOSURE; DISEASE; CANCER; TRENDS; RISK C1 [Blair, Aaron; Freeman, Laura Beane] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20878 USA. [Ritz, Beate] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Wesseling, Catharina] Karolinska Inst, Inst Environm Med, Unit Occupat Med, S-10401 Stockholm, Sweden. RP Blair, A (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9600 Med Ctr Dr,Room 6E558, Rockville, MD 20878 USA. EM blaira@exchange.nih.gov RI Beane Freeman, Laura/C-4468-2015; Ritz, Beate/E-3043-2015 OI Beane Freeman, Laura/0000-0003-1294-4124; FU Intramural NIH HHS; NIEHS NIH HHS [ES10544, P01ES016732] NR 26 TC 10 Z9 11 U1 1 U2 26 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD FEB PY 2015 VL 72 IS 2 BP 81 EP 82 DI 10.1136/oemed-2014-102454 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AY7YZ UT WOS:000347772900001 PM 25540410 ER PT J AU Cukras, C Huynh, N Vitale, S Wong, WT Ferris, FL Sieving, PA AF Cukras, Catherine Huynh, Nancy Vitale, Susan Wong, Wai T. Ferris, Fredrick L., III Sieving, Paul A. TI Subjective and Objective Screening Tests for Hydroxychloroquine Toxicity SO OPHTHALMOLOGY LA English DT Article ID FRACTIONAL POLYNOMIALS; RETINAL TOXICITY; AMERICAN-ACADEMY; CHLOROQUINE; RECOMMENDATIONS; OPHTHALMOLOGY; RETINOPATHY; REGRESSION AB Objective: To compare subjective and objective clinical tests used in the screening for hydroxychloroquine retinal toxicity to multifocal electroretinography (mfERG) reference testing. Design: Prospective, single-center, case control study. Participants: Fifty-seven patients with a previous or current history of hydroxychloroquine treatment of more than 5 years' duration. Methods: Participants were evaluated with a detailed medical history, dilated ophthalmologic examination, color fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain (SD) optical coherence tomography (OCT), automated visual field testing (10-2 visual field mean deviation [VFMD]), and mfERG testing. We used mfERG test parameters as a gold standard to divide participants into 2 groups: those affected by hydroxychloroquine-induced retinal toxicity and those unaffected. Main Outcome Measures: We assessed the association of various imaging and psychophysical variables in the affected versus the unaffected group. Results: Fifty-seven study participants (91.2% female; mean age, 55.7 +/- 10.4 years; mean duration of hydroxychloroquine treatment, 15.0 +/- 7.5 years) were divided into affected (n = 19) and unaffected (n = 38) groups based on mfERG criteria. Mean age and duration of hydroxychloroquine treatment did not differ statistically between groups. Mean OCT retinal thickness measurements in all 9 macular subfields were significantly lower (<40 mu m) in the affected group (P < 0.01 for all comparisons) compared with those in the unaffected group. Mean VFMD was 11 dB lower in the affected group (P < 0.0001). Clinical features indicative of retinal toxicity were scored for the 2 groups and were detected in 68.4% versus 0.0% using color fundus photographs, 73.3% versus 9.1% using FAF images, and 84.2% versus 0.0% on the scoring for the perifoveal loss of the photoreceptor ellipsoid zone on SD-OCT for affected and unaffected participants, respectively. Using a polynomial modeling approach, OCT inner ring retinal thickness measurements and Humphrey 10-2 VFMD were identified as the variables associated most strongly with the presence of hydroxychloroquine as defined by mfERG testing. Conclusions: Optical coherence tomography retinal thickness and 10-2 VFMD are objective measures demonstrating clinically useful sensitivity and specificity for the detection of hydroxychloroquine toxicity as identified by mfERG, and thus may be suitable surrogate tests. (C) 2015 by the American Academy of Ophthalmology. C1 [Cukras, Catherine; Vitale, Susan; Ferris, Fredrick L., III] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. [Huynh, Nancy; Sieving, Paul A.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Wong, Wai T.] NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA. [Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD USA. RP Cukras, C (reprint author), NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. EM cukrasc@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU National Institutes of Health Intramural Research Programs of the National Eye Institute; National Institute on Deafness and Other Communication Disorders FX Supported by the National Institutes of Health Intramural Research Programs of the National Eye Institute and the National Institute on Deafness and Other Communication Disorders. The sponsor or funding organization had no role in the design or conduct of this research. NR 17 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2015 VL 122 IS 2 BP 356 EP 366 DI 10.1016/j.ophtha.2014.07.056 PG 11 WC Ophthalmology SC Ophthalmology GA AZ5WT UT WOS:000348290000028 PM 25444344 ER PT J AU Fisher, DE Jonasson, F Eiriksdottir, G Sigurdsson, S Klein, R Launer, LJ Gudnason, V Cotch, MF AF Fisher, Diana E. Jonasson, Fridbert Eiriksdottir, Gudny Sigurdsson, Sigurdur Klein, Ronald Launer, Lenore J. Gudnason, Vilmundur Cotch, Mary Frances TI Age-Related Macular Degeneration and Mortality in Community-Dwelling Elders The Age, Gene/Environment Susceptibility Reykjavik Study SO OPHTHALMOLOGY LA English DT Article ID BEAVER-DAM-EYE; BLUE-MOUNTAINS-EYE; RISK-FACTORS; CARDIOVASCULAR-DISEASE; VISUAL IMPAIRMENT; OLDER-PEOPLE; MACULOPATHY; ATHEROSCLEROSIS; PROGRESSION; SURVIVAL AB Objective: To investigate the association between age-related macular degeneration (AMD) and mortality in older persons. Design: Population-based prospective cohort study. Participants: Participants 67 to 96 years of age (43.1% male) enrolled between 2002 and 2006 in the Age, Gene/Environment Susceptibility-Reykjavik Study. Methods: Retinal photographs of the macula were acquired digitally and evaluated for the presence of AMD lesions using the Wisconsin Age-Related Maculopathy grading scheme. Mortality was assessed prospectively through 2013 with cause of death available through 2009. The association between AMD and death, resulting from any cause and specifically cardiovascular disease (CVD), was examined using Cox proportional hazards regression with age as the time scale, adjusted for significant risk factors and comorbid conditions. To address a violation in the proportional hazards assumption, analyses were stratified into 2 groups based on the mean age at death (83 years). Main Outcome Measures: Mortality resulting from all causes and CVD. Results: Among 4910 participants, after a median follow-up of 8.6 years, 1742 died (35.5%), of whom 614 (35.2%) had signs of AMD at baseline. Cardiovascular disease was the cause of death for 357 people who died before the end of 2009, of whom 144 (40%) had AMD (101 with early disease and 43 with late disease). After considering covariates, including comorbid conditions, having early AMD at any age or having late AMD in individuals younger than 83 years (n = 4179) were not associated with all-cause or CVD mortality. In individuals 83 years of age and older (n = 731), late AMD was associated significantly with increased risk of all-cause mortality (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.20-2.57) and CVD-related mortality (HR, 2.37; 95% CI, 1.41-3.98). In addition to having AMD, older individuals who died were more likely to be male and to have low body mass index, impaired cognition, and microalbuminuria. Conclusions: Competing risk factors and concomitant conditions are important in determining mortality risk resulting from AMD. Individuals with early AMD are not more likely to die than peers of comparable age. Late AMD becomes a predictor of mortality by the mid-octogenarian years. (C) 2015 by the American Academy of Ophthalmology. C1 [Fisher, Diana E.; Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Jonasson, Fridbert] Landspitali Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland. [Jonasson, Fridbert; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Klein, Ronald] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Fisher, DE (reprint author), Bldg 10-CRC,Room 3-2521, Bethesda, MD 20892 USA. EM diana.fisher@nih.gov RI Gudnason, Vilmundur/K-6885-2015; OI Gudnason, Vilmundur/0000-0001-5696-0084; Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural Research Programs of the National Institute of Aging [ZIAG007380]; National Eye Institute [ZIAEY000401]; National Institutes of Health, Bethesda, Maryland [N01-AG-1-2100, ZIAEY00401]; Icelandic Heart Association, Kopavogur, Iceland; Icelandic Parliament, Reykjavik, Iceland; University of Iceland Research Fund, Reykjavik, Iceland; Helga Jonsdottir and Sigurlidi Kristjansson Research Fund, Reykjavik, Iceland FX Supported by the Intramural Research Programs of the National Institute of Aging (award no.: ZIAG007380) and the National Eye Institute (award no.: ZIAEY000401), National Institutes of Health (contract no.: N01-AG-1-2100), Bethesda, Maryland (grant no.: ZIAEY00401); the Icelandic Heart Association, Kopavogur, Iceland; the Icelandic Parliament, Reykjavik, Iceland; the University of Iceland Research Fund, Reykjavik, Iceland; and the Helga Jonsdottir and Sigurlidi Kristjansson Research Fund, Reykjavik, Iceland. The funders had no role in data collection; management, analysis, and interpretation of the data; preparation, writing, and approval of the manuscript; or decision to submit the manuscript for publication. NR 30 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2015 VL 122 IS 2 BP 382 EP 390 DI 10.1016/j.ophtha.2014.08.006 PG 9 WC Ophthalmology SC Ophthalmology GA AZ5WT UT WOS:000348290000031 PM 25264026 ER PT J AU Altaweel, MM Daniel, E Martin, DF Mittra, RA Grunwald, JE Lai, MM Melamud, A Morse, LS Huang, JY Ferris, FL Fine, SL Maguire, MG AF Altaweel, Michael M. Daniel, Ebenezer Martin, Daniel F. Mittra, Robert A. Grunwald, Juan E. Lai, Michael M. Melamud, Alexander Morse, Lawrence S. Huang, Jiayan Ferris, Frederick L., III Fine, Stuart L. Maguire, Maureen G. CA Comparison Age-related Macular TI Outcomes of Eyes with Lesions Composed of > 50% Blood in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) SO OPHTHALMOLOGY LA English DT Article ID PIGMENT EPITHELIAL TEARS; TISSUE-PLASMINOGEN ACTIVATOR; ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL NEOVASCULAR LESIONS; LARGE SUBMACULAR HEMORRHAGE; SUBRETINAL HEMORRHAGE; INTRAVITREAL RANIBIZUMAB; PNEUMATIC DISPLACEMENT; NATURAL-HISTORY; BEVACIZUMAB AB Objective: To compare baseline characteristics, treatment frequency, visual acuity (VA), and morphologic outcomes of eyes with >50% of the lesion composed of blood (B50 group) versus all other eyes (Other group) enrolled in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Design: Prospective cohort study within a multicenter randomized clinical trial. Participants: CATT patients with neovascular age-related macular degeneration (AMD). Methods: Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different dosing regimens over a 2-year period. Reading center graders evaluated baseline and follow-up morphology in color fundus photographs, fluorescein angiography (FA), and optical coherence tomography (OCT). Masked examiners tested VA. Main Outcome Measures: Morphologic features and VA at 1 and 2 years. Results: The B50 group consisted of 84 of 1185 (7.1%) patients enrolled in CATT. Baseline lesion characteristics differed between groups. In the B50 group, choroidal neovascularization size was smaller (0.73 vs 1.83 disc areas [DA]; P < 0.001), total lesion size was greater (4.55 vs 2.31 DA; P < 0.001), total retinal thickness was greater (524 vs 455 mm; P = 0.02), and mean VA was worse (56.0 vs 60.9 letters; P = 0.002). Increases in mean VA were similar in the B50 and Other groups at 1 year (+9.3 vs +7.2 letters; P = 0.22) and at 2 years (9.0 vs 6.1 letters; P = 0.17). Eyes treated PRN received a similar number of injections in the 2 groups (12.2 vs 13.4; P = 0.27). Mean lesion size in the B50 group decreased by 1.2 DA at both 1 and 2 years (primarily owing to resolution of hemorrhage) and increased in the Other group by 0.33 DA at 1 year and 0.91 DA at 2 years (P < 0.001). Leakage on FA and fluid on OCT were similar between groups at 1 and 2 years. Conclusions: In CATT, the B50 group had a visual prognosis similar to the Other group. Lesion size decreased markedly through 2 years. Eyes like those enrolled in CATT with neovascular AMD lesions composed of >50% blood can be managed similarly to those with less or no blood. (C) 2015 by the American Academy of Ophthalmology. C1 [Altaweel, Michael M.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53705 USA. [Daniel, Ebenezer; Grunwald, Juan E.; Huang, Jiayan; Maguire, Maureen G.] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Martin, Daniel F.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA. [Mittra, Robert A.] VitreoRetinal Surg, Edina, MN USA. [Lai, Michael M.; Melamud, Alexander] Retina Grp Washington, Chevy Chase, MD USA. [Morse, Lawrence S.] Univ Calif Davis, Med Ctr, Dept Ophthalmol, Sacramento, CA 95817 USA. [Ferris, Frederick L., III] NEI, Bethesda, MD 20892 USA. [Fine, Stuart L.] Univ Colorado Denver, Dept Ophthalmol, Aurora, CO USA. RP Altaweel, MM (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, 2870 Univ Ave, Madison, WI 53705 USA. EM mmaltaweel@wisc.edu OI Morse, Lawrence/0000-0002-1758-2348 FU Genentech; National Eye Institute, National Institutes of Health, Department of Health and Human Services [U10 EY017823, U10 EY017825, U10 EY017826, U10 EY017828] FX L.M.: Consultant - Genentech; Lecture fees Genentech.; Supported by cooperative agreements U10 EY017823, U10 EY017825, U10 EY017826, and U10 EY017828 from the National Eye Institute, National Institutes of Health, Department of Health and Human Services. ClinicalTrials.gov number: NCT00593450. NR 39 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2015 VL 122 IS 2 BP 391 EP + DI 10.1016/j.ophtha.2014.08.020 PG 13 WC Ophthalmology SC Ophthalmology GA AZ5WT UT WOS:000348290000032 PM 25307130 ER PT J AU Ali, S Khan, SY Naeem, MA Khan, SN Husnain, T Riazuddin, S Ayyagari, R Riazuddin, S Hejtmancik, JF Riazuddin, SA AF Ali, Shahbaz Khan, Shahid Y. Naeem, Muhammad Asif Khan, Shaheen N. Husnain, Tayyab Riazuddin, Saima Ayyagari, Radha Riazuddin, Sheikh Hejtmancik, J. Fielding Riazuddin, S. Amer TI Phenotypic Variability Associated with the D226N Allele of IMPDH1 SO OPHTHALMOLOGY LA English DT Editorial Material ID DOMINANT RETINITIS-PIGMENTOSA; MUTATIONS; GENE; SPECTRUM C1 [Ali, Shahbaz; Naeem, Muhammad Asif; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh; Riazuddin, S. Amer] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. [Khan, Shahid Y.; Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. [Riazuddin, Saima] Univ Maryland, Sch Med, Dept Otorhinolaryngol, Baltimore, MD 21201 USA. [Ayyagari, Radha] Univ Calif San Diego, Shiley Eye Ctr, La Jolla, CA 92093 USA. [Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan. [Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Riazuddin, SA (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 N Wolfe St,Maumenee Bldg,Room 840A, Baltimore, MD 21287 USA. EM riazuddin@jhmi.edu RI Nasim Khan, Shaheen/F-2135-2015 FU NEI NIH HHS [R01EY021237-01] NR 5 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 2015 VL 122 IS 2 BP 429 EP 431 PG 3 WC Ophthalmology SC Ophthalmology GA AZ5WT UT WOS:000348290000036 PM 25439607 ER PT J AU Layman, AJ Li, C Simonsick, E Ferrucci, L Carey, JP Agrawal, Y AF Layman, Andrew J. Li, Carol Simonsick, Eleanor Ferrucci, Luigi Carey, John P. Agrawal, Yuri TI Association Between Saccular Function and Gait Speed: Data From the Baltimore Longitudinal Study of Aging SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Vestibular evoked myogenic potentials; Aging; Gait; Vestibular dysfunction ID VISUAL-VESTIBULAR INTERACTIONS; EVOKED MYOGENIC POTENTIALS; AGE-RELATED-CHANGES; OLDER-ADULTS; WALKING; HEAD; STABILIZATION; STIMULATION; RELIABILITY; PERFORMANCE AB Objective To investigate whether otolith function (saccular and utricular) is associated with walking performance. Study Design Cross-sectional analysis of observational data collected in the Baltimore Longitudinal Study of Aging. Setting National Institute on Aging Intramural Research Program Clinical Research Unit at Harbor Hospital, Baltimore, Maryland. Patients Community-dwelling participants. Intervention(s) Cervical and ocular vestibular evoked myogenic potentials (VEMPs) were used to assess saccular and utricular function, respectively. Main outcome measure(s) Cervical and ocular VEMP latency and amplitude responses and usual, rapid, and narrow (20 cm) gait speed assessed over a 6-m course. Results In 314 participants (mean age, 73.1 yr; range, 26-96 yr), cervical VEMP amplitude mediated the association between age and gait speedparticularly narrow walk speedin both men and women. Cervical VEMP latency had an independent association with gait speed in age-, height-, and weight-adjusted analyses, although the direction of the association differed by sex. Greater cervical VEMP latency was associated with slower usual, rapid, and narrow gait speed in women but faster rapid gait speed in men. Neither the amplitude nor latency of ocular VEMP was associated with gait speed in men or women. Conclusion These findings suggest that age-related slowing of gait speed is in part mediated by the decreased magnitude of saccular response associated with age. The sex-related differential association between saccular response latency and gait speed requires further study. C1 [Layman, Andrew J.; Li, Carol; Carey, John P.; Agrawal, Yuri] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Simonsick, Eleanor; Ferrucci, Luigi] Harbor Hosp, Longitudinal Studies Sect, NIA, Baltimore, MD USA. RP Agrawal, Y (reprint author), Johns Hopkins Outpatient Ctr, 601 North Caroline St, Baltimore, MD 21287 USA. EM yagrawa1@jhmi.edu FU National Institutes of Health; American Otological Society Clinician Scientist Award; NIA Older Americans Independence Center Research Career Development Core grant FX This study was supported by the National Institutes of Health, the American Otological Society Clinician Scientist Award, and the NIA Older Americans Independence Center Research Career Development Core grant. NR 30 TC 6 Z9 6 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD FEB PY 2015 VL 36 IS 2 BP 260 EP 266 DI 10.1097/MAO.0000000000000544 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AZ8IQ UT WOS:000348459300022 PM 25569369 ER PT J AU Li, C Layman, AJ Geary, R Anson, E Carey, JP Ferrucci, L Agrawal, Y AF Li, Carol Layman, Andrew J. Geary, Robert Anson, Eric Carey, John P. Ferrucci, Luigi Agrawal, Yuri TI Epidemiology of Vestibulo-Ocular Reflex Function: Data From the Baltimore Longitudinal Study of Aging SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Aging; Head-impulse test; Vestibular dysfunction; Vestibulo-ocular reflex ID VESTIBULAR FUNCTION; VIDEO-OCULOGRAPHY; RESPONSES; AGE; SPECTACLES; EPITHELIA; GANGLION; BALANCE; HUMANS; GAIT AB Objective To determine age-related changes in vestibulo-ocular reflex (VOR) function in community-dwelling adults, and evaluate these for associations with demographic characteristics and cardiovascular risk factors. Study Design Cross-sectional analysis within the Baltimore Longitudinal Study of Aging (BLSA), a longitudinal prospective cohort study. Setting Vestibular testing laboratory within an acute care teaching hospital. Patients Community-dwelling adults enrolled in the BLSA. Intervention(s) Horizontal VOR gain measurement using video head-impulse testing and visual acuity testing. Main Outcome Measure(s) VOR gain was calculated as the ratio of eye velocity to head velocity. Demographic and cardiovascular risk factor data were collected through study questionnaires. Results One hundred nine subjects were analyzed with mean age (SD) 69.9 years (14.2), with a range from 26 to 92 years. VOR gain remained stable from age 26 to 79 after which it significantly declined at a rate of 0.012/year (p = 0.033) in adjusted analyses. Individuals aged 80 years or older had a nearly 8-fold increased odds of VOR gain less than 0.80 relative to those aged less than 80 years in multivariate models (prevalence of 13.2% vs. 2.8%; OR 7.79, 95% CI: 1.04-58.38). Otherwise, VOR gain did not differ significantly across demographic or cardiovascular risk groups. Conclusion We report age-related decline in VOR function in individuals aged 80 years and older. Further analyses are in progress to establish the significance of these VOR abnormalities to functional and mobility outcomes in older individuals. C1 [Li, Carol; Layman, Andrew J.; Anson, Eric; Carey, John P.; Agrawal, Yuri] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Geary, Robert] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21205 USA. [Anson, Eric] Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. [Agrawal, Yuri] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Agrawal, Y (reprint author), Johns Hopkins Outpatient Ctr, 601 North Caroline St, Baltimore, MD 21287 USA. EM yagrawa1@jhmi.edu OI Anson, Eric/0000-0002-0075-8386 FU American Otological Society Clinician Scientist Award; NIA Older Americans Independence Center Research Career Development Core Grant FX Supported by the American Otological Society Clinician Scientist Award; NIA Older Americans Independence Center Research Career Development Core Grant. NR 35 TC 15 Z9 15 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD FEB PY 2015 VL 36 IS 2 BP 267 EP 272 DI 10.1097/MAO.0000000000000610 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AZ8IQ UT WOS:000348459300023 PM 25275869 ER PT J AU Lieskovska, J Palenikova, J Sirmarova, J Elsterova, J Kotsyfakis, M Chagas, AC Calvo, E Ruzek, D Kopecky, J AF Lieskovska, J. Palenikova, J. Sirmarova, J. Elsterova, J. Kotsyfakis, M. Chagas, A. Campos Calvo, E. Ruzek, D. Kopecky, J. TI Tick salivary cystatin sialostatin L2 suppresses IFN responses in mouse dendritic cells SO PARASITE IMMUNOLOGY LA English DT Article DE tick; dendritic cell; interferon; cystatin ID TOLL-LIKE RECEPTORS; IXODES-SCAPULARIS; INTERFERON RESPONSE; GENE-EXPRESSION; INFECTION; ESTABLISHMENT; MACROPHAGES; INHIBITION; MECHANISMS; INTERFACE AB Type I interferon (IFN), mainly produced by dendritic cells (DCs), is critical in the host defence against tick-transmitted pathogens. Here, we report that salivary cysteine protease inhibitor from the hard tick Ixodes scapularis, sialostatin L2, affects IFN- mediated immune reactions in mouse dendritic cells. Following IFN receptor ligation, the Janus activated kinases/signal transducer and activator of transcription (JAK/STAT) pathway is activated. We show that sialostatin L2 attenuates phosphorylation of STATs in spleen dendritic cells upon addition of recombinant IFN-. LPS-stimulated dendritic cells release IFN- which in turn leads to the induction of IFN-stimulated genes (ISG) through JAK/STAT pathway activation. The induction of two ISG, interferon regulatory factor 7 (IRF-7) and IP-10, was suppressed by sialostatin L2 in LPS-stimulated dendritic cells. Finally, the interference of sialostatin L2 with IFN action led to the enhanced replication of tick-borne encephalitis virus in DC. In summary, we present here that tick salivary cystatin negatively affects IFN- responses which may consequently increase the pathogen load after transmission via tick saliva. C1 [Lieskovska, J.; Palenikova, J.; Elsterova, J.; Ruzek, D.; Kopecky, J.] Univ South Bohemia, Fac Sci, CZ-37005 Ceske Budejovice, Czech Republic. [Lieskovska, J.; Palenikova, J.; Elsterova, J.; Kotsyfakis, M.; Ruzek, D.; Kopecky, J.] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic. [Sirmarova, J.; Elsterova, J.; Ruzek, D.] Vet Res Inst, Dept Virol, CS-62132 Brno, Czech Republic. [Chagas, A. Campos; Calvo, E.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Lieskovska, J (reprint author), Univ South Bohemia, Fac Sci, Branisovska 1760, CZ-37005 Ceske Budejovice, Czech Republic. EM lieskovs@paru.cas.cz RI Ruzek, Daniel/G-9275-2014; Kotsyfakis, Michail/G-9525-2014; Kopecky, Jan/G-9347-2014; Lieskovska, Jaroslava/G-9309-2014; OI Kotsyfakis, Michail/0000-0002-7526-1876; Ruzek, Daniel/0000-0003-4655-2380; Calvo, Eric/0000-0001-7880-2730 FU Czech Science Foundation [P302/12/2208, 14-25799S]; MEYS of the Czech Republic under the NPU I program [LO1218] FX This work was supported by the Czech Science Foundation, grants No. P302/12/2208 and No. 14-25799S, and MEYS of the Czech Republic (project LO1218) under the NPU I program. We thank Professor F. X. Heinz, Medical University of Vienna, for kindly providing Neudoerfl virus. NR 31 TC 2 Z9 2 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0141-9838 EI 1365-3024 J9 PARASITE IMMUNOL JI Parasite Immunol. PD FEB PY 2015 VL 37 IS 2 BP 70 EP 78 DI 10.1111/pim.12162 PG 9 WC Immunology; Parasitology SC Immunology; Parasitology GA CA2DC UT WOS:000348718100002 PM 25408129 ER PT J AU Cotton, RN Mcdonald-Fleming, R Boyd, A Spates, K Nutman, TB Semnani, RT AF Cotton, R. N. Mcdonald-Fleming, R. Boyd, A. Spates, K. Nutman, T. B. Semnani, R. Tolouei TI Brugia malayi infective larvae fail to activate Langerhans cells and dermal dendritic cells in human skin SO PARASITE IMMUNOLOGY LA English DT Article DE langerhans cells; dermal dendritic cells; Brugia malayi ID TOLL-LIKE RECEPTORS; REGULATORY T-CELLS; DIFFERENTIAL PRODUCTION; HELMINTH-PARASITES; IMMUNE-RESPONSE; IN-VIVO; MIGRATION; EXPRESSION; TLR; LEISHMANIA AB Filarial infection in humans is initiated when a mosquito deposits third-stage parasite larvae (L3) in the skin. Langerhans cells (LCs) and dermal dendritic cells (DDCs) are the first cells that the parasite encounters, and L3s must evade these highly effective antigen-presenting cells to establish infection. To assess LC and DDC responses to L3 in human skin, we employed three models of increasing physiologic relevance: in vitro-generated LCs, epidermal blister explants and full-thickness human skin sections. In vitro-generated LCs expressed TLR1-10 and robustly produced IL-6 and TNF- in response to PolyI:C, but pre-exposure to L3s did not alter inflammatory cytokine production or TLR expression. L3s did not modulate expression of LC markers CDH1, CD207, or CD1a, or the regulatory products TSLP or IDO in epidermal explants or in vitro-generated LC. LC, CD14+ DDC, CD1c+ DC and CD141+ DC from human skin sections were analysed by flow cytometry. While PolyI:C potently induced CCL22 production in LC, CD1c+ DC, and CD141+ DC, and IL-10 production in LC, L3s did not modulate the numbers of or cytokine production by any skin DC subset. L3s broadly failed to activate or modulate LCs or DDCs, suggesting filarial larvae expertly evade APC detection in human skin. C1 [Cotton, R. N.; Mcdonald-Fleming, R.; Boyd, A.; Spates, K.; Nutman, T. B.; Semnani, R. Tolouei] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Semnani, RT (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM rsemnani@niaid.nih.gov OI Cotton, Rachel/0000-0002-1698-4409 NR 40 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0141-9838 EI 1365-3024 J9 PARASITE IMMUNOL JI Parasite Immunol. PD FEB PY 2015 VL 37 IS 2 BP 79 EP 91 DI 10.1111/pim.12169 PG 13 WC Immunology; Parasitology SC Immunology; Parasitology GA CA2DC UT WOS:000348718100003 PM 25545218 ER PT J AU Tekola-Ayele, F Adeyemo, A Aseffa, A Hailu, E Finan, C Davey, G Rotimi, CN Newport, MJ AF Tekola-Ayele, F. Adeyemo, A. Aseffa, A. Hailu, E. Finan, C. Davey, G. Rotimi, C. N. Newport, M. J. TI Clinical and pharmacogenomic implications of genetic variation in a Southern Ethiopian population SO PHARMACOGENOMICS JOURNAL LA English DT Article ID DRUG-INDUCED HEPATOTOXICITY; WARFARIN RESISTANCE; VKORC1; DIVERSITY; POLYMORPHISM; SUSCEPTIBILITY; INDIVIDUALS; VARIANTS; SOFTWARE; PROGRAM AB Africa is home to genetically diverse human populations. We compared the genetic structure of the Wolaita ethnic population from Southern Ethiopia (WETH, n = 120) with HapMap populations using genome-wide variants. We investigated allele frequencies of 443 clinically and pharmacogenomically relevant genetic variants in WETH compared with HapMap populations. We found that WETH were genetically most similar to the Kenya Maasai and least similar to the Japanese in HapMap. Variant alleles associated with increased risk of adverse reactions to drugs used for treating tuberculosis (rs1799929 and rs1495741 in NAT2), thromboembolism (rs7294, rs9923231 and rs9934438 in VKORC1), and HIV/AIDS and solid tumors (rs2242046 in SLC28A1) had significantly higher frequencies in WETH compared with African ancestry HapMap populations. Our results illustrate that clinically relevant pharmacogenomic loci display allele frequency differences among African populations. We conclude that drug dosage guidelines for important global health diseases should be validated in genetically diverse African populations. C1 [Tekola-Ayele, F.; Adeyemo, A.; Rotimi, C. N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Aseffa, A.; Hailu, E.] Armauer Hansen Res Inst, Addis Ababa, Ethiopia. [Finan, C.] Wellcome Trust Sanger Inst, Cambridge, England. [Davey, G.] Brighton & Sussex Med Sch, Brighton, E Sussex, England. RP Tekola-Ayele, F (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bldg 12A,Room 4047,12 South Dr, Bethesda, MD 20892 USA. EM ayeleft@mail.nih.gov RI Aseffa, Abraham/J-3248-2016; OI Aseffa, Abraham/0000-0002-8028-1150; Adeyemo, Adebowale/0000-0002-3105-3231; Tekola-Ayele, Fasil/0000-0003-4194-9370 FU Wellcome Trust [079791]; Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, in the Center for Research on Genomics and Global Health (CRGGH); National Institute of Diabetes and Digestive and Kidney Diseases FX The research project was supported by the Wellcome Trust (grant no. 079791), and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, in the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is also supported by the National Institute of Diabetes and Digestive and Kidney Diseases. We thank staff of the Mossy Foot Treatment and Prevention Association of Ethiopia for coordinating the fieldwork. NR 44 TC 5 Z9 5 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD FEB PY 2015 VL 15 IS 1 BP 101 EP 108 DI 10.1038/tpj.2014.39 PG 8 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA AZ8IT UT WOS:000348459700015 PM 25069476 ER PT J AU Rossi, P Shi, L Liu, GH Barbieri, CM Lee, HW Grant, TD Luft, JR Xiao, R Acton, TB Snell, EH Montelione, GT Baker, D Lange, OF Sgourakis, NG AF Rossi, Paolo Shi, Lei Liu, Gaohua Barbieri, Christopher M. Lee, Hsiau-Wei Grant, Thomas D. Luft, Joseph R. Xiao, Rong Acton, Thomas B. Snell, Edward H. Montelione, Gaetano T. Baker, David Lange, Oliver F. Sgourakis, Nikolaos G. TI A hybrid NMR/SAXS-based approach for discriminating oligomeric protein interfaces using Rosetta SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE protein complex; nuclear magnetic resonance spectroscopy; CS-Rosetta modeling; residual dipolar coupling; small-angle X-ray scattering ID RESIDUAL DIPOLAR COUPLINGS; SPARSE NMR DATA; RNA COMPLEX; SAXS DATA; REVEALS; DOCKING; MACROMOLECULES; BACTERIOPHAGE; SPECTROSCOPY; ALIGNMENT AB Oligomeric proteins are important targets for structure determination in solution. While in most cases the fold of individual subunits can be determined experimentally, or predicted by homology-based methods, protein-protein interfaces are challenging to determine de novo using conventional NMR structure determination protocols. Here we focus on a member of the bet-V1 superfamily, Aha1 from Colwellia psychrerythraea. This family displays a broad range of crystallographic interfaces none of which can be reconciled with the NMR and SAXS data collected for Aha1. Unlike conventional methods relying on a dense network of experimental restraints, the sparse data are used to limit conformational search during optimization of a physically realistic energy function. This work highlights a new approach for studying minor conformational changes due to structural plasticity within a single dimeric interface in solution. Proteins 2015; 83:309-317. (c) 2014 Wiley Periodicals, Inc. C1 [Rossi, Paolo; Liu, Gaohua; Barbieri, Christopher M.; Xiao, Rong; Acton, Thomas B.; Montelione, Gaetano T.] Rutgers State Univ, Dept Mol Biol & Biochem, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. [Rossi, Paolo; Liu, Gaohua; Barbieri, Christopher M.; Xiao, Rong; Acton, Thomas B.; Montelione, Gaetano T.] Rutgers State Univ, Northeast Struct Genom Consortium, Piscataway, NJ 08854 USA. [Shi, Lei; Baker, David; Lange, Oliver F.; Sgourakis, Nikolaos G.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Lee, Hsiau-Wei] Univ Georgia, Complex Carbohydrate Res Ctr, Dept Chem, Athens, GA 30602 USA. [Lee, Hsiau-Wei] Univ Georgia, Northeast Struct Genom Consortium, Athens, GA 30602 USA. [Lee, Hsiau-Wei] Univ Georgia, Dept Biochem & Mol Biol, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. [Grant, Thomas D.; Luft, Joseph R.; Snell, Edward H.] Hauptman Woodward Med Res Inst, Buffalo, NY 14203 USA. [Grant, Thomas D.; Luft, Joseph R.; Snell, Edward H.] Northeast Struct Genom Consortium, Buffalo, NY 14203 USA. [Grant, Thomas D.; Luft, Joseph R.; Snell, Edward H.] SUNY Buffalo, Dept Biol Struct, Buffalo, NY 14203 USA. [Montelione, Gaetano T.] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA. [Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Sgourakis, Nikolaos G.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Sgourakis, NG (reprint author), NIDDK, Chem Phys Lab, NIH, 9000 Rockville Pike,Bldg 5,Rm B1-31, Bethesda, MD 20892 USA. EM sgourakisn@mail.nih.gov RI Baker, David/K-8941-2012 OI Baker, David/0000-0001-7896-6217 FU NIH [GM76222, GM088396]; National Institute of General Medical Sciences Protein Structure Initiative [U54-GM094597]; DTRA [HDTRA1-10-c-0057]; HHMI; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX Grant sponsor: NIH; Grant numbers: GM76222 (to D.B.) and GM088396 (to E.H.S., T.D.G., and J.R.L.); Grant sponsor: National Institute of General Medical Sciences Protein Structure Initiative; Grant number: U54-GM094597 (to G.T.M.); Grant sponsor: DTRA; Grant number: HDTRA1-10-c-0057 (to E.H.S.); Grant sponsors: HHMI (to D.B.) and Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (to N.G.S.). NR 37 TC 10 Z9 10 U1 0 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-3585 EI 1097-0134 J9 PROTEINS JI Proteins PD FEB PY 2015 VL 83 IS 2 BP 309 EP 317 DI 10.1002/prot.24719 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CA2FN UT WOS:000348724500010 PM 25388768 ER PT J AU Burbelo, PD Lebovitz, EE Notkins, AL AF Burbelo, Peter D. Lebovitz, Evan E. Notkins, Abner L. TI Luciferase immunoprecipitation systems for measuring antibodies in autoimmune and infectious diseases SO Translational Research LA English DT Review ID HEPATITIS-C VIRUS; STRONGYLOIDES-STERCORALIS INFECTION; STIFF-PERSON SYNDROME; EPSTEIN-BARR-VIRUS; LUPUS-ERYTHEMATOSUS; WUCHERERIA-BANCROFTI; AUTOANTIBODY ASSAYS; 4-ANTIGEN MIXTURE; SJOGRENS-SYNDROME; KAPOSIS-SARCOMA AB Antibody profiles have the potential to revolutionize personalized medicine by providing important information related to autoimmunity against self-proteins and exposure to infectious agents. One immunoassay technology, luciferase immunoprecipitation systems (LIPS), harnesses light-emitting recombinant proteins to generate robust, high-quality antibody data often spanning a large dynamic range of detection. Here, we describe the general format of LIPS and discuss studies using the technology to measure autoantibodies in several human autoimmune diseases including type 1 diabetes, Sjogren's syndrome, systemic lupus erythematosus, and immunodeficiencies secondary to anticytokine autoantibodies. We also describe the usefulness of evaluating antibodies against single or multiple antigens from infectious agents for diagnosis, pathogen discovery, and for obtaining individual exposure profiles. These diverse findings support the notion that the LIPS is a useful technology for generating antibody profiles for personalized diagnosis and monitoring of human health. C1 [Burbelo, Peter D.; Lebovitz, Evan E.; Notkins, Abner L.] NIDCR, Dent Clin Res Core, NIH, Bethesda, MD 20892 USA. [Burbelo, Peter D.; Lebovitz, Evan E.; Notkins, Abner L.] NIH, Ctr Clin, Dept Perioperat Med, Bethesda, MD 20892 USA. [Burbelo, Peter D.; Lebovitz, Evan E.; Notkins, Abner L.] NIDCR, Expt Med Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. RP Burbelo, PD (reprint author), NIDCR, Dent Clin Res Core, NIH, Bldg 10,Room 5N102,10 Ctr Dr, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov FU intramural research program of the National Institute of Dental and Craniofacial Research, National Institutes of Health FX This work was supported by the intramural research program of the National Institute of Dental and Craniofacial Research, National Institutes of Health. NR 64 TC 9 Z9 9 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-5244 EI 1878-1810 J9 TRANSL RES JI Transl. Res. PD FEB PY 2015 VL 165 IS 2 BP 325 EP 335 DI 10.1016/j.trsl.2014.08.006 PG 11 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA CA0WB UT WOS:000348633200008 PM 25241936 ER PT J AU Shamji, MH Bellido, V Scadding, GW Layhadi, JA Cheung, DKM Calderon, MA Asare, A Gao, Z Turka, LA Tchao, N Togias, A Phippard, D Durham, SR AF Shamji, M. H. Bellido, V. Scadding, G. W. Layhadi, J. A. Cheung, D. K. M. Calderon, M. A. Asare, A. Gao, Z. Turka, L. A. Tchao, N. Togias, A. Phippard, D. Durham, S. R. TI Effector cell signature in peripheral blood following nasal allergen challenge in grass pollen allergic individuals SO ALLERGY LA English DT Article DE basophils; IL-4; nasal allergen challenge; seasonal allergic rhinitis; T cells ID DENDRITIC CELLS; INDUCED RHINITIS; MESSENGER-RNA; MUCOSA; PROVOCATION; MEDIATORS; RESPONSES; RELEASE; IMMUNOTHERAPY; EOSINOPHILS AB BackgroundSeveral studies have demonstrated the time course of inflammatory mediators in nasal fluids following nasal allergen challenge (NAC), whereas the effects of NAC on cells in the periphery are unknown. We examined the time course of effector cell markers (for basophils, dendritic cells and T cells) in peripheral blood after nasal grass pollen allergen challenge. MethodsTwelve participants with seasonal allergic rhinitis underwent a control (diluent) challenge followed by NAC after an interval of 14days. Nasal symptoms and peak nasal inspiratory flow (PNIF) were recorded along with peripheral basophil, T-cell and dendritic cell responses (flow cytometry), T-cell proliferative responses (thymidine incorporation), and cytokine expression (FluoroSpot assay). ResultsRobust increases in nasal symptoms and decreases in PNIF were observed during the early (0-1h) response and modest significant changes during the late (1-24h) response. Sequential peaks in peripheral blood basophil activation markers were observed (CD107a at 3h, CD63 at 6h, and CD203c(bright) at 24h). T effector/memory cells (CD4(+)CD25(lo)) were increased at 6h and accompanied by increases in CD80(+) and CD86(+) plasmacytoid dendritic cells (pDCs). Ex vivo grass antigen-driven T-cell proliferative responses and the frequency of IL-4(+)CD4(+) T cells were significantly increased at 6h after NAC when compared to the control day. ConclusionBasophil, T-cell, and dendritic cell activation increased the frequency of allergen-driven IL-4(+)CD4(+) T cells, and T-cell proliferative responses are detectable in the periphery after NAC. These data confirm systemic cellular activation following a local nasal provocation. C1 [Shamji, M. H.; Layhadi, J. A.; Cheung, D. K. M.; Durham, S. R.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Immunomodulat & Tolerance Grp, London SW7 2AZ, England. [Bellido, V.; Scadding, G. W.; Layhadi, J. A.; Cheung, D. K. M.; Calderon, M. A.; Durham, S. R.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England. [Asare, A.; Gao, Z.; Turka, L. A.; Tchao, N.; Phippard, D.] Immune Tolerance Network, Bethesda, MD USA. [Turka, L. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Togias, A.] NIAID, Bethesda, MD 20892 USA. RP Durham, SR (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst, Sir Alexander Fleming Bldg, London SW7 2AZ, England. EM s.durham@imperial.ac.uk FU Immune Tolerance Network (NIH), an international clinical research consortium headquartered at the University of California San Francisco [N01 AI15416]; National Institute of Allergy and Infectious Diseases; Juvenile Diabetes Research Foundation; Wellcome Trust; Royal Brompton Hospital Charitable Trust Fund FX This research was performed with the support of the Immune Tolerance Network (NIH Contract #N01 AI15416; www.immunetolerance.org), an international clinical research consortium headquartered at the University of California San Francisco and supported by the National Institute of Allergy and Infectious Diseases and the Juvenile Diabetes Research Foundation. Dr Guy Scadding is supported by a Wellcome Trust Clinical Fellowship. This research was also supported by a grant from the Royal Brompton Hospital Charitable Trust Fund. NR 31 TC 7 Z9 8 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD FEB PY 2015 VL 70 IS 2 BP 171 EP 179 DI 10.1111/all.12543 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA AZ0UM UT WOS:000347960300005 PM 25377909 ER PT J AU Muntner, P Gutierrez, OM Zhao, H Fox, CS Wright, NC Curtis, JR McClellan, W Wang, H Kilgore, M Warnock, DG Bowling, CB AF Muntner, Paul Gutierrez, Orlando M. Zhao, Hong Fox, Caroline S. Wright, Nicole C. Curtis, Jeffrey R. McClellan, William Wang, Henry Kilgore, Meredith Warnock, David G. Bowling, C. Barrett TI Validation Study of Medicare Claims to Identify Older US Adults With CKD Using the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease (CKD); health care claims data; sensitivity; specificity; predictive value; claims-based algorithm; albuminuria; estimated glomerular filtration rate (eGFR); end-stage renal disease (ESRD) ID GLOMERULAR-FILTRATION-RATE; COLLABORATIVE METAANALYSIS; ADMINISTRATIVE DATA; POPULATION COHORTS; KIDNEY-DISEASE; UNITED-STATES; ALL-CAUSE; ALBUMINURIA; RISK; MORTALITY AB Background: Health care claims data may provide a cost-efficient approach for studying chronic kidney disease (CKD). Study Design: Prospective cohort study. Setting & Participants: We compared characteristics and outcomes for individuals with CKD defined using laboratory measurements versus claims data from 6,982 REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study participants who had Medicare fee-for-service coverage. Predictors: Presence of CKD as defined by both the REGARDS Study (CKDREGARDS) and Medicare data (CKDMedicare), presence of CKDREGARDS but not CKDMedicare, and presence of CKDMedicare but not CKDREGARDS, and absence of both CKDREGARDS and CKDMedicare. Outcomes: Mortality and incident end-stage renal disease (ESRD). Measurements: The research study definition of CKD (CKDREGARDS) included estimated glomerular filtration rate (eGFR), 60 mL/min/1.73 m(2) or albumin-creatinine ratio > 30 mg/g at the REGARDS Study visit. CKD in Medicare (CKDMedicare) was identified during the 2 years before each participant's REGARDS visit using a claims-based algorithm. Results: Overall, 32% of participants had CKDREGARDS and 6% had CKDMedicare. Sensitivity, specificity, and positive and negative predictive values of CKDMedicare for identifying CKDREGARDS were 15.5% (95% CI, 14.0%-17.1%), 97.7% (95% CI, 97.2%-98.1%), 75.6% (95% CI, 71.4%-79.5%), and 71.5% (95% CI, 70.4%-72.6%), respectively. Mortality and ESRD incidence rates, expressed per 1,000 person-years, were higher for participants with versus without CKDMedicare (mortality: 72.5 [95% CI, 61.3-83.7] vs 33.3 [95% CI, 31.5-35.2]; ESRD: 16.4 [95% CI, 11.2-21.6] vs 1.3 [95% CI, 0.9-1.6]) and with versus without CKDREGARDS (mortality: 59.9 [95% CI, 55.4-64.4] vs 25.5 [95% CI, 23.6-27.4]; ESRD: 6.8 [95% CI, 5.4-8.3] vs 0.1 [95% CI, 0.0-0.3]). Among participants with CKDREGARDS, those with abdominal obesity, diabetes, anemia, lower eGFR, more outpatient visits, hospitalization, and a nephrologist visit in the 2 years before their REGARDS visit were more likely to have CKDMedicare. Limitations: CKDREGARDS relied on eGFR and albuminuria assessed at a single visit. Conclusions: CKD, whether defined in claims or through research study measurements, was associated with increased mortality and ESRD. However, individuals with CKD identified in claims may represent a select high-risk population. (C) 2015 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Muntner, Paul; Gutierrez, Orlando M.; Zhao, Hong; Wright, Nicole C.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA. [Gutierrez, Orlando M.; Curtis, Jeffrey R.; Warnock, David G.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [McClellan, William] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Wang, Henry] Univ Alabama Birmingham, Dept Emergency Med, Birmingham, AL 35294 USA. [Kilgore, Meredith] Univ Alabama Birmingham, Dept Healthcare Org & Policy, Birmingham, AL 35294 USA. [Bowling, C. Barrett] Atlanta VA Med Ctr, Atlanta, GA USA. [Bowling, C. Barrett] Emory Univ, Dept Med, Atlanta, GA 30322 USA. RP Muntner, P (reprint author), Univ Alabama Birmingham, Dept Epidemiol, 1700 Univ Blvd,LHL 450, Birmingham, AL 35294 USA. EM pmuntner@uab.edu FU National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Department of Health and Human Services [U01 NS041588]; Agency for Healthcare Research and Quality [R01 HS018517]; Amgen Corporation; National Institute on Aging [R03AG042336]; T. Franklin Williams Scholarship Award - Atlantic Philanthropies Inc; T. Franklin Williams Scholarship Award (John A. Hartford Foundation); T. Franklin Williams Scholarship Award (Association of Specialty Professors); T. Franklin Williams Scholarship Award (American Society of Nephrology); T. Franklin Williams Scholarship Award (American Geriatrics Society) FX This research project is supported by cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Department of Health and Human Services, and R01 HS018517 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIH. Representatives of the funding agency have been involved in the review of the manuscript but not directly involved in the collection, management, analysis, or interpretation of the data. Additional funding was provided by an investigator-initiated grant-in-aid from Amgen Corporation to Dr Warnock. Amgen played no role in the study design, collection, analysis, and interpretation of data for this manuscript. Additional support was provided through the National Institute on Aging (grant R03AG042336) and the T. Franklin Williams Scholarship Award (funding provided by Atlantic Philanthropies Inc, the John A. Hartford Foundation, the Association of Specialty Professors, the American Society of Nephrology, and the American Geriatrics Society) to Dr Bowling. NR 24 TC 3 Z9 3 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2015 VL 65 IS 2 BP 249 EP 258 DI 10.1053/j.ajkd.2014.07.012 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA AZ4MT UT WOS:000348196400011 PM 25242367 ER PT J AU Liu, KD Yang, W Go, AS Anderson, AH Feldman, HI Fischer, MJ He, J Kallem, RR Kusek, JW Master, SR Miller, ER Rosas, SE Steigerwalt, S Tao, KX Weir, MR Hsu, CY AF Liu, Kathleen D. Yang, Wei Go, Alan S. Anderson, Amanda H. Feldman, Harold I. Fischer, Michael J. He, Jiang Kallem, Radhakrishna R. Kusek, John W. Master, Stephen R. Miller, Edgar R., III Rosas, Sylvia E. Steigerwalt, Susan Tao, Kaixiang Weir, Matthew R. Hsu, Chi-yuan CA CRIC Study Investigators TI Urine Neutrophil Gelatinase-Associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Neutrophil gelatinase-associated lipocalin (NGAL); renal tubular injury; renal tubular dysfunction; biomarker; chronic kidney disease (CKD); Chronic Renal Insufficiency Cohort (CRIC) Study; cardiovascular disease; ischemic atherosclerotic event ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; INJURY MOLECULE-1 KIM-1; HEART-FAILURE; ATHEROSCLEROSIS RISK; ALL-CAUSE; NGAL; MORTALITY; DAMAGE; BIOMARKERS AB Background: Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria). Study Design: Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study. Setting & Participants: 3,386 participants with estimated glomerular filtration rate of 20 to 70 mL/min/1.73 m(2) enrolled from June 2003 through August 2008. Predictor: Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. Outcomes: Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011. Measurements: Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). Results: There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5 ng/mL] vs lowest [<= 6.9 ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. Limitations: Urine NGAL was measured only once. Conclusions: Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths. (C) 2015 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Liu, Kathleen D.; Hsu, Chi-yuan] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Yang, Wei; Anderson, Amanda H.; Feldman, Harold I.; Kallem, Radhakrishna R.; Tao, Kaixiang] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Go, Alan S.; Hsu, Chi-yuan] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Fischer, Michael J.] Jesse Brown VAMC, Dept Med, Chicago, IL USA. [Fischer, Michael J.] Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL USA. [He, Jiang] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD USA. [Master, Stephen R.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Miller, Edgar R., III] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Rosas, Sylvia E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02115 USA. [Rosas, Sylvia E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Steigerwalt, Susan] St John Hosp & Med Ctr, St Claire Specialty Phys, Detroit, MI USA. [Weir, Matthew R.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. RP Hsu, CY (reprint author), Univ Calif San Francisco, Div Nephrol, 521 Parnassus Ave,C443,Box 0532, San Francisco, CA 94143 USA. EM hsuchi@medicine.ucsf.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902]; Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences (NCATS) [UL1TR000003]; Johns Hopkins University grant [UL1 TR-000424]; University of Maryland General Clinical Research Center grant [M01 RR-16500]; Clinical and Translational Science Collaborative of Cleveland from the NCATS component of the NIH [UL1TR000439]; NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research grant [UL1TR000433]; University of Illinois at Chicago Clinical and Translational Science Award [UL1RR029879]; Tulane University Translational Research in Hypertension and Renal Biology grant [P30GM103337]; Kaiser Permanente NIH/National Center for Research Resources UCSF-CTSI grant [UL1 RR-024131]; CKD Biomarker Consortium [U01DK85649] FX Funding for the CRIC Study was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by the following: the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences (NCATS) UL1TR000003, Johns Hopkins University grant UL1 TR-000424, University of Maryland General Clinical Research Center grant M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, grant UL1TR000439 from the NCATS component of the NIH and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research grant UL1TR000433, University of Illinois at Chicago Clinical and Translational Science Award UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology grant P30GM103337, and Kaiser Permanente NIH/National Center for Research Resources UCSF-CTSI grant UL1 RR-024131. Drs Liu, Go, Feldman, and Hsu also are supported by grant U01DK85649 as members of the CKD Biomarker Consortium. NR 41 TC 12 Z9 14 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2015 VL 65 IS 2 BP 267 EP 274 DI 10.1053/j.ajkd.2014.07.025 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AZ4MT UT WOS:000348196400013 PM 25311702 ER PT J AU Cho, HY Jedlicka, AE Gladwell, W Marzec, J McCaw, ZR Bienstock, RJ Kleeberger, SR AF Cho, Hye-Youn Jedlicka, Anne E. Gladwell, Wesley Marzec, Jacqui McCaw, Zackary R. Bienstock, Rachelle J. Kleeberger, Steven R. TI Association of Nrf2 Polymorphism Haplotypes with Acute Lung Injury Phenotypes in Inbred Strains of Mice SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID TRANSCRIPTION FACTOR NRF2; GENOME-WIDE ASSOCIATION; MOUSE STRAINS; KEAP1 GENE; STRUCTURE PREDICTION; PROMOTER REGION; MODELING SERVER; CANCER; DNA; SUSCEPTIBILITY AB Aims: Nrf2 is a master transcription factor for antioxidant response element (ARE)-mediated cytoprotective gene induction. A protective role for pulmonary Nrf2 was determined in model oxidative disorders, including hyperoxia-induced acute lung injury (ALI). To obtain additional insights into the function and genetic regulation of Nrf2, we assessed functional single nucleotide polymorphisms (SNPs) of Nrf2 in inbred mouse strains and tested whether sequence variation is associated with hyperoxia susceptibility. Results: Nrf2 SNPs were compiled from publicly available databases and by re-sequencing DNA from inbred strains. Hierarchical clustering of Nrf2 SNPs categorized the strains into three major haplotypes. Hyperoxia susceptibility was greater in haplotypes 2 and 3 strains than in haplotype 1 strains. A promoter SNP -103 T/C adding an Sp1 binding site in haplotype 2 diminished promoter activation basally and under hyperoxia. Haplotype 3 mice bearing nonsynonymous coding SNPs located in (1862 A/T, His543Gln) and adjacent to (1417 T/C, Thr395Ile) the Neh1 domain showed suppressed nuclear transactivation of pulmonary Nrf2 relative to other strains, and overexpression of haplotype 3 Nrf2 showed lower ARE responsiveness than overexpression of haplotype 1 Nrf2 in airway cells. Importantly, we found a significant correlation of Nrf2 haplotypes and hyperoxic lung injury phenotypes. Innovation and Conclusion: The results indicate significant influence of Nrf2 polymorphisms and haplotypes on gene function and hyperoxia susceptibility. Our findings further support Nrf2 as a genetic determinant in ALI pathogenesis and provide useful tools for investigators who use mouse strains classified by Nrf2 haplotypes to elucidate the role for Nrf2 in oxidative disorders. Antioxid. Redox Signal. 22, 325-338. C1 [Cho, Hye-Youn; Gladwell, Wesley; Marzec, Jacqui; McCaw, Zackary R.; Kleeberger, Steven R.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Jedlicka, Anne E.] Johns Hopkins Univ Bloomberg Sch Publ Hlth, Dept Mol Biol & Immunol, Baltimore, MD USA. [Bienstock, Rachelle J.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Cho, HY (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA. EM cho2@niehs.nih.gov FU Intramural Research Program of the National Institute of Environmental Health Sciences FX This research was supported, in part, by the Intramural Research Program of the National Institute of Environmental Health Sciences. Hyperoxia exposures were conducted at the NIEHS Inhalation Facility under contract to Alion Science and Technology, Inc. The authors thank Dr. Daniel Morgan and Mr. Herman Price for coordinating the exposures. Drs. Don Cook and Michael Fessler at the NIEHS provided an excellent critical review of this article. NR 60 TC 5 Z9 5 U1 1 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD FEB 1 PY 2015 VL 22 IS 4 BP 325 EP 338 DI 10.1089/ars.2014.5942 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AZ6BD UT WOS:000348302200004 PM 25268541 ER PT J AU Steffen, BT Guan, WH Remaley, AT Paramsothy, P Heckbert, SR McClelland, RL Greenland, P Michos, ED Tsai, MY AF Steffen, Brian T. Guan, Weihua Remaley, Alan T. Paramsothy, Pathmaja Heckbert, Susan R. McClelland, Robyn L. Greenland, Philip Michos, Erin D. Tsai, Michael Y. TI Use of Lipoprotein Particle Measures for Assessing Coronary Heart Disease Risk Post-American Heart Association/American College of Cardiology Guidelines The Multi-Ethnic Study of Atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE apolipoproteins; coronary disease; lipids; lipoproteins; magnetic resonance spectroscopy; risk factors ID APOLIPOPROTEIN-A-I; CARDIOVASCULAR-DISEASE; ARTERY-DISEASE; MYOCARDIAL-INFARCTION; APO-B; CHOLESTEROL; MEN; POPULATION; PREDICTION; WOMEN AB Objective-The American College of Cardiology and American Heart Association have issued guidelines indicating that the contribution of apolipoprotein B-100 (ApoB) to cardiovascular risk assessment remains uncertain. The present analysis evaluates whether lipoprotein particle measures convey risk of coronary heart disease (CHD) in 4679 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Approach and Results-Cox regression analysis was performed to determine associations between lipids or lipoproteins and primary CHD events. After adjustment for nonlipid variables, lipoprotein particle levels in fourth quartiles were found to convey significantly greater risk of incident CHD when compared to first quartile levels (hazard ratio [HR]; 95% confidence interval [CI]): ApoB (HR, 1.84; 95% CI, 1.25-2.69), ApoB/ApoA-I (HR, 1.91; 95% CI, 1.32-2.76), total low-density lipoprotein-particles (LDL-P; HR, 1.77; 95% CI, 1.21-2.58), and the LDL-P/HDL-P (high-density lipoprotein-P) ratio (HR, 2.28; 95% CI, 1.54-3.37). Associations between lipoprotein particle measures and CHD were attenuated after adjustment for standard lipid panel variables. Using the American Heart Association/American College of Cardiology risk calculator as a baseline model for CHD risk assessment, significant net reclassification improvement scores were found for ApoB/ApoA-I (0.18; P=0.007) and LDL-P/high-density lipoprotein-P (0.15; P<0.001). C-statistics revealed no significant increase in CHD event discrimination for any lipoprotein measure. Conclusions-Lipoprotein particle measures ApoB/ApoA-I and LDL-P/high-density lipoprotein-P marginally improved net reclassification improvement scores, but null findings for corresponding c-statistic are not supportive of lipoprotein testing. The attenuated associations of lipoprotein particle measures with CHD after the adjustment for lipids indicate that their measurement does not detect risk that is unaccounted for by the standard lipid panel. However, the possibility that lipoprotein measures may identify CHD risk in a subpopulation of individuals with normal cholesterol, but elevated lipoprotein particle numbers cannot be ruled out. C1 [Steffen, Brian T.; Tsai, Michael Y.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Guan, Weihua] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Remaley, Alan T.] NHLBI, Dept Lab Med, NIH, Mol Dis Branch, Bethesda, MD 20892 USA. [Paramsothy, Pathmaja] Univ Washington, Med Ctr, Dept Med, Sch Med,Div Cardiol, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [McClelland, Robyn L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Greenland, Philip] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Michos, Erin D.] Johns Hopkins Univ, Dept Med, Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD USA. RP Tsai, MY (reprint author), 420 Delaware St SE,Mayo Mail Code 609, Minneapolis, MN 55455 USA. EM tsaix001@umn.edu FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169] FX This research was supported by the following contracts, N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. NR 26 TC 5 Z9 5 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 2015 VL 35 IS 2 BP 448 EP 454 DI 10.1161/ATVBAHA.114.304349 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AZ4TE UT WOS:000348215100027 PM 25477346 ER PT J AU Igari, M Shen, HW Hagino, Y Fukushima, S Kasahara, Y Lesch, KP Murphy, DL Hall, FS Uhl, GR Ikeda, K Yaegashi, N Sora, I AF Igari, Moe Shen, Hao-Wei Hagino, Yoko Fukushima, Setsu Kasahara, Yoshiyuki Lesch, Klaus-Peter Murphy, Dennis L. Hall, Frank Scott Uhl, George R. Ikeda, Kazutaka Yaegashi, Nobuo Sora, Ichiro TI Attenuated methamphetamine-induced locomotor sensitization in serotonin transporter knockout mice is restored by serotonin 1B receptor antagonist treatment SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE 5-HT1B receptor; addiction; in-vivo microdialysis; knockout; locomotion; methamphetamine; mouse; SB 216641; sensitization; serotonin transporter ID INDUCED BEHAVIORAL SENSITIZATION; ENHANCES COCAINE REINFORCEMENT; CONDITIONED PLACE PREFERENCE; IN-VIVO MICRODIALYSIS; 5-HT1B RECEPTORS; DOPAMINE-TRANSPORTER; SEEKING BEHAVIOR; NEUROTRANSMITTER RELEASE; ACUTE WITHDRAWAL; DEFICIENT MICE AB Repeated administration of methamphetamine (METH) enhances acute locomotor responses to METH administered in the same context, a phenomenon termed as 'locomotor sensitization'. Although many of the acute effects of METH are mediated by its influences on the compartmentalization of dopamine, serotonin systems have also been suggested to influence the behavioral effects of METH in ways that are not fully understood. The present experiments examined serotonergic roles in METH-induced locomotor sensitization by assessing: (a) the effect of serotonin transporter (SERT; Slc6A4) knockout (KO) on METH-induced locomotor sensitization; (b) extracellular monoamine levels in METH-treated animals as determined by in-vivo microdialysis; and (c) effects of serotonin (5-HT) receptor antagonists on METH-induced behavioral sensitization, with focus on effects of the 5-HT1B receptor antagonist SB 216641 and a comparison with the 5-HT2 receptor antagonist ketanserin. Repeated METH administration failed to induce behavioral sensitization in homozygous SERT KO (SERT-/-) mice under conditions that produced substantial sensitization in wild-type or heterozygous SERT KO (SERT+/-) mice. The selective 5-HT1B antagonist receptor SB 216641 restored METH-induced locomotor sensitization in SERT-/-mice, whereas ketanserin was ineffective. METH-induced increases in extracellular 5-HT (5-HTex) levels were substantially reduced in SERT-/-mice, although SERT genotype had no effect on METH-induced increases in extracellular dopamine. These experiments demonstrate that 5-HT actions, including those at 5-HT1B receptors, contribute to METH-induced locomotor sensitization. Modulation of 5-HT1B receptors might aid therapeutic approaches to the sequelae of chronic METH use. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Igari, Moe; Fukushima, Setsu; Kasahara, Yoshiyuki; Sora, Ichiro] Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 980, Japan. [Yaegashi, Nobuo] Tohoku Univ, Grad Sch Med, Dept Gynecol & Obstet, Sendai, Miyagi 980, Japan. [Shen, Hao-Wei; Hagino, Yoko; Ikeda, Kazutaka] Tokyo Inst Psychiat, Dept Mol Psychiat, Tokyo, Japan. [Lesch, Klaus-Peter] Univ Wurzburg, Dept Psychiat & Psychotherapy, D-97070 Wurzburg, Germany. [Murphy, Dennis L.] NIMH, Intramural Res Program, Clin Neuropharmacol Sect, Clin Sci Lab, Bethesda, MD 20892 USA. [Hall, Frank Scott; Uhl, George R.] Natl Inst Drug Abuse, Intramural Res Program, Mol Neurobiol Branch, Baltimore, MD USA. RP Hall, FS (reprint author), Univ Toledo, Coll Pharm & Pharmaceut Sci, Dept Pharmacol, Mail Stop 1015,3000 Arlington Ave, Toledo, OH 43614 USA. EM frank.hall@utoledo.edu RI Lesch, Klaus-Peter/J-4906-2013; Hall, Frank/C-3036-2013; OI Lesch, Klaus-Peter/0000-0001-8348-153X; Hall, Frank/0000-0002-0822-4063; Shen, Hao-wei/0000-0002-2766-5139 FU Japanese Ministry of Health, Labour and Welfare; Global COE program by the Japanese Ministry of Education, Culture, Sports, Science, and Technology; Intramural Research Program of the National Institute on Drug Abuse (NIH/DHHS, USA); Deutsche Forschungsgemeinschaft [Le 629/4-2, SFB 581] FX The present study was supported by the Japanese Ministry of Health, Labour and Welfare; Global COE program by the Japanese Ministry of Education, Culture, Sports, Science, and Technology; the Intramural Research Program of the National Institute on Drug Abuse (NIH/DHHS, USA; F.S.H. and G.R.U.); and a grant from the Deutsche Forschungsgemeinschaft (Le 629/4-2, SFB 581 to K.-P.L.). The authors also thank Professor Yoshitaka Kimura for advice for the statistical analysis and Dr Koh Iwasaki for discussion and advice. NR 87 TC 0 Z9 0 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0955-8810 EI 1473-5849 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD FEB PY 2015 VL 26 IS 1-2 SI SI BP 167 EP 179 DI 10.1097/FBP.0000000000000120 PG 13 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA AZ3QC UT WOS:000348140800018 PM 25485646 ER PT J AU Beck, TN Lloyd, D Kuskovsky, R Minah, J Arora, K Plotkin, BJ Green, JM Boshoff, HI Barry, C Deschamps, J Konaklieva, MI AF Beck, Tim N. Lloyd, Dina Kuskovsky, Rostislav Minah, Jeanette Arora, Kriti Plotkin, Balbina J. Green, Jacalyn M. Boshoff, Helena I. Barry, Clifton, III Deschamps, Jeffrey Konaklieva, Monika I. TI Non-transpeptidase binding arylthioether beta-lactams active against Mycobacterium tuberculosis and Moraxella catarrhalis SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Mycobacterium tuberculosis; Moraxella catarrhalis; beta-Lactams; Antimicrobial resistance ID STAPHYLOCOCCUS-AUREUS; ANTIBIOTIC-RESISTANCE; IDENTIFICATION; ENZYMES; PROBES; AGENTS; MRSA AB The prevalence of drug resistance in both clinical and community settings as a consequence of alterations of biosynthetic pathways, enzymes or cell wall architecture is a persistent threat to human health. We have designed, synthesized, and tested a novel class of non-transpeptidase, beta-lactamase resistant monocyclic beta-lactams that carry an arylthio group at C4. These thioethers exhibit inhibitory and cidal activity against serine beta-lactamase producing Mycobacterium tuberculosis wild type strain (Mtb) and multiple (n = 8) beta-lactamase producing Moraxella catarrhalis clinical isolates. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Beck, Tim N.; Lloyd, Dina; Kuskovsky, Rostislav; Minah, Jeanette; Konaklieva, Monika I.] Amer Univ, Dept Chem, Washington, DC 20016 USA. [Plotkin, Balbina J.; Green, Jacalyn M.] Midwestern Univ, Dept Microbiol & Immunol, Chicago, IL 60515 USA. [Arora, Kriti; Boshoff, Helena I.; Barry, Clifton, III] NIAID, TB Res Sect, LCID, NIH, Bethesda, MD 20892 USA. [Deschamps, Jeffrey] Naval Res Lab, Washington, DC 20375 USA. RP Konaklieva, MI (reprint author), Amer Univ, Dept Chem, Washington, DC 20016 USA. EM mkonak@american.edu RI Barry, III, Clifton/H-3839-2012 FU American University Research Grant; Department of Chemistry at American University, Washington, D.C.; Midwestern University, Downers Grove, IL; Intramural Research Program of the NIH, NIAID FX This work was funded in part, by the American University Research Grant and the Department of Chemistry at American University, Washington, D.C. and by Midwestern University, Downers Grove, IL. This research was supported in part by the Intramural Research Program of the NIH, NIAID. NR 31 TC 1 Z9 1 U1 0 U2 7 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 FEB 1 PY 2015 VL 23 IS 3 BP 632 EP 647 DI 10.1016/j.bmc.2014.11.025 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA AZ2BO UT WOS:000348039700026 PM 25549898 ER PT J AU Liu, L Tang, MS Walsh, MJ Brimacombe, KR Pragani, R Tanega, C Rohde, JM Baker, HL Fernandez, E Blackman, B Bougie, JM Leister, WH Auld, DS Shen, M Lai, K Boxer, MB AF Liu, Li Tang, Manshu Walsh, Martin J. Brimacombe, Kyle R. Pragani, Rajan Tanega, Cordelle Rohde, Jason M. Baker, Heather L. Fernandez, Elizabeth Blackman, Burchelle Bougie, James M. Leister, William H. Auld, Douglas S. Shen, Min Lai, Kent Boxer, Matthew B. TI Structure activity relationships of human galactokinase inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Galactosemia; Structure-activity relationships; Galactokinase ID VERBAL DYSPRAXIA; GALACTOSEMIA; GALACTOSE-1-PHOSPHATE AB Classic Galactosemia is a rare inborn error of metabolism that is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT), an enzyme within the Leloir pathway that is responsible for the conversion of galactose-1-phosphate (gal-1-p) and UDP-glucose to glucose-1-phosphate and UDPgalactose. This deficiency results in elevated intracellular concentrations of its substrate, gal-1-p, and this increased concentration is believed to be the major pathogenic mechanism in Classic Galactosemia. Galactokinase (GALK) is an upstream enzyme of GALT in the Leloir pathway and is responsible for conversion of galactose and ATP to gal-1-p and ADP. Therefore, it was hypothesized that the identification of a small-molecule inhibitor of human GALK would act to prevent the accumulation of gal-1-p and offer a novel entry therapy for this disorder. Herein we describe a quantitative high-throughput screening campaign that identified a single chemotype that was optimized and validated as a GALK inhibitor. Published by Elsevier Ltd. C1 [Liu, Li; Walsh, Martin J.; Brimacombe, Kyle R.; Pragani, Rajan; Tanega, Cordelle; Rohde, Jason M.; Baker, Heather L.; Fernandez, Elizabeth; Blackman, Burchelle; Bougie, James M.; Leister, William H.; Auld, Douglas S.; Shen, Min; Boxer, Matthew B.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Tang, Manshu; Lai, Kent] Univ Utah, Dept Pediat, Div Med Genet, Salt Lake City, UT 84132 USA. RP Boxer, MB (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM boxerm@mail.nih.gov FU Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research Grant [U54MH084681]; Intramural Research Program of the National Center for Advancing Translational Sciences at the National Institutes of Health. Research Grant [R03MH085689, R01HD074844-2] FX We thank Danielle van Leer, Misha Itkin, Crystal McKnight, Christopher LeClair and Paul Shinn for assistance with compound management. We also thank Arnold L. Rheingold and Curtis Moore at UCSD for X-ray determination of 32. This research was supported by the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research Grant U54MH084681 and the Intramural Research Program of the National Center for Advancing Translational Sciences at the National Institutes of Health. Research Grant support to K.L. include R03MH085689 and R01HD074844-2. NR 16 TC 3 Z9 3 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD FEB 1 PY 2015 VL 25 IS 3 BP 721 EP 727 DI 10.1016/j.bmcl.2014.11.061 PG 7 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA AY9XT UT WOS:000347901700056 PM 25553891 ER PT J AU Guan, SY Tan, SM Li, Y Torres, J Uzel, G Xiang, LM Law, SKA AF Guan, Siyu Tan, Suet-Mien Li, Yan Torres, Jaume Uzel, Gulbu Xiang, Liming Law, S. K. Alex TI Characterization of single amino acid substitutions in the beta 2 integrin subunit of patients with leukocyte adhesion deficiency (LAD)-1 SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE LAD-1; Missense mutation; beta 2 (CD18) integrin; Expression; Cell adhesion ID HEMATOLOGICALLY IMPORTANT MUTATIONS; CELL-SURFACE EXPRESSION; TORSION ANGLE DYNAMICS; I-LIKE DOMAIN; POINT MUTATION; CD18; LFA-1; MAC-1; ALPHA(L)BETA(2); IDENTIFICATION AB Leukocyte adhesion deficiency 1 (LAD-1) is caused by defects in the beta 2 integrin subunit. We studied 18 missense mutations, 14 of which fail to support the surface expression of the beta 2 integrins. Integrins with the beta 2-G150D mutation fail to bind ligands, possibly due to the failure of the alpha 1 segment of the beta I domain to assume an et-helical structure. Integrins with the beta 2-G716A mutation are not maintained in their resting states, and the patient has the severe phenotype of LAD-1. The beta 2-S453N and beta 2-P648L mutants support the expression of integrins and adhesion functions. They should be re-classified as polymorphic variants. (C) 2014 Elsevier Inc. All rights reserved. C1 [Guan, Siyu; Tan, Suet-Mien; Li, Yan; Torres, Jaume; Law, S. K. Alex] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore. [Uzel, Gulbu] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Xiang, Liming] Nanyang Technol Univ, Sch Phys & Math Sci, Singapore 637551, Singapore. RP Law, SKA (reprint author), Nanyang Technol Univ, Sch Biol Sci, 60 Nanyang Dr, Singapore 637551, Singapore. EM alaw@ntu.edu.sg RI Li, Yan/G-4642-2013 OI Li, Yan/0000-0003-1963-839X FU Tier 1 grant from Nanyang Technological University Academic Research Fund (AcRF) [RG 93/07] FX This work was supported by Tier 1 grant from Nanyang Technological University Academic Research Fund (AcRF) RG 93/07. NR 48 TC 3 Z9 3 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 EI 1096-0961 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD FEB PY 2015 VL 54 IS 2 BP 177 EP 182 DI 10.1016/j.bcmd.2014.11.005 PG 6 WC Hematology SC Hematology GA AZ5HH UT WOS:000348250300008 PM 25514840 ER PT J AU Gavini, N Hoots, WK Mensah, GA Hanspal, M AF Gavini, Nara Hoots, W. Keith Mensah, George A. Hanspal, Manjit TI An analysis of the NIH-supported sickle cell disease research portfolio SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE Sickle cell disease; Grant mechanisms; National Heart, Lung, and Blood Institute (US); Research Projects Grants ID 1ST MOLECULAR DISEASE; HEMOGLOBIN; ANEMIA; TRANSPLANTATION; PATHOPHYSIOLOGY; MANAGEMENT; THERAPIES; FUTURE; PAIN AB Sickle cell disease (SCD), an inherited blood disorder is due to a single amino acid substitution on the beta chain of hemoglobin, and is characterized by anemia, severe infections, acute and chronic pain, and multi-organ damage. The National Institutes of Health (NIH) is dedicated to support basic, translational and clinical science research to improve care and ultimately, to find a cure for SCD that causes such suffering. This report provides a detailed analysis of grants funded by the NIH for SCD research in Fiscal Years 2007 through 2013. During this period, the NIH supported 247 de novo grants totaling $272,210,367 that address various aspects of SCD. 83% of these funds supported research project grants investigating the following 5 scientific themes: Pathology of Sickle Red Blood Cells; Globin Gene Expression; Adhesion and Vascular Dysfunction; Neurological Complications and Organ-specific Dysfunction; and Pain Management and Intervention. The remaining 17% of total funds supported career development and training grants; Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants; large Center grants; and Conference grants. Further analysis showed that the National Heart, Lung, and Blood Institute (NHLBI) is the largest funder of SCD research within NIH with 67% of total grants, contributing 77% of total funds; followed by the National Institute for Digestive Diseases and Kidney (NIDDK) that is funding 19% of grants, contributing 13% of total funds. The remaining 14% of grants totaling 10% of the funds were supported by all other NIH Institutes/Centers (ICs) combined. In summary, the NIH is using multiple funding mechanisms to support a sickle cell disease research agenda that is intended to advance the detection, treatment, and cure of this debilitating genetic disease. Published by Elsevier Inc. C1 [Gavini, Nara; Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, Bethesda, MD 20892 USA. [Hoots, W. Keith; Hanspal, Manjit] NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA. RP Hanspal, M (reprint author), NHLBI, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM hanspalm@nhlbi.nih.gov NR 27 TC 0 Z9 0 U1 3 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 EI 1096-0961 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD FEB PY 2015 VL 54 IS 2 BP 198 EP 205 DI 10.1016/j.bcmd.2014.11.001 PG 8 WC Hematology SC Hematology GA AZ5HH UT WOS:000348250300012 PM 25466208 ER PT J AU Sinder, BP Salemi, JD Ominsky, MS Caird, MS Marini, JC Kozloff, KM AF Sinder, Benjamin P. Salemi, Joseph D. Ominsky, Michael S. Caird, Michelle S. Marini, Joan C. Kozloff, Kenneth M. TI Rapidly growing Brtl/ plus mouse model of osteogenesis imperfecta improves bone mass and strength with sclerostin antibody treatment SO BONE LA English DT Article DE Osteogenesis imperfecta; Sclerostin antibody; Collagen; Bone mass; Anabolic therapy; Dynamic histomorphometry ID GROWTH-HORMONE TREATMENT; ALENDRONATE TREATMENT; MINERAL DENSITY; MURINE MODEL; CHILDREN; MICE; HISTOMORPHOMETRY; OSTEOPOROSIS; PERIOSTEAL; RESORPTION AB Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk that presents most severely in children. Anti-resorptive bisphosphonates are frequently used to treat pediatric OI and controlled clinical trials have shown that bisphosphonate therapy improves vertebral outcomes but has little benefit on long bone fracture rate. New treatments which increase bone mass throughout the pediatric OI skeleton would be beneficial. Sclerostin antibody (Scl-Ab) is a potential candidate anabolic therapy for pediatric OI and functions by stimulating osteoblastic bone formation via the canonical Wnt signaling pathway. To explore the effect of Scl-Ab on the rapidly growing OI skeleton, we treated rapidly growing 3 week old Brtl/+ mice, harboring a typical heterozygous OI-causing Gly --> Cys substitution on col1a1, for 5 weeks with Scl-Ab. Scl-Ab had anabolic effects in Brtl/+ and led to new cortical bone formation and increased cortical bone mass. This anabolic action resulted in improved mechanical strength to WTVeh levels without altering the underlying brittle nature of the material. While Scl-Ab was anabolic in trabecular bone of the distal femur in both genotypes, the effect was less strong in these rapidly growing Brtl/+ mice compared to WT. In conclusion, Scl-Ab was able to stimulate bone formation in a rapidly growing Brtl/+ murine model of OI, and represents a potential new therapy to improve bone mass and reduce fracture risk in pediatric OI. (C) 2014 Elsevier Inc. All rights reserved. C1 [Sinder, Benjamin P.; Salemi, Joseph D.; Caird, Michelle S.; Kozloff, Kenneth M.] Univ Michigan, Dept Orthopaed Surg, Orthopaed Res Labs, Ann Arbor, MI 48109 USA. [Sinder, Benjamin P.; Salemi, Joseph D.; Kozloff, Kenneth M.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. [Ominsky, Michael S.] Amgen Inc, Dept Metab Disorders, Thousand Oaks, CA 91320 USA. [Marini, Joan C.] NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. RP Kozloff, KM (reprint author), 2015 Biomed Sci Res Bldg,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM kenkoz@umich.edu FU NIH [R01AR062522] FX The authors thank Bonnie Nolan, Kathy Sweet and Logan White for their contributions. Scl-Ab was provided by Amgen and UCB Pharma. Funding support from NIH to KMK (R01AR062522) is gratefully acknowledged. Study designed and conducted by BPS and KMK. Data collected by BPS and JDS. Data analyzed and interpreted by BPS, JDS, MSO, MSC, JCM, and KMK. Manuscript was written by BPS and KMK and revised and approved by all authors. KMK takes responsibility for the integrity of the data analysis. MSO is an employee and stock owner of Amgen Inc. All others state that they have no conflicts of interest. NR 40 TC 17 Z9 17 U1 2 U2 12 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 FEB PY 2015 VL 71 BP 115 EP 123 DI 10.1016/j.bone.2014.10.012 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AY7XU UT WOS:000347770000015 PM 25445450 ER PT J AU Horne, HN Phelan-Emrick, DF Pollack, CE Markakis, D Wenzel, J Ahmed, S Garza, MA Shapiro, GR Bone, LR Johnson, LB Ford, JG AF Horne, Hisani N. Phelan-Emrick, Darcy F. Pollack, Craig E. Markakis, Diane Wenzel, Jennifer Ahmed, Saifuddin Garza, Mary A. Shapiro, Gary R. Bone, Lee R. Johnson, Lawrence B. Ford, Jean G. TI Effect of patient navigation on colorectal cancer screening in a community-based randomized controlled trial of urban African American adults SO CANCER CAUSES & CONTROL LA English DT Article DE Colorectal cancer; Patient navigator; Health disparities; Randomized controlled trial ID RACIAL DISPARITIES; GENDER-DIFFERENCES; HEALTH LITERACY; COMMUNICATION; CARE; COLONOSCOPY; COMORBIDITY; MINORITIES; SURVIVAL; RISK AB In recent years, colorectal cancer (CRC) screening rates have increased steadily in the USA, though racial and ethnic disparities persist. In a community-based randomized controlled trial, we investigated the effect of patient navigation on increasing CRC screening adherence among older African Americans. Participants in the Cancer Prevention and Treatment Demonstration were randomized to either the control group, receiving only printed educational materials (PEM), or the intervention arm where they were assigned a patient navigator in addition to PEM. Navigators assisted participants with identifying and overcoming screening barriers. Logistic regression analyses were used to assess the effect of patient navigation on CRC screening adherence. Up-to-date with screening was defined as self-reported receipt of colonoscopy/sigmoidoscopy in the previous 10 years or fecal occult blood testing (FOBT) in the year prior to the exit interview. Compared with controls, the intervention group was more likely to report being up-to-date with CRC screening at the exit interview (OR 1.55, 95 % CI 1.07-2.23), after adjusting for select demographics. When examining the screening modalities separately, the patient navigator increased screening for colonoscopy/sigmoidoscopy (OR 1.53, 95 % CI 1.07-2.19), but not FOBT screening. Analyses of moderation revealed stronger effects of navigation among participants 65-69 years and those with an adequate health literacy level. In a population of older African Americans adults, patient navigation was effective in increasing the likelihood of CRC screening. However, more intensive navigation may be necessary for adults over 70 years and individuals with low literacy levels. C1 [Horne, Hisani N.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Rockville, MD USA. [Horne, Hisani N.] NCI, NIH, DCEG, HREB, Bethesda, MD 20892 USA. [Phelan-Emrick, Darcy F.; Pollack, Craig E.; Markakis, Diane] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Pollack, Craig E.] Johns Hopkins Sch Med, Dept Gen Internal Med, Baltimore, MD USA. [Wenzel, Jennifer] Johns Hopkins Sch Med, Dept Oncol, Dept Acute & Chron Care, Baltimore, MD USA. [Wenzel, Jennifer] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Ahmed, Saifuddin] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA. [Ahmed, Saifuddin] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Garza, Mary A.] Univ Maryland, Sch Publ Hlth, Dept Behav & Community Hlth, College Pk, MD 20742 USA. [Shapiro, Gary R.] Hlth Partners Canc Program, Minneapolis, MN USA. [Shapiro, Gary R.] Inst Educ & Res, Minneapolis, MN USA. [Bone, Lee R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Johnson, Lawrence B.] Pk West Hlth Syst, Baltimore, MD USA. [Ford, Jean G.] Brooklyn Hosp Ctr, Brooklyn, NY USA. RP Horne, HN (reprint author), NCI, NIH, DCEG, HREB, 9609 Med Ctr Dr,Rm 7E234,MSC 7234, Bethesda, MD 20892 USA. EM hisani.horne@nih.gov FU Cancer Prevention and Treatment Demonstration for Ethnic and Racial Minorities of the Centers for Medicare and Medicaid Services [1A0CMS300066]; Community Networks Program of the National Cancer Institute [U54CA153710]; Maryland Cigarette Restitution Fund; Mentored Research Scientist Development Award [K01CA140358] FX The authors would like to thank the Cancer Prevention and Treatment Demonstration participants, staff, and Community Advisory Committee. This work was supported by the Cancer Prevention and Treatment Demonstration for Ethnic and Racial Minorities of the Centers for Medicare and Medicaid Services (Cooperative Agreement #1A0CMS300066), the Community Networks Program (Grant U54CA153710) of the National Cancer Institute, the Maryland Cigarette Restitution Fund. In addition, Dr. M. A. Garza was supported, in part, through her Mentored Research Scientist Development Award to Promote Diversity (K01CA140358). NR 38 TC 8 Z9 8 U1 0 U2 6 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 FEB PY 2015 VL 26 IS 2 BP 239 EP 246 DI 10.1007/s10552-014-0505-0 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AZ4IF UT WOS:000348184100008 PM 25516073 ER PT J AU Song, M Choi, JY Yang, JJ Sung, H Lee, Y Lee, HW Kong, SH Lee, HJ Kim, HH Kim, SG Yang, HK Kang, D AF Song, Minkyo Choi, Ji-Yeob Yang, Jae Jeong Sung, Hyuna Lee, Yunhee Lee, Hwi-Won Kong, Seong-Ho Lee, Hyuk-Joon Kim, Hyung-Ho Kim, Sang Gyun Yang, Han-Kwang Kang, Daehee TI Obesity at adolescence and gastric cancer risk SO CANCER CAUSES & CONTROL LA English DT Article DE Gastric cancer; Epidemiology; Risk; Obesity; Body mass index; Adolescence ID BODY-MASS INDEX; PROSPECTIVE COHORT; FOLLOW-UP; ADENOCARCINOMA; OVERWEIGHT; ESOPHAGUS; HEIGHT; ASSOCIATION; MECHANISMS; CHILDHOOD AB During the last few decades, prevalence of obesity has risen rapidly worldwide, markedly in children and adolescents. Epidemiologic studies have associated obesity to several cancer types, yet little is known for the effect of early life exposure to obesity on cancer risk in later life, especially in gastric cancer. Thus, the present study aimed to investigate the association of body mass index (BMI) of adolescence and the risk of gastric cancer. A multicenter case-control study was conducted between 2010 and 2014 in Korea with 1,492 incident gastric cancer cases and 1,492 controls matched by age and sex. The BMI at age 18 was calculated by using weight and height from questionnaire. The association with the risk of gastric cancer was evaluated using odds ratios by logistic regression model adjusted for potential confounding factors. Compared with BMI 21.75 kg/m(2), higher BMI at age 18 was associated with higher risk of gastric cancer showing a nonlinear, threshold effect. Statistically significant odds ratio was observed in men with BMI higher than 25.3 kg/m(2) (OR 1.13, 95 % CI 1.01-1.27) and in women with BMI 25.3 kg/m(2) and above (OR 1.25, 95 % CI 1.01-1.55). Similar to some other cancer types, overweight or obese in adolescence was found to be associated with the increased risk of gastric cancer. The results imply for stratified approach of tactics in prevention of gastric cancer in different population. C1 [Song, Minkyo; Yang, Jae Jeong; Lee, Yunhee; Lee, Hwi-Won; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Song, Minkyo; Choi, Ji-Yeob; Lee, Yunhee; Lee, Hwi-Won; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea. [Song, Minkyo; Yang, Jae Jeong] Seoul Natl Univ, Med Res Ctr, Inst Environm Med, Seoul, South Korea. [Choi, Ji-Yeob; Kong, Seong-Ho; Lee, Hyuk-Joon; Yang, Han-Kwang; Kang, Daehee] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. [Sung, Hyuna] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Kong, Seong-Ho; Lee, Hyuk-Joon; Yang, Han-Kwang] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea. [Kim, Hyung-Ho] Seoul Natl Univ, Bundang Hosp, Dept Surg, Songnam, South Korea. [Kim, Sang Gyun] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Kim, Sang Gyun] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul, South Korea. RP Kang, D (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, 103 Yongon Daehangno, Seoul, South Korea. EM dhkang@snu.ac.kr OI Song, Minkyo/0000-0002-9412-2871 FU BRL (Basic Research Laboratory) program through the National Research Foundation of Korea - Ministry of Education, Science and Technology [2012-0000347]; National Research Foundation of Korea (NRF) A3 Foresight program FX This research was supported by BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000347) and by the National Research Foundation of Korea (NRF) A3 Foresight program. NR 23 TC 2 Z9 3 U1 0 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2015 VL 26 IS 2 BP 247 EP 256 DI 10.1007/s10552-014-0506-z PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AZ4IF UT WOS:000348184100009 PM 25471061 ER PT J AU Cote, ML Alhajj, T Ruterbusch, JJ Bernstein, L Brinton, LA Blot, WJ Chen, C Gass, M Gaussoin, S Henderson, B Lee, E Horn-Ross, PL Kolonel, LN Kaunitz, A Liang, XL Nicholson, WK Park, AB Petruzella, S Rebbeck, TR Setiawan, VW Signorello, LB Simon, MS Weiss, NS Wentzensen, N Yang, HP Zeleniuch-Jacquotte, A Olson, SH AF Cote, Michele L. Alhajj, Tala Ruterbusch, Julie J. Bernstein, Leslie Brinton, Louise A. Blot, William J. Chen, Chu Gass, Margery Gaussoin, Sarah Henderson, Brian Lee, Eunjung Horn-Ross, Pamela L. Kolonel, Laurence N. Kaunitz, Andrew Liang, Xiaolin Nicholson, Wanda K. Park, Amy B. Petruzella, Stacey Rebbeck, Timothy R. Setiawan, V. Wendy Signorello, Lisa B. Simon, Michael S. Weiss, Noel S. Wentzensen, Nicolas Yang, Hannah P. Zeleniuch-Jacquotte, Anne Olson, Sara H. TI Risk factors for endometrial cancer in black and white women: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2) SO CANCER CAUSES & CONTROL LA English DT Article DE Endometrial neoplasms; Race/ethnicity; Obesity; Parity; Diabetes ID BODY-MASS INDEX; REPRODUCTIVE FACTORS; CIGARETTE-SMOKING; UNITED-STATES; POSTMENOPAUSAL WOMEN; CONTRACEPTIVE USE; NURSES HEALTH; METAANALYSIS; TRENDS; PREVALENCE AB Endometrial cancer (EC) is the most common gynecologic cancer in the USA. Over the last decade, the incidence rate has been increasing, with a larger increase among blacks. The aim of this study was to compare risk factors for EC in black and white women. Data from seven cohort and four case-control studies were pooled. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95 % confidence intervals for each risk factor in blacks and whites separately. Data were pooled for 2,011 black women (516 cases and 1,495 controls) and 19,297 white women (5,693 cases and 13,604 controls). BMI a parts per thousand yen 30 was associated with an approximate threefold increase in risk of EC in both black and white women (ORblack 2.93, 95 % CI 2.11, 4.07 and ORwhite 2.99, 95 % CI 2.74, 3.26). Diabetes was associated with a 30-40 % increase in risk among both groups. Increasing parity was associated with decreasing risk of EC in blacks and whites (p value = 0.02 and < 0.001, respectively). Current and former smoking was associated with decreased risk of EC among all women. Both black and white women who used oral contraceptives for 10 +years were also at reduced risk of EC (OR 0.49, 95 % CI 0.27, 0.88 and OR 0.69, 95 % CI 0.58, 0.83, respectively). Previous history of hypertension was not associated with EC risk in either group. The major known risk factors for EC exert similar effects on black and white women. Differences in the incidence rates between the two populations may be due to differences in the prevalence of risk factors. C1 [Cote, Michele L.; Alhajj, Tala; Ruterbusch, Julie J.; Simon, Michael S.] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI 48201 USA. [Cote, Michele L.; Simon, Michael S.] Karmanos Canc Inst, Populat Studies & Dispar Res Program, Detroit, MI USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA. [Brinton, Louise A.; Wentzensen, Nicolas; Yang, Hannah P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Blot, William J.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Blot, William J.] Int Epidemiol Fdn, Rockville, MD USA. [Chen, Chu; Weiss, Noel S.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Gass, Margery; Park, Amy B.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Gaussoin, Sarah] Wake Forest Sch Med, Winston Salem, NC USA. [Henderson, Brian; Setiawan, V. Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Lee, Eunjung; Horn-Ross, Pamela L.] Canc Prevent Inst Calif, Fremont, CA USA. [Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Kaunitz, Andrew] Univ Florida, Coll Med Jacksonville, Jacksonville, FL USA. [Liang, Xiaolin; Petruzella, Stacey; Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Nicholson, Wanda K.] Univ N Carolina, Sch Med, Diabet & Obes Core, Ctr Womens Res, Chapel Hill, NC USA. [Rebbeck, Timothy R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Weiss, Noel S.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Environm Med, New York, NY USA. RP Cote, ML (reprint author), Wayne State Univ, Sch Med, Dept Oncol, 4100 John R Mailstop MM04EP, Detroit, MI 48201 USA. EM cotem@karmanos.org RI Brinton, Louise/G-7486-2015; OI Brinton, Louise/0000-0003-3853-8562; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI); NCI [R01 CA91019, R01 CA77398, NO1-CN-25514, NO1-CN-25522, NO1-CN-25515, NO1-CN-25512, NO1-CN-25513, NO1-CN-25516, NO1-CN-25511, NO1-CN-25524, NO1-CN-25518, NO1-CN-75022, NO1-CN-25476, NO1-CN-25404]; NIH [CA164973, CA054281, CA063464, R01CA098661, P30CA016087, R01 CA092447, R01 CA74877, R01 CA83918, R35 CA39779, R01 CA75977, R03 CA80636, N01 HD23166, K05 CA92002, R01 CA105212, R01 CA87538, P01 CA77596]; National Institute of Environmental Health Sciences [ES000260]; National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC); National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN26820110 0046C, HHSN268201100001C, HHSN268201100002C, HHSN268 201100003C, HHSN268201100004C, HHSN271201100004C]; U.S. Army Medical Research Program DAMD [17-96-607]; Fred Hutchinson Cancer Research Center FX National Institute of Health American Association of Retired Persons Diet and Health Study: This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI). California Teachers Study: NCI Grants R01 CA91019 and R01 CA77398. The collection of cancer incidence data was supported by the California Department of Public Health and the NCI Surveillance, Epidemiology and End Results Program (SEER) as part of the statewide cancer reporting program. Multiethnic Cohort Study: NIH Grants CA164973, CA054281, and CA063464. New York University Women's Health Study: NIH Grants R01CA098661 and P30CA016087 and National Institute of Environmental Health Sciences Grant ES000260. Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: Supported by individual contracts from the NCI to the University of Colorado Denver (NO1-CN-25514), Georgetown University (NO1-CN-25522), Pacific Health Research Institute (NO1-CN-25515), Henry Ford Health System (NO1-CN-25512), University of Minnesota (NO1-CN-25513), Washington University (NO1-CN-25516), University of Pittsburgh (NO1-CN-25511), University of Utah (NO1-CN-25524), Marshfield Clinic Research Foundation (NO1-CN-25518), University of Alabama at Birmingham (NO1-CN-75022), Westat, Inc. (NO1-CN-25476), University of California, Los Angeles (NO1-CN-25404). Southern Community Cohort Study (SCCS): NIH Grant R01 CA092447. Data on SCCS cancer cases used in this publication were provided by the Alabama Statewide Cancer Registry; Kentucky Cancer Registry, Lexington, KY; Tennessee Department of Health, Office of Cancer Surveillance; Florida Cancer Data System; North Carolina Central Cancer Registry, North Carolina Division of Public Health; Georgia Comprehensive Cancer Registry; Louisiana Tumor Registry; Mississippi Cancer Registry; South Carolina Central Cancer Registry; Virginia Department of Health, Virginia Cancer Registry; Arkansas Department of Health, Cancer Registry, 4815 W. Markham, Little Rock, AR 72205. The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Mississippi Cancer Registry. Women's Health Initiative: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN26820110 0046C, HHSN268201100001C, HHSN268201100002C, HHSN268 201100003C, HHSN268201100004C, and HHSN271201100004C. Bay Area Women's Health Study: NIH Grant R01 CA74877, and the U.S. Army Medical Research Program DAMD Grant 17-96-607. Estrogen, Diet, Genetics and Endometrial Cancer Study: NIH Grant R01 CA83918. Fred Hutchinson Cancer Research Center Studies: NIH Grants R35 CA39779, R01 CA75977, R03 CA80636, N01 HD23166, K05 CA92002, R01 CA105212, R01 CA87538 and funds from the Fred Hutchinson Cancer Research Center. Women's Insight and Shared Experience Study: NIH Grant P01 CA77596. NR 49 TC 11 Z9 11 U1 4 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 FEB PY 2015 VL 26 IS 2 BP 287 EP 296 DI 10.1007/s10552-014-0510-3 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AZ4IF UT WOS:000348184100013 PM 25534916 ER PT J AU Caputo, E Wang, E Valentino, A Crispi, S De Giorgi, V Fico, A Ficili, B Capone, M Anniciello, A Cavalcanti, E Botti, G Mozzillo, N Ascierto, PA Marincola, FM Travali, S AF Caputo, Emilia Wang, Ena Valentino, Anna Crispi, Stefania De Giorgi, Valeria Fico, Annalisa Ficili, Bartolomea Capone, Mariaelena Anniciello, AnnaMaria Cavalcanti, Ernesta Botti, Gerardo Mozzillo, Nicola Ascierto, Paolo A. Marincola, Francesco M. Travali, Salvatore TI Ran signaling in melanoma: Implications for the development of alternative therapeutic strategies SO CANCER LETTERS LA English DT Article DE Targeted therapy; Aurora kinase A in melanoma; Gene expression; Pathway analysis; Ran signaling ID SQUAMOUS-CELL CARCINOMA; METASTATIC MELANOMA; AURORA-A; TUMOR PROGRESSION; B-RAF; CANCER; GENE; EXPRESSION; INHIBITION; MUTATIONS AB We performed a comparative study between two human metastatic melanoma cell lines (A375 and 526), and melanocytes (FOM78) by gene expression profiling and pathway analysis, using Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) software. Genes involved in Ran signaling were significantly over-represented (p <= 0.001) and up-regulated in melanoma cells. A melanoma-associated molecular pathway was identified, where Ran, Aurora Kinase A (AurkA) and TERT were up-regulated, while c-myc and PTEN were down-regulated. A consistent high Ran and AurkA gene expression was detected in about 48% and 53%, respectively, of 113 tissue samples from metastatic melanoma patients. AurkA down-regulation was observed in melanoma cells, by Ran knockdown, suggesting AurkA protein is a Ran downstream target. Furthermore, AurkA inhibition, by exposure of melanoma cells to MLN8054, a specific AurKA inhibitor, induced apoptosis in both melanoma cell lines and molecular alterations in the IPA-identified molecular pathway. These alterations differed between cell lines, with an up-regulation of c-myc protein level observed in 526 cells and a slight reduction seen in A375 cells. Moreover, Ran silencing did not affect the A375 invasive capability, while it was enhanced in 526 cells, suggesting that Ran knockdown, by AurkA down-regulation, resulted in a Ran-independent enhanced melanoma cell invasion. Finally, AurK A inhibition induced a PTEN up-regulation and its action was independent of B-RAF mutational status. These findings provide insights relevant for the development of novel therapeutic strategies as well as for a better understanding of mechanisms underlying therapy resistance in melanoma. (c) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Caputo, Emilia; Valentino, Anna; Crispi, Stefania; Fico, Annalisa] CNR, IGBA Buzzati Traverso, Inst Genet & Biophys, I-80131 Naples, Italy. [Caputo, Emilia; Ficili, Bartolomea; Travali, Salvatore] Univ Catania, Dipartimento Sci Biomed, I-95124 Catania, Italy. [Wang, Ena; De Giorgi, Valeria; Marincola, Francesco M.] NIH, IDIS, DTM, CC,CHI, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar. [Crispi, Stefania] CNR, IBB, I-8013 Naples, Italy. [Capone, Mariaelena; Anniciello, AnnaMaria; Cavalcanti, Ernesta; Botti, Gerardo; Mozzillo, Nicola; Ascierto, Paolo A.] Ist Nazl Tumori Fdn G Pascale, I-80131 Naples, Italy. RP Caputo, E (reprint author), CNR, IGBA Buzzati Traverso, Inst Genet & Biophys, I-80131 Naples, Italy. EM emilia.caputo@igb.cnr.it RI De Giorgi, Valeria/D-4582-2017; OI CAPUTO, EMILIA/0000-0002-6485-8802; Crispi, Stefania/0000-0002-7566-1554 FU BIAM EPI-FORM "Ricerca e Competitivita"; NIH NIDDK [1 R21DK070192-01] FX The authors wish to thank Dr. E.J. Patriarca for his critical comments. AV was supported by BIAM EPI-FORM "Ricerca e Competitivita" 2007-2013. This work was supported by a sub-grant (1 R21DK070192-01) to EC from NIH NIDDK. NR 48 TC 2 Z9 3 U1 0 U2 5 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 FEB 1 PY 2015 VL 357 IS 1 BP 286 EP 296 DI 10.1016/j.canlet.2014.11.033 PG 11 WC Oncology SC Oncology GA AZ2TB UT WOS:000348084100028 PM 25444926 ER PT J AU Chae, JP Park, MS Hwang, YS Min, BH Kim, SH Lee, HS Park, MJ AF Chae, Jeong-Pil Park, Mi Seon Hwang, Yoo-Seok Min, Byung-Hwa Kim, Sang-Hyun Lee, Hyun-Shik Park, Mae-Ja TI Evaluation of developmental toxicity and teratogenicity of diclofenac using Xenopus embryos SO CHEMOSPHERE LA English DT Article DE Diclofenac; Teratogenicity; Embryotoxicity; FETAX; Xenopus laevis ID ANTIINFLAMMATORY DRUG; FETAX ASSAY; EXPOSURE; EMBRYOTOXICITY; HIPPOCAMPUS; INHIBITION; CULTURE; MICE AB Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and anti-pyretic properties. This compound is therefore used to treat pain, inflammatory disorders, and dysmenorrhea. Due to its multimodal mechanism of action and ability to penetrate placenta, diclofenac is known to have undesirable side effects including teratogenicity. However, limited data exist on its teratogenicity, and a detailed investigation regarding harmful effects of this drug during embryogenesis is warranted. Here, we analyzed the developmental toxic effects of diclofenac using Xenopus embryos according to the Frog Embryo Teratogenesis Assay-Xenopus (FETAX) protocol. Diclofenac treatment exerted a teratogenic effect on Xenopus embryos with a teratogenic index (TI) value of 2.64 TI; if this value is higher than 1.2, the cutoff value indicative of toxicity. In particular, mortality of embryos treated with diclofenac increased in a concentration-dependent manner and a broad spectrum of malformations such as shortening and kinking of the axis, abdominal bulging, and prominent blister formation, was observed. The shape and length of internal organs also differed compared to the control group embryos and show developmental retardation on histological label. However, the expression of major tissue-specific markers did not change when analyzed by reverse transcription-polymerase chain reaction (RT-PCR). In conclusion, diclofenac treatment can promote teratogenicity that results in morphological anomalies, but not disrupt the developmental tissue arrangement during Xenopus embryogenesis. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Chae, Jeong-Pil; Park, Mae-Ja] Kyungpook Natl Univ, Coll Med, Dept Anat, Taegu 700422, South Korea. [Park, Mi Seon; Min, Byung-Hwa] Natl Fisheries Res & Dev Inst, Aquaculture Management Div, Pusan 619705, South Korea. [Hwang, Yoo-Seok] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. [Kim, Sang-Hyun] Kyungpook Natl Univ, Coll Med, Dept Pharmacol, Taegu 700422, South Korea. [Lee, Hyun-Shik] Kyungpook Natl Univ, Sch Life Sci, ABRC, Plus KNU Creat BioRes Grp BK21, Taegu 702701, South Korea. RP Lee, HS (reprint author), Kyungpook Natl Univ, Coll Nat Sci, Sch Life Sci, Taegu 702701, South Korea. EM leeh@knu.ac.kr; mjpark@knu.ac.kr FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2010-0005909, NRF-2012R1A1A2042334]; Grant from the Next-Generation BioGreen 21 Program, Rural Development Administration, South Korea [PJ009564]; Kyungpook National University Research Fund FX This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0005909, NRF-2012R1A1A2042334), a Grant from the Next-Generation BioGreen 21 Program (PJ009564), Rural Development Administration, South Korea, and the Kyungpook National University Research Fund (2012). NR 28 TC 6 Z9 7 U1 1 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 EI 1879-1298 J9 CHEMOSPHERE JI Chemosphere PD FEB PY 2015 VL 120 BP 52 EP 58 DI 10.1016/j.chemosphere.2014.05.063 PG 7 WC Environmental Sciences SC Environmental Sciences & Ecology GA AZ1MN UT WOS:000348003200008 PM 24992311 ER PT J AU Gonzalez, A Peris, TS Vreeland, A Kiff, CJ Kendall, PC Compton, SN Albano, AM Birmaher, B Ginsburg, GS Keeton, CP March, J McCracken, J Rynn, M Sherrill, J Walkup, JT Piacentini, J AF Gonzalez, Araceli Peris, Tara S. Vreeland, Allison Kiff, Cara J. Kendall, Philip C. Compton, Scott N. Albano, Anne Marie Birmaher, Boris Ginsburg, Golda S. Keeton, Courtney P. March, John McCracken, James Rynn, Moira Sherrill, Joel Walkup, John T. Piacentini, John TI Parental Anxiety as a Predictor of Medication and CBT Response for Anxious Youth SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE Children; Adolescents; Parent; Anxiety; Treatment ID COGNITIVE-BEHAVIORAL THERAPY; ATTENTION MODIFICATION PROGRAM; RANDOMIZED CLINICAL-TRIAL; CHILDHOOD ANXIETY; DISORDERED YOUTH; MATERNAL ANXIETY; CHILDREN; ADOLESCENTS; PSYCHOPATHOLOGY; INDIVIDUALS AB The aim of this investigation was to evaluate how parental anxiety predicted change in pediatric anxiety symptoms across four different interventions: cognitive-behavioral therapy, medication (sertraline; SRT), their combination (COMB), and pill placebo. Participants were 488 youths (ages 7-17) with separation anxiety disorder, generalized anxiety disorder, and/or social phobia and their primary caregivers. Latent growth curve modeling assessed how pre-treatment parental trait anxiety symptoms predicted trajectories of youth anxiety symptom change across 12 weeks of treatment at four time points. Interactions between parental anxiety and treatment condition were tested. Parental anxiety was not associated with youth's pre-treatment anxiety symptom severity. Controlling for parental trait anxiety, youth depressive symptoms, and youth age, youths who received COMB benefitted most. Counter to expectations, parental anxiety influenced youth anxiety symptom trajectory only within the SRT condition, whereas parental anxiety was not significantly associated with youth anxiety trajectories in the other treatment conditions. Specifically, within the SRT condition, higher levels of parental anxiety predicted a faster and greater reduction in youth anxiety over the acute treatment period compared to youths in the SRT condition whose parents had lower anxiety levels. While all active treatments produced favorable outcomes, results provide insight regarding the treatment-specific influence of parental anxiety on the time course of symptom change. C1 [Gonzalez, Araceli; Peris, Tara S.; Vreeland, Allison; Kiff, Cara J.; McCracken, James; Piacentini, John] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Kendall, Philip C.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Compton, Scott N.; March, John] Duke Univ, Med Ctr, Dept Psychiat & Behav Serv, Durham, NC USA. [Albano, Anne Marie; Rynn, Moira] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY USA. [Birmaher, Boris] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. [Ginsburg, Golda S.; Keeton, Courtney P.] Johns Hopkins Univ, Sch Med, Div Child & Adolescent Psychiat, Baltimore, MD USA. [Sherrill, Joel] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Walkup, John T.] Weill Cornell Med Coll, Div Child & Adolescent Psychiat, New York, NY USA. RP Gonzalez, A (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,Semel Room 67-467, Los Angeles, CA 90024 USA. EM AraceliGonzalez@mednet.ucla.edu RI Gonzalez, Araceli/L-9062-2015 OI Gonzalez, Araceli/0000-0001-7462-405X FU NIMH NIH HHS [U01MH64088, U01 MH064107, U01MH64092, U01 MH064003, U01MH064089, U01 MH064089, U01MH064003, U01 MH064092, U01MH64003, U01MH63747, T32MH073517, U01 MH064088, R01 MH064089, U01 MH063747, U01MH64107, K24 MH096760, T32 MH073517] NR 57 TC 2 Z9 2 U1 4 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-398X EI 1573-3327 J9 CHILD PSYCHIAT HUM D JI Child Psychiat. Hum. Dev. PD FEB PY 2015 VL 46 IS 1 BP 84 EP 93 DI 10.1007/s10578-014-0454-6 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AZ6WS UT WOS:000348359400009 PM 24610431 ER PT J AU Clayton, JA Davis, AF AF Clayton, Janine A. Davis, Alison F. TI Sex/Gender Disparities and Women's Eye Health SO CURRENT EYE RESEARCH LA English DT Review DE Disparities; eye health; gender; sex; women's health ID OPEN-ANGLE GLAUCOMA; UNITED-STATES; AUTOIMMUNE-DISEASES; PREGNANCY; CARE; RETINOPATHY; MORTALITY; VISION; GENDER; RISK AB Our eyes are, both literally and figuratively, windows to the world, and ophthalmic approaches offer a tremendous space for conducting research to learn more. Male/female differences in ocular health and disease are prevalent but we know far too little about root causes to design and implement diagnostic, preventive, and treatment strategies to address sex-and gender-based disparities in eye health. Herein, we discuss several ophthalmic diseases and other conditions with ocular manifestations, with a focus upon those that disproportionately affect women. Because the vast majority of biomedical research in this area comes from studies of mixed-gender populations, or of male-predominant populations, there is a pressing need for sex-and/or gender-based research at various points along the basic to clinical biomedical research continuum. Moreover, the multitude of factors that affect eye health call for a balanced look at the influence of biology, culture, and societal contributors. As clinicians, we owe our patients the best care for their needs, and that care must be derived from research that shows what is effective, for whom, and under what conditions. C1 [Clayton, Janine A.; Davis, Alison F.] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. RP Clayton, JA (reprint author), NIH, Off Res Womens Hlth, 6707 Democracy Blvd,400, Bethesda, MD 20892 USA. EM Janine.Clayton@nih.gov FU Office of Research on Women's Health, National Institutes of Health FX This work was funded by Office of Research on Women's Health, National Institutes of Health NR 32 TC 0 Z9 0 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0271-3683 EI 1460-2202 J9 CURR EYE RES JI Curr. Eye Res. PD FEB PY 2015 VL 40 IS 2 BP 102 EP 109 DI 10.3109/02713683.2014.986333 PG 8 WC Ophthalmology SC Ophthalmology GA AZ4TB UT WOS:000348214800003 PM 25548854 ER PT J AU Sen, HN Davis, J Ucar, D Fox, A Chan, CC Goldstein, DA AF Sen, Hatice Nida Davis, Janet Ucar, Didar Fox, Austin Chan, Chi Chao Goldstein, Debra A. TI Gender Disparities in Ocular Inflammatory Disorders SO CURRENT EYE RESEARCH LA English DT Review DE Disparity; gender; ocular inflammation; sex; uveitis ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; JUVENILE IDIOPATHIC ARTHRITIS; KOYANAGI-HARADA-DISEASE; PLACOID PIGMENT EPITHELIOPATHY; ACTIVE ANTIRETROVIRAL THERAPY; HORMONE REPLACEMENT THERAPY; ENVIRONMENTAL RISK-FACTORS; ACUTE ANTERIOR UVEITIS; EYE CARE CENTER; TERM-FOLLOW-UP AB Ocular inflammatory disorders disproportionately affect women, and the majority of affected women are of childbearing age. The role of sex or reproductive hormones has been proposed in many other inflammatory or autoimmune disorders, and findings from non-ocular autoimmune diseases suggest a complex interaction between sex hormones, genetic factors and the immune system. However, despite the age and sex bias, factors that influence this disparity are complicated and unclear. This review aims to evaluate the gender disparities in prevalence, incidence and severity of the most common infectious and non-infectious ocular inflammatory disorders. C1 [Sen, Hatice Nida; Ucar, Didar; Fox, Austin; Chan, Chi Chao] NEI, NIH, Bethesda, MD 20892 USA. [Davis, Janet] Univ Miami, Bascom Palmer Eye Inst, Miami, FL USA. [Ucar, Didar] Cerrahpasa Univ, Dept Ophthalmol, Istanbul, Turkey. [Goldstein, Debra A.] Northwestern Feinberg Sch Med, Dept Ophthalmol, Chicago, IL USA. RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,10-10N109, Bethesda, MD 20892 USA. EM senh@nei.nih.gov FU National Eye Institute; Research to Prevent Blindness (NY) FX None of the authors have any commercial relationship with regards to the subject of this manuscript. H.N.S., C.C.C., D.U. and A.F.'s work has been supported by the National Eye Institute Intramural Research Program. D.A.G. is supported by an unrestricted grant from Research to Prevent Blindness (NY). NR 154 TC 0 Z9 0 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0271-3683 EI 1460-2202 J9 CURR EYE RES JI Curr. Eye Res. PD FEB PY 2015 VL 40 IS 2 BP 146 EP 161 DI 10.3109/02713683.2014.932388 PG 16 WC Ophthalmology SC Ophthalmology GA AZ4TB UT WOS:000348214800006 PM 24987987 ER PT J AU Singh, A Lester, C Drapp, R Hu, DZ Glimcher, LH Jones, D AF Singh, Anju Lester, Chantel Drapp, Rebecca Hu, Dorothy Z. Glimcher, Laurie H. Jones, Dallas TI Tetraspanin CD9 and ectonucleotidase CD73 identify an osteochondroprogenitor population with elevated osteogenic properties SO DEVELOPMENT LA English DT Article DE Osteochondroprogenitor; Osteoblast; Skeletal stem cell ID MESENCHYMAL STEM-CELLS; PROGENITOR CELLS; REGENERATION; BONES AB Cell-based bone regeneration strategies offer promise for traumatic bone injuries, congenital defects, non-union fractures and other skeletal pathologies. Postnatal bone remodeling and fracture healing provide evidence that an osteochondroprogenitor cell is present in adult life that can differentiate to remodel or repair the fractured bone. However, cell-based skeletal repair in the clinic is still in its infancy, mostly due to poor characterization of progenitor cells and lack of knowledge about their in vivo behavior. Here, we took acombined approachof high-throughput screening, flow-based cell sorting and in vivo transplantation to isolate markers that identify osteochondroprogenitor cells. We show that the presence of tetraspanin CD9 enriches for osteochondroprogenitors within CD105(+) mesenchymal cells and that these cells readily form bone upon transplantation. In addition, we have used Thy1.2 and the ectonucleotidase CD73 to identify subsets within the CD9(+) population that lead to endochondral or intramembranous-like bone formation. Utilization of this unique cell surface phenotype to enrich for osteochondroprogenitor cells will allow for further characterization of the molecular mechanisms that regulate their osteogenic properties. C1 [Singh, Anju] NIH, Dept Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Lester, Chantel] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Drapp, Rebecca] N Carolina State Univ, Coll Vet Med, Raleigh, NC 27607 USA. [Hu, Dorothy Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Glimcher, Laurie H.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [Jones, Dallas] Abide Therapeut, San Diego, CA 92121 USA. RP Singh, A (reprint author), NIH, Dept Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. EM anju.singh@nih.gov; lglimche@med.cornell.edu FU National Institutes of Health [HD055601, K99AR055668]; Arthritis Foundation FX This work was supported by National Institutes of Health grants [HD055601 to L.H.G. and K99AR055668 to D.J.]. A.S. was supported by a fellowship from the Arthritis Foundation. Deposited in PMC for release after 12 months. NR 20 TC 1 Z9 1 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD FEB 1 PY 2015 VL 142 IS 3 BP 438 EP 443 DI 10.1242/dev.113571 PG 6 WC Developmental Biology SC Developmental Biology GA AZ5HT UT WOS:000348251800005 PM 25564652 ER PT J AU May-Simera, HL Petralia, RS Montcouquiol, M Wang, YX Szarama, KB Liu, Y Lin, WC Deans, MR Pazour, GJ Kelley, MW AF May-Simera, Helen L. Petralia, Ronald S. Montcouquiol, Mireille Wang, Ya-Xian Szarama, Katherine B. Liu, Yun Lin, Weichun Deans, Michael R. Pazour, Gregory J. Kelley, Matthew W. TI Ciliary proteins Bbs8 and Ift20 promote planar cell polarity in the cochlea SO DEVELOPMENT LA English DT Article DE Actin; Cilia; Cochlea; Microtubules; Polarity; Mouse ID BARDET-BIEDL-SYNDROME; LEFT-RIGHT ASYMMETRY; INTRAFLAGELLAR TRANSPORT; HAIR-CELLS; BASAL BODY; INNER-EAR; COMPLEX; MOUSE; ZEBRAFISH; DISEASE AB Primary cilia have been implicated in the generation of planar cell polarity (PCP). However, variations in the severity of polarity defects in different cilia mutants, coupled with recent demonstrations of non-cilia- related actions of some cilia genes, make it difficult to determine the basis of these polarity defects. To address this issue, we evaluated PCP defects in cochlea from a selection of mice with mutations in cilia-related genes. Results indicated notable PCP defects, including mis-oriented hair cell stereociliary bundles, in Bbs8 and Ift20 single mutants that are more severe than in other cilia gene knockouts. In addition, deletion of either Bbs8 or Ift20 results in disruptions in asymmetric accumulation of the core PCP molecule Vangl2 in cochlear cells, suggesting a role for Bbs8 and/or Ift20, possibly upstream of core PCP asymmetry. Consistent with this, co-immunoprecipitation experiments indicate direct interactions of Bbs8 and Ift20 with Vangl2. We observed localization of Bbs and Ift proteins to filamentous actin as well as microtubules. This could implicate these molecules in selective trafficking of membrane proteins upstream of cytoskeletal reorganization, and identifies new roles for cilia-related proteins in cochlear PCP. C1 [May-Simera, Helen L.; Szarama, Katherine B.; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, Lab Cochlear Dev, NIH, Bethesda, MD 20892 USA. [Petralia, Ronald S.; Wang, Ya-Xian] Natl Inst Deafness & Other Commun Disorders, Adv Imaging Core, NIH, Bethesda, MD 20892 USA. [Montcouquiol, Mireille] INSERM, Planar Polar & Plast Grp, U862, F-33077 Bordeaux, France. [Szarama, Katherine B.] St Jude Childrens Res Hosp, Dept Cell & Mol Biol, Memphis, TN 38105 USA. [Liu, Yun; Lin, Weichun] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75235 USA. [Deans, Michael R.] Univ Utah, Sch Med, Dept Otolaryngol Head & Neck Surg, Salt Lake City, UT 84132 USA. [Deans, Michael R.] Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA. [Pazour, Gregory J.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. RP May-Simera, HL (reprint author), NIH, Neurobiol Neurodegenerat & Repair Lab, Retinal Cell Biol Degenerat Sect, 6 Ctr Dr, Bethesda, MD 20892 USA. EM maysimerah@nei.nih.gov OI Pazour, Gregory/0000-0002-6285-8796 FU National Institutes of Health; National Institute of Deafness and other Communication Disorders; National Eye Institute; National Institutes of General Medical Sciences [GM060992]; National Institute of Neurological Disorders and Stroke [5R01NS055028]; National Institute of Deafness and other Communication Disorders [R01DC013066]; National Eye Institute [R01EY021146] FX This work was supported by intramural and extramural funds from the National Institutes of Health. Intramural funds from the National Institute of Deafness and other Communication Disorders to H.L.M.-S., R.S.P., Y.-X.W., K.B.S. and M.W.K. Intramural funds from the National Eye Institute to H.L.M.-S. Extramural funds from the National Institutes of General Medical Sciences [GM060992 to G.J.P.], National Institute of Neurological Disorders and Stroke [5R01NS055028 to Y.L. and W.L.], National Institute of Deafness and other Communication Disorders [R01DC013066 to M.R.D.] and National Eye Institute [R01EY021146 to M.R.D.]. Intramural INSERM and ANR-14-CE13-0013-01 (M.M.). Deposited in PMC for release after 12 months. NR 62 TC 12 Z9 12 U1 0 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD FEB 1 PY 2015 VL 142 IS 3 BP 555 EP 566 DI 10.1242/dev.113696 PG 12 WC Developmental Biology SC Developmental Biology GA AZ5HT UT WOS:000348251800016 PM 25605782 ER PT J AU Porcella, SF Carlson, JH Sturdevant, DE Sturdevant, GL Kanakabandi, K Virtaneva, K Wilder, H Whitmire, WM Song, LH Caldwell, HD AF Porcella, Stephen F. Carlson, John H. Sturdevant, Daniel E. Sturdevant, Gail L. Kanakabandi, Kishore Virtaneva, Kimmo Wilder, Hannah Whitmire, William M. Song, Lihua Caldwell, Harlan D. TI Transcriptional Profiling of Human Epithelial Cells Infected with Plasmid-Bearing and Plasmid-Deficient Chlamydia trachomatis SO INFECTION AND IMMUNITY LA English DT Article ID TOLL-LIKE RECEPTOR; CONJUNCTIVAL TRANSCRIPTOME; DISEASE PATHOGENESIS; MURIDARUM INFECTION; VACCINE; HYPERSENSITIVITY; REGULATOR; VIRULENCE; EXPRESSION; SECRETION AB Chlamydia trachomatis is an obligate intracellular epitheliotropic bacterial pathogen of humans. Infection of the eye can result in trachoma, the leading cause of preventable blindness in the world. The pathophysiology of blinding trachoma is driven by multiple episodes of reinfection of conjunctival epithelial cells, producing an intense chronic inflammatory response resulting in submucosal tissue remodeling and scarring. Recent reports have shown that infection with trachoma organisms lacking the cryptic chlamydial plasmid is highly attenuated in macaque eyes, a relevant experimental model of human trachoma infection. To better understand the molecular basis of plasmid-mediated infection attenuation and the potential modulation of host immunity, we conducted transcriptional profiling of human epithelial cells infected with C. trachomatis plasmid-bearing (A2497) and plasmid-deficient (A2497P(-)) organisms. Infection of human epithelial cells with either strain increased the expression of host genes coding for proinflammatory (granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage colony-stimulating factor [MCSF], interleukin-6 [IL-6], IL-8, IL-1 alpha, CXCL1, CXCL2, CXCL3, intercellular adhesion molecule 1 [ICAM1]), chemoattraction (CCL20, CCL5, CXCL10), immune suppression (PD-L1, NFKB1B, TNFAIP3, CGB), apoptosis (CASP9, FAS, IL-24), and cell growth and fibrosis (EGR1 and IL-20) proteins. Statistically significant increases in the levels of expression of many of these genes were found in A2497-infected cells compared to the levels of expression in A2497P(-)-infected cells. Our findings suggest that the chlamydial plasmid plays a focal role in the host cell inflammatory response to infection and immune avoidance. These results provide new insights into the role of the chlamydial plasmid as a chlamydial virulence factor and its contributions to trachoma pathogenesis. C1 [Carlson, John H.; Sturdevant, Gail L.; Whitmire, William M.; Caldwell, Harlan D.] NIAID, Lab Intracellular Parasites, NIH, Hamilton, MT USA. [Porcella, Stephen F.; Sturdevant, Daniel E.; Kanakabandi, Kishore; Virtaneva, Kimmo; Wilder, Hannah] NIAID, Genom Unit, Res Technol Sect, NIH, Hamilton, MT 59840 USA. [Song, Lihua] Beijing Inst Microbiol & Epidemiol, Beijing, Peoples R China. RP Porcella, SF (reprint author), NIAID, Genom Unit, Res Technol Sect, NIH, Hamilton, MT 59840 USA. EM sporcella@niaid.nih.gov OI Song, Lihua/0000-0002-7299-5719 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 35 TC 11 Z9 11 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2015 VL 83 IS 2 BP 534 EP 543 DI 10.1128/IAI.02764-14 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AZ0ST UT WOS:000347955700009 PM 25404022 ER PT J AU Larson, CL Beare, PA Voth, DE Howe, D Cockrell, DC Bastidas, RJ Valdivia, RH Heinzen, RA AF Larson, Charles L. Beare, Paul A. Voth, Daniel E. Howe, Dale Cockrell, Diane C. Bastidas, Robert J. Valdivia, Raphael H. Heinzen, Robert A. TI Coxiella burnetii Effector Proteins That Localize to the Parasitophorous Vacuole Membrane Promote Intracellular Replication SO INFECTION AND IMMUNITY LA English DT Article ID IV SECRETION SYSTEM; SNARE-LIKE PROTEINS; LEGIONELLA-PNEUMOPHILA; REPEAT PROTEINS; HOST-CELL; IDENTIFICATION; PATHWAY; TRANSLOCATION; MATURATION; REGULATOR AB The intracellular bacterial pathogen Coxiella burnetii directs biogenesis of a parasitophorous vacuole (PV) that acquires host endolysosomal components. Formation of a PV that supports C. burnetii replication requires a Dot/Icm type 4B secretion system (T4BSS) that delivers bacterial effector proteins into the host cell cytosol. Thus, a subset of T4BSS effectors are presumed to direct PV biogenesis. Recently, the PV-localized effector protein CvpA was found to promote C. burnetii intracellular growth and PV expansion. We predict additional C. burnetii effectors localize to the PV membrane and regulate eukaryotic vesicle trafficking events that promote pathogen growth. To identify these vacuolar effector proteins, a list of predicted C. burnetii T4BSS substrates was compiled using bioinformatic criteria, such as the presence of eukaryote-like coiled-coil domains. Adenylate cyclase translocation assays revealed 13 proteins were secreted in a Dot/Icm-dependent fashion by C. burnetii during infection of human THP-1 macrophages. Four of the Dot/Icm substrates, termed Coxiella vacuolar protein B (CvpB), CvpC, CvpD, and CvpE, labeled the PV membrane and LAMP1-positive vesicles when ectopically expressed as fluorescently tagged fusion proteins. C. burnetii Delta cvpB, Delta cvpC, Delta cvpD, and Delta cvpE mutants exhibited significant defects in intracellular replication and PV formation. Genetic complementation of the Delta cvpD and Delta cvpE mutants rescued intracellular growth and PV generation, whereas the growth of C. burnetii Delta cvpB and Delta cvpC was rescued upon cohabitation with wild-type bacteria in a common PV. Collectively, these data indicate C. burnetii encodes multiple effector proteins that target the PV membrane and benefit pathogen replication in human macrophages. C1 [Larson, Charles L.; Beare, Paul A.; Howe, Dale; Cockrell, Diane C.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT USA. [Voth, Daniel E.] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. [Bastidas, Robert J.; Valdivia, Raphael H.] Duke Univ, Ctr Microbial Pathogenesis, Dept Mol Genet & Microbiol, Durham, NC USA. RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT USA. EM rheinzen@niaid.nih.gov FU NIH NIAID grants [AI072485, R01AI087669]; Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This study was supported by funding from NIH NIAID grants AI072485 (R.H.V.) and R01AI087669 (D.E.V.) and by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (R.A.H.). NR 63 TC 24 Z9 24 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2015 VL 83 IS 2 BP 661 EP 670 DI 10.1128/IAI.02763-14 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AZ0ST UT WOS:000347955700021 PM 25422265 ER PT J AU Khazanov, GK Cui, LH Merikangas, KR Angst, J AF Khazanov, Gabriela Kattan Cui, Lihong Merikangas, Kathleen Ries Angst, Jules TI Treatment Patterns of Youth with Bipolar Disorder: Results from the National Comorbidity Survey-Adolescent Supplement (NCS-A) SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE Epidemiology; Bipolar; Adolescents; Services; Treatment ID MENTAL-HEALTH-SERVICES; CHILDREN; DIAGNOSIS; PREVALENCE; WORLD; COMMUNITY; EPISODES; DESIGN; SAMPLE; MOOD AB Despite growing evidence that bipolar disorder often emerges in adolescence, there are limited data regarding treatment patterns of youth with bipolar disorder in community samples. Our objective was to present the prevalence and clinical correlates of treatment utilization for a nationally representative sample of US adolescents with bipolar disorder. Analyses are based on data from the National Comorbidity Survey-Adolescent Supplement, a face-to-face survey of 10,123 adolescents (ages 13-18) identified in household and school settings. We found that of adolescents meeting DSM-IV criteria for bipolar I or II disorder (N = 250), 49 % were treated for depression or mania, 13 % were treated for conditions other than depression or mania, and 38 % did not report receiving treatment. Treatment for depression or mania was associated with increased rates of suicide attempts, as well as greater role disability and more comorbid alcohol use relative to those who had not received treatment. Treated adolescents had triple the rate of ADHD and double the rates of behavior disorders than those without treatment. Our findings demonstrate that a substantial proportion of youth with bipolar disorder do not receive treatment, and of those who do, many receive treatment for comorbid conditions rather than for their mood-related symptoms. Treatment was more common among youth with severe manifestations and consequences of bipolar disorder and those with behavior problems. These trends highlight the need to identify barriers to treatment for adolescents with bipolar disorder and demonstrate that those in treatment are not representative of youth with bipolar disorder in the general population. C1 [Khazanov, Gabriela Kattan; Cui, Lihong; Merikangas, Kathleen Ries] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA. [Angst, Jules] Univ Zurich, Hosp Psychiat, Zurich, Switzerland. RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, Bldg 35A,Rm 2E410,35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM merikank@mail.nih.gov FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH002808-08, U01-MH60220] NR 40 TC 2 Z9 2 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 EI 1573-2835 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD FEB PY 2015 VL 43 IS 2 BP 391 EP 400 DI 10.1007/s10802-014-9885-6 PG 10 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA AZ7UC UT WOS:000348422100015 PM 24958307 ER PT J AU Geers, AL Fowler, SL Wellman, JA Helfer, SG Close, S France, CR AF Geers, Andrew L. Fowler, Stephanie L. Wellman, Justin A. Helfer, Suzanne G. Close, Shane France, Christopher R. TI Prior experience with a pain stimulus as a predictor of placebo analgesia SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Pain; Placebo; Analgesia; Prior experience; Expectation; Cold pressor ID IRRITABLE-BOWEL-SYNDROME; DISPOSITIONAL OPTIMISM; ACCURATE EXPECTATIONS; BRAIN ACTIVITY; MECHANISMS; ANTICIPATION; ASSIMILATION; PERSEVERANCE; COMPONENTS; REDUCTION AB Placebo effects are important in pain reduction, but the effects are inconsistent. Prior experience with a pain stimulus may moderate placebo analgesia. The current study tests the effect of prior experience with a pain stimulus on placebo analgesia during a laboratory pain task. Healthy normotensive undergraduates (66 women, 68 men) who either did or did not report prior experience with pain from submerging a limb in cold water were enrolled. In the laboratory, an experimenter applied an inert, medicinal-smelling cream to participants' non-dominant hand. Participants randomized to the no-expectation group were told that the cream was a hand cleanser. Participants randomized to the placebo expectation group were told that the cream would reduce the pain associated with the cold pressor task. Participants then completed the cold pressor task and reported their pain on the short form of the McGill Pain Questionnaire. Analysis of variance revealed a main effect of expectation (p < .05), such that participants in the placebo expectation group reported less pain. An interaction was also found between expectation and prior experience (p < .05), such that participants with prior experience with pain from cold water immersion showed no difference in pain reports between expectation groups. In a pain context, prior experience with the pain stimulus may prevent a placebo expectation from reducing the experience of pain. C1 [Geers, Andrew L.; Close, Shane] Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. [Fowler, Stephanie L.] NCI, Bethesda, MD 20892 USA. [Wellman, Justin A.] Hartwick Coll, Oneonta, NY 13820 USA. [Helfer, Suzanne G.] Adrian Coll, Adrian, MI USA. [France, Christopher R.] Ohio Univ, Athens, OH 45701 USA. RP Geers, AL (reprint author), Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. EM ageers@utnet.utoledo.edu FU NINDS NIH HHS [R03 NS051687] NR 33 TC 3 Z9 3 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 EI 1573-3521 J9 J BEHAV MED JI J. Behav. Med. PD FEB PY 2015 VL 38 IS 1 BP 136 EP 142 DI 10.1007/s10865-014-9586-1 PG 7 WC Psychology, Clinical SC Psychology GA AZ4JM UT WOS:000348187300014 PM 25056444 ER PT J AU Betts, K Abusleme, L Freeman, AF Sarmadi, M Fahle, G Pittaluga, S Cuellar-Rodriguez, J Hickstein, D Holland, SM Su, H Moutsopoulos, NM AF Betts, K. Abusleme, L. Freeman, A. F. Sarmadi, M. Fahle, G. Pittaluga, S. Cuellar-Rodriguez, J. Hickstein, D. Holland, S. M. Su, H. Moutsopoulos, N. M. TI A 17-year old patient with DOCK8 deficiency, severe oral HSV-1 and aggressive periodontitis - A case of virally induced periodontitis? SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE DOCK8 deficiency; Oral HSV-1; Aggressive periodontitis ID PORPHYROMONAS-GINGIVALIS; HERPESVIRUSES; INFLAMMATION AB We present a 17-year old girl with DOCK-8 deficiency, severe untreated oral HSV-1 infection and associated aggressive periodontitis. DOCK-8 deficiency is a primary immunodeficiency, caused by biallelicloss-of-function mutations in the DOCK8 gene, often leading to severe viral and fungal mucocutaneous infections. Nevertheless, to date DOCK8 has not been associated with severe periodontitis and inflammatory bone loss around teeth. Understanding whether DOCK8 deficiency or severe HSV-1 infection underlies susceptibility to periodontitis is central to this case and may provide insights into susceptibility factors for periodontitis in the general population. Our clinical and microbiological data suggest that severe HSV-1 infection is the driver of periodontal inflammation in this case. Published by Elsevier B.V. C1 [Betts, K.; Abusleme, L.; Sarmadi, M.; Moutsopoulos, N. M.] NIDCR, Oral Immun & Inflammat Unit, OPCB, NIH, Bethesda, MD USA. [Freeman, A. F.; Cuellar-Rodriguez, J.; Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD USA. [Fahle, G.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD USA. [Pittaluga, S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hickstein, D.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Su, H.] NIAID, Host Def Lab, NIH, Bethesda, MD USA. RP Moutsopoulos, NM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Immun & Inflammat Unit, Oral & Pharyngeal Canc Branch, NIH, BL 30,Room 327,30 Convent Dr, Bethesda, MD 20892 USA. EM nmoutsop@mail.nih.gov RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 FU NIH, National Institute of Dental and Craniofacial Research (NIDCR); NIH, National Institute of Allergy and Infectious Diseases (NIAID) FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research (NIDCR) and National Institute of Allergy and Infectious Diseases (NIAID). NR 17 TC 1 Z9 2 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 EI 1873-5967 J9 J CLIN VIROL JI J. Clin. Virol. PD FEB PY 2015 VL 63 BP 46 EP 50 DI 10.1016/j.jcv.2014.12.003 PG 5 WC Virology SC Virology GA AZ2BT UT WOS:000348040300010 PM 25600604 ER PT J AU Werner-Lin, A Ratner, R Hoskins, LM Lieber, C AF Werner-Lin, Allison Ratner, Rachel Hoskins, Lindsey M. Lieber, Caroline TI A Survey of Genetic Counselors About the Needs of 18-25 Year Olds from Families with Hereditary Breast and Ovarian Cancer Syndrome SO JOURNAL OF GENETIC COUNSELING LA English DT Article DE Genetic counseling; Hereditary cancer syndromes; Hereditary breast and ovarian cancer; Medical education; Human development; Family communication ID BRCA MUTATIONS; RISK; PREVENTION; TAMOXIFEN; WOMEN; TEENS AB As a result of modern treatments, the life of women who test positive for BRCA mutations may be plotted along the arc of preventive medicine rather than the slope of diagnostics. Despite evidence supporting the benefits of risk reduction, protocols for early detection and prevention among women from families affected by hereditary breast and ovarian cancer (HBOC) are not yet proven, and clinical trials have not been undertaken for patients aged 18 to 25. The absence of psychosocial data may leave genetic counselors without uniform guidance on how to manage the care of these patients. This project sought to investigate perspectives on counseling 18-25 year-old patients from families with hereditary cancer syndromes, with specific emphasis on HBOC, given their unique developmental, familial, and medical challenges. Certified genetic counselors were recruited through the NSGC's Cancer Genetics Special Interest Group listserv. Researchers constructed an online survey which included 41 items and elicited information about: counselor demographics, training, and practice settings; approaches to cancer risk assessment; and common challenges in work with 18- to 25-year-old patients. The survey was also informed by previous work by researchers with 18 to 25-year-olds with BRCA gene mutations. Eighty-six surveys were completed. Researchers used a combination of grounded theory and content analysis for open-ended responses, supported and triangulated with statistical analysis to maximize the interpretation of data. Genetic counselors who responded to this survey experience 18-25 year old patients presenting for cancer risk assessment differently than older patients, and some reported adapting their counseling style to address these differences. Respondents differed in the extent to which they felt well-versed in the developmental needs of patients in this age group. Respondents aged 39 and under reported feeling familiar with this stage in life, having more recently completed it; respondents aged 40 and over reported they were less familiar with, and more interested in learning about, this age group. A primary challenge in cancer risk assessment of these patients, reported primarily by counselors aged 39 and under, is navigating family dynamics in counseling sessions and addressing the developmentally labile young adult. With respect to BRCA-related cancer risk, where penetrance is incomplete, onset in early adulthood is rare. Evidence-based treatment/prevention options exist, but providers may not have clarity regarding how or when to provide directive counsel. A rich understanding of the themes inherent in how people grow and change over time might enhance the counselor's capacity to assess patients and their family members. The integration of a developmental approach to genetic counseling has the potential to reduce the imperative for non-directive counseling. C1 [Werner-Lin, Allison] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Ratner, Rachel; Lieber, Caroline] Sarah Lawrence Coll, Bronxville, NY 10708 USA. [Hoskins, Lindsey M.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Werner-Lin, A (reprint author), Univ Penn, Sch Social Policy & Practice, 3701 Locust Walk, Philadelphia, PA 19104 USA. EM awer@sp2.upenn.edu NR 37 TC 1 Z9 1 U1 1 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1059-7700 EI 1573-3599 J9 J GENET COUNS JI J. Genet. Couns. PD FEB PY 2015 VL 24 IS 1 BP 78 EP 87 DI 10.1007/s10897-014-9739-y PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AZ3MG UT WOS:000348131000009 PM 25011978 ER PT J AU Zinocker, S Schindler, CE Skinner, J Rogosch, T Waisberg, M Schickel, JN Meffre, E Kayentao, K Ongoiba, A Traore, B Pierce, SK AF Zinoecker, Severin Schindler, Christine E. Skinner, Jeff Rogosch, Tobias Waisberg, Michael Schickel, Jean-Nicolas Meffre, Eric Kayentao, Kassoum Ongoieba, Aiessata Traore, Boubacar Pierce, Susan K. TI The V Gene Repertoires of Classical and Atypical Memory B Cells in Malaria-Susceptible West African Children SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PLASMODIUM-FALCIPARUM; ACQUIRED-IMMUNITY; ENDEMIC AREA; ANTIBODIES; INDIVIDUALS; RESPONSES; INFECTION; EXHAUSTION; POPULATION; EXPRESSION AB Immunity to Plasmodium falciparum malaria is naturally acquired in individuals living in malaria-endemic areas of Africa. Abs play a key role in mediating this immunity; however, the acquisition of the components of Ab immunity, long-lived plasma cells and memory B cells (MBCs), is remarkably inefficient, requiring years of malaria exposure. Although long-lived classical MBCs (CD19(+)/CD20(+)/CD21(+)/CD27(+)/CD10(-)) are gradually acquired in response to natural infection, exposure to P. falciparum also results in a large expansion of what we have termed atypical MBCs (CD19(+)/CD20(+)/CD21(-)/CD27(-)/CD10(-)). At present, the function of atypical MBCs in malaria is not known, nor are the factors that drive their differentiation. To gain insight into the relationship between classical and atypical IgG(+) MBCs, we compared the Ab H and L chain V gene repertoires of children living in a malaria-endemic region in Mali. We found that these repertoires were remarkably similar by a variety of criteria, including V gene usage, rate of somatic hypermutation, and CDR-H3 length and composition. The similarity in these repertoires suggests that classical MBCs and atypical MBCs differentiate in response to similar Ag-dependent selective pressures in malaria-exposed children and that atypical MBCs do not express a unique V gene repertoire. C1 [Zinoecker, Severin; Schindler, Christine E.; Skinner, Jeff; Waisberg, Michael; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Rogosch, Tobias] Univ Marburg, Dept Pediat, Lab Neonatol & Pediat Immunol, D-35032 Marburg, Germany. [Waisberg, Michael] Univ Virginia, Dept Pathol, Sch Med, Charlottesville, VA 22908 USA. [Schickel, Jean-Nicolas; Meffre, Eric] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06510 USA. [Kayentao, Kassoum; Ongoieba, Aiessata; Traore, Boubacar] Univ Sci Tech & Technol Bamako, Mali Int Ctr Excellence Res, Bamako, Mali. RP Zinocker, S (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,MSC 8180, Rockville, MD 20852 USA. EM severin.zinocker@gmail.com; spierce@nih.gov RI Rogosch, Tobias/A-1522-2009; OI Rogosch, Tobias/0000-0002-1674-1423; Skinner, Jeff/0000-0001-5697-0442 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 47 TC 11 Z9 11 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 FEB 1 PY 2015 VL 194 IS 3 BP 929 EP 939 DI 10.4049/jimmunol.1402168 PG 11 WC Immunology SC Immunology GA AZ3NK UT WOS:000348134000013 PM 25556245 ER PT J AU Dewas, C Chen, X Honda, T Junttila, I Linton, J Udey, MC Porcella, SF Sturdevant, DE Feigenbaum, L Koo, L Williams, J Paul, WE AF Dewas, Cedric Chen, Xi Honda, Tetsuya Junttila, Ilkka Linton, Jay Udey, Mark C. Porcella, Stephen F. Sturdevant, Daniel E. Feigenbaum, Lionel Koo, Lily Williams, Joy Paul, William E. TI TSLP Expression: Analysis with a ZsGreen TSLP Reporter Mouse SO JOURNAL OF IMMUNOLOGY LA English DT Article ID THYMIC STROMAL LYMPHOPOIETIN; AIRWAY EPITHELIAL-CELLS; REGULATORY T-CELLS; DENDRITIC CELLS; CYTOKINE PRODUCTION; ATOPIC-DERMATITIS; OX40 LIGAND; INDUCE; KERATINOCYTES; DIFFERENTIATION AB Thymic stromal lymphopoietin (TSLP) is a type I cytokine that plays a central role in induction of allergic inflammatory responses. Its principal targets have been reported to be dendritic cells and/or CD4 T cells; epithelial cells are a principal source. We report in this study the development of a reporter mouse (TSLP- ZsG) in which a Zs-Green (ZsG)-encoding construct has been inserted by recombineering into a bacterial artificial chromosome immediately at the translation initiating ATG of TSLP. The expression of ZsG by mice transgenic for the recombinant BAC appears to be a faithful surrogate for TSLP expression, particularly in keratinocytes and medullary thymic epithelial cells. Limited ZsG and TSLP mRNA was observed in bone marrow-derived mast cells, basophils, and dendritic cells. Using the TSLP- ZsG reporter mouse, we show that TNF-alpha and IL-4/IL-13 are potent inducers of TSLP expression by keratinocytes and that local activation of Th2 and Th1 cells induces keratinocyte TSLP expression. We suggest that the capacity of TSLP to both induce Th2 differentiation and to be induced by activated Th2 cells raises the possibility that TSLP may be involved in a positive feedback loop to enhance allergic inflammatory conditions. C1 [Dewas, Cedric; Chen, Xi; Junttila, Ilkka; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Honda, Tetsuya] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Linton, Jay; Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Porcella, Stephen F.; Sturdevant, Daniel E.; Koo, Lily] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] NCI, Lab Anim Sci Program, NIH, Bethesda, MD 20892 USA. [Williams, Joy] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIH, Bldg 10,Room 11N311, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases Division of Intramural Research Project [Z01 AI000493-28]; Intramural Research Program, Center for Cancer Research, National Cancer Institute FX This work was supported in part by National Institute of Allergy and Infectious Diseases Division of Intramural Research Project Z01 AI000493-28 and by the Intramural Research Program, Center for Cancer Research, National Cancer Institute. NR 42 TC 5 Z9 5 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2015 VL 194 IS 3 BP 1372 EP 1380 DI 10.4049/jimmunol.1400519 PG 9 WC Immunology SC Immunology GA AZ3NK UT WOS:000348134000057 PM 25539812 ER PT J AU Kruszka, P Li, D Harr, MH Wilson, NR Swarr, D McCormick, EM Chiavacci, RM Li, M Martinez, AF Hart, RA McDonald-McGinn, DM Deardorff, MA Falk, MJ Allanson, JE Hudson, C Johnson, JP Saadi, I Hakonarson, H Muenke, M Zackai, EH AF Kruszka, Paul Li, Dong Harr, Margaret H. Wilson, Nathan R. Swarr, Daniel McCormick, Elizabeth M. Chiavacci, Rosetta M. Li, Mindy Martinez, Ariel F. Hart, Rachel A. McDonald-McGinn, Donna M. Deardorff, Matthew A. Falk, Marni J. Allanson, Judith E. Hudson, Cindy Johnson, John P. Saadi, Irfan Hakonarson, Hakon Muenke, Maximilian Zackai, Elaine H. TI Mutations in SPECC1L, encoding sperm antigen with calponin homology and coiled-coil domains 1-like, are found in some cases of autosomal dominant Opitz G/BBB syndrome SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID CONGENITAL DIAPHRAGMATIC-HERNIA; 22Q11.2 DELETION; GBBB SYNDROME; MALE TRANSMISSION; BBB-SYNDROME; XP22; GENE; MID1 AB Background Opitz G/BBB syndrome is a heterogeneous disorder characterised by variable expression of midline defects including cleft lip and palate, hypertelorism, laryngealtracheoesophageal anomalies, congenital heart defects, and hypospadias. The X-linked form of the condition has been associated with mutations in the MID1 gene on Xp22. The autosomal dominant form has been linked to chromosome 22q11.2, although the causative gene has yet to be elucidated. Methods and results In this study, we performed whole exome sequencing on DNA samples from a three-generation family with characteristics of Opitz G/BBB syndrome with negative MID1 sequencing. We identified a heterozygous missense mutation c.1189A>C (p.Thr397Pro) in SPECC1L, located at chromosome 22q11.23. Mutation screening of an additional 19 patients with features of autosomal dominant Opitz G/BBB syndrome identified a c.3247G>A (p.Gly1083Ser) mutation segregating with the phenotype in another three-generation family. Conclusions Previously, SPECC1L was shown to be required for proper facial morphogenesis with disruptions identified in two patients with oblique facial clefts. Collectively, these data demonstrate that SPECC1L mutations can cause syndromic forms of facial clefting including some cases of autosomal dominant Opitz G/BBB syndrome and support the original linkage to chromosome 22q11.2. C1 [Kruszka, Paul; Martinez, Ariel F.; Hart, Rachel A.; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Li, Dong; Chiavacci, Rosetta M.; Hakonarson, Hakon] Univ Penn, Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Li, Dong; Chiavacci, Rosetta M.; Hakonarson, Hakon] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Harr, Margaret H.; Swarr, Daniel; McCormick, Elizabeth M.; Li, Mindy; McDonald-McGinn, Donna M.; Deardorff, Matthew A.; Falk, Marni J.; Zackai, Elaine H.] Univ Penn, Childrens Hosp Philadelphia, Div Human Genet, Clin Genet Ctr, Philadelphia, PA 19104 USA. [Harr, Margaret H.; Swarr, Daniel; McCormick, Elizabeth M.; Li, Mindy; McDonald-McGinn, Donna M.; Deardorff, Matthew A.; Falk, Marni J.; Zackai, Elaine H.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Wilson, Nathan R.; Saadi, Irfan] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 USA. [Allanson, Judith E.] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. [Hudson, Cindy; Johnson, John P.] Shodair Childrens Hosp, Helena, MT USA. [Johnson, John P.] Floating Hosp Children, Tufts Med Ctr, Boston, MA USA. RP Zackai, EH (reprint author), Childrens Hosp Philadelphia, Clin Genet Ctr, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM zackai@email.chop.edu FU National Institutes of Health Kansas IDeA Network for Biomedical Research Excellence grant (National Institute of General Medical Sciences) [P20 GM103418]; Kansas Intellectual and Developmental Disabilities Research Center grant (P30 Eunice Kennedy Shriver National Institute of Child Health and Human Development) [HD 002528]; Center of Biomedical Research Excellence grant (National Institute of General Medical Sciences) [P20 GM104936]; Division of Intramural Research of the National Human Genome Research Institute, the National Institutes of Health FX This project was supported in part by the National Institutes of Health Kansas IDeA Network for Biomedical Research Excellence grant (National Institute of General Medical Sciences P20 GM103418, I.S.), Kansas Intellectual and Developmental Disabilities Research Center grant (P30 Eunice Kennedy Shriver National Institute of Child Health and Human Development, HD 002528, I.S.), and Center of Biomedical Research Excellence grant (National Institute of General Medical Sciences P20 GM104936, I.S.), the Division of Intramural Research of the National Human Genome Research Institute, the National Institutes of Health. NR 29 TC 6 Z9 7 U1 0 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD FEB PY 2015 VL 52 IS 2 BP 104 EP 110 DI 10.1136/jmedgenet-2014-102677 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AZ4PD UT WOS:000348203900005 PM 25412741 ER PT J AU Raskolnikov, D Rais-Bahrami, S George, AK Turkbey, B Shakir, NA Okoro, C Rothwax, JT Walton-Diaz, A Siddiqui, MM Su, D Stamatakis, L Yan, PK Kruecker, J Xu, S Merino, MJ Choyke, PL Wood, BJ Pinto, PA AF Raskolnikov, Dima Rais-Bahrami, Soroush George, Arvin K. Turkbey, Baris Shakir, Nabeel A. Okoro, Chinonyerem Rothwax, Jason T. Walton-Diaz, Annerleim Siddiqui, M. Minhaj Su, Daniel Stamatakis, Lambros Yan, Pingkun Kruecker, Jochen Xu, Sheng Merino, Maria J. Choyke, Peter L. Wood, Bradford J. Pinto, Peter A. TI The Role of Image Guided Biopsy Targeting in Patients with Atypical Small Acinar Proliferation SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; image guided biopsy; ultrasound; high-intensity focused; transrectal; magnetic resonance imaging ID PROSTATIC INTRAEPITHELIAL NEOPLASIA; TRANSRECTAL ULTRASOUND BIOPSY; ACTIVE SURVEILLANCE; CANCER-DETECTION; FUSION AB Purpose: Men diagnosed with atypical small acinar proliferation are counseled to undergo early rebiopsy because the risk of prostate cancer is high. However, random rebiopsies may not resample areas of concern. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy offers an opportunity to accurately target and later retarget specific areas in the prostate. We describe the ability of magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy to detect prostate cancer in areas with an initial diagnosis of atypical small acinar proliferation. Materials and Methods: Multiparametric magnetic resonance imaging of the prostate and magnetic resonance imaging/transrectal ultrasound fusion guided biopsy were performed in 1,028 patients from March 2007 to February 2014. Of the men 20 met the stringent study inclusion criteria, which were no prostate cancer history, index biopsy showing at least 1 core of atypical small acinar proliferation with benign glands in all remaining cores and fusion targeted rebiopsy with at least 1 targeted core directly resampling an area of the prostate that previously contained atypical small acinar proliferation. Results: At index biopsy median age of the 20 patients was 60 years (IQR 57-64) and median prostate specific antigen was 5.92 ng/ml (IQR 3.34-7.48). At fusion targeted rebiopsy at a median of 11.6 months 5 of 20 patients (25%, 95% CI 6.02-43.98) were diagnosed with primary Gleason grade 3, low volume prostate cancer. On fusion rebiopsy cores that directly retargeted areas of previous atypical small acinar proliferation detected the highest tumor burden. Conclusions: When magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detects isolated atypical small acinar proliferation on index biopsy, early rebiopsy is unlikely to detect clinically significant prostate cancer. Cores that retarget areas of previous atypical small acinar proliferation are more effective than random rebiopsy cores. C1 [Raskolnikov, Dima; Rais-Bahrami, Soroush; George, Arvin K.; Shakir, Nabeel A.; Okoro, Chinonyerem; Rothwax, Jason T.; Walton-Diaz, Annerleim; Siddiqui, M. Minhaj; Su, Daniel; Stamatakis, Lambros; Wood, Bradford J.; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Xu, Sheng; Wood, Bradford J.; Pinto, Peter A.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA. [Xu, Sheng; Wood, Bradford J.; Pinto, Peter A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Yan, Pingkun; Kruecker, Jochen] Philips Res North Amer, Briarcliff Manor, NY USA. RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210,Bldg 10,CRC Room 2W-5940, Bethesda, MD 20892 USA. EM pintop@mail.nih.gov OI Shakir, Nabeel/0000-0002-9066-3670; Siddiqui, Mohummad/0000-0002-4484-6820; Rais-Bahrami, Soroush/0000-0001-9466-9925 FU NIH, National Cancer Institute, Center for Cancer Research; NIH, National Cancer Institute, Center for Interventional Oncology; National Institutes of Health Medical Research Scholars Program; NIH; Howard Hughes Medical Institute FX Supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and the Center for Interventional Oncology, and the National Institutes of Health Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc., The Doris Duke Charitable Foundation, The Alexandria Real Estate Equities, Inc. and Mr. and Mrs. Joel S. Marcus, and the Howard Hughes Medical Institute, and other private donors (complete list of donors available at http://fnih.org/work/education-training-0/medical-research-scholars-prog ram). NIH and Philips Healthcare have a cooperative research and development agreement. NIH and Philips share intellectual property in the field. NR 21 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD FEB PY 2015 VL 193 IS 2 BP 473 EP 478 DI 10.1016/j.juro.2014.08.083 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AY6YZ UT WOS:000347709800023 PM 25150645 ER PT J AU An, L Li, SZ Murdoch, JB Araneta, MF Johnson, C Shen, J AF An, Li Li, Shizhe Murdoch, James B. Araneta, Maria Ferraris Johnson, Christopher Shen, Jun TI Detection of Glutamate, Glutamine, and Glutathione by Radiofrequency Suppression and Echo Time Optimization at 7 Tesla SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE glutamate; glutamine; glutathione; J-suppression; TE-optimization ID MAGNETIC-RESONANCE-SPECTROSCOPY; HUMAN BRAIN; IN-VIVO; ANTERIOR CINGULATE; N-ACETYLASPARTATE; NMR-SPECTROSCOPY; METABOLITES; MRS; DEPRESSION; GLUCOSE AB PurposeTo achieve detection of glutamate (Glu), glutamine (Gln), and glutathione (GSH) by minimizing the N-acetyl-aspartate (NAA) multiplet signals at 2.49 ppm using a echo time (TE) -optimized PRESS pulse sequence and a novel J-suppression radiofrequency pulse. MethodsUsing density matrix simulations, a PRESS sequence with (TE1, TE2)=(69, 37) ms and an inserted 90 degrees J-suppression pulse were found to minimize the NAA multiplet at 2.49 ppm. ResultsNAA phantom experiments confirmed the successful suppression of the NAA multiplet at 2.49 ppm. A study of eight healthy volunteers found both Glu and Gln to be significantly higher in gray matter (GM) dominant medial prefrontal cortex voxels than in white matter (WM) dominant right frontal cortex voxels. Time-course H-1 spectra acquired during intravenous [U-C-13(6)]glucose infusion showed gradually changing Glu C4 and Gln C4 proton resonance signals in a spectral pattern predicted by numerical simulations. ConclusionReliable detection of Glu, Gln, and GSH was achieved. Glu and Gln levels were significantly higher in frontal lobe GM than in frontal lobe WM. It is feasible to use the proposed proton MR spectroscopy method to measure the kinetics of C-13 incorporation into Glu and Gln during infusion of C-13 labeled glucose. Magn Reson Med 73:451-458, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [An, Li; Li, Shizhe; Araneta, Maria Ferraris; Johnson, Christopher; Shen, Jun] NIMH, NIH, Bethesda, MD 20892 USA. [Murdoch, James B.] Toshiba Med Res Inst USA, Mayfield Village, OH USA. RP An, L (reprint author), Bldg 10,Room 3D46,10 Ctr Dr,MSC 1216, Bethesda, MD 20892 USA. EM li.an@nih.gov FU NIH; NIMH FX This work was supported by the intramural programs of the NIH and NIMH. NR 29 TC 5 Z9 5 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 2015 VL 73 IS 2 BP 451 EP 458 DI 10.1002/mrm.25150 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ3PO UT WOS:000348139500002 PM 24585452 ER PT J AU Gai, ND Rochitte, C Nacif, MS Bluemke, DA AF Gai, Neville D. Rochitte, Carlos Nacif, Marcelo S. Bluemke, David A. TI Optimized Three-Dimensional Sodium Imaging of the Human Heart on a Clinical 3T Scanner SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE sodium MRI; heart; 3D imaging ID MYOCARDIAL-INFARCTION; MAGNETIC-RESONANCE; PROJECTION TECHNIQUE; RELAXATION-TIMES; SKELETAL-MUSCLE; HUMAN BRAIN; ECHO TIMES; MRI; SIGNAL; INTENSITY AB PurposeOptimization of sequence and sequence parameters to allow three-dimensional (3D) sodium imaging of the entire human heart in vivo in a clinically reasonable time. Theory and MethodsA stack of spirals pulse sequence was optimized for cardiac imaging by considering factors such as spoiling, nutation angles, repetition time, echo time, T1/T2 relaxation, off-resonance, data acquisition window, motion, and segmented k-space acquisition. Simulations based on Bloch equations as well as the exact trajectory used for data acquisition provided the basis for choice of parameter combinations for sodium imaging. Sodium phantom scanning was used to validate the choice of parameters and for corroboration with simulations. In vivo cardiac imaging in six volunteers was also performed with an optimized sequence. ResultsPhantom studies showed good correlation with simulation results. Images obtained from human volunteers showed that the heart can be imaged with a nominal resolution of 5 x 5 x 10 mm(3) and with a signal-to-noise ratio >15 (in the septum) in about 6-10 minutes. Long axis views of the reformatted human heart show true 3D imaging capability. ConclusionOptimization of the sequence and its parameters allowed in vivo 3D sodium imaging of the entire human heart in a clinically reasonable time. Magn Reson Med 73:623-632, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Gai, Neville D.; Bluemke, David A.] NIH, Bethesda, MD 20892 USA. [Rochitte, Carlos] Univ Sao Paulo, Sch Med, Inst Heart, InCor, Sao Paulo, Brazil. [Rochitte, Carlos] HCOR Hosp Coracao, Sao Paulo, Brazil. [Nacif, Marcelo S.] Univ Fed Fluminense, Sch Med, Rio De Janeiro, Brazil. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA. RP Gai, ND (reprint author), NIH, Radiol & Imaging Sci RAD&IS, Ctr Clin, 9000 Rockville Pike,Bldg 10, Bethesda, MD 20892 USA. EM gaind@cc.nih.gov OI Bluemke, David/0000-0002-8323-8086 FU NIH Clinical Center FX We thank Yuxi Pang, Christian Stehning, and Michael Schar of Philips Medical Systems and Marco Irkens of Rapid Biomedical for initial help with the coil. This work was supported by the intramural research program of the NIH Clinical Center. NR 42 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 2015 VL 73 IS 2 BP 623 EP 632 DI 10.1002/mrm.25175 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ3PO UT WOS:000348139500019 PM 24639022 ER PT J AU Ritchie, MD Holzinger, ER Li, RW Pendergrass, SA Kim, D AF Ritchie, Marylyn D. Holzinger, Emily R. Li, Ruowang Pendergrass, Sarah A. Kim, Dokyoon TI Methods of integrating data to uncover genotype-phenotype interactions SO NATURE REVIEWS GENETICS LA English DT Review ID GENOME-WIDE ASSOCIATION; BREAST-CANCER RISK; ALLELE-SPECIFIC EXPRESSION; EVOLUTION NEURAL-NETWORK; GENETIC-VARIANTS; EXPERIMENTAL VALIDATION; INDUCED CYTOTOXICITY; FUNCTIONAL VARIATION; PROTEIN EXPRESSION; CLINICAL-OUTCOMES AB Recent technological advances have expanded the breadth of available omic data, from whole-genome sequencing data, to extensive transcriptomic, methylomic and metabolomic data. A key goal of analyses of these data is the identification of effective models that predict phenotypic traits and outcomes, elucidating important biomarkers and generating important insights into the genetic underpinnings of the heritability of complex traits. There is still a need for powerful and advanced analysis strategies to fully harness the utility of these comprehensive high-throughput data, identifying true associations and reducing the number of false associations. In this Review, we explore the emerging approaches for data integration-including meta-dimensional and multi-staged analyses-which aim to deepen our understanding of the role of genetics and genomics in complex outcomes. With the use and further development of these approaches, an improved understanding of the relationship between genomic variation and human phenotypes may be revealed. C1 [Ritchie, Marylyn D.; Li, Ruowang; Pendergrass, Sarah A.; Kim, Dokyoon] Penn State Univ, Dept Biochem & Mol Biol, Ctr Syst Genom, University Pk, PA 16802 USA. [Holzinger, Emily R.] NHGRI, Inherited Dis Res Branch, Baltimore, MD 21224 USA. RP Ritchie, MD (reprint author), Penn State Univ, Dept Biochem & Mol Biol, Ctr Syst Genom, University Pk, PA 16802 USA. EM marylyn.ritchie@psu.edu FU US National Institutes of Health [LM010040, HL065962]; US National Science Foundation [DGE1255832]; [Z01 HG00153-08-IDRB] FX Support for the authors was provided by the US National Institutes of Health grants LM010040 (ATHENA) and HL065962 (the P-STAR Network Resource of the PGRN). E.R.H. was funded by grant Z01 HG00153-08-IDRB. R.L. was funded by the US National Science Foundation under Grant number DGE1255832. Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the US National Science Foundation. NR 100 TC 103 Z9 108 U1 22 U2 110 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 EI 1471-0064 J9 NAT REV GENET JI Nat. Rev. Genet. PD FEB PY 2015 VL 16 IS 2 BP 85 EP 97 DI 10.1038/nrg3868 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AZ3RN UT WOS:000348144500008 PM 25582081 ER PT J AU Krupovic, M Koonin, EV AF Krupovic, Mart Koonin, Eugene V. TI Polintons: a hotbed of eukaryotic virus, transposon and plasmid evolution SO NATURE REVIEWS MICROBIOLOGY LA English DT Article ID LARGE DNA VIRUSES; COMPARATIVE GENOMICS; BACTERIOPHAGE PRD1; CAPPING APPARATUS; BACILLUS-CEREUS; GIANT VIRUSES; ORIGIN; VIROPHAGE; INSIGHTS; ELEMENTS AB Polintons (also known as Mavericks) are large DNA transposons that are widespread in the genomes of eukaryotes. We have recently shown that Polintons encode virus capsid proteins, which suggests that these transposons might form virions, at least under some conditions. In this Opinion article, we delineate the evolutionary relationships among bacterial tectiviruses, Polintons, adenoviruses, virophages, large and giant DNA viruses of eukaryotes of the proposed order 'Megavirales', and linear mitochondrial and cytoplasmic plasmids. We hypothesize that Polintons were the first group of eukaryotic double-stranded DNA viruses to evolve from bacteriophages and that they gave rise to most large DNA viruses of eukaryotes and various other selfish genetic elements. C1 [Krupovic, Mart] Mol Gene Chez Extremophiles, Dept Microbiol, F-75015 Paris, France. [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Krupovic, M (reprint author), Mol Gene Chez Extremophiles, Dept Microbiol, 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 FU US Department of Health and Human Services FX E.V.K. is supported by the intramural funds of the US Department of Health and Human Services (to the National Library of Medicine). NR 77 TC 28 Z9 28 U1 3 U2 35 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 EI 1740-1534 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD FEB PY 2015 VL 13 IS 2 BP 105 EP 115 DI 10.1038/nrmicro3389 PG 11 WC Microbiology SC Microbiology GA AZ3RQ UT WOS:000348144800010 PM 25534808 ER PT J AU Fowler, JS Logan, J Volkow, ND Shumay, E McCall-Perez, F Jayne, M Wang, GJ Alexoff, DL Apelskog-Torees, K Hubbard, B Carter, P King, P Fahn, S Gilmor, M Telang, F Shea, C Xu, YW Muench, L AF Fowler, Joanna S. Logan, Jean Volkow, Nora D. Shumay, Elena McCall-Perez, Fred Jayne, Millard Wang, Gene-Jack Alexoff, David L. Apelskog-Torees, Karen Hubbard, Barbara Carter, Pauline King, Payton Fahn, Stanley Gilmor, Michelle Telang, Frank Shea, Colleen Xu, Youwen Muench, Lisa TI Evidence that Formulations of the Selective MAO-B Inhibitor, Selegiline, which Bypass First-Pass Metabolism, also Inhibit MAO-A in the Human Brain SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID TYRAMINE PRESSOR SENSITIVITY; MONOAMINE-OXIDASE INHIBITORS; MAJOR DEPRESSIVE DISORDER; HIGH-DOSE SELEGILINE; TRANSDERMAL SYSTEM; L-DEPRENYL; DOPAMINE TRANSPORTER; DOUBLE-BLIND; HEALTHY-SUBJECTS; EFFICACY AB Selegiline (L-deprenyl) is a selective, irreversible inhibitor of monoamine oxidase B (MAO-B) at the conventional dose (10 mg/day oral) that is used in the treatment of Parkinson's disease. However, controlled studies have demonstrated antidepressant activity for high doses of oral selegiline and for transdermal selegiline suggesting that when plasma levels of selegiline are elevated, brain MAO-A might also be inhibited. Zydis selegiline (Zelapar) is an orally disintegrating formulation of selegiline, which is absorbed through the buccal mucosa producing higher plasma levels of selegiline and reduced amphetamine metabolites compared with equal doses of conventional selegiline. Although there is indirect evidence that Zydis selegiline at high doses loses its selectivity for MAO-B, there is no direct evidence that it also inhibits brain MAO-A in humans. We measured brain MAO-A in 18 healthy men after a 28-day treatment with Zydis selegiline (2.5, 5.0, or I 0 mg/day) and in 3 subjects receiving the selegiline transdermal system (Emsam patch, 6 mg/day) using positron emission tomography and the MAO-A radiotracer [C-11]clorgyline. We also measured dopamine transporter (DAT) availability in three subjects from the 10 mg group. The I 0 mg Zydis selegiline dose significantly inhibited MAO-A (36.9 +/- 19.7%, range 11-70%, p<0.007)) but not DAT; and while Emsam also inhibited MAO-A (33.2 +/- 28.9 (range 9-68%) the difference did not reach significance (p=0.10)) presumably because of the small sample size. Our results provide the first direct evidence of brain MAO-A inhibition in humans by formulations of selegiline, which are currently postulated but not verified to target brain MAO-A in addition to MAO-B. C1 [Fowler, Joanna S.; Alexoff, David L.; Hubbard, Barbara; Carter, Pauline; King, Payton; Shea, Colleen; Xu, Youwen] Brookhaven Natl Lab, Biol Environm & Climate Sci Dept, Upton, NY 11973 USA. [Logan, Jean] NYU, Dept Radiol, Langone Med Ctr, New York, NY 10016 USA. [Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA. [Volkow, Nora D.; Shumay, Elena; Jayne, Millard; Wang, Gene-Jack; Apelskog-Torees, Karen; Telang, Frank; Muench, Lisa] NIAAA, NIH, Bethesda, MD USA. [McCall-Perez, Fred] Targeted Med Pharma Inc, Los Angeles, CA USA. [Fahn, Stanley] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Gilmor, Michelle] Novartis Pharmaceut, E Hanover, NJ USA. RP Fowler, JS (reprint author), Brookhaven Natl Lab, Dept Biosci, Bldg 555, Upton, NY 11973 USA. EM fowler@bnl.gov OI Logan, Jean/0000-0002-6993-9994 FU Valeant Pharmaceuticals International FX This study was funded by Valeant Pharmaceuticals International. The authors disclose no other conflict of interest that might potentially bias this work. NR 45 TC 10 Z9 11 U1 5 U2 24 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 FEB PY 2015 VL 40 IS 3 BP 650 EP 657 DI 10.1038/npp.2014.214 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AY6ET UT WOS:000347660900013 PM 25249059 ER PT J AU Shaw, P Sudre, G Wharton, A Weingart, D Sharp, W Sarlls, J AF Shaw, Philip Sudre, Gustavo Wharton, Amy Weingart, Daniel Sharp, Wendy Sarlls, Joelle TI White Matter Microstructure and the Variable Adult Outcome of Childhood Attention Deficit Hyperactivity Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID 33-YEAR FOLLOW-UP; DEFICIT/HYPERACTIVITY DISORDER; DIFFUSION-TENSOR; RADIAL DIFFUSIVITY; CORPUS-CALLOSUM; REACTION-TIME; MOUSE-BRAIN; ADHD; GRAY; CONNECTIVITY AB Changes in cerebral cortical anatomy have been tied to the clinical course of attention deficit hyperactivity disorder (ADHD). We now ask if alterations in white matter tract microstructure are likewise linked with the adult outcome of childhood ADHD. Seventy-five young adults, 32 with ADHD persisting from childhood and 43 with symptom remission were contrasted against 74 never-affected comparison subjects. Using diffusion tensor imaging, we defined fractional anisotropy, a metric related to white matter microstructure, along with measures of diffusion perpendicular (radial) and parallel (axial) to the axon. Analyses were adjusted for head motion, age and sex, and controlled for multiple comparisons and medication history. Tract-based analyses showed that greater adult inattention, but not hyperactivity-impulsivity, was associated with significantly lower fractional anisotropy in the left uncinate (standardized beta = -0.37, t=3.28, p=0.002) and inferior fronto-occipital fasciculi (standardized beta = -0.37, t=3.29, p=0.002). The ADHD group with symptoms persisting into adulthood had significantly lower fractional anisotropy than the never-affected controls in these tracts, differences associated with medium to large effect sizes. By contrast, the ADHD group that remitted by adulthood did not differ significantly from controls. The anomalies were found in tracts that connect components of neural systems pertinent to ADHD, such as attention control (inferior fronto-occipital fasciculus) and emotion regulation and the processing of reward (the uncinate fasciculus). Change in radial rather than axial diffusivity was the primary driver of this effect, suggesting pathophysiological processes including altered myelination as future targets for pharmacological and behavioral interventions. C1 [Shaw, Philip; Sudre, Gustavo; Wharton, Amy; Weingart, Daniel] NHGRI, Sect Neurobehav Clin Res, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Shaw, Philip; Sharp, Wendy] NIMH, Intramural Program, Bethesda, MD 20892 USA. [Sarlls, Joelle] NINDS, NIH MRI Res Facil, NIH, Bethesda, MD 20892 USA. RP Shaw, P (reprint author), NHGRI, Sect Neurobehav Clin Res, Social & Behav Res Branch, 9000 Rockville,Bldg 31,B1 B37, Bethesda, MD 20892 USA. EM shawp@mail.nih.gov FU Intramural NIH HHS NR 58 TC 8 Z9 8 U1 4 U2 9 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 FEB PY 2015 VL 40 IS 3 BP 746 EP 754 DI 10.1038/npp.2014.241 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AY6ET UT WOS:000347660900023 PM 25241803 ER PT J AU Wang, Z Wang, Y Wang, ZY Gutkind, JS Wang, ZL Wang, F Lu, J Niu, G Teng, GJ Chen, XY AF Wang, Zhe Wang, Yu Wang, Zhiyong Gutkind, J. Silvio Wang, Zhongliang Wang, Fu Lu, Jie Niu, Gang Teng, Gaojun Chen, Xiaoyuan TI Engineered Mesenchymal Stem Cells with Enhanced Tropism and Paracrine Secretion of Cytokines and Growth Factors to Treat Traumatic Brain Injury SO STEM CELLS LA English DT Article DE Mesenchymal stem cell; CXC chemokine receptor 4; Traumatic brain injury; Imaging; Angiogenesis; Neuron ID MARROW STROMAL CELLS; ANTICANCER ACTIVITIES; TISSUE REGENERATION; DELIVERY-SYSTEM; TNF-ALPHA; BONE; MIGRATION; MICE; ENGRAFTMENT; APOPTOSIS AB Traumatic brain injury (TBI) is the leading cause of death and disability worldwide. Mesenchymal stem cells (MSCs) are promising for the treatment of various diseases and injuries. Many strategies have been applied to attract MSCs to injury site after systemic infusion. In this study, we evidenced that the CXC chemokine receptor 4 (CXCR4)-SDF1 alpha (stromal cell-derived factor 1 alpha) axis in engineered MSCs serves not only to attract MSC migration to TBI but also to activate Akt kinase signaling pathway in MSCs to promote paracrine secretion of cytokines and growth factors. This leads to enhanced vasculogenesis and neuroprotection at the boundary of TBI for improved blood supply, recovery of axon connectivity, and behavioral ability and results in positive feedback loop to enhance additional MSC tropism to injury. These findings indicate a new aspect of SDF1 alpha in mediating CXCR4 engineered MSCs for brain trauma homing and recovery. This potential mechanism may be applicable to other injuries, where CXCR4-SDF1 alpha interaction is highly associated. C1 [Wang, Zhe; Wang, Yu; Wang, Zhongliang; Wang, Fu; Lu, Jie; Niu, Gang; Chen, Xiaoyuan] Natl Inst Hlth, Lab Mol Imaging & Nanomed, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA. [Wang, Zhiyong; Gutkind, J. Silvio] Natl Inst Hlth, Oral & Pharyngeal Canc Branch, Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. [Wang, Yu; Teng, Gaojun] Zhongda Hosp, Dept Radiol, Jiangsu Key Lab Mol & Funct Imaging, Nanjing 210009, Peoples R China. [Wang, Zhongliang; Wang, Fu] Xidian Univ, Sch Life Sci & Technol, Xian, Shaanxi, Peoples R China. RP Teng, GJ (reprint author), Zhongda Hosp, Dept Radiol, Jiangsu Key Lab Mol & Funct Imaging, Nanjing 210009, Peoples R China. EM gjteng@vip.sina.com; shawn.chen@nih.gov OI Wang, Fu/0000-0001-9222-0833 FU CNRM program at Henry M. Jackson Foundation; Intramural Research Program (IRP), NIBIB/NIH FX This work was supported, in part, by CNRM program at Henry M. Jackson Foundation, and the Intramural Research Program (IRP), NIBIB/NIH. NR 52 TC 13 Z9 14 U1 12 U2 42 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 FEB PY 2015 VL 33 IS 2 BP 456 EP 467 DI 10.1002/stem.1878 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA AZ4RW UT WOS:000348211300014 PM 25346537 ER PT J AU Guy, GP Machlin, SR Ekwueme, DU Yabroff, KR AF Guy, Gery P., Jr. Machlin, Steven R. Ekwueme, Donatus U. Yabroff, K. Robin TI Prevalence and Costs of Skin Cancer Treatment in the US, 2002-2006 and 2007-2011 SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID METAANALYSIS; MELANOMA AB Background: Skin cancer, the most common cancer in the U.S., is a major public health problem. The incidence of nonmelanoma and melanoma skin cancer is increasing; however, little is known about the economic burden of treatment. Purpose: To examine trends in the treated prevalence and treatment costs of nonmelanoma and melanoma skin cancers. Methods: This study used data on adults from the 2002-2011 Medical Expenditure Panel Survey full-year consolidated files and information from corresponding medical conditions and medical event files to estimate the treated prevalence and treatment cost of nonmelanoma skin cancer, melanoma skin cancer, and all other cancer sites. Analyses were conducted in January 2014. Results: The average annual number of adults treated for skin cancer increased from 3.4 million in 2002-2006 to 4.9 million in 2007-2011 (p<0.001). During this period, the average annual total cost for skin cancer increased from $3.6 billion to $8.1 billion (p=-0.001), representing an increase of 126.2%, while the average annual total cost for all other cancers increased by 25.1%. During 2007-2011, nearly 5 million adults were treated for skin cancer annually, with average treatment costs of $8.1 billion each year. Conclusions: These findings demonstrate that the health and economic burden of skin cancer treatment is substantial and increasing. Such findings highlight the importance of skin cancer prevention efforts, which may result in future savings to the healthcare system. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Guy, Gery P., Jr.; Ekwueme, Donatus U.] CDC, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Machlin, Steven R.] NCI, Ctr Financing Access & Cost Trends, Agcy Healthcare Res & Qual, Rockville, MD USA. [Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. RP Guy, GP (reprint author), CDC, Div Canc Prevent & Control, 4770 Buford Highway NE,MS F-76, Atlanta, GA 30341 USA. EM irm2@cdc.gov OI Yabroff, K. Robin/0000-0003-0644-5572 FU Social & Scientific Systems, Inc. FX We would like to thank Zhengyi Fang of Social & Scientific Systems, Inc. for programming support. NR 12 TC 56 Z9 57 U1 4 U2 15 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 FEB PY 2015 VL 48 IS 2 BP 183 EP 187 DI 10.1016/j.amepre.2014.08.036 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AZ2YY UT WOS:000348096300010 PM 25442229 ER PT J AU Song, JY Pittaluga, S Dunleavy, K Grant, N White, T Jiang, LY Davies-Hill, T Raffeld, M Wilson, WH Jaffe, ES AF Song, Joo Y. Pittaluga, Stefania Dunleavy, Kieron Grant, Nicole White, Therese Jiang, Liuyan Davies-Hill, Theresa Raffeld, Mark Wilson, Wyndham H. Jaffe, Elaine S. TI Lymphomatoid Granulomatosis-A Single Institute Experience Pathologic Findings and Clinical Correlations SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE lymphomatoid granulomatosis; Epstein-Barr virus; immunodeficiency; immunosurveillance; lung; lymphoproliferative disorder ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; T-CELL LEUKEMIA/LYMPHOMA; VIRUS-INFECTION; B-LYMPHOCYTES; TISSUE; MICRODISSECTION; IMMUNOGLOBULIN; PROLIFERATION; EXPRESSION; PHENOTYPE AB Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructive Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorder. It is hypothesized that these patients have dysregulated immune surveillance of EBV. We reviewed the biopsies of 55 patients with LYG who were referred for a prospective trial at the National Cancer Institute (1995 to 2010) and evaluated the histologic, immunohistochemical, in situ hybridization, and molecular findings of these biopsies in conjunction with clinical information. Grading of the lesions was based on morphologic features and the number of EBV-positive B cells. The median age was 46 years (M:F 2.2:1). Clinically, all patients had lung involvement (100%), with the next most common site being the central nervous system (38%). No patient had nodal or bone marrow disease. All patients had past EBV exposure by serology but with a low median EBV viral load. We reviewed 122 biopsies; the most common site was lung (73%), followed by skin/subcutaneous tissue (17%); other sites included kidney, nasal cavity, gastrointestinal tract, conjunctiva, liver, and adrenal gland. Histologically, the lesions showed angiocentricity, were rich in T cells, had large atypical B cells, and were positive for EBV. Grading was performed predominantly on the lung biopsy at diagnosis; they were distributed as follows: LYG grade 1 (30%), grade 2 (22%), and grade 3 (48%). Necrosis was seen in all grades, with a greater degree in high-grade lesions. Immunoglobulin gene rearrangement studies were performed, and a higher percentage of clonal rearrangements were seen in LYG grade 2 (50%) and grade 3 (69%) as compared with grade 1 (8%). LYG is a distinct entity that can usually be differentiated from other EBV-associated B-cell lymphoproliferative disorders on the basis of the combination of clinical presentation, histology, and EBV studies. Grading of these lesions is important because it dictates the treatment choice. C1 [Song, Joo Y.; Pittaluga, Stefania; Davies-Hill, Theresa; Raffeld, Mark; Jaffe, Elaine S.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Dunleavy, Kieron; Grant, Nicole; White, Therese; Wilson, Wyndham H.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Song, Joo Y.] City Hope Med Ctr, Dept Pathol & Lab Med, Duarte, CA USA. [Jiang, Liuyan] Mayo Clin, Lab Med & Pathol, Jacksonville, FL 32224 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. EM ejaffe@mail.nih.gov RI Song, Joo/E-5356-2016 OI Song, Joo/0000-0003-3497-2513 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX Supported by the intramural research program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 39 TC 10 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2015 VL 39 IS 2 BP 141 EP 156 PG 16 WC Pathology; Surgery SC Pathology; Surgery GA AZ0SP UT WOS:000347955200001 PM 25321327 ER PT J AU Laskin, WB Lasota, JP Fetsch, JF Felisiak-Golabek, A Wang, ZF Miettinen, M AF Laskin, William B. Lasota, Jerzy P. Fetsch, John F. Felisiak-Golabek, Anna Wang, Zeng-Feng Miettinen, Markku TI Intranodal Palisaded Myofibroblastoma: Another Mesenchymal Neoplasm With CTNNB1 (beta-catenin Gene) Mutations Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 18 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE intranodal palisaded myofibroblastoma; beta-catenin; cyclin D1; PCR; Sanger sequencing ID SPINDLE-CELL TUMOR; FAMILIAL ADENOMATOUS POLYPOSIS; CYCLIN D1 OVEREXPRESSION; OF-THE-LITERATURE; AMIANTHOID FIBERS; LYMPH-NODE; DESMOID TUMORS; EXPRESSION; CANCER; CARCINOMAS AB Intranodal palisaded myofibroblastoma is a benign, lymph node-based myofibroblastic tumor of unknown pathogenesis. We report the clinicopathologic, immunohistochemical, and molecular genetic features of this rare entity. The study cohort consisted of 14 men and 4 women ranging in age from 31 to 65 (mean, 47; median 49) years with tumors arising in inguinal lymph nodes (n= 15), a neck lymph node (n= 1), and undesignated lymph nodes (n= 2). Most individuals presented with a painless mass or lump. Possible trauma/injury to the inguinal region was documented in 4 cases. Tumors ranged in size from 1.0 to 4.2 (mean, 3.1; median; 3.0) cm. Microscopically, the process presented as a well-circumscribed, oftentimes pseudoencapsulated nodule (n = 17) or nodules (n = 1). Tumors consisted of a cellular proliferation of cytologically bland, spindled cells arranged in short fascicles and whorls within a finely collagenous (n = 11) or myxocollagenous (n = 7) matrix. In 12 tumors, scattered fibromatosis-like fascicles of spindled cells were noted. Histologic features characteristic of the process included nuclear palisades (n = 16 cases), collagenous bodies (n = 15), and perinuclear intracytoplasmic hyaline globules (n = 10). Mitotic activity ranged from 0 to 8 (mean, 2; median, 1) mitotic figures/50 high-powered fields with no atypical division figures identified. Immunohistochemically, all tumors tested expressed smooth muscle actin and/or muscle-specific actin (n = 5, each), and nuclear beta-catenin and cyclin D1 (n = 8, each). The latter 2 results prompted a screening for mutations in the beta-catenin gene glycogen synthase kinase-3 beta phosphorylation mutational "hotspot" region in exon 3 using polymerase chain reaction amplification and Sanger sequencing. Single nucleotide substitutions leading to missense mutations at the protein level were identified in 7 of 8 (88%) analyzed tumors and are responsible for the abnormal expression of beta-catenin and cyclin D1. These results demonstrate that mutational activation of the beta-catenin gene is likely a pivotal event in the pathogenesis of intranodal palisaded myofibroblastoma. C1 [Laskin, William B.] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA. [Lasota, Jerzy P.; Felisiak-Golabek, Anna; Wang, Zeng-Feng; Miettinen, Markku] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Fetsch, John F.] Joint Pathol Ctr, Dept Soft Tissue Pathol, Silver Spring, MD USA. RP Laskin, WB (reprint author), NW Mem Hosp, Dept Pathol, Feinberg Pavil 7-325,251 East Huron St, Chicago, IL 60012 USA. EM wbl769@northwestern.edu FU Intramural NIH HHS [ZIA BC011427-01] NR 64 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2015 VL 39 IS 2 BP 197 EP 205 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA AZ0SP UT WOS:000347955200006 PM 25025452 ER PT J AU Tomanek, RJ Yu, Q Lo, CW AF Tomanek, Robert J. Yu, Qing Lo, Cecilia W. TI Coronary Anomalies in Mice with Congenital Heart Defects SO ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY LA English DT Article DE persistent truncus arteriosus; transposition of great arteries; double outlet right ventricle; coronary arteries; vascular smooth muscle; fistula ID SMOOTH-MUSCLE DIFFERENTIATION; OF-THE-LITERATURE; NEURAL CREST; ARTERY FORMATION; GREAT-ARTERIES; PROEPICARDIAL CELLS; TRUNCUS ARTERIOSUS; CARDIAC DEFECTS; OUTFLOW TRACT; GROWTH AB Background: Coronary anomalies are frequently associated with congenital cardiac defects. Accordingly, we tested the hypothesis that the development of the tunica media of coronary arteries/arterioles is compromised in mice with cardiac defects of the outflow tract (persistent truncus arteriosus, double outlet right ventricle and transposition of the great arteries) by studying hearts of G7-9 generation mice bred from mutagenized mice caused by N-ethyl-N-nitrosourea. Mice were studied at embryonic days E16.5, E17.5, and postnatal days 1 and 11. Data were based on immunohistochemistry of serial sections. Results: In 21 of 24 mice with outflow tract defects, the development of smooth muscle in arteries and arterioles was retarded; most commonly arterioles had an incomplete layer of smooth muscle or in a few instances, lacked a tunica media. In this model, an absence of a coronary ostium occurred in only 2 mice, indicating that the mechanisms underlying the formation of coronary ostia and the recruitment and differentiation of vascular smooth muscle differ. Coronary fistulas were present in 20% and dilated vessels in 30% of the hearts with cardiac defects. Conclusions: The data suggest that vascular smooth muscle recruitment and differentiation are not necessarily linked to other coronary anomalies, such as absence of a main coronary artery or branching patterns. Anat Rec, 298:408-417, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Tomanek, Robert J.] Univ Iowa, Dept Anat & Cell Biol, Carver Coll Med, Iowa City, IA 52242 USA. [Yu, Qing; Lo, Cecilia W.] NIH, Dev Biol Lab, Bethesda, MD 20892 USA. [Lo, Cecilia W.] Univ Pittsburg, Sch Med, Dept Dev Biol, Pittsburgh, PA USA. RP Tomanek, RJ (reprint author), Univ Iowa, Dept Anat & Cell Biol, 1-402 BSB, Iowa City, IA 52242 USA. EM robert-tomanek@uiowa.edu FU National Institutes of Health [HL075446] FX Grant sponsor: National Institutes of Health; Grant number: HL075446. NR 39 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-8486 EI 1932-8494 J9 ANAT REC JI Anat. Rec. PD FEB PY 2015 VL 298 IS 2 BP 408 EP 417 DI 10.1002/ar.23056 PG 10 WC Anatomy & Morphology SC Anatomy & Morphology GA AY7BN UT WOS:000347716400007 PM 25266175 ER PT J AU Ogdie, A Yu, YD Haynes, K Love, TJ Maliha, S Jiang, YH Troxel, AB Hennessy, S Kimmel, SE Margolis, DJ Choi, H Mehta, NN Gelfand, JM AF Ogdie, Alexis Yu, YiDing Haynes, Kevin Love, Thorvardur Jon Maliha, Samantha Jiang, Yihui Troxel, Andrea B. Hennessy, Sean Kimmel, Steven E. Margolis, David J. Choi, Hyon Mehta, Nehal N. Gelfand, Joel M. TI Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID HEALTH IMPROVEMENT NETWORK; MODIFYING ANTIRHEUMATIC DRUGS; PRACTICE RESEARCH DATABASE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; DANISH NATIONWIDE COHORT; MYOCARDIAL-INFARCTION; PRIMARY-CARE; VASCULAR EVENTS; DISEASE; MORTALITY AB Objectives We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis without known PsA compared with the general population after adjusting for traditional cardiovascular risk factors. Methods A population-based longitudinal cohort study from 1994 to 2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the UK. Patients aged 18-89 years of age with PsA, RA or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents and the composite outcome (MACE). Cox proportional hazards models were used to calculate the HRs for each outcome adjusted for traditional risk factors. A priori, we hypothesised an interaction between disease status and disease-modifying antirheumatic drug (DMARD) use. Results Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=81 573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in patients with PsA not prescribed a DMARD (HR 1.24, 95% CI 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95% CI 1.28 to 1.50, DMARD: HR 1.58, 95% CI 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95% CI 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95% CI 1.17 to 1.73). Conclusions Cardiovascular risk should be addressed with all patients affected by psoriasis, PsA or RA. C1 [Ogdie, Alexis] Univ Penn, Perelman Sch Med, Ctr Pharmacoepidemiol Res & Training, Div Rheumatol,Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Yu, YiDing] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Yu, YiDing] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Haynes, Kevin; Troxel, Andrea B.; Hennessy, Sean] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Ctr Pharmacoepidemiol Res & Training,Dept Biostat, Philadelphia, PA 19104 USA. [Love, Thorvardur Jon] Univ Iceland, Reykjavik, Iceland. [Maliha, Samantha] NYU, Sch Med, New York, NY USA. [Jiang, Yihui] Univ Penn, Perelman Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Kimmel, Steven E.] Univ Penn, Perelman Sch Med, Ctr Therapeut Effectiveness Res, Dept Med,Ctr Clin Epidemiol & Biostat,Ctr Pharmac, Philadelphia, PA 19104 USA. [Margolis, David J.; Gelfand, Joel M.] Univ Penn, Perelman Sch Med, Ctr Dermatoepidemiol & Translat, Dept Dermatol,Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Choi, Hyon] Boston Univ, Sch Med, Rheumatol Sect, Boston, MA 02118 USA. [Choi, Hyon] Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA 02118 USA. [Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometabol Dis, Bethesda, MD 20892 USA. [Gelfand, Joel M.] Univ Penn, Perelman Sch Med, Ctr Pharmacoepidemiol Res & Training, Dept Biostat & Epidemiol,Ctr Clin Epidemiol & Bio, Philadelphia, PA 19104 USA. RP Ogdie, A (reprint author), Univ Penn, Perelman Sch Med, Ctr Pharmacoepidemiol Res & Training, Div Rheumatol,Ctr Clin Epidemiol & Biostat, 8 Penn Tower,1 Convent Ave, Philadelphia, PA 19104 USA. EM alexis.ogdie@uphs.upenn.edu RI Love, Thorvardur/M-2987-2015; OI Ogdie, Alexis/0000-0002-4639-0775; Troxel, Andrea/0000-0002-1393-3075 FU American College of Rheumatology [R01HL089744, K24AR064310]; Clinical and Translational Science Award at the University of Pennsylvania from the National Center for Research Resources [8UL1TR000003]; American College of Rheumatology Research and Education Foundation; NIH [K23AR063764]; Doris Duke Charitable Foundation; Center for Clinical Epidemiology and Biostatistics; Icelandic Research Fund [120433021]; [R01AG025152]; [K23HL097151-01] FX This project was funded by the American College of Rheumatology (AO), R01HL089744 (JMG), K24AR064310 (JMG). Data from The Health Improvement Network is supported by the Clinical and Translational Science Award at the University of Pennsylvania (8UL1TR000003 from the National Center for Research Resources). AO was supported by the American College of Rheumatology Research and Education Foundation and is now supported by NIH K23AR063764. YY was supported by a grant from the Doris Duke Charitable Foundation and a grant from the Center for Clinical Epidemiology and Biostatistics. SH was supported by R01AG025152. TJL was supported by The Icelandic Research Fund, #120433021. NNM was supported by K23HL097151-01. This work was completed independent of the funders. NR 50 TC 62 Z9 64 U1 4 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD FEB PY 2015 VL 74 IS 2 BP 326 EP 332 DI 10.1136/annrheumdis-2014-205675 PG 7 WC Rheumatology SC Rheumatology GA AY3BA UT WOS:000347458300003 PM 25351522 ER PT J AU Tan, S Yao, JH Flynn, JA Yao, L Ward, MM AF Tan, Sovira Yao, Jianhua Flynn, John A. Yao, Lawrence Ward, Michael M. TI Quantitative syndesmophyte measurement in ankylosing spondylitis using CT: longitudinal validity and sensitivity to change over 2 years SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID ABDOMINAL COMPUTED-TOMOGRAPHY; RADIOGRAPHIC PROGRESSION; DOSE REDUCTION; BONE-FORMATION; INFLAMMATION; SPONDYLOARTHRITIS; INFLIXIMAB; SEVERITY; TESTS AB Objectives Accurate measurement of syndesmophyte development and growth in ankylosing spondylitis (AS) is needed for studies of biomarkers and of treatments to slow spinal fusion. We tested the longitudinal validity and sensitivity to change of quantitative measurement of syndesmophytes using CT. Methods We performed lumbar spine CT scans on 33 patients with AS at baseline, 1 year and 2 years. Volumes and heights of syndesmophytes were computed in four intervertebral disk spaces. We compared the computed changes to a physician's ratings of change based on CT scan inspection. Sensitivity to change of the computed measures was compared with that of the modified Stoke AS Spinal Score (radiography) and a scoring method based on MRI. Results At years 1 and 2, respectively 24 (73%) and 26 (79%) patients had syndesmophyte volume increases by CT. At years 1 and 2, the mean (SD) computed volume increases per patient were, respectively 87 (186) and 201 (366) mm(3). Computed volume changes were strongly associated with the physician's visual ratings of change (p<0.0002 and p<0.0001 for changes at years 1 and 2, respectively). The sensitivity to change over 1 year was higher for the CT volume measure (1.84) and the CT height measure (1.22) than either the MRI measure (0.50) or radiography (0.29). Conclusions CT-based syndesmophytes measurements had very good longitudinal validity and better sensitivity to change than radiography or MRI. This method shows promise for longitudinal clinical studies of syndesmophyte development and growth. C1 [Tan, Sovira; Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Yao, Jianhua; Yao, Lawrence] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Flynn, John A.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Ward, MM (reprint author), NIAMSD, NIH, CRC, Bldg 10,Room 4-1339, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health; Clinical Center, National Institutes of Health; Johns Hopkins University School of Medicine General Clinical Research Center from the National Center for Research Resources/NIH [M01-RR00052] FX This work was supported by the Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and by the Clinical Center, National Institutes of Health, and the Johns Hopkins University School of Medicine General Clinical Research Center (grant number M01-RR00052 from the National Center for Research Resources/NIH). NR 31 TC 4 Z9 4 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD FEB PY 2015 VL 74 IS 2 BP 437 EP 443 DI 10.1136/annrheumdis-2013-203946 PG 7 WC Rheumatology SC Rheumatology GA AY3BA UT WOS:000347458300019 PM 24297375 ER PT J AU Jin, TC Xiao, TS AF Jin, Tengchuan Xiao, Tsan Sam TI Activation and assembly of the inflammasomes through conserved protein domain families SO APOPTOSIS LA English DT Article DE Inflammasome; Death domain superfamily; CARD; PYD; Filament formation ID CASPASE-RECRUITMENT DOMAIN; PYRIN DOMAIN; CRYSTAL-STRUCTURE; ONLY PROTEIN; INFLAMMATORY CASPASES; NLRP3 INFLAMMASOME; INTRACELLULAR LPS; HUMAN-MONOCYTES; KAPPA-B; ASC AB Inflammasomes are oligomeric protein complexes assembled through interactions among the death domain superfamily members, in particular the CARD and PYD domains. Recent progress has shed lights on how the ASC PYD can polymerize to form filaments using multiple domain:domain interfaces, and how the caspase4 CARD can recognize LPS to activate the non-classical inflammasome pathway. Comprehensive understanding of the molecular mechanisms of inflammasome activation and assembly require more extensive structural and biophysical dissection of the inflammasome components and complexes, in particular additional CARD or PYD filaments. Because of the variations in death domain structures and complexes observed so far, future work will undoubtedly shed lights on the mechanisms of inflammasome assembly as well as more surprises on the versatile structure and function of the death domain superfamily. C1 [Jin, Tengchuan; Xiao, Tsan Sam] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Xiao, Tsan Sam] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. RP Jin, TC (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tengchuan@gmail.com; tsx@case.edu RI Xiao, Tsan/A-8590-2010; Jin, Tengchuan/B-5883-2014; OI Jin, Tengchuan/0000-0002-1395-188X; Xiao, Tsan/0000-0001-9688-475X FU Intramural NIH HHS [ZIA AI000960-04] NR 46 TC 3 Z9 3 U1 1 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 EI 1573-675X J9 APOPTOSIS JI Apoptosis PD FEB PY 2015 VL 20 IS 2 SI SI BP 151 EP 156 DI 10.1007/s10495-014-1053-5 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AZ0PQ UT WOS:000347947600004 PM 25398536 ER PT J AU Kasumba, IN Bestor, A Tilly, K Rosa, PA AF Kasumba, Irene N. Bestor, Aaron Tilly, Kit Rosa, Patricia A. TI Use of an Endogenous Plasmid Locus for Stable in trans Complementation in Borrelia burgdorferi SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; RPOS REGULATORY PATHWAY; MAMMALIAN HOST; INFECTIOUS CYCLE; CIRCULAR PLASMID; TICK VECTOR; OSPC; PROTEIN; TRANSFORMATION; REPLICATION AB Targeted mutagenesis and complementation are important tools for studying genes of unknown function in the Lyme disease spirochete Borrelia burgdorferi. A standard method of complementation is reintroduction of a wild-type copy of the targeted gene on a shuttle vector. However, shuttle vectors are present at higher copy numbers than B. burgdorferi plasmids and are potentially unstable in the absence of selection, thereby complicating analyses in the mouse-tick infectious cycle. B. burgdorferi has over 20 plasmids, with some, such as linear plasmid 25 (lp25), carrying genes required by the spirochete in vivo but relatively unstable during in vitro cultivation. We propose that complementation on an endogenous plasmid such as lp25 would overcome the copy number and in vivo stability issues of shuttle vectors. In addition, insertion of a selectable marker on lp25 could ensure its stable maintenance by spirochetes in culture. Here, we describe the construction of a multipurpose allelic-exchange vector containing a multiple-cloning site and either of two selectable markers. This suicide vector directs insertion of the complementing gene into the bbe02 locus, a site on lp25 that was previously shown to be nonessential during both in vitro and in vivo growth. We demonstrate the functional utility of this strategy by restoring infectivity to an ospC mutant through complementation at this site on lp25 and stable maintenance of the ospC gene throughout mouse infection. We conclude that this represents a convenient and widely applicable method for stable gene complementation in B. burgdorferi. C1 [Kasumba, Irene N.; Bestor, Aaron; Tilly, Kit; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Kasumba, IN (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM kasumba.irene@nih.gov FU NIAID, NIH FX This research was supported by the Intramural Research Program of the NIAID, NIH. NR 56 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 2015 VL 81 IS 3 BP 1038 EP 1046 DI 10.1128/AEM.03657-14 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA AZ0CU UT WOS:000347914800026 PM 25452278 ER PT J AU Gregg, RA Baumann, MH Partilla, JS Bonano, JS Vouga, A Tallarida, CS Velvadapu, V Smith, GR Peet, MM Reitz, AB Negus, SS Rawls, SM AF Gregg, Ryan A. Baumann, Michael H. Partilla, John S. Bonano, Julie S. Vouga, Alexandre Tallarida, Christopher S. Velvadapu, Venkata Smith, Garry R. Peet, M. Melissa Reitz, Allen B. Negus, S. Stevens Rawls, Scott M. TI Stereochemistry of mephedrone neuropharmacology: enantiomer-specific behavioural and neurochemical effects in rats SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article ID ACID AMIDE HYDROLASE; PRECIPITATED NICOTINE WITHDRAWAL; CENTRAL-NERVOUS-SYSTEM; CANNABINOID RECEPTOR; MONOACYLGLYCEROL LIPASE; NUCLEUS-ACCUMBENS; MOLECULAR CHARACTERIZATION; ENDOCANNABINOID SYSTEM; ARRIVE GUIDELINES; CONCISE GUIDE AB BACKGROUND AND PURPOSE Synthetic cathinones, commonly referred to as 'bath salts', are a group of amphetamine-like drugs gaining popularity worldwide. 4-Methylmethcathinone (mephedrone, MEPH) is the most commonly abused synthetic cathinone in the UK, and exerts its effects by acting as a substrate-type releaser at monoamine transporters. Similar to other cathinone-related compounds, MEPH has a chiral centre and exists stably as two enantiomers: R-mephedrone (R-MEPH) and S-mephedrone (S-MEPH). EXPERIMENTAL APPROACH Here, we provide the first investigation into the neurochemical and behavioural effects of R-MEPH and S-MEPH. We analysed both enantiomers in rat brain synaptosome neurotransmitter release assays and also investigated their effects on locomotor activity (e.g. ambulatory activity and repetitive movements), behavioural sensitization and reward. KEY RESULTS Both enantiomers displayed similar potency as substrates (i.e. releasers) at dopamine transporters, but R-MEPH was much less potent than S-MEPH as a substrate at 5-HT transporters. Locomotor activity was evaluated in acute and repeated administration paradigms, with R-MEPH producing greater repetitive movements than S-MEPH across multiple doses. After repeated drug exposure, only R-MEPH produced sensitization of repetitive movements. R-MEPH produced a conditioned place preference whereas S-MEPH did not. Lastly, R-MEPH and S-MEPH produced biphasic profiles in an assay of intracranial self-stimulation (ICSS), but R-MEPH produced greater ICSS facilitation than S-MEPH. CONCLUSIONS AND IMPLICATIONS Our data are the first to demonstrate stereospecific effects of MEPH enantiomers and suggest that the predominant dopaminergic actions of R-MEPH (i.e. the lack of serotonergic actions) render this stereoisomer more stimulant-like when compared with S-MEPH. This hypothesis warrants further study. C1 [Gregg, Ryan A.; Vouga, Alexandre; Tallarida, Christopher S.; Rawls, Scott M.] Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA. [Gregg, Ryan A.; Vouga, Alexandre; Tallarida, Christopher S.; Rawls, Scott M.] Temple Univ, Sch Med, Ctr Substance Abuse Res, Philadelphia, PA 19140 USA. [Baumann, Michael H.; Partilla, John S.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD USA. [Bonano, Julie S.; Negus, S. Stevens] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA. [Velvadapu, Venkata; Smith, Garry R.; Reitz, Allen B.] Fox Chase Chem Divers Ctr Inc, Doylestown, PA USA. [Peet, M. Melissa] Western Michigan Univ, Dept Psychol, Kalamazoo, MI 49008 USA. RP Gregg, RA (reprint author), Temple Univ, Sch Med, Ctr Substance Abuse Res, Dept Pharmacol, 3500 North Broad St, Philadelphia, PA 19140 USA. EM tud51613@temple.edu FU National Institute on Drug Abuse [DA025314, DA01342, DA032718, DA033930, DA037649] FX The authors would like to thank the National Institute on Drug Abuse for funding through grants DA025314, DA01342, DA032718, DA033930 and DA037649. NR 60 TC 10 Z9 10 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1188 EI 1476-5381 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD FEB PY 2015 VL 172 IS 3 BP 883 EP 894 DI 10.1111/bph.12951 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AY8EP UT WOS:000347787500012 PM 25255824 ER PT J AU Viaud, S Daillere, R Boneca, IG Lepage, P Langella, P Chamaillard, M Pittet, MJ Ghiringhelli, F Trinchieri, G Goldszmid, R Zitvogel, L AF Viaud, S. Daillere, R. Boneca, I. G. Lepage, P. Langella, P. Chamaillard, M. Pittet, M. J. Ghiringhelli, F. Trinchieri, G. Goldszmid, R. Zitvogel, L. TI Gut microbiome and anticancer immune response: really hot Sh(star)t! SO CELL DEATH AND DIFFERENTIATION LA English DT Review ID INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTORS; GERM-FREE MICE; INDUCED COLITIS; COLON TUMORIGENESIS; BETA-GLUCURONIDASE; COLORECTAL-CANCER; INNATE IMMUNITY; LUNG-CANCER AB The impact of gut microbiota in eliciting innate and adaptive immune responses beneficial for the host in the context of effective therapies against cancer has been highlighted recently. Chemotherapeutic agents, by compromising, to some extent, the intestinal integrity, increase the gut permeability and selective translocation of Gram-positive bacteria in secondary lymphoid organs. There, anticommensal pathogenic Th17 T-cell responses are primed, facilitating the accumulation of Th1 helper T cells in tumor beds after chemotherapy as well as tumor regression. Importantly, the redox equilibrium of myeloid cells contained in the tumor microenvironment is also influenced by the intestinal microbiota. Hence, the anticancer efficacy of alkylating agents (such as cyclophosphamide) and platinum salts (oxaliplatin, cis-platin) is compromised in germ-free mice or animals treated with antibiotics. These findings represent a paradigm shift in our understanding of the mode of action of many compounds having an impact on the host-microbe mutualism. C1 [Viaud, S.; Daillere, R.; Zitvogel, L.] INSERM, Gustave Roussy, U1015, F-94805 Villejuif, France. [Viaud, S.; Daillere, R.; Zitvogel, L.] Univ Paris Sud, Le Kremlin Bicetre, France. [Boneca, I. G.] INSERM, Unit Biol & Genet Bacterial Cell Wall, Paris, France. [Boneca, I. G.] INSERM, Grp Avenir, Paris, France. [Lepage, P.; Langella, P.] Inst Natl Rech Agronom, Micalis UMR1319, Jouy En Josas, France. [Lepage, P.; Langella, P.] AgroParisTech, Micalis UMR1319, F-78350 Jouy En Josas, France. [Chamaillard, M.] Univ Lille Nord France, Lille, France. [Chamaillard, M.] Inst Pasteur, Ctr Infect & Immun Lille, F-59019 Lille, France. [Chamaillard, M.] CNRS, Unite Mixte Rech, Lille, France. [Chamaillard, M.] INSERM, F-59045 Lille, France. [Pittet, M. J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Pittet, M. J.] Harvard Univ, Sch Med, Boston, MA USA. [Ghiringhelli, F.] INSERM, Ctr Georges Francois, U866, Dijon, France. [Ghiringhelli, F.] INSERM, Grp Avenir, Dijon, France. [Ghiringhelli, F.] Univ Bourgogne, Fac Med, Dijon, France. [Trinchieri, G.; Goldszmid, R.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. [Zitvogel, L.] Ctr Invest Clin Biotherapie CICBT 507, Villejuif, France. RP Zitvogel, L (reprint author), INSERM, Gustave Roussy, U1015, 114 Rue Edouard Vaillant, F-94805 Villejuif, France. EM laurence.zitvogel@gustaveroussy.fr RI Chamaillard, Mathias/L-6542-2013; Lepage, Patricia/D-4362-2014; Boneca, Ivo/H-1677-2014 OI Chamaillard, Mathias/0000-0002-0243-9717; Boneca, Ivo/0000-0001-8122-509X FU Institut National du Cancer (INCa); Ligue contre le cancer (LIGUE labellisee); SIRIC Socrate; LABEX; PACRI Onco-Immunology; European Research Council [202283]; ISREC Foundation FX We thank our colleagues from the Gustave Roussy animal facility and Institut Pasteur axenic mice facility. This work was supported by Institut National du Cancer (INCa), la Ligue contre le cancer (LIGUE labellisee), SIRIC Socrate, LABEX and PACRI Onco-Immunology, European Research Council starting grant (PGN from SHAPE to VIR no. 202283 to IGB) and ISREC Foundation. NR 134 TC 19 Z9 21 U1 10 U2 50 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD FEB PY 2015 VL 22 IS 2 SI SI BP 199 EP 214 DI 10.1038/cdd.2014.56 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AY9AR UT WOS:000347842500003 PM 24832470 ER PT J AU John, WG Little, R Sacks, DB Weykamp, C Lenters-Westra, E Hornsby, T Zhao, Z Siebelder, C Tennill, A English, E AF John, W. Garry Little, Randie Sacks, David B. Weykamp, Cas Lenters-Westra, Erna Hornsby, Theresa Zhao, Zhen Siebelder, Carla Tennill, Alethea English, Emma TI Multicentre evaluation of the Premier Hb9210 HbA1c analyser SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article DE affinity chromatography; diabetes; glycated haemoglobin; HbA(1c); multicentre evaluation ID HEMOGLOBIN A(1C) MEASUREMENT; WORLDWIDE STANDARDIZATION; AFFINITY-CHROMATOGRAPHY; CONSENSUS STATEMENT; DIABETES-MELLITUS; S TRAITS; GLYCOHEMOGLOBIN; HBA(1C); RISK; COMPLICATIONS AB Background: The accurate and precise quantification of HbA(1c) is essential for the diagnosis and routine monitoring of patients with diabetes. We report an evaluation of the Trinity Biotech Premier Hb9210 analyser (Bray, Ireland/Kansas City, MO, USA), a boronate affinity chromatography-based high performance liquid chromatography (HPLC) system for the measurement of glycated haemoglobin. Methods: We evaluated the analytical performance of the Hb9210 as part of a multicentre evaluation. The effect of haemoglobin variants, other potential interferences and the performance in comparison to both the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) reference systems, was assessed. Most of the centres participating also act as reference laboratories for both the IFCC standardisation network for HbA(1c) and the NGSP. Results: The combined data from all centres showed total coefficients of variation (CV) of 2.71%, 2.32% and 2.14% at low, medium and high values, respectively, for mmol/mol (SI units) and 1.62%, 1.59% and 1.68% for % (NGSP units), which are well below the recommended upper limits of 3% CV for mmol/mol (SI units) and 2% CV for % (NGSP). The analyser showed a good correlation to HbA(1c) methods currently used in clinical practice and the IFCC reference method procedure. Haemoglobin variants AC, AS, AE and AD do not affect the measurement of HbA(1c). Overall the Hb9210 performs well across the whole analytical range. Conclusions: The Hb9210 performs well and is suitable for clinical application in the analysis of HbA(1c). C1 [English, Emma] Univ Nottingham, Royal Derby Hosp, Sch Med, Nottingham DE22 3DT, England. [John, W. Garry; Hornsby, Theresa] Norfolk & Norwich Univ Hosp, Dept Clin Biochem, Norwich, Norfolk, England. [Little, Randie; Tennill, Alethea] Univ Missouri, Sch Med, Dept Pathol & Anat Sci, Columbia, MO USA. [Sacks, David B.; Zhao, Zhen] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Weykamp, Cas; Siebelder, Carla] Queen Beatrix Hosp, European Reference Lab, Winterswijk, Netherlands. [Lenters-Westra, Erna] European Reference Lab, Isala, Zwolle, Netherlands. RP English, E (reprint author), Univ Nottingham, Royal Derby Hosp, Sch Med, Nottingham DE22 3DT, England. EM emma.english@nottingham.ac.uk OI Little, Randie/0000-0001-6450-8012; Sacks, David/0000-0003-3100-0735 FU Intramural Research Program of the National Institutes of Health FX This work was funded in part by the Intramural Research Program of the National Institutes of Health (to D.B.S. and Z.Z.). NR 20 TC 3 Z9 3 U1 0 U2 4 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 EI 1437-4331 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD FEB PY 2015 VL 53 IS 2 BP 319 EP 327 DI 10.1515/cclm-2014-0589 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AY6BA UT WOS:000347651500028 PM 25274956 ER PT J AU Zhang, CZ Fang, EF Zhang, HT Liu, LL Yun, JP AF Zhang, Chris Zhiyi Fang, Evandro Fei Zhang, Hai-Tao Liu, Li-Li Yun, Jing-Ping TI Momordica Charantia lectin exhibits antitumor activity towards hepatocellular carcinoma SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE MCL; Bid; Apoptosis; Hepatocellular carcinoma ID CANCER-CELL APOPTOSIS; SIGNALING PATHWAYS; INDUCE APOPTOSIS; IN-VITRO; PROTEIN; INHIBITION; ACTIVATION; EXPRESSION; RESISTANCE; AUTOPHAGY AB Background The incidence and mortality of hepatocellular carcinoma (HCC) remain high worldwide. Drug screening from natural plants is one of the potential therapeutic approaches on HCC. Methods The antitumor effect of momordica charantia lectin (MCL) was examined, using MTT, colony formation, AnnexinV/PI staining, western blot and animal model. Results MCL treatment induced G2/M phase arrest, autophagy, DNA fragmentation, mitochondrial injury, and subsequently cell apoptosis in HCC cells. Activation of caspase and MAPK pathway was involved in MCL-induced apoptosis. In vitro and in vivo studies showed that up-regulation of truncated Bid (tBid) upon MCL treatment. Correlation analysis revealed that Bid expression was reversely associated with the IC50 of MCL. Bid suppression using Bid siRNA, BI-6C9 (Bid inhibitor) and Z-IETD-FMK (caspase 8 inhibitor) dramatically attenuated MCL-induced cell proliferation inhibition, caspase 3 activation, Delta Im depolarization and apoptosis. In addition, combination of MCL and sorafenib exerted stronger lethal activity towards HCC in vitro and in vivo. Conclusion Our data show that the natural compound MCL manifests antitumor activities towards HCC and therefore suggest MCL as a promising chemotherapeutic agent. C1 [Zhang, Chris Zhiyi; Liu, Li-Li; Yun, Jing-Ping] Sun Yat Sen Univ, Ctr Canc, Dept Pathol, Guangzhou 510060, Guangdong, Peoples R China. [Zhang, Chris Zhiyi; Yun, Jing-Ping] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Guangdong, Peoples R China. [Fang, Evandro Fei] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. [Zhang, Hai-Tao] Guangdong Med Coll, Dept Biochem & Mol Biol, Zhanjiang, Peoples R China. RP Zhang, CZ (reprint author), Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Guangdong, Peoples R China. EM ls01zzy@hotmail.com; yunjp@sysucc.org.cn FU National Natural Science Foundation of China [81201717]; China Postdoctoral Science Foundation [2012 M511867] FX We thank Dr. George Gong Chen from The Chinese University of Hong Kong for his valuable advices on our study. This work was supported by grants from the National Natural Science Foundation of China (No. 81201717) and the China Postdoctoral Science Foundation (No. 2012 M511867). NR 29 TC 11 Z9 12 U1 1 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2015 VL 33 IS 1 BP 1 EP 11 DI 10.1007/s10637-014-0156-8 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AZ0QI UT WOS:000347949400001 PM 25200916 ER PT J AU Beane, JD Griffin, KF Levy, EB Pandalai, P Wood, B Abi-Jaoudeh, N Beresnev, T Shutack, Y Webb, CC Avital, I Rudloff, U AF Beane, Joal D. Griffin, Kayla F. Levy, Elliot B. Pandalai, Prakash Wood, Bradford Abi-Jaoudeh, Nadine Beresnev, Tatiana Shutack, Yvonne Webb, Carole C. Avital, Itzhak Rudloff, Udo TI Duodenal ischemia and upper GI bleeding are dose-limiting toxicities of 24-h continuous intra-arterial pancreatic perfusion of gemcitabine following vascular isolation of the pancreatic head: early results from the Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) study SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Pancreatic cancer; Gemcitabine; Fixed dose rate; Regional intra-arterial chemotherapy; Regional pancreatic perfusion; Duodenal ischemia ID PROLONGED-INFUSION GEMCITABINE; PHASE-I; CARCINOMA; ADENOCARCINOMA; EMBOLIZATION; SURVIVAL; LEUKEMIA; THERAPY; TRIAL AB Background Regional chemotherapy is used successfully in the treatment of both primary and secondary malignancies, in particular of the peritoneal surface and the liver, and is currently explored as an attractive approach for patients with locally advanced pancreatic ductal adenocarcinoma. To establish the feasibility and toxicity of regional intra-arterial gemcitabine delivered as a 24-h continuous infusion to the pancreas as a novel treatment option for patients with locally advanced PDAC a phase I clinical trial was conducted. Methods Between April 2011 and September 2013 six patients with biopsy confirmed, borderline or unresectable pancreatic adenocarcinoma, and having received at least one line of systemic chemotherapy, underwent vascular redistribution of the inflow to the head of the pancreas by arterial coil embolization followed by perfusion catheter placement within the splenic artery. Patients were treated with increasing doses of gemcitabine administered by continuous splenic arterial infusion over 24 h with inter-patient and intra-patient dose escalation scheme. The primary endpoint was toxicity of the intra-arterial gemcitabine regimen and to establish the maximum tolerated dose. Results Catheter placement and gemcitabine infusion was successful in all patients enrolled to date (n = 6). Four out of six patients experienced catheter tip migration requiring replacement or revision. Patients received a median of four doses of 24-h gemcitabine infusion. Two patients developed grade 3 and 4 duodenal ischemia and upper gastrointestinal bleeding. Median overall survival was 15.3 months and median time to progression was 3 months. Three patients (50 %, n = 3/6) progressed systemically. Two patients had stable disease > 4 months following treatment and underwent pancreaticoduodenectomy. Conclusions While technically feasible to treat locally advanced pancreatic ductal adenocarcinoma, prolonged regional pancreatic perfusion with gemcitabine following pancreatic arterial redistribution carries a high risk for gastrointestinal toxicity. Shorter infusion schedules with frequent on treatment evaluations should be considered for future clinical trials. C1 [Beane, Joal D.; Griffin, Kayla F.; Pandalai, Prakash; Beresnev, Tatiana; Shutack, Yvonne; Webb, Carole C.; Rudloff, Udo] NCI, Thorac & GI Oncol Branch, Hatfield Ctr, Bethesda, MD 20892 USA. [Levy, Elliot B.; Wood, Bradford; Abi-Jaoudeh, Nadine] NCI, Dept Intervent Radiol, Bethesda, MD 20892 USA. [Avital, Itzhak] Bon Secours Canc Inst, Richmond, VA USA. RP Rudloff, U (reprint author), NCI, Thorac & GI Oncol Branch, Hatfield Ctr, CCR 4 West 5940 10 Ctr Dr, Bethesda, MD 20892 USA. EM rudloffu@mail.nih.gov NR 29 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2015 VL 33 IS 1 BP 109 EP 118 DI 10.1007/s10637-014-0157-7 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AZ0QI UT WOS:000347949400012 PM 25236592 ER PT J AU LoConte, NK Razak, ARA Ivy, P Tevaarwerk, A Leverence, R Kolesar, J Siu, L Lubner, SJ Mulkerin, DL Schelman, WR Deming, DA Holen, KD Carmichael, L Eickhoff, J Liu, G AF LoConte, Noelle K. Razak, Albiruni R. A. Ivy, Percy Tevaarwerk, Amye Leverence, Rachael Kolesar, Jill Siu, Lillian Lubner, Sam J. Mulkerin, Daniel L. Schelman, William R. Deming, Dustin A. Holen, Kyle D. Carmichael, Lakeesha Eickhoff, Jens Liu, Glenn TI A multicenter phase 1 study of gamma -secretase inhibitor RO4929097 in combination with capecitabine in refractory solid tumors SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE RO4929097; Capecitabine; Phase 1; Colorectal cancer ID BREAST-CANCER; THERAPY; CELLS; LUNG; JAG1; ACTIVATION; EXPRESSION; LEUKEMIA; TRIAL; POOR AB Background RO4929097 is an oral inhibitor of gamma -secretase that results in Notch signaling inhibition. Prior work has demonstrated that Notch signaling inhibition enhances chemotherapy sensitivity of cancer cells. This phase I study was conducted to determine maximum tolerated dose (MTD), toxicities and efficacy of RO4929097 and capecitabine in advanced solid tumors. Methods Patients with refractory solid tumors received capecitabine at a fixed dose of 1,000 mg/m(2) twice daily with escalating doses of RO4929097 on a 21-day cycle in a 3 + 3 design. Capecitabine was administered for 14 days and the RO49029097 once daily, 3 days per week, both for a 21 day cycle. Results Thirty patients were treated on six dose levels (20 to 150 mg). The maximally tolerated dose was not reached. One dose limiting toxicity was observed at each level 3 through 6 (hypophosphatemia, fatigue, and nausea/vomiting). Three confirmed partial responses were observed: two patients with fluoropyrimide-refractory colon cancer and one patient with cervical cancer. Autoinduction of RO4929097 was demonstrated with increasing dose levels and duration. Conclusions The recommended phase 2 dose is capecitabine 1,000 mg/m(2) orally twice daily on days 1 through 14 with RO4929097 20 mg orally once daily on days 1-3, 8-10 and 15-17 with a 21 day cycle. Clinical benefit was observed in cervical and colon cancer. Autoinduction of RO4929097 was seen both with increasing cycle number and increasing dose. Plasma concentrations of RO4929097 were above those needed for Notch inhibition. C1 [LoConte, Noelle K.; Tevaarwerk, Amye; Leverence, Rachael; Kolesar, Jill; Lubner, Sam J.; Mulkerin, Daniel L.; Schelman, William R.; Deming, Dustin A.; Holen, Kyle D.; Carmichael, Lakeesha; Eickhoff, Jens; Liu, Glenn] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53792 USA. [Razak, Albiruni R. A.; Siu, Lillian] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Ivy, Percy] NCI, Bethesda, MD 20892 USA. [Leverence, Rachael; Kolesar, Jill] Univ Wisconsin, Sch Pharm, Madison, WI 53792 USA. [Carmichael, Lakeesha; Eickhoff, Jens] Univ Wisconsin, Dept Biostat, Madison, WI 53792 USA. RP LoConte, NK (reprint author), Univ Wisconsin, Carbone Canc Ctr, 600 Highland Ave,CSC K4-548, Madison, WI 53792 USA. EM ns3@medicine.wisc.edu RI Liu, Geoffrey/N-4421-2016 FU National Cancer Institute [U01 CA062491, U01-CA132123]; University of Wisconsin Carbone Cancer Center [P30 CA014520]; Princess Margaret Hospital Phase I Consortium; National Institutes of Health Clinical and Translational Science Awards program [9U54TR000021] FX The investigators gratefully acknowledge the patients and families who participated in this study. Funding was provided by the National Cancer Institute Grant U01 CA062491 (University of Wisconsin) and U01-CA132123 (Princess Margaret Hospital). Further support is provided by the University of Wisconsin Carbone Cancer Center Core Grant P30 CA014520 and the Princess Margaret Hospital Phase I Consortium. Amye Tevaarwerk is supported by the National Institutes of Health Clinical and Translational Science Awards program 9U54TR000021. NR 22 TC 9 Z9 9 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2015 VL 33 IS 1 BP 169 EP 176 DI 10.1007/s10637-014-0166-6 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AZ0QI UT WOS:000347949400018 PM 25318436 ER PT J AU Knox, JJ Qin, R Strosberg, JR Tan, B Kaubisch, A El-Khoueiry, AB Bekaii-Saab, TS Rousey, SR Chen, HX Erlichman, C AF Knox, Jennifer J. Qin, Rui Strosberg, Jonathan R. Tan, Benjamin Kaubisch, Andreas El-Khoueiry, Anthony B. Bekaii-Saab, Tanios S. Rousey, Steven R. Chen, Helen X. Erlichman, Charles TI A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Hepatocellular carcinoma; Bevacizumab; Temsirolimus; Phase II ID SORAFENIB; ERLOTINIB; RAPAMYCIN AB Background There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC. Methods A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or > 18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle. Results Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1-18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively. Conclusion This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule. C1 [Knox, Jennifer J.] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada. [Qin, Rui; Erlichman, Charles] Mayo Clin, Rochester, MN USA. [Strosberg, Jonathan R.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Tan, Benjamin] Washington Univ, Sch Med, St Louis, MO USA. [Kaubisch, Andreas] Montefiore Med Ctr, Bronx, NY 10467 USA. [El-Khoueiry, Anthony B.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Bekaii-Saab, Tanios S.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA. [Rousey, Steven R.] Metro Minnesota CCOP, St Louis Pk, MN USA. [Chen, Helen X.] NCI, Bethesda, MD 20892 USA. RP Knox, JJ (reprint author), Univ Toronto, Princess Margaret Canc Ctr, 5-210,610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM jennifer.knox@uhn.ca RI Bekaii-Saab, Tanios/E-2733-2011 FU NCI [N01-CM-2011-00099, N01-CM-2011-00032, N01-CM-2011-00100, N01-CM-2011-00038, N01-CM-2011-00070] FX This trial is supported by the NCI. N01-CM-2011-00099 (P2C), N01-CM-2011-00032 (PMH), N01-CM-2011-00100 (Moffitt), N01-CM-2011-00038 (California), N01-CM-2011-00070 (OSU) contracts NR 20 TC 7 Z9 8 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2015 VL 33 IS 1 BP 241 EP 246 DI 10.1007/s10637-014-0169-3 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AZ0QI UT WOS:000347949400026 PM 25318437 ER PT J AU Kim, HJ Brennan, PJ Heaslip, D Udey, MC Modlin, RL Belisle, JT AF Kim, Hee Jin Brennan, Patrick J. Heaslip, Darragh Udey, Mark C. Modlin, Robert L. Belisle, John T. TI Carbohydrate-Dependent Binding of Langerin to SodC, a Cell Wall Glycoprotein of Mycobacterium leprae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID C-TYPE LECTIN; DC-SIGN; SELECTIVE RECOGNITION; GLYCOSYLATION SITES; TUBERCULOSIS; RECEPTORS; IDENTIFICATION; LIGANDS; LIPOARABINOMANNAN; ORGANIZATION AB Langerhans cells participate in the immune response in leprosy by their ability to activate T cells that recognize the pathogen, Mycobacterium leprae, in a langerin-dependent manner. We hypothesized that langerin, the distinguishing C-type lectin of Langerhans cells, would recognize the highly mannosylated structures in pathogenic Mycobacterium spp. The coding region for the extracellular and neck domain of human langerin was cloned and expressed to produce a recombinant active trimeric form of human langerin (r-langerin). Binding assays performed in microtiter plates, by two-dimensional (2D) Western blotting, and by surface plasmon resonance demonstrated that r-langerin possessed carbohydrate-dependent affinity to glycoproteins in the cell wall of M. leprae. This lectin, however, yielded less binding to mannose-capped lipoarabinomannan (ManLAM) and even lower levels of binding to phosphatidylinositol mannosides. However, the superoxide dismutase C (SodC) protein of the M. leprae cell wall was identified as a langerin-reactive ligand. Tandem mass spectrometry verified the glycosylation of a recombinant form of M. leprae SodC (rSodC) produced in Mycobacterium smegmatis. Analysis of r-langerin affinity by surface plasmon resonance revealed a carbohydrate-dependent affinity of rSodC (equilibrium dissociation constant [K-D] = 0.862 mu M) that was 20-fold greater than for M. leprae ManLAM (K-D = 18.69 mu M). These data strongly suggest that a subset of the presumptively mannosylated M. leprae glycoproteins act as ligands for langerin and may facilitate the interaction of M. leprae with Langerhans cells. C1 [Kim, Hee Jin; Brennan, Patrick J.; Heaslip, Darragh; Belisle, John T.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. [Udey, Mark C.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Modlin, Robert L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA 90095 USA. [Modlin, Robert L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. RP Belisle, JT (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. EM john.belisle@colostate.edu RI Belisle, John/B-8944-2017 OI Belisle, John/0000-0002-2539-2798 FU NIH, NIAID [R01-AI022553, R01-AI047868, R01-AI082575]; NIAMS (NIH) [P50-AR063020, R01-AR040312] FX This study was supported by NIH, NIAID grants R01-AI022553, R01-AI047868, and R01-AI082575 and NIAMS (NIH) grants P50-AR063020 and R01-AR040312. NR 39 TC 3 Z9 3 U1 1 U2 17 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 2015 VL 197 IS 3 BP 615 EP 625 DI 10.1128/JB.02080-14 PG 11 WC Microbiology SC Microbiology GA AY6LD UT WOS:000347676800021 PM 25422308 ER PT J AU Kubler, A Luna, B Larsson, C Ammerman, NC Andrade, BB Orandle, M Bock, KW Xu, ZY Bagci, U Molura, DJ Marshall, J Burns, J Winglee, K Ahidjo, BA Cheung, LS Klunk, M Jain, SK Kumar, NP Babu, S Sher, A Friedland, JS Elkington, PTG Bishai, WR AF Kuebler, Andre Luna, Brian Larsson, Christer Ammerman, Nicole C. Andrade, Bruno B. Orandle, Marlene Bock, Kevin W. Xu, Ziyue Bagci, Ulas Molura, Daniel J. Marshall, John Burns, Jay Winglee, Kathryn Ahidjo, Bintou Ahmadou Cheung, Laurene S. Klunk, Mariah Jain, Sanjay K. Kumar, Nathella Pavan Babu, Subash Sher, Alan Friedland, Jon S. Elkington, Paul T. G. Bishai, William R. TI Mycobacterium tuberculosis dysregulates MMP/TIMP balance to drive rapid cavitation and unrestrained bacterial proliferation SO JOURNAL OF PATHOLOGY LA English DT Article DE tuberculosis; matrix metalloproteinase; computed tomography; cavity ID PULMONARY TUBERCULOSIS; MATRIX METALLOPROTEINASES; RESISTANT TUBERCULOSIS; MULTIDRUG-RESISTANT; COMPUTED-TOMOGRAPHY; RABBIT MODEL; T-CELLS; INFECTION; MICE; PATHOLOGY AB Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP-1, are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model resulted in consistent progression of consolidation to human-like cavities (100% by day 28), with resultant bacillary burdens (>10(7) CFU/g) far greater than those found in matched granulomatous tissue (10(5) CFU/g). Using a novel, breath-hold computed tomography (CT) scanning and image analysis protocol, we showed that cavities developed rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue, as estimated by changes in lung density during controlled pulmonary expansion (R-2=0.6356, p < 0.0001). We demonstrated that the expression of interstitial collagenase (MMP-1) was specifically greater in cavitary compared to granulomatous lesions (p < 0.01), and that TIMP-3 significantly decreased at the cavity surface. Our findings demonstrated that an MMP-1/TIMP imbalance is associated with the progression of consolidated regions to cavities containing very high bacterial burdens. Our model provided mechanistic insight, correlating with human disease at the pathological, microbiological and molecular levels. It also provided a strategy to investigate therapeutics in the context of complex TB pathology. We used these findings to predict a MMP/TIMP balance in active TB and confirmed this in human plasma, revealing the potential of MMP/TIMP levels as key components of a diagnostic matrix aimed at distinguishing active from latent TB (PPV = 92.9%, 95% CI 66.1-99.8%, NPV = 85.6%; 95% CI 77.0-91.9%). Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd C1 [Kuebler, Andre; Friedland, Jon S.; Elkington, Paul T. G.] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. [Kuebler, Andre; Luna, Brian; Winglee, Kathryn; Ahidjo, Bintou Ahmadou; Cheung, Laurene S.; Jain, Sanjay K.; Bishai, William R.] Johns Hopkins Univ, Sch Med, Ctr TB Res, Baltimore, MD USA. [Larsson, Christer] Umea Univ, Dept Mol Biol, S-90187 Umea, Sweden. [Ammerman, Nicole C.] KwaZulu Natal Res Inst TB & HIV K RITH, Durban, South Africa. [Andrade, Bruno B.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Orandle, Marlene; Bock, Kevin W.] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Xu, Ziyue; Bagci, Ulas; Molura, Daniel J.] NIH, Bethesda, MD 20892 USA. [Marshall, John] Johns Hopkins Sch Med, Baltimore, MD USA. [Burns, Jay] Johns Hopkins Univ, Baltimore, MD USA. [Klunk, Mariah; Jain, Sanjay K.] Ctr Infect Dis & Inflammat Imaging Res CI3R, Baltimore, MD USA. [Elkington, Paul T. G.] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England. [Ahidjo, Bintou Ahmadou; Bishai, William R.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. [Kumar, Nathella Pavan; Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, Madras, Tamil Nadu, India. [Kumar, Nathella Pavan] Natl Inst Res TB, Madras, Tamil Nadu, India. [Babu, Subash] NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bishai, WR (reprint author), Johns Hopkins Ctr TB Res, CRB 2 Room 108,1550 Orleans St, Baltimore, MD USA. EM wbishai1@jhmi.edu OI Xu, Ziyue/0000-0002-5728-6869; Elkington, Paul/0000-0003-0390-0613; Larsson, Christer/0000-0002-5714-924X; Bagci, Ulas/0000-0001-7379-6829; Luna, PhD, Brian/0000-0001-6718-4551 FU Howard Hughes Medical Institute; National Institutes of Health (NIH) [R01 AI 079590, R01 AI037856, R01 AI036973]; Imperial College London; NIH Director's New Innovator Awards [DP2-OD6492, R01-HL116316] FX WRB acknowledges the support of the Howard Hughes Medical Institute and the National Institutes of Health (NIH; Grant Nos R01 AI 079590; R01 AI037856 and R01 AI036973; AK and JSF were supported by a grant from Imperial College London; and SKJ was supported by NIH Director's New Innovator Awards (Nos DP2-OD6492 and R01-HL116316). NR 51 TC 14 Z9 16 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 EI 1096-9896 J9 J PATHOL JI J. Pathol. PD FEB PY 2015 VL 235 IS 3 BP 431 EP 444 DI 10.1002/path.4432 PG 14 WC Oncology; Pathology SC Oncology; Pathology GA AY6YQ UT WOS:000347709000006 PM 25186281 ER PT J AU Altarifi, AA Rice, KC Negus, SS AF Altarifi, Ahmad A. Rice, Kenner C. Negus, S. Stevens TI Effects of mu-Opioid Receptor Agonists in Assays of Acute Pain-Stimulated and Pain-Depressed Behavior in Male Rats: Role of mu-Agonist Efficacy and Noxious Stimulus Intensity SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INTRACRANIAL SELF-STIMULATION; INTRINSIC EFFICACY; PRECLINICAL ASSAYS; THERMAL ANTINOCICEPTION; DISCRIMINATIVE STIMULUS; POSTOPERATIVE PAIN; MONKEY BRAIN; MORPHINE; ANALGESIA; BINDING AB Pain is associated with stimulation of some behaviors and depression of others, and mu-opioid receptor agonists are among the most widely used analgesics. This study used parallel assays of pain-stimulated and pain-depressed behavior in male Sprague-Dawley rats to compare antinociception profiles for six mu-agonists that varied in efficacy at mu-opioid receptors (from highest to lowest: methadone, fentanyl, morphine, hydrocodone, buprenorphine, and nalbuphine). Intraperitoneal injection of diluted lactic acid served as an acute noxious stimulus to either stimulate stretching or depress operant responding maintained by electrical stimulation in an intracranial self-stimulation (ICSS). All mu-agonists blocked both stimulation of stretching and depression of ICSS produced by 1.8% lactic acid. The high-efficacy agonists methadone and fentanyl were more potent at blocking acid-induced depression of ICSS than acid-stimulated stretching, whereas lower-efficacy agonists displayed similar potency across assays. All mu-agonists except morphine also facilitated ICSS in the absence of the noxious stimulus at doses similar to those that blocked acid-induced depression of ICSS. The potency of the low-efficacy mu-agonist nalbuphine, but not the high-efficacy mu-agonist methadone, to block acid-induced depression of ICSS was significantly reduced by increasing the intensity of the noxious stimulus to 5.6% acid. These results demonstrate sensitivity of acid-induced depression of ICSS to a range of clinically effective mu-opioid analgesics and reveal distinctions between opioids based on efficacy at the mu-receptor. These results also support the use of parallel assays of pain-stimulated and -depressed behaviors to evaluate analgesic efficacy of candidate drugs. C1 [Altarifi, Ahmad A.] Jordan Univ Sci & Technol, Sch Med, Dept Pharmacol, Irbid 22110, Jordan. [Altarifi, Ahmad A.; Negus, S. Stevens] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Rice, Kenner C.] NIAAA, Bethesda, MD USA. RP Altarifi, AA (reprint author), Jordan Univ Sci & Technol, Sch Med, Dept Pharmacol, POB 3030, Irbid 22110, Jordan. EM altarifiaa@vcu.edu FU National Institutes of Health National Institute of Neurological Disorders and Stroke [R01-NS070715]; Jordan University of Science and Technology; Intramural Research Program of the National Institutes of Health [National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism] FX This research was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant R01-NS070715]; and by a training grant from the Jordan University of Science and Technology. A portion of this work was also supported by the Intramural Research Program of the National Institutes of Health [National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism]. NR 63 TC 7 Z9 7 U1 0 U2 5 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 FEB PY 2015 VL 352 IS 2 BP 208 EP 217 DI 10.1124/jpet.114.219873 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AY8RY UT WOS:000347822200002 PM 25406170 ER PT J AU Amar, MJA Sakurai, T Sakurai-Ikuta, A Sviridov, D Freeman, L Ahsan, L Remaley, AT AF Amar, Marcelo J. A. Sakurai, Toshihiro Sakurai-Ikuta, Akiko Sviridov, Denis Freeman, Lita Ahsan, Lusana Remaley, Alan T. TI A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E-Knockout Mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID A-I; INTRAVENOUS-INFUSION; CHOLESTEROL EFFLUX; TRANSGENIC MICE; HYPERTRIGLYCERIDEMIA; ATHEROSCLEROSIS; DISEASE; CII; PANCREATITIS; HUMANS AB Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux and their other beneficial antiatherogenic properties. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) for binding to lipoproteins and stimulating cholesterol efflux as well as a motif based on the last helix of apolipoprotein C-II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to be comparable to the full-length apoC-II protein in activating lipolysis by LPL. When added to serum from a patient with apoC-II deficiency, it restored normal levels of LPL-induced lipolysis and also enhanced lipolysis in serum from patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a (30 mg/kg) in apolipoprotein E-knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides of 38 +/- 6% and 85 +/- 7%, respectively, at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to completely block the hypertriglyceridemic effect of the 5A peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II, which promotes cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II deficiency and other forms of hypertriglyceridemia. C1 [Amar, Marcelo J. A.; Sakurai, Toshihiro; Sakurai-Ikuta, Akiko; Sviridov, Denis; Freeman, Lita; Ahsan, Lusana; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Cardiopulm Branch, NIH, Bethesda, MD 20892 USA. RP Amar, MJA (reprint author), NIH, Bldg 10,Room 8N-228,10 Ctr Dr MSC 1666, Bethesda, MD 20892 USA. EM ma90x@nih.gov FU Intramural Research Program of the National Institutes of Health [National Heart, Lung, and Blood Institute] FX This research was supported by Intramural Research Program of the National Institutes of Health [National Heart, Lung, and Blood Institute] NR 46 TC 16 Z9 17 U1 1 U2 5 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 FEB PY 2015 VL 352 IS 2 BP 227 EP 235 DI 10.1124/jpet.114.220418 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AY8RY UT WOS:000347822200004 PM 25395590 ER PT J AU McLain, AC Sundaram, R Louis, GMB AF McLain, Alexander C. Sundaram, Rajeshwari Louis, Germaine M. Buck TI Joint analysis of longitudinal and survival data measured on nested timescales by using shared parameter models: an application to fecundity data SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Binary data; Discrete survival; Empirical Bayes predictions; Semiparametric models; Shared parameter models ID RANDOM EFFECTS MISSPECIFICATION; MENSTRUAL-CYCLE; LIKELIHOOD APPROACH; CIRCADIAN-RHYTHMS; PREGNANCY; TIME; INTERCOURSE; FECUNDABILITY; INFERTILITY; CONCEPTION AB We consider the joint modelling, analysis and prediction of a longitudinal binary process and a discrete time-to-event outcome. We consider data from a prospective pregnancy study, which provides day level information regarding the behaviour of couples attempting to conceive. Reproductive epidemiologists are particularly interested in developing a model for individualized predictions of time to pregnancy (TTP). A couple's intercourse behaviour should be an integral part of such a model and is one of the main focuses of the paper. In our motivating data, the intercourse observations are a long series of binary data with a periodic probability of success and the amount of available intercourse data is a function of both the menstrual cycle length and TTP. Moreover, these variables are dependent and observed on different, and nested, timescales (TTP is measured in menstrual cycles whereas intercourse is measured on days within a menstrual cycle) further complicating its analysis. Here, we propose a semiparametric shared parameter model for the joint modelling of the binary longitudinal data (intercourse behaviour) and the discrete survival outcome (TTP). Further, we develop couple-based dynamic predictions for the intercourse profiles, which in turn are used to assess the risk for subfertility (i.e. TTP longer than six menstrual cycles). C1 [McLain, Alexander C.; Sundaram, Rajeshwari; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 USA. RP Sundaram, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, 6100 Execut Blvd, Rockville, MD 20852 USA. EM sundaramr2@mail.nih.gov OI Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural Research Program of the National Institute of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported in part by the Intramural Research Program of the National Institute of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. This work was completed while the first author was a Research Fellow with Dr Sundaram. The authors also acknowledge that this study utilized the high performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, Maryland (http://biowulf.nih.gov). The authors thank the Joint Editor, the Associate Editor and two reviewers for comments and suggestions that considerably improved this paper. NR 45 TC 2 Z9 2 U1 2 U2 9 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0035-9254 EI 1467-9876 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PD FEB PY 2015 VL 64 IS 2 BP 339 EP 357 DI 10.1111/rssc.12075 PG 19 WC Statistics & Probability SC Mathematics GA AY9TM UT WOS:000347893400006 PM 27122641 ER PT J AU Baz, M Paskel, M Matsuoka, Y Zengel, J Cheng, X Treanor, JJ Jin, H Subbarao, K AF Baz, Mariana Paskel, Myeisha Matsuoka, Yumiko Zengel, James Cheng, Xing Treanor, John J. Jin, Hong Subbarao, Kanta TI A Live Attenuated Equine H3N8 Influenza Vaccine Is Highly Immunogenic and Efficacious in Mice and Ferrets SO JOURNAL OF VIROLOGY LA English DT Article ID A-VIRUS; EXPERIMENTAL-INFECTION; HEALTHY-ADULTS; SEROLOGICAL EVIDENCE; RESPIRATORY-DISEASE; HORSES; TRANSMISSION; DOGS; REPLICATION; PROTECTION AB Equine influenza viruses (EIV) are responsible for rapidly spreading outbreaks of respiratory disease in horses. Although natural infections of humans with EIV have not been reported, experimental inoculation of humans with these viruses can lead to a productive infection and elicit a neutralizing antibody response. Moreover, EIV have crossed the species barrier to infect dogs, pigs, and camels and therefore may also pose a threat to humans. Based on serologic cross-reactivity of H3N8 EIV from different lineages and sublineages, A/equine/Georgia/1/1981 (eq/GA/81) was selected to produce a live attenuated candidate vaccine by reverse genetics with the hemagglutinin and neuraminidase genes of the eq/GA/81 wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 (H2N2) vaccine donor virus, which is the backbone of the licensed seasonal live attenuated influenza vaccine. In both mice and ferrets, intranasal administration of a single dose of the eq/GA/81 ca vaccine virus induced neutralizing antibodies and conferred complete protection from homologous wt virus challenge in the upper respiratory tract. One dose of the eq/GA/81 ca vaccine also induced neutralizing antibodies and conferred complete protection in mice and nearly complete protection in ferrets upon heterologous challenge with the H3N8 (eq/Newmarket/03) wt virus. These data support further evaluation of the eq/GA/81 ca vaccine in humans for use in the event of transmission of an equine H3N8 influenza virus to humans. IMPORTANCE Equine influenza viruses have crossed the species barrier to infect other mammals such as dogs, pigs, and camels and therefore may also pose a threat to humans. We believe that it is important to develop vaccines against equine influenza viruses in the event that an EIV evolves, adapts, and spreads in humans, causing disease. We generated a live attenuated H3N8 vaccine candidate and demonstrated that the vaccine was immunogenic and protected mice and ferrets against homologous and heterologous EIV. C1 [Baz, Mariana; Paskel, Myeisha; Matsuoka, Yumiko; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Zengel, James; Cheng, Xing; Jin, Hong] MedImmune LLC, Mountain View, CA USA. [Treanor, John J.] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU Intramural Research Program of the NIAID, NIH FX This research was supported by the Intramural Research Program of the NIAID, NIH, and was performed as part of a Cooperative Research and Development Agreement between the Laboratory of Infectious Diseases, NIAID, and MedImmune, LLC. NR 47 TC 3 Z9 4 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD FEB PY 2015 VL 89 IS 3 BP 1652 EP 1659 DI 10.1128/JVI.02449-14 PG 8 WC Virology SC Virology GA AY8QJ UT WOS:000347818100014 PM 25410860 ER PT J AU Afione, S DiMattia, MA Halder, S Di Pasquale, G Agbandje-McKenna, M Chiorini, JA AF Afione, Sandra DiMattia, Michael A. Halder, Sujata Di Pasquale, Giovanni Agbandje-McKenna, Mavis Chiorini, John A. TI Identification and Mutagenesis of the Adeno-Associated Virus 5 Sialic Acid Binding Region SO JOURNAL OF VIROLOGY LA English DT Article ID EFFICIENT TRANSDUCTION; HEPARIN-BINDING; GENE-TRANSFER; PARVOVIRUS; TYPE-2; RECEPTORS; SEROTYPES; VECTORS; CELLS; ENTRY AB As a genus, the dependoviruses use a diverse group of cell surface carbohydrates for attachment and entry. Despite the fact that a majority of adeno-associated viruses (AAVs) utilize sialic acid (SIA) for binding and transduction, this virus-carbohydrate interaction is poorly understood. Utilizing X-ray crystallography, two SIA binding regions were mapped for AAV5. The first site mapped to the depression in the center of the 3-fold axis of symmetry, while the second site was located under the beta HI loop close to the 5-fold axis. Mutagenesis of amino acids 569 and 585 or 587 within the 3-fold depression resulted in elimination or alteration in SIA-dependent transduction, respectively. This change in SIA binding was confirmed using glycan microarrays. Mutagenesis of the second site identified a role in transduction that was SIA independent. Further studies of the mutants at the 3-fold site demonstrated a change in transduction activity and cell tropism in vivo as well as resistance to neutralization by a polyclonal antibody raised against the wild-type virus. IMPORTANCE Despite the fact that a majority of AAVs utilize sialic acid for binding and transduction, this virus-carbohydrate interaction is poorly understood. Utilizing X-ray crystallography, the sialic acid binding regions of AAV5 were identified and studied using a variety of approaches. Mutagenesis of this region resulted in elimination or alteration in sialic acid-dependent transduction in cell lines. This change in sialic acid glycan binding was confirmed using glycan arrays. Further study also demonstrated a change in transduction and activity and cell tropism in vivo as well as resistance to neutralization by antibodies raised against the wild-type virus. C1 [Afione, Sandra; Di Pasquale, Giovanni; Chiorini, John A.] NIDCR, NIH, Mol Physiol & Therapeut Branch, Bethesda, MD USA. [DiMattia, Michael A.; Halder, Sujata; Agbandje-McKenna, Mavis] Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. RP Agbandje-McKenna, M (reprint author), Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. EM mckenna@ufl.edu; jchiorini@dir.nidcr.nih.gov FU NIH NIDCR intramural research grant; University of Florida College of Medicine; McKnight Brain Institute; NIH [R01 GM082946] FX This work was supported by an NIH NIDCR intramural research grant to J.A.C. and funds from the University of Florida College of Medicine, the McKnight Brain Institute, and NIH R01 GM082946 to M.A.-M. NR 44 TC 8 Z9 8 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 FEB PY 2015 VL 89 IS 3 BP 1660 EP 1672 DI 10.1128/JVI.02503-14 PG 13 WC Virology SC Virology GA AY8QJ UT WOS:000347818100015 PM 25410855 ER PT J AU Tseng, YS Gurda, BL Chipman, P McKenna, R Afione, S Chiorini, JA Muzyczka, N Olson, NH Baker, TS Kleinschmidt, J Agbandje-McKenna, M AF Tseng, Yu-Shan Gurda, Brittney L. Chipman, Paul McKenna, Robert Afione, Sandra Chiorini, John A. Muzyczka, Nicholas Olson, Norman H. Baker, Timothy S. Kleinschmidt, Juergen Agbandje-McKenna, Mavis TI Adeno-Associated Virus Serotype 1 (AAV1)- and AAV5-Antibody Complex Structures Reveal Evolutionary Commonalities in Parvovirus Antigenic Reactivity SO JOURNAL OF VIROLOGY LA English DT Article ID GENE-THERAPY VECTOR; NEUTRALIZING MONOCLONAL-ANTIBODY; HEPARAN-SULFATE PROTEOGLYCAN; LEBERS CONGENITAL AMAUROSIS; MINK DISEASE PARVOVIRUS; DIRECTED EVOLUTION; CANINE PARVOVIRUS; VIRAL VECTORS; CRYOELECTRON MICROSCOPY; EFFICIENT TRANSDUCTION AB The clinical utility of the adeno-associated virus (AAV) gene delivery system has been validated by the regulatory approval of an AAV serotype 1 (AAV1) vector for the treatment of lipoprotein lipase deficiency. However, neutralization from preexisting antibodies is detrimental to AAV transduction efficiency. Hence, mapping of AAV antigenic sites and engineering of neutralization-escaping vectors are important for improving clinical efficacy. We report the structures of four AAV-monoclonal antibody fragment complexes, AAV1-ADK1a, AAV1-ADK1b, AAV5-ADK5a, and AAV5-ADK5b, determined by cryo-electron microscopy and image reconstruction to a resolution of similar to 11 to 12 angstrom. Pseudoatomic modeling mapped the ADK1a epitope to the protrusions surrounding the icosahedral 3-fold axis and the ADK1b and ADK5a epitopes, which overlap, to the wall between depressions at the 2- and 5-fold axes (2/5-fold wall), and the ADK5b epitope spans both the 5-fold axis-facing wall of the 3-fold protrusion and portions of the 2/5-fold wall of the capsid. Combined with the six antigenic sites previously elucidated for different AAV serotypes through structural approaches, including AAV1 and AAV5, this study identified two common AAV epitopes: one on the 3-fold protrusions and one on the 2/5-fold wall. These epitopes coincide with regions with the highest sequence and structure diversity between AAV serotypes and correspond to regions determining receptor recognition and transduction phenotypes. Significantly, these locations overlap the two dominant epitopes reported for autonomous parvoviruses. Thus, rather than the amino acid sequence alone, the antigenic sites of parvoviruses appear to be dictated by structural features evolved to enable specific infectious functions. C1 [Tseng, Yu-Shan; Gurda, Brittney L.; Chipman, Paul; McKenna, Robert; Agbandje-McKenna, Mavis] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. [Afione, Sandra; Chiorini, John A.] NIDCR, NIH, Mol Physiol & Therapeut Branch, Bethesda, MD USA. [Muzyczka, Nicholas] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA. [Olson, Norman H.; Baker, Timothy S.] Univ Calif San Diego, Dept Chem & Biochem, San Diego, CA 92103 USA. [Olson, Norman H.; Baker, Timothy S.] Univ Calif San Diego, Div Biol Sci, San Diego, CA 92103 USA. [Kleinschmidt, Juergen] German Canc Res Ctr, Res Program Infect & Canc, Heidelberg, Germany. RP Agbandje-McKenna, M (reprint author), Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. EM mckenna@ufl.edu OI Gurda, Brittney /0000-0002-0174-9385 FU NIH [R01 GM082946, R37 GM33050, 1S10 RR020016]; University of Florida (UF) Division of Sponsored Research and the College of Medicine; UF ICBR Electron microscopy and Hybridoma cores; University of California-San Diego (UCSD); Agouron Foundation FX This project was funded by NIH R01 GM082946 (to M.A.-M., R.M., and N.M), R37 GM33050 (to T.S.B.), and 1S10 RR020016 (to T.S.B.), by NIH Intramural funds (to J.A.C.), by support from the University of Florida (UF) Division of Sponsored Research and the College of Medicine to establish cryo-EM facilities, the UF ICBR Electron microscopy and Hybridoma cores, and by support from the University of California-San Diego (UCSD) and the Agouron Foundation (to T.S.B.) to establish cryo-EM facilities at UCSD. NR 93 TC 5 Z9 5 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD FEB PY 2015 VL 89 IS 3 BP 1794 EP 1808 DI 10.1128/JVI.02710-14 PG 15 WC Virology SC Virology GA AY8QJ UT WOS:000347818100025 PM 25410874 ER PT J AU Galpern, WR AF Galpern, Wendy R. TI Clinical trials for multiple system atrophy SO LANCET NEUROLOGY LA English DT Editorial Material ID STATEMENT; DIAGNOSIS C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Galpern, WR (reprint author), NINDS, NIH, 6001 Execut Blvd 2225, Bethesda, MD 20892 USA. EM galpernw@ninds.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD FEB PY 2015 VL 14 IS 2 BP 126 EP 127 DI 10.1016/S1474-4422(14)70311-4 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AY9KS UT WOS:000347869400002 PM 25498733 ER PT J AU Pilapong, C Pongpiajun, S Mankhetkorn, S AF Pilapong, Chalermchai Pongpiajun, Siwatt Mankhetkorn, Samlee TI Visualizing reactive oxygen species inside cancer cells after stimulation with polycyclic aromatic hydrocarbon via spontaneous formation of Au nanoclusters SO MATERIALS LETTERS LA English DT Article DE Gold nanocluster; Reactive oxygen species; Chloroauric acid ID FLUORESCENT GOLD NANOCLUSTERS; HYDROGEN-PEROXIDE; NANOPARTICLES; REDUCTION AB This research was designed to visualize cellular response - in particular the generation of intracellular ROS - to stimulation by polycyclic aromatic hydrocarbon (PAH). We used chloroauric acid (HAuCl4) as a molecular probe for visualizing intracellular ROS generated by the stimulation of benzo[a]pyrene (BaP). The chloroauric acid undergoes a spontaneous reduction reaction, assisted by the intracellular ROS, into gold nanoclusters (AuNCs). As a result, we can visualize the ROS via optical imaging technique. According to MTT assay, the chloroauric acid exhibited good biocompatibility. The AuNCs produced in the cells were approximately 2-3 nm in diameter with a green fluorescent property. Cellular imaging showed that BaP induced the formation of AuNCs within the cells, leading to a high relative cellular fluorescent intensity with a considerable extent of scatter light. Thus, this probe is an efficient molecular imaging probe for visualizing intracellular ROS. (C) 2014 Elsevier B.V. All rights reserved. C1 [Pilapong, Chalermchai; Mankhetkorn, Samlee] Chiang Mai Univ, Fac Associated Med Sci, Dept Radiol Technol, CEMI, Chiang Mai 50200, Thailand. [Pongpiajun, Siwatt] NIDA, Sch Social & Environm Dev, NIDA Ctr Res & Dev Disaster Prevent & Management, Bangkok 10240, Thailand. RP Pilapong, C (reprint author), Chiang Mai Univ, Fac Associated Med Sci, Dept Radiol Technol, CEMI, Chiang Mai 50200, Thailand. EM chalermchai.pilapong@cmu.ac.th FU National Institute Development Administration (NIDA), Thailand FX We would like to thank National Institute Development Administration (NIDA), Thailand, for providing financial support through Post-Doctoral Research Fellowship. NR 21 TC 0 Z9 0 U1 4 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-577X EI 1873-4979 J9 MATER LETT JI Mater. Lett. PD FEB 1 PY 2015 VL 140 BP 162 EP 165 DI 10.1016/j.matlet.2014.10.157 PG 4 WC Materials Science, Multidisciplinary; Physics, Applied SC Materials Science; Physics GA AY7TF UT WOS:000347761000042 ER PT J AU Resnik, DB AF Resnik, David B. TI Unequal treatment of human research subjects SO MEDICINE HEALTH CARE AND PHILOSOPHY LA English DT Article DE Human subjects research; Justice; Equal treatment; Ethics; Regulation ID HEALTH-SERVICES RESEARCH; CLINICAL-RESEARCH; RESEARCH PARTICIPANTS; PEDIATRIC RESEARCH; INFORMED-CONSENT; JUSTICE; BOARDS; RISK; US; EXPLOITATION AB Unequal treatment of human research subjects is a significant ethical concern, because justice in research involving human subjects requires equal protection of rights and equal protection from harm and exploitation. Disputes sometimes arise concerning the issue of unequal treatment of research subjects. Allegedly unequal treatment occurs when subjects are treated differently and there is a genuine dispute concerning the appropriateness of equal treatment. Patently unequal treatment occurs when subjects are treated differently and there is not a genuine dispute about the appropriateness of equal treatment. Allegedly unequal treatment will probably always occur in research with human subjects due to disagreements about fundamental questions of justice. The best way to deal with allegedly unequal treatment is to promote honest and open discussions of the issues at stake. Research regulations can help to minimize patently unequal treatment by providing rules for investigators, ethical review boards, institutions, and sponsors to follow. However, patently unequal treatment may still occur because the regulations are subject to interpretation. Federal agencies have provided interpretive guidance that can help promote consistent review and oversight of human subjects research. Additional direction may be needed on topics that are not adequately covered by current guidance or regulations. International guidelines can help promote equal treatment of human subjects around the globe. While minor variations in the treatment of research subjects should be tolerated and even welcomed, major ones (i.e. those that significantly impact human rights or welfare) should be avoided or minimized. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-06] NR 63 TC 0 Z9 0 U1 2 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1386-7423 EI 1572-8633 J9 MED HEALTH CARE PHIL JI Med. Health Care Philos. PD FEB PY 2015 VL 18 IS 1 BP 23 EP 32 DI 10.1007/s11019-014-9569-6 PG 10 WC Ethics; History & Philosophy Of Science SC Social Sciences - Other Topics; History & Philosophy of Science GA AY6TR UT WOS:000347699000004 PM 24879129 ER PT J AU Murphy, NA Hall, JA Mast, MS Ruben, MA Frauendorfer, D Blanch-Hartigan, D Roter, DL Nguyen, L AF Murphy, Nora A. Hall, Judith A. Mast, Marianne Schmid Ruben, Mollie A. Frauendorfer, Denise Blanch-Hartigan, Danielle Roter, Debra L. Nguyen, Laurent TI Reliability and Validity of Nonverbal Thin Slices in Social Interactions SO PERSONALITY AND SOCIAL PSYCHOLOGY BULLETIN LA English DT Article DE nonverbal behavior; coding; thin slices; reliability; validity ID PERSONALITY PSYCHOLOGY; KNOWLEDGEABLE INFORMANTS; BEHAVIORAL OBSERVATION; SELF-REPORTS; ACCURACY; COMMUNICATION; STABILITY; CUES; INTELLIGENCE; SITUATIONS AB Four studies investigated the reliability and validity of thin slices of nonverbal behavior from social interactions including (a) how well individual slices of a given behavior predict other slices in the same interaction; (b) how well a slice of a given behavior represents the entirety of that behavior within an interaction; (c) how long a slice is necessary to sufficiently represent the entirety of a behavior within an interaction; (d) which slices best capture the entirety of behavior, across different behaviors; and (e) which behaviors (of six measured behaviors) are best captured by slices. Notable findings included strong reliability and validity for thin slices of gaze and nods, and that a 1.5-min slice from the start of an interaction may adequately represent some behaviors. Results provide useful information to researchers making decisions about slice measurement of behavior. C1 [Murphy, Nora A.] Loyola Marymount Univ, Los Angeles, CA 90045 USA. [Hall, Judith A.; Ruben, Mollie A.] Northeastern Univ, Boston, MA 02115 USA. [Mast, Marianne Schmid; Frauendorfer, Denise] Univ Lausanne, CH-1015 Lausanne, Switzerland. [Blanch-Hartigan, Danielle] NCI, Bethesda, MD 20892 USA. [Roter, Debra L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Nguyen, Laurent] Swiss Fed Inst Technol Lausanne EPFL, Lausanne, Switzerland. [Nguyen, Laurent] Idiap Res Inst, Lausanne, Switzerland. RP Murphy, NA (reprint author), Loyola Marymount Univ, Dept Psychol, 1 LMU Dr, Los Angeles, CA 90045 USA. EM nora.murphy@lmu.edu OI Ruben, Mollie/0000-0001-8918-8932 NR 53 TC 1 Z9 2 U1 7 U2 28 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0146-1672 EI 1552-7433 J9 PERS SOC PSYCHOL B JI Pers. Soc. Psychol. Bull. PD FEB PY 2015 VL 41 IS 2 BP 199 EP 213 DI 10.1177/0146167214559902 PG 15 WC Psychology, Social SC Psychology GA AZ0RM UT WOS:000347952300004 PM 25488925 ER PT J AU Lee, SY Chen, SL Chang, YH Chen, PS Huang, SY Tzeng, NS Wang, CL Wang, LJ Lee, IH Wang, TY Chen, KC Yang, YK Hong, JS Lu, RB AF Lee, S. -Y. Chen, S. -L. Chang, Y. -H. Chen, P. -S. Huang, S. -Y. Tzeng, N. -S. Wang, C. -L. Wang, L. -J. Lee, I. -H. Wang, T. -Y. Chen, K. -C. Yang, Y. -K. Hong, J. -S. Lu, R. -B. TI Correlation of plasma brain-derived neurotrophic factor and metabolic profiles in drug-naive patients with bipolar II disorder after a twelve-week pharmacological intervention SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE bipolar II disorder; body mass index; metabolic syndrome; brain-derived neurotrophic factor ID OPEN-LABEL TRIAL; FACTOR BDNF; DEPRESSED-PATIENTS; HUMAN PLATELETS; MOOD EPISODES; SERUM; SCHIZOPHRENIA; PLASTICITY; LITHIUM; DISEASE AB ObjectiveBrain-derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of bipolar disorder (BD) and metabolic syndrome. We investigated the correlation between plasma BDNF with mood symptoms and metabolic indices in patients with BD-II over a 12-week pharmacological intervention. MethodDrug-naive patients with BD-II (n=117) were recruited. Metabolic profiles [cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI)] and plasma BDNF wtrun "tblautotrun "tblsctrun "tbl_contere measured at baseline and 2, 8, and 12weeks after beginning medication. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. ResultsSeventy-six (65.0%) patients completed the intervention. Plasma BDNF levels were significantly associated with BMI (P=9.6E-5), low-density lipoprotein (P=0.034) and total (P=0.001) cholesterol, but not with the Hamilton Depression Rating Scale-17 and Young Mania Rating Scale scores over the 12-week treatment. ConclusionWe found initial evidence of a positive correlation between plasma BDNF levels and BMI, low-density lipoprotein and total cholesterol in drug-naive patients with BD-II. The specific function of BDNF in regulating and maintaining peripheral metabolic health requires additional investigation. C1 [Lee, S. -Y.] Kaohsiung Vet Gen Hosp, Dept Psychiat, Kaohsiung, Taiwan. [Lee, S. -Y.; Chen, S. -L.; Chang, Y. -H.; Chen, P. -S.; Wang, C. -L.; Lee, I. -H.; Chen, K. -C.; Yang, Y. -K.; Lu, R. -B.] Natl Cheng Kung Univ, Dept Psychiat, Coll Med, Tainan 70428, Taiwan. [Chen, S. -L.; Lu, R. -B.] Kaohsiung Med Univ, Sch Med, Dept Neurol, Kaohsiung, Taiwan. [Chang, Y. -H.] Natl Cheng Kung Univ, Inst Allied Hlth Sci, Coll Med & Hosp, Tainan 70428, Taiwan. [Huang, S. -Y.; Tzeng, N. -S.] Triserv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan. [Wang, L. -J.] Kaohsiung Chang Gung Mem Hosp, Dept Child & Adolescent Psychiat, Kaohsiung, Taiwan. [Wang, L. -J.] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan. [Wang, T. -Y.] Tainan Hosp, Dept Hlth, Dept Psychiat, Tainan, Taiwan. [Chen, K. -C.; Lu, R. -B.] Natl Cheng Kung Univ Hosp, Dept Psychiat, Yunlin, Taiwan. [Yang, Y. -K.] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 70428, Taiwan. [Hong, J. -S.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Lu, R. -B.] Inst Behav Med, Tainan, Taiwan. [Lu, R. -B.] Natl Hlth Res Inst, Ctr Neuropsychiat Res, Miaoli, Taiwan. RP Lu, RB (reprint author), Natl Cheng Kung Univ, Inst Behav Med, Dept Psychiat, Addict Ctr,Coll Med & Hosp, 138 Sheng Li Rd, Tainan 70428, Taiwan. EM rblu@mail.ncku.edu.tw FU Taiwan National Science Council [NSC98-2314-B-006-022-MY3, NSC100-2314-B-075B-010-MY3]; Taiwan Department of Health [DOH 95-TD-M-113-055]; Taiwan National Health Research Institute [NHRI-EX-97-9738NI]; National Cheng Kung University Project for Promoting Academic Excellence and Developing World Class Research Centers FX This work was supported in part by grant NSC98-2314-B-006-022-MY3 (to RBL) and NSC100-2314-B-075B-010-MY3 (to SYL) from the Taiwan National Science Council, grant DOH 95-TD-M-113-055 (to RBL) from the Taiwan Department of Health, grant NHRI-EX-97-9738NI (to RBL) from the Taiwan National Health Research Institute, and the National Cheng Kung University Project for Promoting Academic Excellence and Developing World Class Research Centers. NR 67 TC 3 Z9 3 U1 0 U2 8 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 FEB PY 2015 VL 131 IS 2 BP 120 EP 128 DI 10.1111/acps.12324 PG 9 WC Psychiatry SC Psychiatry GA AY1SS UT WOS:000347372900005 PM 25131388 ER PT J AU Esposito, G Valenzi, S Islam, T Mash, C Bornstein, MH AF Esposito, G. Valenzi, S. Islam, T. Mash, C. Bornstein, M. H. TI Immediate and selective maternal brain responses to own infant faces SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Mother-infant interaction; Infant face ID EVENT-RELATED POTENTIALS; GAMMA-BAND ACTIVITY; OSCILLATIONS; PERCEPTION; MOTHERS; CORTEX; MEMORY AB Infant faces elicit caregiving in adults. In previous research on brain responses to images of infant faces, the faces were unknown to participants. This study investigated EEG in primiparous mothers of 3- to 6-month-old infants viewing their own infant's face compared to an unfamiliar but appearance-matched infant's face. Spectral power was calculated and compared, and power at three EEG bands (delta, theta, and gamma) was found to differ between faces. Brain responses among primiparous mothers distinguish images of their own versus unfamiliar infants. (C) 2014 Elsevier B.V. All rights reserved. C1 [Esposito, G.] Univ Trento, Dept Psychol & Cognit Sci, Rovereto, TN, Italy. [Esposito, G.] Nanyang Technol Univ, Div Psychol, Singapore 639798, Singapore. [Valenzi, S.] RIKEN, Brain Sci Inst, Lab Adv Brain Signal Proc, Saitama, Japan. [Islam, T.] RIKEN, Brain Sci Inst, Lab Dev Gene Regulat, Saitama, Japan. [Mash, C.; Bornstein, M. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Esposito, G (reprint author), Univ Trento, Dept Psychol & Cognit Sci, Rovereto, TN, Italy. EM gianluca.esposito@unitn.it; Marc_H_Bornstein@nih.gov FU Japan Society for the Promotion of Science [24730563, 2402747, JSPS PE09064]; FPR Program (RIKEN Brain Science Institute); Intramural Research Program of the NIH-NICHD (USA) FX All participants in this study are gratefully acknowledged. This research was supported by the ST fellowship from Japan Society for the Promotion of Science (JSPS PE09064), Grant-in-aid for Scientific Research from Japan Society for the Promotion of Science (Projects #24730563 and #2402747), the FPR Program (RIKEN Brain Science Institute), and the Intramural Research Program of the NIH-NICHD (USA). NR 28 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD FEB 1 PY 2015 VL 278 BP 40 EP 43 DI 10.1016/j.bbr.2014.09.018 PG 4 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AY5AQ UT WOS:000347586300005 PM 25242285 ER PT J AU Griffey, S Piccinino, L Gallivan, J Lotenberg, LD Tuncer, D AF Griffey, Susan Piccinino, Linda Gallivan, Joanne Lotenberg, Lynne Doner Tuncer, Diane TI Applying national survey results for strategic planning and program improvement: The National Diabetes Education Program SO EVALUATION AND PROGRAM PLANNING LA English DT Article DE Program evaluation; Strategic planning; Program improvement; Diabetes; National health ID BEHAVIOR AB Since the 19705, the federal government has spearheaded major national education programs to reduce the burden of chronic diseases in the United States. These prevention and disease management programs communicate critical information to the public, those affected by the disease, and health care providers. The National Diabetes Education Program (NDEP), the leading federal program on diabetes sponsored by the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), uses primary and secondary quantitative data and qualitative audience research to guide program planning and evaluation. Since 2006, the NDEP has filled the gaps in existing quantitative data sources by conducting its own population-based survey, the NDEP National Diabetes Survey (NNDS). The NNDS is conducted every 2-3 years and tracks changes in knowledge, attitudes and practice indicators in key target audiences. This article describes how the NDEP has used the NNDS as a key component of its evaluation framework and how it applies the survey results for strategic planning and program improvement. The NDEP's use of the NNDS illustrates how a program evaluation framework that includes periodic population-based surveys can serve as an evaluation model for similar national health education programs. (C) 2014 The Authors. Published by Elsevier Ltd. C1 [Griffey, Susan; Piccinino, Linda] Social & Sci Syst, Silver Spring, MD 20910 USA. [Gallivan, Joanne; Tuncer, Diane] NIH, Natl Diabet Educ Program, Bethesda, MD 20892 USA. [Lotenberg, Lynne Doner] Hager Sharp, Washington, DC 20005 USA. RP Griffey, S (reprint author), 8615 Meadowsweet Ct, Columbia, MD 21045 USA. EM suegriffey@gmail.com; lpiccinino@s-3.com; joanne_gallivan@nih.gov; LDLotenberg@HagerSharp.com; diane.tuncer@nih.gov OI Griffey, Sue/0000-0003-3779-090X FU PHS HHS [HHSN27601200001U, HHSN276201200001U] NR 18 TC 3 Z9 3 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7189 EI 1873-7870 J9 EVAL PROGRAM PLANN JI Eval. Program Plan. PD FEB PY 2015 VL 48 SI SI BP 83 EP 89 DI 10.1016/j.evalprogplan.2014.10.002 PG 7 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA AY3SC UT WOS:000347501800009 PM 25463016 ER PT J AU Jaffray, DA Atun, R Barton, M Baumann, M Gospodarowicz, M Hoskin, P Knaul, FM Lievens, Y Rosenblatt, E Torode, J Van Dyk, J Vikram, B AF Jaffray, D. A. Atun, R. Barton, M. Baumann, M. Gospodarowicz, M. Hoskin, P. Knaul, F. M. Lievens, Y. Rosenblatt, E. Torode, J. Van Dyk, J. Vikram, B. CA Union Int Canc Control's Global Ta TI Radiation Therapy and the Global Health Agenda SO CLINICAL ONCOLOGY LA English DT Editorial Material ID NONCOMMUNICABLE DISEASES; RADIOTHERAPY; WORLD C1 [Jaffray, D. A.; Gospodarowicz, M.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Jaffray, D. A.; Gospodarowicz, M.] Univ Toronto, Toronto, ON, Canada. [Atun, R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Barton, M.] UNSW, Ingham Inst Appl Med Res, CCORE, Liverpool, NSW, Australia. [Baumann, M.] Tech Univ Dresden, D-01062 Dresden, Germany. [Baumann, M.] Helmholtz Zentrum Dresden Rossendorf, Dresden, Germany. [Hoskin, P.] Mt Vernon Hosp, Northwood HA6 2RN, Middx, England. [Knaul, F. M.] Harvard Univ, Harvard Global Equ Initiat, Boston, MA USA. [Lievens, Y.] Ghent Univ Hosp, Ghent, Belgium. [Rosenblatt, E.] IAEA, A-1400 Vienna, Austria. [Torode, J.] Union Int Canc Control, Geneva, Switzerland. [Van Dyk, J.] Univ Western Ontario, London, ON, Canada. [Vikram, B.] NCI, Bethesda, MD 20892 USA. RP Jaffray, DA (reprint author), Princess Margaret Canc Ctr, TECHNA Inst, 610 Univ Ave, Toronto, ON, Canada. EM david.jaffray@rmp.uhn.on.ca RI Barton, Michael/M-7183-2015; OI Barton, Michael/0000-0003-0112-0680; Delaney, Geoff/0000-0002-1829-396X NR 12 TC 4 Z9 4 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 EI 1433-2981 J9 CLIN ONCOL-UK JI Clin. Oncol. PD FEB PY 2015 VL 27 IS 2 BP 67 EP 69 DI 10.1016/j.clon.2014.11.025 PG 3 WC Oncology SC Oncology GA AY3FO UT WOS:000347470200001 PM 25575690 ER PT J AU Hsu, AP McReynolds, LJ Holland, SM AF Hsu, Amy P. McReynolds, Lisa J. Holland, Steven M. TI GATA2 deficiency SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE GATA2; haploinsufficiency; lymphedema; myelodysplastic syndrome; nontuberculous mycobacteria; pulmonary alveolar proteinosis ID ACUTE MYELOID-LEUKEMIA; FAMILIAL MYELODYSPLASTIC SYNDROME; PROGENITOR-CELL FUNCTION; NK LYMPHOID DEFICIENCY; GENOME-WIDE ANALYSIS; SPORADIC MONOCYTOPENIA; TRANSCRIPTION FACTOR; AUTOSOMAL-DOMINANT; MONOMAC SYNDROME; ASXL1 MUTATIONS AB Purpose of review GATA2 deficiency is a germline disease that causes a wide spectrum of phenotypes including viral and bacterial infections, cytopenias, myelodysplasia, myeloid leukemias, pulmonary alveolar proteinosis and lymphedema. The age of clinical presentation ranges from early childhood to late adulthood, with most occurring in adolescence to early adulthood. We review the expanding GATA2-deficient phenotype, molecular genetics of disease and developments in treatment. Recent findings GATA2 mutations have been found in up to 10% of those with congenital neutropenia and/or aplastic anemia. Heterozygous mutations appear to cause haploinsufficiency due to either protein dysfunction or uniallelic reduced transcription. Disease-associated mutations in intronic regulatory elements or variations within the 5' leader exons indicate that regulation of GATA2 is critical. Those with GATA2 mutations are at high risk for myelodysplasia, cytogenetic abnormalities, acute myeloid leukemia or chronic myelomonocytic leukemia. Bone marrow transplantation has been successful for both hematopoietic and pulmonary alveolar proteinosis repair. Summary GATA2 is a zinc finger transcription factor essential for embryonic and definitive hematopoiesis as well as lymphatic angiogenesis. GATA2 deficiency is caused by a variety of mutations in the GATA2 gene and can have variable presentation, onset and outcome. Patients are susceptible to mycobacterial, viral and fungal infections and can develop myelodysplasia, acute or chronic leukemias, lymphedema and pulmonary alveolar proteinosis. Hematopoietic stem cell transplantation reverses most of the clinical phenotype with good long-term outcomes. C1 [Hsu, Amy P.; McReynolds, Lisa J.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [McReynolds, Lisa J.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), CRC B3-4141 MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov FU Division of Intramural Research, NIAID, NIH; National Cancer Institute [CA060441] FX This work supported by the Division of Intramural Research, NIAID, NIH. L.J.M. is supported by grant CA060441 from the National Cancer Institute to the Johns Hopkins University. NR 48 TC 12 Z9 12 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-4050 EI 1473-6322 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD FEB PY 2015 VL 15 IS 1 BP 104 EP 109 DI 10.1097/ACI.0000000000000126 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA AX9ZX UT WOS:000347258500014 PM 25397911 ER PT J AU Lodish, M AF Lodish, Maya TI Cushing's syndrome in childhood: update on genetics, treatment, and outcomes SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE childhood; Cushing's disease; medical therapy; pituitary adenoma; radiation ID MCCUNE-ALBRIGHT-SYNDROME; MACRONODULAR ADRENAL-HYPERPLASIA; PHOSPHODIESTERASE 11A4 PDE11A; ENDOCRINE NEOPLASIA TYPE-1; QUALITY-OF-LIFE; PITUITARY-ADENOMAS; BILATERAL ADRENALECTOMY; ADRENOCORTICAL DISEASE; SURGICAL CURE; STEREOTACTIC RADIOSURGERY AB Purpose of reviewTo provide an update on the genes associated with Cushing's syndrome in children, as well as to familiarize the clinician with recent treatment guidelines and outcome data for children with Cushing's syndrome.Recent findingsThe list of genes associated with Cushing's syndrome continues to grow. In addition, treatment for childhood Cushing's syndrome is evolving. As long-term follow-up data on children becomes available, clinicians need to be aware of the issues that require attention.SummaryKnowledge of the specific genetic causes of Cushing's syndrome has potential implications for treatment, surveillance, and counseling. Advances in surgical technique, radiation modalities, and medical therapies offer the potential for additional treatment options in Cushing's syndrome. Early identification and management of post-treatment morbidities in children treated for Cushing's syndrome is crucial in order to optimize care. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Sect Endocrinol & Genet, Bethesda, MD 20892 USA. RP Lodish, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Sect Endocrinol & Genet, 10 Ctr Dr, Bethesda, MD 20892 USA. EM lodishma@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH) FX Funding: This work was supported by the intramural programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH). NR 65 TC 1 Z9 1 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2015 VL 22 IS 1 BP 48 EP 54 DI 10.1097/MED.0000000000000127 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX6IW UT WOS:000347027000010 PM 25517021 ER PT J AU Sigurdardottir, LG Markt, SC Rider, JR Haneuse, S Fall, K Schernhammer, ES Tamimi, RM Flynn-Evans, E Batista, JL Launer, L Harris, T Aspelund, T Stampfer, MJ Gudnason, V Czeisler, CA Lockley, SW Valdimarsdottir, UA Mucci, LA AF Sigurdardottir, Lara G. Markt, Sarah C. Rider, Jennifer R. Haneuse, Sebastien Fall, Katja Schernhammer, Eva S. Tamimi, Rulla M. Flynn-Evans, Erin Batista, Julie L. Launer, Lenore Harris, Tamara Aspelund, Thor Stampfer, Meir J. Gudnason, Vilmundur Czeisler, Charles A. Lockley, Steven W. Valdimarsdottir, Unnur A. Mucci, Lorelei A. TI Urinary Melatonin Levels, Sleep Disruption, and Risk of Prostate Cancer in Elderly Men SO EUROPEAN UROLOGY LA English DT Article DE Circadian rhythm; Melatonin levels; Prostate cancer ID 6-SULFATOXYMELATONIN AB Melatonin has anticarcinogenic properties in experimental models. We undertook a case-cohort study of 928 Icelandic men without prostate cancer (PCa) nested within the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort to investigate the prospective association between first morning-void urinary 6-sulfatoxymelatonin (aMT6s) levels and the subsequent risk for PCa, under the hypothesis that men with lower aMT6s levels have an increased risk for advanced PCa. We used weighted Cox proportional hazards models to assess the association between first morning-void aMT6s levels and PCa risk, adjusting for potential confounders. A total of 111 men were diagnosed with incident PCa, including 24 with advanced disease. Men who reported sleep problems at baseline had lower morning aMT6s levels compared with those who reported no sleep problems. Men with morning aMT6s levels below the median had a fourfold statistically significant increased risk for advanced disease compared with men with levels above the median (hazard ratio: 4.04; 95% confidence interval, 1.26-12.98). These results require replication in larger prospective studies with longer follow-up. Patient summary: In this report, we evaluated the prospective association between urinary aMT6s levels and risk of PCa in an Icelandic population. We found that lower levels of aMT6s were associated with an increased risk for advanced PCa. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Sigurdardottir, Lara G.; Fall, Katja; Aspelund, Thor; Valdimarsdottir, Unnur A.; Mucci, Lorelei A.] Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland. [Sigurdardottir, Lara G.; Gudnason, Vilmundur; Valdimarsdottir, Unnur A.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Sigurdardottir, Lara G.] Iceland Canc Soc, Reykjavik, Iceland. [Markt, Sarah C.; Rider, Jennifer R.; Fall, Katja; Schernhammer, Eva S.; Tamimi, Rulla M.; Batista, Julie L.; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rider, Jennifer R.; Schernhammer, Eva S.; Tamimi, Rulla M.; Batista, Julie L.; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Haneuse, Sebastien] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fall, Katja] Univ Orebro, Clin Epidemiol Unit, SE-70182 Orebro, Sweden. [Fall, Katja] Orebro Univ Hosp, SE-70182 Orebro, Sweden. [Flynn-Evans, Erin; Czeisler, Charles A.; Lockley, Steven W.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA. [Flynn-Evans, Erin; Czeisler, Charles A.; Lockley, Steven W.] Brigham & Womens Hosp, Dept Med, Div Sleep & Circadian Disorders, Boston, MA 02115 USA. [Flynn-Evans, Erin; Czeisler, Charles A.; Lockley, Steven W.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Launer, Lenore; Harris, Tamara] Natl Inst Aging, Lab Epidemiol & Populat Sci, Bethesda, MD USA. [Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. RP Markt, SC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM sec110@mail.harvard.edu RI Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; OI Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433; Rider, Jennifer/0000-0002-2637-6036; Fall, Katja/0000-0002-3649-2639 FU RANNIS (the Icelandic Research Fund); National Institutes of Health (NIH) National Center for Research Resources [UL1-RR-025758, KL2-RR-025757]; Icelandic Cancer Society; NIH National Cancer Institute [R25-CA-098566, T32-CA-09001-35]; Prostate Cancer Foundation; NIH National Institutes on Aging (NIA) [N01-AG-12100]; Icelandic Heart Association; Icelandic Parliament; NIH NIA [P01-AG-009975] FX This study was supported in part by RANNIS (the Icelandic Research Fund); the Harvard Catalyst Award (awards UL1-RR-025758 and KL2-RR-025757) from the National Institutes of Health (NIH) National Center for Research Resources; the Icelandic Cancer Society; NIH National Cancer Institute training grants (grants R25-CA-098566 and T32-CA-09001-35 to SCM); and the Prostate Cancer Foundation (to LAM and JRR). The AGES-Reykjavik is supported by Contract N01-AG-12100 from the NIH National Institutes on Aging (NIA) Intramural Research Program, the Icelandic Heart Association, and the Icelandic Parliament. CAC was supported in part by NIH NIA grant P01-AG-009975. The funding agencies had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. NR 10 TC 14 Z9 14 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD FEB PY 2015 VL 67 IS 2 BP 191 EP 194 DI 10.1016/j.eururo.2014.07.008 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA AX6LJ UT WOS:000347033500013 PM 25107635 ER PT J AU Simon, SL Braby, LA Chang, PY Goodhead, DT Hora, S Kocher, DC Mabuchi, K Puskin, JS Richardson, D Rosenstein, M Tucker, J Vano, E AF Simon, Steven L. Braby, Leslie A. Chang, Polly Y. Goodhead, Dudley T. Hora, Stephen Kocher, David C. Mabuchi, Kiyohiko Puskin, Jerome S. Richardson, David Rosenstein, Marvin Tucker, James Vano, Eliseo TI BIOLOGICAL EFFECTIVENESS OF PHOTONS AND ELECTRONS AS A FUNCTION OF ENERGY SO HEALTH PHYSICS LA English DT Article DE National Council on Radiation Protection and Measurements; cancer; radiation risk; relative biological effectiveness C1 [Simon, Steven L.; Mabuchi, Kiyohiko] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Braby, Leslie A.] Texas A&M Univ, Dept Nucl Engn, College Stn, TX 77843 USA. [Chang, Polly Y.] SRI Int, Menlo Pk, CA 94025 USA. [Goodhead, Dudley T.] MRC, Harwell OX11 0RD, Berks, England. [Hora, Stephen] Univ So Calif, Ctr Risk & Econ Anal Terrorism Events, Los Angeles, CA 90089 USA. [Kocher, David C.] Oak Ridge Ctr Risk Anal, Oak Ridge, TN 37830 USA. [Puskin, Jerome S.] US EPA, Washington, DC 20460 USA. [Richardson, David] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Tucker, James] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. [Vano, Eliseo] Univ Complutense, Dept Radiol, Sch Med, E-28040 Madrid, Spain. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov NR 3 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2015 VL 108 IS 2 BP 143 EP 144 DI 10.1097/HP.0000000000000256 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA AX6YN UT WOS:000347064100009 PM 25551494 ER PT J AU Coleman, CN Sullivan, JM Bader, JL Murrain-Hill, P Koerner, JF Garrett, AL Weinstock, DM Case, C Hrdina, C Adams, SA Whitcomb, RC Graeden, E Shankman, R Lant, T Maidment, BW Hatchett, RC AF Coleman, C. Norman Sullivan, Julie M. Bader, Judith L. Murrain-Hill, Paula Koerner, John F. Garrett, Andrew L. Weinstock, David M. Case, Cullen, Jr. Hrdina, Chad Adams, Steven A. Whitcomb, Robert C. Graeden, Ellie Shankman, Robert Lant, Timothy Maidment, Bert W. Hatchett, Richard C. TI PUBLIC HEALTH AND MEDICAL PREPAREDNESS FOR A NUCLEAR DETONATION: THE NUCLEAR INCIDENT MEDICAL ENTERPRISE SO HEALTH PHYSICS LA English DT Article DE National Council on Radiation Protection and Measurements; emergency planning; nuclear war; radiological terrorism ID SCARCE RESOURCES; RADIATION VICTIMS; GLOBAL CONSENSUS; DECISION-MODEL; MASS-CASUALTY; MANAGEMENT; EMERGENCIES; ALLOCATION; TRIAGE; TOOLS AB Resilience and the ability to mitigate the consequences of a nuclear incident are enhanced by (1) effective planning, preparation and training; (2) ongoing interaction, formal exercises, and evaluation among the sectors involved; (3) effective and timely response and communication; and (4) continuous improvements based on new science, technology, experience, and ideas. Public health and medical planning require a complex, multifaceted systematic approach involving federal, state, local, tribal, and territorial governments; private sector organizations; academia; industry; international partners; and individual experts and volunteers. The approach developed by the U.S. Department of Health and Human Services Nuclear Incident Medical Enterprise (NIME) is the result of efforts from government and nongovernment experts. It is a "bottom-up" systematic approach built on the available and emerging science that considers physical infrastructure damage, the spectrum of injuries, a scarce resources setting, the need for decision making in the face of a rapidly evolving situation with limited information early on, timely communication, and the need for tools and just-in-time information for responders who will likely be unfamiliar with radiation medicine and uncertain and overwhelmed in the face of the large number of casualties and the presence of radioactivity. The components of NIME can be used to support planning for, response to, and recovery from the effects of a nuclear incident. Recognizing that it is a continuous work-in-progress, the current status of the public health and medical preparedness and response for a nuclear incident is provided. C1 [Coleman, C. Norman; Sullivan, Julie M.; Bader, Judith L.; Murrain-Hill, Paula; Koerner, John F.; Garrett, Andrew L.; Shankman, Robert] Dept Hlth & Human Serv, Off Emergency Management, Off Assistant Secretary Preparedness & Response, Washington, DC USA. [Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Weinstock, David M.; Case, Cullen, Jr.] Natl Marrow Donor Program, Radiat Injury Treatment Network, Minneapolis, MN USA. [Hrdina, Chad] Dept Hlth & Human Serv, Off Policy & Planning, Off Assistant Secretary Preparedness & Response, Washington, DC USA. [Adams, Steven A.] Ctr Dis Control & Prevent, Div Strateg Natl Stockpile, Off Publ Hlth Preparedness & Response, Atlanta, GA USA. [Whitcomb, Robert C.] Ctr Dis Control & Prevent, Radiat Studies Branch, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA USA. [Graeden, Ellie] Gryphon Sci LLC, Rockville, MD USA. [Lant, Timothy; Hatchett, Richard C.] Dept Hlth & Human Serv, Biomed Adv Res & Dev Author, Off Assistant Secretary Preparedness & Response, Washington, DC USA. [Maidment, Bert W.] NIAID, Radiat Nucl Countermeasures Program, NIH, Bethesda, MD 20892 USA. RP Coleman, CN (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM ccoleman@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 53 TC 9 Z9 9 U1 3 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2015 VL 108 IS 2 BP 149 EP 160 DI 10.1097/HP.0000000000000249 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA AX6YN UT WOS:000347064100011 PM 25551496 ER PT J AU Bouville, A Toohey, RE Boice, JD Beck, HL Dauer, LT Eckerman, KF Hagemeyer, D Leggett, RW Mumma, MT Napier, B Pryor, KH Rosenstein, M Schauer, DA Sherbini, S Stram, DO Thompson, JL Till, JE Yoder, C Zeitlin, C AF Bouville, Andre Toohey, Richard E. Boice, John D., Jr. Beck, Harold L. Dauer, Larry T. Eckerman, Keith F. Hagemeyer, Derek Leggett, Richard W. Mumma, Michael T. Napier, Bruce Pryor, Kathy H. Rosenstein, Marvin Schauer, David A. Sherbini, Sami Stram, Daniel O. Thompson, James L. Till, John E. Yoder, Craig Zeitlin, Cary TI DOSE RECONSTRUCTION FOR THE MILLION WORKER STUDY: STATUS AND GUIDELINES SO HEALTH PHYSICS LA English DT Article DE National Council on Radiation Protection and Measurements; dose assessment; exposure, occupational; radiation risk ID FILM DOSIMETER RESPONSE; US RADIOLOGIC TECHNOLOGISTS; RADIATION WORKERS; MILITARY PARTICIPANTS; MORTALITY; COHORT; UNCERTAINTY; PLUTONIUM; METHODOLOGY; EXPOSURES AB The primary aim of the epidemiologic study of one million U.S. radiation workers and veterans [the Million Worker Study (MWS)] is to provide scientifically valid information on the level of radiation risk when exposures are received gradually over time and not within seconds, as was the case for Japanese atomic bomb survivors. The primary outcome of the epidemiologic study is cancer mortality, but other causes of death such as cardiovascular disease and cerebrovascular disease will be evaluated. The success of the study is tied to the validity of the dose reconstruction approaches to provide realistic estimates of organ-specific radiation absorbed doses that are as accurate and precise as possible and to properly evaluate their accompanying uncertainties. The dosimetry aspects for the MWS are challenging in that they address diverse exposure scenarios for diverse occupational groups being studied over a period of up to 70 y. The dosimetric issues differ among the varied exposed populations that are considered: atomic veterans, U.S. Department of Energy workers exposed to both penetrating radiation and intakes of radionuclides, nuclear power plant workers, medical radiation workers, and industrial radiographers. While a major source of radiation exposure to the study population comes from external gamma-or x-ray sources, for some of the study groups, there is a meaningful component of radionuclide intakes that requires internal radiation dosimetry assessments. Scientific Committee 6-9 has been established by the National Council on Radiation Protection and Measurements (NCRP) to produce a report on the comprehensive organ dose assessment (including uncertainty analysis) for the MWS. The NCRP dosimetry report will cover the specifics of practical dose reconstruction for the ongoing epidemiologic studies with uncertainty analysis discussions and will be a specific application of the guidance provided in NCRP Report Nos. 158, 163, 164, and 171. The main role of the Committee is to provide guidelines to the various groups of dosimetrists involved in the MWS to ensure that certain dosimetry criteria are considered: calculation of annual absorbed doses in the organs of interest, separation of low and high linear-energy transfer components, evaluation of uncertainties, and quality assurance and quality control. It is recognized that the MWS and its approaches to dosimetry are a work in progress and that there will be flexibility and changes in direction as new information is obtained with regard to both dosimetry and the epidemiologic features of the study components. This paper focuses on the description of the various components of the MWS, the available dosimetry results, and the challenges that have been encountered. It is expected that the Committee will complete its report in 2016. C1 [Bouville, Andre] NCI, Rockville, MD 20850 USA. [Toohey, Richard E.] MH Chew & Associates, Oak Ridge, TN USA. [Boice, John D., Jr.; Schauer, David A.] Natl Council Radiat Protect & Measurements, Bethesda, MD USA. [Beck, Harold L.] US DOE, New York, NY USA. [Dauer, Larry T.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Eckerman, Keith F.; Leggett, Richard W.] Oak Ridge Natl Lab, Oak Ridge, TN USA. [Hagemeyer, Derek] Oak Ridge Associated Univ, Oak Ridge, TN USA. [Mumma, Michael T.] Int Epidemiol Inst, Rockville, MD USA. [Napier, Bruce; Pryor, Kathy H.] Pacific NW Natl Lab, Richland, WA 99352 USA. [Sherbini, Sami] US Nucl Regulatory Commiss, Washington, DC 20555 USA. [Stram, Daniel O.] Univ So Calif, Los Angeles, CA USA. [Thompson, James L.] US Nucl Regulatory Commiss, Arlington, TX USA. [Till, John E.] Risk Assessment Corp, Neeses, SC USA. [Yoder, Craig] Landauer Inc, Glenwood, IL USA. [Zeitlin, Cary] SW Res Inst, Boulder, CO USA. RP Bouville, A (reprint author), NCI, 9609 Med Ctr Dr,Room 7E590,MSC 9778, Rockville, MD 20850 USA. EM andre.bouville@nih.gov OI Dauer, Lawrence/0000-0002-5629-8462 FU U.S. Department of Energy [DE-SC0008944]; U.S. Nuclear Regulatory Commission; U.S. Environmental Protection Agency; National Aeronautics and Space Administration; National Cancer Institute [U01 CA137026]; Vanderbilt-Ingram Cancer Center [404-357-9682] FX This research was supported in part by contracts and grants from the U.S. Department of Energy (Grant No. DE-SC0008944 awarded to NCRP), which included interagency support from the U.S. Nuclear Regulatory Commission, the U.S. Environmental Protection Agency and the National Aeronautics and Space Administration; the National Cancer Institute (Grant No. U01 CA137026); and a Discovery Grant from the Vanderbilt-Ingram Cancer Center (Center no. 404-357-9682). We also acknowledge Paul Blake, Director, Chief, Nuclear Test Personnel Review, Defense Threat Reduction Agency, Department of Defense and his staff for their technical support of the atomic veterans project. Similarly, Han Kang and Tim Bullman, Environmental Epidemiology Service, U.S. Department of Veterans Affairs, were instrumental in providing support and assistance throughout the conduct of the atomic veteran study. NR 56 TC 13 Z9 13 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2015 VL 108 IS 2 BP 206 EP 220 DI 10.1097/HP.0000000000000231 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA AX6YN UT WOS:000347064100019 PM 25551504 ER PT J AU Ortiz, R Niciu, MJ Lukkahati, N Saligan, LN Nugent, AC Luckenbaugh, DA Machado-Vieira, R Zarate, CA AF Ortiz, Robin Niciu, Mark J. Lukkahati, Nada Saligan, Leorey N. Nugent, Allison C. Luckenbaugh, David A. Machado-Vieira, Rodrigo Zarate, Carlos A., Jr. TI Shank3 as a potential biomarker of antidepressant response to ketamine and its neural correlates in bipolar depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Ketamine; Bipolar depression; Shank3; MRI; PET ID D-ASPARTATE ANTAGONIST; ADD-ON TRIAL; MAJOR DEPRESSION; HUMAN BRAIN; BEHAVIOR; DISORDERS; HIPPOCAMPAL; EXPRESSION; GLUTAMATE; SYNAPSES AB Background: Shank3, a post-synaptic density protein involved in N-methyl-D-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the pathophysiology of bipolar disorder. We hypothesized that elevated baseline plasma Shank3 levels might predict antidepressant response to the NMDA receptor antagonist ketamine. Methods: Twenty-nine subjects with bipolar depression received a double-blind, randomized, subanesthetic dose (.5 mg/kg) ketamine infusion. Of the patients for whom Shank3 levels were collected, 15 completed baseline 3-Tesla MRl and 17 completed post-ketamine [F-18]-FDG PET. Results: Higher baseline Shank3 levels predicted antidepressant response at Days 1 (r=.39, p=.047), 2 (r=-.45, p=.02), and 3 (r=-.42, p=.03) and were associated with larger average (r =.58, p=.02) and right amygdala volume (r=.65, p=.009). Greater baseline Shank3 also predicted increased glucose metabolism in the hippocampus (r=.51, p=.04) and amygdala (r=.58, p=.02). Limitations: Limitations include the small sample size, inability to assess the source of peripheral Shank3, and the lack of a placebo group for baseline Shank3 levels and comparative structural/functional neuroimaging. Conclusions: Shank3 is a potential biomarker of antidepressant response to ketamine that correlates with baseline amygdala volume and increased glucose metabolism in the amygdala and hippocampus. Published by Elsevier B.V. C1 [Ortiz, Robin; Niciu, Mark J.; Nugent, Allison C.; Luckenbaugh, David A.; Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, NIH, Expt Therapeut & Pathophysiol Branch, CRC, Bethesda, MD 20892 USA. [Lukkahati, Nada; Saligan, Leorey N.] NINR, NIH, Bethesda, MD 20892 USA. [Lukkahati, Nada] Univ Nevada, Sch Nursing, Las Vegas, NV 89154 USA. RP Zarate, CA (reprint author), NIMH, NIH, Expt Therapeut & Pathophysiol Branch, CRC, Bldg 10,10 Ctr Dr,Room 7-5342, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Niciu, Mark/J-1766-2014; OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Niciu, Mark/0000-0002-5612-3021; Nugent, Allison/0000-0003-2569-2480 FU National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH) FX This study was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH). The NIMH had no further role in study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 25 TC 8 Z9 8 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB 1 PY 2015 VL 172 BP 307 EP 311 DI 10.1016/j.jad.2014.10.015 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AX0LD UT WOS:000346643000043 PM 25451430 ER PT J AU Irfanoglu, MO Modi, P Nayak, A Hutchinson, EB Sarlls, J Pierpaoli, C AF Irfanoglu, M. Okan Modi, Pooja Nayak, Amritha Hutchinson, Elizabeth B. Sarlls, Joelle Pierpaoli, Carlo TI DR-BUDDI (Diffeomorphic Registration for Blip-Up blip-Down Diffusion Imaging) method for correcting echo planar imaging distortions SO NEUROIMAGE LA English DT Article DE Echo planar imaging; Diffusion tensor imaging; Reversed phase encoding; Diffeomorphic image registration ID GEOMETRIC DISTORTION; WEIGHTED MRI; HUMAN BRAIN; SPIN-ECHO; IMAGES; TENSOR; EPI; TRACTOGRAPHY; ORIENTATION; FRAMEWORK AB We propose an echo planar imaging (EPI) distortion correction method (DR-BUDDI), specialized for diffusion MRI, which uses data acquired twice with reversed phase encoding directions, often referred to as blip-up blip-down acquisitions. DR-BUDDI can incorporate information from an undistorted structural MRI and also use diffusion-weighted images (DWI) to guide the registration, improving the quality of the registration in the presence of large deformations and in white matter regions. DR-BUDDI does not require the transformations for correcting blip-up and blip-down images to be the exact inverse of each other. Imposing the theoretical "blip-up blipdown distortion symmetry" may not be appropriate in the presence of common clinical scanning artifacts such as motion, ghosting, Gibbs ringing, vibrations, and low signal-to-noise. The performance of DR-BUDDI is evaluated with several data sets and compared to other existing blip-up blip-down correction approaches. The proposed method is robust and generally outperforms existing approaches. The inclusion of the DWIs in the correction process proves to be important to obtain a reliable correction of distortions in the brain stem. Methods that do not use DWIs may produce a visually appealing correction of the non-diffusion weighted images, but the directionally encoded color maps computed from the tensor reveal an abnormal anatomy of the white matter pathways. (C) 2014 Elsevier Inc. All rights reserved. C1 [Irfanoglu, M. Okan; Modi, Pooja; Nayak, Amritha; Hutchinson, Elizabeth B.; Pierpaoli, Carlo] NICHHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. [Irfanoglu, M. Okan; Nayak, Amritha; Hutchinson, Elizabeth B.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Sarlls, Joelle] NINDS, NIH MRI Res Facil, NIH, Bethesda, MD 20892 USA. RP Irfanoglu, MO (reprint author), NICHHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. EM irfanoglumo@helix.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH); Department of Defense in the Center for Neuroscience and Regenerative Medicine (CNRM) (HJF Award) [30613610.0160855] FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH). Support for this work included funding from Department of Defense in the Center for Neuroscience and Regenerative Medicine (CNRM) (HJF Award #: 30613610.0160855). The authors would also like to thank the Henry M. Jackson Foundation (HJF) for their administrative support and Dr. Holland for making his correction tool available to us. Finally, we would like to thank the NIH Diffusion-Weighted EPI Distortion Correction Working Group, consisting of Dr. Andrew Knutsen, Dr. Cibu Thomas, Dr. Stephano Marenco, Dr. Souheil Inati, Dr. Ziad Saad, Dr. John Butman, Dr. Dzung Pham, Dr. Govind Bhagavatheeshwaran, Dr. Vinai Roopchansingh, Dr. Sean Marrett, Dr. Lalith Talagala, and Dr. Alexandru Avram for providing a discussion environment that initiated this work. We also thank Liz Salak for editing this manuscript. NR 52 TC 8 Z9 8 U1 0 U2 12 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 FEB 1 PY 2015 VL 106 BP 284 EP 299 DI 10.1016/j.neuroimage.2014.11.042 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AX7NG UT WOS:000347101900026 PM 25433212 ER PT J AU Klein, WMP Shepperd, JA Suls, J Rothman, AJ Croyle, RT AF Klein, William M. P. Shepperd, James A. Suls, Jerry Rothman, Alexander J. Croyle, Robert T. TI Realizing the Promise of Social Psychology in Improving Public Health SO PERSONALITY AND SOCIAL PSYCHOLOGY REVIEW LA English DT Review DE social psychology; health psychology; health behavior; public health ID DECISION-MAKING; REASONED ACTION; PLANNED BEHAVIOR; UNITED-STATES; BREAST-CANCER; TEAM SCIENCE; INTERVENTIONS; MODELS; RECOMMENDATIONS; DETERMINANTS AB The theories, phenomena, empirical findings, and methodological approaches that characterize contemporary social psychology hold much promise for addressing enduring problems in public health. Indeed, social psychologists played a major role in the development of the discipline of health psychology during the 1970s and 1980s. The health domain allows for the testing, refinement, and application of many interesting and important research questions in social psychology, and offers the discipline a chance to enhance its reach and visibility. Nevertheless, in a review of recent articles in two major social-psychological journals (Personality and Social Psychology Bulletin and Journal of Personality and Social Psychology), we found that only 3.2% of 467 studies explored health-related topics. In this article, we identify opportunities for research at the interface of social psychology and health, delineate barriers, and offer strategies that can address these barriers as the discipline continues to evolve. C1 [Klein, William M. P.; Suls, Jerry; Croyle, Robert T.] NCI, Rockville, MD USA. [Shepperd, James A.] Univ Florida, Gainesville, FL USA. [Rothman, Alexander J.] Univ Minnesota, Minneapolis, MN USA. RP Klein, WMP (reprint author), NCI, Behav Res Program, 9609 Med Ctr Dr,Room 3E140, Bethesda, MD 20892 USA. EM kleinwm@mail.nih.gov NR 112 TC 5 Z9 5 U1 3 U2 38 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1088-8683 EI 1532-7957 J9 PERS SOC PSYCHOL REV JI Pers. Soc. Psychol. Rev. PD FEB PY 2015 VL 19 IS 1 BP 77 EP 92 DI 10.1177/1088868314539852 PG 16 WC Psychology, Social SC Psychology GA AX8PM UT WOS:000347171100004 PM 24981514 ER PT J AU Dowling, WE Hogan, RJ AF Dowling, William E. Hogan, Robert J. TI Focus on Ebola Virus Research SO VIRAL IMMUNOLOGY LA English DT Editorial Material C1 [Dowling, William E.] NIAID, Div Microbiol & Infect Dis, Rockville, MD 20852 USA. [Hogan, Robert J.] Univ Georgia, Coll Vet Med, Dept Vet Biosci, Athens, GA USA. [Hogan, Robert J.] Univ Georgia, Coll Vet Med, Dept Diagnost Imaging & Infect Dis, Athens, GA USA. RP Dowling, WE (reprint author), NIAID, Div Microbiol & Infect Dis, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 3 U2 151 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0882-8245 EI 1557-8976 J9 VIRAL IMMUNOL JI Viral Immunol. PD FEB 1 PY 2015 VL 28 IS 1 SI SI BP 1 EP 2 DI 10.1089/vim.2015.1501 PG 2 WC Immunology; Virology SC Immunology; Virology GA AY4AH UT WOS:000347520100001 PM 25565061 ER PT J AU Moraski, GC Miller, PA Bailey, MA Ollinger, J Parish, T Boshoff, HI Cho, S Anderson, JR Mulugeta, S Franzblau, SG Miller, MJ AF Moraski, Garrett C. Miller, Patricia A. Bailey, Mai Ann Ollinger, Juliane Parish, Tanya Boshoff, Helena I. Cho, Sanghyun Anderson, Jeffery R. Mulugeta, Surafel Franzblau, Scott G. Miller, Marvin J. TI Putting Tuberculosis (TB) To Rest: Transformation of the Sleep Aid, Ambien, and "Anagrams" Generated Potent Antituberculosis Agents SO ACS INFECTIOUS DISEASES LA English DT Article DE tuberculosis; zolpidem; imidazopyridine analogues; anti-TB; Ambien ID NONREPLICATING MYCOBACTERIUM-TUBERCULOSIS; IN-VITRO; ZOLPIDEM; INHIBITORS; CANDIDATE; INSOMNIA; VIVO AB Zolpidem (Ambien, 1) is an imidazo[1,2-a]pyridine-3-acetamide and an approved drug for the treatment of insomnia. As medicinal chemists enamored by how structure imparts biological function, we found it to have strikingly similar structure to the antitubercular imidazo[1,2-a]pyridine-3-carboxyamides. Zolpidem was found to have antituberculosis activity (MIC of 10-50 mu M) when screened against replicating Mycobacterium tuberculosis (Mtb) H(37)Rv. Manipulation of the Zolpidem structure, notably, to structural isomers ("anagrams"), attains remarkably improved potency (5, MIC of 0.004 mu M) and impressive potency against clinically relevant drug-sensitive, multi- and extensively drug-resistant Mtb strains (MIC < 0.03 mu M). Zolpidem anagrams and analogues were synthesized and evaluated for their antitubercular potency, toxicity, and spectrum of activity against nontubercular mycobacteria and Gram-positive and Gram-negative bacteria. These efforts toward the rational design of isomeric anagrams of a well-known sleep aid underscore the possibility that further optimization of the imidazo[1,2-a]pyridine core may well "put TB to rest". C1 [Moraski, Garrett C.; Miller, Patricia A.; Miller, Marvin J.] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [Bailey, Mai Ann; Ollinger, Juliane; Parish, Tanya] Infect Dis Res Inst, TB Discovery Res, Seattle, WA 98102 USA. [Boshoff, Helena I.] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Cho, Sanghyun; Anderson, Jeffery R.; Mulugeta, Surafel; Franzblau, Scott G.] Univ Illinois, Coll Pharm, Inst TB Res, Chicago, IL 60612 USA. RP Miller, MJ (reprint author), Univ Notre Dame, Dept Chem & Biochem, 251 Nieuwland Sci Hall, Notre Dame, IN 46556 USA. EM mmiller1@nd.edu FU Intramural Research Program of NIAID [2R01 AI054193]; NSF [CHE-0741793]; Eli Lilly and Co. FX We dedicate this paper to the memory of Professor Jeremiah P. Freeman (August 3, 1929-February 14, 2014). This work was funded, in part, by the Intramural Research Program of NIAID (HB), by Grant 2R01 AI054193 (to M.J.M.), and in-kind contributions from Dow AgroScience. The Mass Spectrometry and Proteomics Facility (Bill Boggess and Michelle Joyce) is supported by Grant CHE-0741793 from the NSF. The work at IDRI was funded in part by Eli Lilly and Co. in support of the mission of the Lilly TB Drug Discovery Initiative. We thank Prof. Jennifer DuBois, Jed Fisher, and Lowell Markley for regular scientific discussions and Torey Ailing, James Ahn, Julie Early, and Stephanie Florio for technical assistance. NR 38 TC 11 Z9 11 U1 3 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2373-8227 J9 ACS INFECT DIS JI ACS Infect. Dis. PD FEB PY 2015 VL 1 IS 2 BP 85 EP 90 DI 10.1021/id500008t PG 6 WC Chemistry, Medicinal; Infectious Diseases SC Pharmacology & Pharmacy; Infectious Diseases GA DB4DH UT WOS:000368463200002 PM 25984566 ER PT J AU Tanner, AE Philbin, MM DuVal, A Ellen, J Kapogiannis, B Fortenberry, JD AF Tanner, Amanda E. Philbin, Morgan M. DuVal, Anna Ellen, Jonathan Kapogiannis, Bill Fortenberry, J. Dennis TI TRANSITIONING ADOLESCENTS WITH HIV TO ADULT CARE: EXAMINING PROCESSES AT TWELVE ADOLESCENT MEDICINE CLINICS SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 [Tanner, Amanda E.] Univ North Carolina Greensboro, Greensboro, NC 27412 USA. [Philbin, Morgan M.] Columbia Univ, New York, NY 10027 USA. [Philbin, Morgan M.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [DuVal, Anna] Johns Hopkins Sch Med, Baltimore, MD USA. [Ellen, Jonathan] Johns Hopkins Med, All Childrens Hosp, Baltimore, MD USA. [Kapogiannis, Bill] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Baltimore, MD USA. [Fortenberry, J. Dennis] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2015 VL 56 IS 2 SU 1 MA 30 BP S16 EP S16 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA DK6XU UT WOS:000375069900031 ER PT J AU Buehring, B Fidler, E Krueger, D Ward, RE Caserotti, P Strotmeyer, ES Harris, TB Binkley, N AF Buehring, B. Fidler, E. Krueger, D. Ward, R. E. Caserotti, P. Strotmeyer, E. S. Harris, T. B. Binkley, N. TI EFFECT OF AGE AND SEX ON JUMPING MECHANOGRAPHY AND OTHER MEASURES OF MUSCLE MASS AND FUNCTION SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO) CY MAR 26-29, 2015 CL Milan, ITALY SP WCO, IOF, EsCEO C1 [Buehring, B.; Fidler, E.; Krueger, D.; Binkley, N.] Univ Wisconsin, Madison, WI USA. [Ward, R. E.; Strotmeyer, E. S.] Univ Pittsburgh, Pittsburgh, PA USA. [Caserotti, P.] Univ Southern Denmark, Odense, Denmark. [Harris, T. B.] NIH, Bethesda, MD 20892 USA. RI Buehring, Bjoern/L-5581-2013 OI Buehring, Bjoern/0000-0003-3841-624X NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD FEB PY 2015 VL 26 SU 1 MA OC24 BP S49 EP S49 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DI8QX UT WOS:000373767100033 ER PT J AU Schileo, E Palmadori, I Taddei, F Coran, A Sigurdsson, S Gudnason, V Harris, TB Foresta, C AF Schileo, E. Palmadori, I. Taddei, F. Coran, A. Sigurdsson, S. Gudnason, V. Harris, T. B. Foresta, C. TI SIMILAR PROXIMAL FEMUR STRENGTH FROM DIFFERENT BONE STRUCTURAL TRAITS: KLINEFELTER SYNDROME PATIENTS AND POST-MENOPAUSAL WOMEN SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO) CY MAR 26-29, 2015 CL Milan, ITALY SP WCO, IOF, EsCEO C1 [Schileo, E.; Palmadori, I.; Taddei, F.] Ist Ortoped Rizzoli, Bologna, Italy. [Coran, A.; Foresta, C.] Univ Padua, Padua, Italy. [Sigurdsson, S.; Gudnason, V.] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland. [Harris, T. B.] NIA, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD FEB PY 2015 VL 26 SU 1 MA P272 BP S151 EP S151 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DI8QX UT WOS:000373767100241 ER PT J AU Lebdai, S Verhoest, G Parikh, H Jacquet, SF Bensalah, K Chautard, D Leclercq, NR Azzouzi, AR Bigot, P AF Lebdai, Souhil Verhoest, Gregory Parikh, Hemang Jacquet, Solene Florence Bensalah, Karim Chautard, Denis Leclercq, Nathalie Rioux Azzouzi, Abdel Rahmene Bigot, Pierre TI Identification and validation of TGFBI as a promising prognosis marker of clear cell renal cell carcinoma SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Mass spectrometry; Renal cancer; Proteomics; Transforming growth factor beta-induced protein ig-h3; Prognosis; SSIGN score ID CANCER; GENE; EXPRESSION; BETA-IG-H3; BIGH3; BETA AB Objective: To identify prognostic biomarkers in clear cell renal cell carcinoma (ccRCC) using a proteomic approach. Material and methods: We performed a comparative proteomic profiling of ccRCC and normal renal tissues from 9 different human specimens. We assessed differential protein expression by iTRAQ (isobaric tagging reagent for absolute quantity) labeling with regard to tumor aggressiveness according to the stage, size, grade, and necrosis (SSIGN) score and continued our results using Western blot (9 patients) and immunohistochemistry (135 patients) analysis. Results: After proteomic analysis, 928 constitutive proteins were identified. Among these proteins, 346 had a modified expression in tumor compared with that of normal tissue. Pathway and integrated analyses indicated the presence of an up-regulation of the pentose phosphate pathway in aggressive tumors. In total, 14 proteins were excreted and could potentially become biomarkers. Overexpression of transforming growth factor, beta-induced (TGFBI) in ccRCC was confirmed using Western blot and immunohistochemistry analysis. A significant association was found between the presence of TGFBI expression with tumor category T3-4 (P < 0.0001), Fuhrman grades III and IV (P < 0.00011, tumor size >4 cm (P < 0.0001), presence of tumor necrosis (P < 0.0001), nodal involvement (n = 0.009), metastasis (P = 0.012), SSIGN score >= 5 (P < 0.0001), cancer progression (P < 0.0001), and cancer-specific death (P < 0.0001). Cancer-specific survival was significantly better for patients with no cytoplasmic TGFBI expression (1-, 3-, 5-y cancer-specific survival of 94.7%, 87.8%, and 73.4% vs. 92.9%, 71.2%, and 49.8%, respectively; P < 0.0001). Conclusion: We identified 346 proteins involved in renal carcinogenesis and continued the presence of a metabolic shift in aggressive tumors. TGFBI was overexpressed in tumors with high SSIGN scores and was significantly associated with oncologic outcomes. (C) 2014 Elsevier Inc. All rights reserved. C1 [Lebdai, Souhil; Chautard, Denis; Azzouzi, Abdel Rahmene; Bigot, Pierre] Angers Univ Hosp, Dept Urol, Angers, France. [Verhoest, Gregory; Bensalah, Karim] Pontchaillou Univ Hosp, Dept Urol, Rennes, France. [Parikh, Hemang] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Jacquet, Solene Florence; Leclercq, Nathalie Rioux] Pontchaillou Univ Hosp, Dept Pathol, Rennes, France. [Bigot, Pierre] Univ Pierre & Marie Currie, Paris, France. RP Bigot, P (reprint author), Angers Univ Hosp, Dept Urol, Angers, France.; Bigot, P (reprint author), Univ Pierre & Marie Currie, Paris, France. EM pibigot@chu-angers.fr FU Association Francaise d'Urologie (AFU); La ligue contre le cancer FX This study was funded by the Association Francaise d'Urologie (AFU) (Grant AFU 2010) and La ligue contre le cancer. NR 26 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD FEB PY 2015 VL 33 IS 2 DI 10.1016/j.urolonc.2014.06.005 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA EC5RF UT WOS:000388193200016 ER PT J AU Francis, TC Chandra, R Friend, DM Finkel, E Dayrit, G Miranda, J Brooks, JM Iniguez, SD O'Donnell, P Kravitz, A Lobo, MK AF Francis, T. Chase Chandra, Ramesh Friend, Danielle M. Finkel, Eric Dayrit, Genesis Miranda, Jorge Brooks, Julie M. Iniguez, Sergio D. O'Donnell, Patricio Kravitz, Alexxai Lobo, Mary Kay TI Nucleus Accumbens Medium Spiny Neuron Subtypes Mediate Depression-Related Outcomes to Social Defeat Stress SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Depression; Medium spiny neurons; Nucleus accumbens; Optogenetics; Pharmacogenetics; Social defeat stress ID DEEP BRAIN-STIMULATION; PATHWAY STRIATAL NEURONS; DISTINCT ROLES; DELTA-FOSB; OPTOGENETIC CONTROL; PROJECTION NEURONS; REWARD CIRCUITRY; GENE-EXPRESSION; DISORDERS; BEHAVIOR AB BACKGROUND: The nucleus accumbens is a critical mediator of depression-related outcomes to social defeat stress. Previous studies demonstrate distinct neuroplasticity adaptations in the two medium spiny neuron (MSN) subtypes, those enriched in dopamine receptor D1 versus dopamine receptor D2, in reward and reinforcement leading to opposing roles for these MSNs in these behaviors. However, the distinct roles of nucleus accumbens MSN subtypes, in depression, remain poorly understood. METHODS: Using whole-cell patch clamp electrophysiology, we examined excitatory input to MSN subtypes and intrinsic excitability measures in D1-green fluorescent protein and D2-green fluorescent protein bacterial artificial chromosome transgenic mice that underwent chronic social defeat stress (CSDS). Optogenetic and pharmacogenetic approaches were used to bidirectionally alter firing of D1-MSNs or D2-MSNs after CSDS or before a subthreshold social defeat stress in D1-Cre or D2-Cre bacterial artificial chromosome transgenic mice. RESULTS: We demonstrate that the frequency of excitatory synaptic input is decreased in D1-MSNs and increased in D2-MSNs in mice displaying depression-like behaviors after CSDS. Enhancing activity in D1-MSNs results in resilient behavioral outcomes, while inhibition of these MSNs induces depression-like outcomes after CSDS. Bidirectional modulation of D2-MSNs does not alter behavioral responses to CSDS; however, repeated activation of D2-MSNs in stress naive mice induces social avoidance following subthreshold social defeat stress. CONCLUSIONS: Our studies uncover novel functions of MSN subtypes in depression-like outcomes. Notably, bidirectional alteration of D1-MSN activity promotes opposite behavioral outcomes to chronic social stress. Therefore, targeting D1-MSN activity may provide novel treatment strategies for depression or other affective disorders. C1 [Francis, T. Chase; Chandra, Ramesh; Finkel, Eric; Dayrit, Genesis; Miranda, Jorge; Brooks, Julie M.; O'Donnell, Patricio; Lobo, Mary Kay] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. [Friend, Danielle M.; Kravitz, Alexxai] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD USA. [Dayrit, Genesis; Iniguez, Sergio D.] Calif State Univ San Bernardino, Dept Psychol, San Bernardino, CA 92407 USA. [Miranda, Jorge] Univ Nacl Autonoma Mexico, Unidad Biomed, Fac Estudios Super Iztacala, Tlalnepantla, Mexico. RP Lobo, MK (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, 20 Penn St,HSF2,Rm 265, Baltimore, MD 21201 USA. EM mklobo@umary-land.edu RI Iniguez, Sergio/J-2410-2015; Lobo, Mary Kay/K-7734-2015; Chandra, Ramesh/K-7672-2012; OI Lobo, Mary Kay/0000-0002-9419-2079; Chandra, Ramesh/0000-0002-4473-5071; O'Donnell, Patricio/0000-0001-7788-624X; Francis, Tanner/0000-0001-6396-2897 FU Brain and Behavioral Research Foundation National Alliance for Research on Schizophrenia and Depression Young Investigator grant FX This study was supported by the Brain and Behavioral Research Foundation National Alliance for Research on Schizophrenia and Depression Young Investigator grant. NR 59 TC 36 Z9 37 U1 8 U2 35 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 FEB 1 PY 2015 VL 77 IS 3 BP 212 EP 222 DI 10.1016/j.biopsych.2014.07.021 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AX3NG UT WOS:000346845500010 PM 25173629 ER PT J AU Park, M Reynolds, CF AF Park, Mijung Reynolds, Charles F., III TI Depression Among Older Adults with Diabetes Mellitus SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Diabetes; Depression; Mood disorders; Aging; Collaborative care ID PRIMARY-CARE PATIENTS; LATE-LIFE DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; RECURRENT MAJOR DEPRESSION; BEHAVIORAL ACTIVATION TREATMENTS; COMORBIDITY-SURVEY-REPLICATION; COLLABORATIVE CARE; FOLLOW-UP; MENTAL-HEALTH; RISK-FACTOR AB Older adults with Diabetes Mellitus (DM) experience greater risk for comorbid depression compared to those who do not have DM. Undetected, untreated or under-treated depression impinges an individual's ability to manage their DM successfully, hinders their adherence to treatment regime, and undermines provider-patient relationships. Thus, in the context of caring for older adults with DM, comorbid depression presents special challenges and opportunities for clinicians. In this article, the authors summarize the clinical presentation of late-life depression, potential mechanisms of comorbidity of depression and DM, importance of depression in the successful management of DM, and available best practice models for depression treatment. C1 [Park, Mijung] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15213 USA. [Reynolds, Charles F., III] Aging Inst UPMC Senior Serv, Hartford Ctr Excellence Geriatr Psychiat, Ctr Excellence Late Life Depress Prevent & Treatm, NIMH, Pittsburgh, PA 15213 USA. [Reynolds, Charles F., III] Univ Pittsburgh, Pittsburgh, PA 15213 USA. RP Park, M (reprint author), Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, 3500 Victoria St,421 Victoria Bldg, Pittsburgh, PA 15213 USA. EM parkm@pitt.edu FU NCATS NIH HHS [UL1 TR000005]; NIA NIH HHS [P30 AG024827]; NIMH NIH HHS [P30 MH090333] NR 162 TC 6 Z9 7 U1 4 U2 29 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD FEB PY 2015 VL 31 IS 1 BP 117 EP + DI 10.1016/j.cger.2014.08.022 PG 22 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AX1CX UT WOS:000346686900011 PM 25453305 ER PT J AU Keet, CA Frischmeyer-Guerrerio, PA Wood, RA AF Keet, Corinne A. Frischmeyer-Guerrerio, Pamela A. Wood, Robert A. TI Preface Pediatric Allergy SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Keet, Corinne A.; Wood, Robert A.] Johns Hopkins Sch Med, Baltimore, MD 21202 USA. [Frischmeyer-Guerrerio, Pamela A.] NIAID, Food Allergy Res Unit, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Keet, CA (reprint author), Johns Hopkins Sch Med, CMSC 1102 600 N Wolfe St, Baltimore, MD 21202 USA. EM ckeet1@jhmi.edu; rwood@jhmi.edu; pfrisch1@jhmi.edu OI Keet, Corinne/0000-0002-6585-239X NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 EI 1557-8607 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD FEB PY 2015 VL 35 IS 1 BP XIII EP XIV DI 10.1016/j.iac.2014.09.015 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA AX1CU UT WOS:000346686700001 PM 25459587 ER PT J AU Lyons, JJ Milner, JD Stone, KD AF Lyons, Jonathan J. Milner, Joshua D. Stone, Kelly D. TI Atopic Dermatitis in Children Clinical Features, Pathophysiology, and Treatment SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article DE Atopic dermatitis; Eczema; Allergy; Netherton syndrome; Hyper-IgE syndrome ID WET-WRAP DRESSINGS; HYPER-IGE SYNDROME; STAPHYLOCOCCUS-AUREUS COLONIZATION; SEVERE COMBINED IMMUNODEFICIENCY; WISKOTT-ALDRICH-SYNDROME; OF-FUNCTION MUTATIONS; SKIN BARRIER FUNCTION; VERSUS-HOST-DISEASE; STRATUM-CORNEUM; FILAGGRIN MUTATIONS AB Atopic dermatitis (AD) is a chronic, relapsing, highly pruritic skin condition resulting from disruption of the epithelial barrier and associated immune dysregulation in the skin of genetically predisposed hosts. AD generally develops in early childhood, has a characteristic age-dependent distribution, and is commonly associated with elevated IgE, peripheral eosinophilia, and other allergic diseases. Medications such as antihistamines have demonstrated poor efficacy in controlling AD-associated itch. Education of patients regarding the primary underlying defects and provision of a comprehensive skin care plan is essential for disease maintenance and management of flares. C1 [Lyons, Jonathan J.; Milner, Joshua D.; Stone, Kelly D.] NIAID, Lab Allerg Dis, Genet & Pathophysiol Allergy Sect, NIH, Bethesda, MD 20892 USA. RP Stone, KD (reprint author), NIAID, Lab Allerg Dis, 10 Ctr Dr,Bldg 10,Room 12C103, Bethesda, MD 20892 USA. EM stonek@niaid.nih.gov OI Lyons, Jonathan/0000-0002-2346-8189 FU Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 102 TC 10 Z9 10 U1 0 U2 22 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 EI 1557-8607 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD FEB PY 2015 VL 35 IS 1 BP 161 EP + DI 10.1016/j.iac.2014.09.008 PG 24 WC Allergy; Immunology SC Allergy; Immunology GA AX1CU UT WOS:000346686700011 PM 25459583 ER PT J AU Williams, KW Sharma, HP AF Williams, Kelli W. Sharma, Hemant P. TI Anaphylaxis and Urticaria SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article DE Anaphylaxis; Urticaria; Treatment; Prevention ID CHRONIC IDIOPATHIC URTICARIA; EXERCISE-INDUCED ANAPHYLAXIS; WORLD ALLERGY ORGANIZATION; EMERGENCY-DEPARTMENT VISITS; CELL DE-GRANULATION; QUALITY-OF-LIFE; UNITED-STATES; CHOLINERGIC URTICARIA; TRYPTASE LEVELS; LATEX ALLERGY AB Anaphylaxis and urticaria are common presenting allergic complaints. Affecting up to 2% of the population, anaphylaxis is a serious, life-threatening allergic reaction. Although not life-threatening, urticaria is a rash of transient, erythematous, pruritic wheals that can be bothersome and affects up to 25% of the population. All cases of anaphylaxis warrant thorough clinical evaluation by the allergist-immunologist, although most cases of urticaria are self-limited and do not require specialist referral. This article offers an overview of our current knowledge on the epidemiology, pathogenesis, triggers, diagnosis, and treatment of anaphylaxis and urticaria. C1 [Williams, Kelli W.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Sharma, Hemant P.] Childrens Natl Hlth Syst, Childrens Natl Med Ctr, Div Allergy & Immunol, Washington, DC 20010 USA. RP Sharma, HP (reprint author), Childrens Natl Hlth Syst, Childrens Natl Med Ctr, Div Allergy & Immunol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM HSharma@childrensnational.org FU Mylan Specialty FX Nothing to disclose (K.W. Williams); Spokesperson for unbranded anaphylaxis education campaign sponsored by Mylan Specialty; Consultant, Nutricia NA (H.P. Sharma). NR 158 TC 0 Z9 0 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 EI 1557-8607 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD FEB PY 2015 VL 35 IS 1 BP 199 EP + DI 10.1016/j.iac.2014.09.010 PG 23 WC Allergy; Immunology SC Allergy; Immunology GA AX1CU UT WOS:000346686700013 PM 25459585 ER PT J AU Smith, MA Reaman, GH AF Smith, Malcolm A. Reaman, Gregory H. TI Remaining Challenges in Childhood Cancer and Newer Targeted Therapeutics SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Targeted therapy; Personalized medicine; Pediatric cancer drug development; Innovative clinical trials; Preclinical testing ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LARGE-CELL LYMPHOMA; PRECLINICAL TESTING PROGRAM; ANAPLASTIC LYMPHOMA; ANTITUMOR-ACTIVITY; KINASE INHIBITION; PHASE-II; NEUROBLASTOMA; MODELS; METHYLATION AB Despite the enormously important and gratifying advances in cancer treatment outcomes for children with cancer, cancer remains the biggest cause of death from disease in children. Because the etiology and biology of cancers that occur in children differ dramatically from those that occur in adults, the immediate extrapolation of efficacy and safety of new cancer drugs to childhood cancer indications is not possible. We discuss factors that will play key roles in guiding pediatric oncologists as they select lines of research to pursue in their quest for more effective treatments for children with cancer. C1 [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Reaman, Gregory H.] US FDA, Off Hematol & Oncol Prod, OND, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Smith, MA (reprint author), NCI, Canc Therapy Evaluat Program, 9609 Med Ctr Dr,RM 5-W414,MSC 9737, Bethesda, MD 20892 USA. EM Malcolm.Smith@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 43 TC 5 Z9 5 U1 0 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0031-3955 EI 1557-8240 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD FEB PY 2015 VL 62 IS 1 BP 301 EP + DI 10.1016/j.pcl.2014.09.018 PG 13 WC Pediatrics SC Pediatrics GA AX1BD UT WOS:000346682500019 PM 25435124 ER PT J AU Uehara, S Murayama, N Nakanishi, Y Nakamura, C Hashizume, T Zeldin, DC Yamazaki, H Uno, Y AF Uehara, Shotaro Murayama, Norie Nakanishi, Yasuharu Nakamura, Chika Hashizume, Takanori Zeldin, Darryl C. Yamazaki, Hiroshi Uno, Yasuhiro TI Immunochemical quantification of cynomolgus CYP2J2, CYP4A and CYP4F enzymes in liver and small intestine SO XENOBIOTICA LA English DT Article DE Cynomolgus monkey; cytochrome P450; expression; liver; small intestine ID CYTOCHROME-P450 ENZYMES; DRUG-METABOLISM; MICROSOMES; GENE; EBASTINE; JAPANESE; POLYMORPHISM; INVOLVEMENT; EXPRESSION; VARIANTS AB 1. An increasing number of studies have indicated the roles of CYP4 proteins in drug metabolism; however, CYP4 expression has not been measured in cynomolgus monkeys, an important animal species for drug metabolism studies. 2. In this study, cynomolgus CYP4A11, CYP4F2/3, CYP4F11 and CYP4F12, along with CYP2J2, were immunoquantified using selective antibodies in 28 livers and 35 small intestines, and their content was compared with CYP1A, CYP2A, CYP2B6, CYP2C9/19, CYP2D, CYP2E1, CYP3A4 and CYP3A5, previously quantified. 3. In livers, CYP2J2, CYP4A11, CYP4F2/3, CYP4F11 and CYP4F12, varied 1.3- to 4.3-fold, represented 11.2, 14.4, 8.0, 2.7 and 0.3% of total immunoquantified CYP1-4 proteins, respectively. 4. In small intestines, CYP2J2, CYP4F2/3, CYP4F11 and CYP4F12, varied 2.4- to 9.7-fold, represented 6.9, 36.4, 2.4 and 9.3% of total immunoquantified CYP1-4 proteins, respectively, making CYP4F the most abundant P450 subfamily in small intestines. CYP4A11 was under the detection limit in all of the samples analyzed. 5. Significant correlations were found in liver for CYP4A11 with lauric acid 11-/12-hydroxylation and for CYP4F2/3 and CYP4F11 with astemizole hydroxylation. 6. This study revealed the relatively abundant contents of cynomolgus CYP2J2, CYP4A11 and CYP4Fs in liver and/or small intestine, suggesting their potential roles for the metabolism of xenobitotics and endogenous substrates. C1 [Uehara, Shotaro; Nakanishi, Yasuharu; Nakamura, Chika; Uno, Yasuhiro] Shin Nippon Biomed Labs Ltd, Pharmacokinet & Bioanal Ctr, Wakayama, Japan. [Uehara, Shotaro; Murayama, Norie; Yamazaki, Hiroshi] Showa Pharmaceut Univ, Lab Drug Metab & Pharmacokinet, Machida, Tokyo 1948543, Japan. [Hashizume, Takanori] Osaka Ohtani Univ, Fac Pharm, Tondabayashi, Osaka, Japan. [Zeldin, Darryl C.] NIEHS, Div Intramural Res, Durham, NC USA. RP Yamazaki, H (reprint author), Showa Pharmaceut Univ, Lab Drug Metab & Pharmacokinet, 3-3165 Higashi Tamagawa Gakuen, Machida, Tokyo 1948543, Japan. EM hyamazak@ac.shoyaku.ac.jp; uno-yasuhiro@snbl.co.jp OI Yamazaki, Hiroshi/0000-0002-1068-4261 FU Intramural NIH HHS [ZIA ES025034-20]; PHS HHS [Z01 025034] NR 31 TC 3 Z9 3 U1 0 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0049-8254 EI 1366-5928 J9 XENOBIOTICA JI Xenobiotica PD FEB PY 2015 VL 45 IS 2 BP 124 EP 130 DI 10.3109/00498254.2014.952800 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AX0NK UT WOS:000346648700003 PM 25138712 ER PT J AU Holmes, SE Bachran, C Fuchs, H Weng, A Melzig, MF Flavell, SU Flavell, DJ AF Holmes, Suzanne E. Bachran, Christopher Fuchs, Hendrik Weng, Alexander Melzig, Matthias F. Flavell, Sopsamorn U. Flavell, David J. TI Triterpenoid saponin augmention of saporin-based immunotoxin cytotoxicity for human leukaemia and lymphoma cells is partially immunospecific and target molecule dependent SO IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY LA English DT Article DE Augmentation; immunotoxin; leukemia; lymphoma; saponins ID CHOLESTEROL INTERACTION; ANTI-CD19 IMMUNOTOXIN; MEMBRANE CHOLESTEROL; GYPSOPHILA SAPONINS; CONTINUOUS-INFUSION; BURKITT-LYMPHOMA; PHASE-I; TOXINS; CYTOSKELETON; PROTEINS AB Context: Saponinum album (SA) is a complex mixture of triterpenoid saponins previously shown to augment the cytotoxicity of the type I ribosome-inactivating protein saporin and an EGF-saporin target toxin that could potentially be used to improve the therapeutic window of targeted toxins. Objective: To investigate the augmentative property of SA on saporin and saporin-based immunotoxins (IT) directed against five different cell surface target molecules on human leukemia and lymphoma cells. Materials and methods: After determining the optimum dose of SA for each cell line, the extent of SA-mediated augmentation was established for saporin and five saporin-based ITs using XTT and an annexin V apoptosis assay. Immunospecificity was investigated using three different blocking assays. Dose-scheduling was also investigated using the XTT assay. Results: Uncorrected SA-mediated augmentation ranged at best from 31.5 million-fold to, at worse, 174-fold. However, when the calculated fold-increases were adjusted for the non-immunospecific effects of SA on an off-target IT, the true augmentative effects of SA were found to be largely non-immunospecific. Antibody blocking studies demonstrated that the augmentative effect of SA was only partially immunospecific. Separate exposure of target cells to IT and SA at different times demonstrated that immunospecific augmentation of IT by SA could be achieved but only if cells were exposed to IT first and SA second. Conclusions: SA significantly, although variably, augments the cytotoxicity of saporin and saporin-based immunotoxins. Concomitant exposure to both IT and SA can result in non-immunospecific cytotoxicity that can be overcome by temporally separating exposure to each. C1 [Holmes, Suzanne E.; Flavell, Sopsamorn U.; Flavell, David J.] Southampton Gen Hosp, Simon Flavell Leukaemia Res Lab, Southampton SO16 6YD, Hants, England. [Bachran, Christopher] NIAID, NIH, Bethesda, MD 20892 USA. [Fuchs, Hendrik; Weng, Alexander] Charite, Klin Chem & Pathobiochem, Inst Lab Med, D-13353 Berlin, Germany. [Melzig, Matthias F.] Free Univ Berlin, Inst Pharm, Berlin, Germany. RP Flavell, DJ (reprint author), Southampton Gen Hosp, Simon Flavell Leukaemia Res Lab, Southampton SO16 6YD, Hants, England. EM davidf@leukaemiabusters.org.uk FU UK registered charity Leukaemia Busters FX The authors report that there are no declarations of interest. This research work was supported by the UK registered charity Leukaemia Busters. NR 50 TC 4 Z9 4 U1 1 U2 12 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0892-3973 EI 1532-2513 J9 IMMUNOPHARM IMMUNOT JI Immunopharmacol. Immunotoxicol. PD FEB PY 2015 VL 37 IS 1 BP 42 EP 55 DI 10.3109/08923973.2014.971964 PG 14 WC Immunology; Pharmacology & Pharmacy; Toxicology SC Immunology; Pharmacology & Pharmacy; Toxicology GA AW9HN UT WOS:000346568100006 PM 25347443 ER PT J AU Lyu, JH Park, DW Huang, B Kang, SH Lee, SJ Lee, C Bae, YS Lee, JG Baek, SH AF Lyu, Ji Hyo Park, Dae-Weon Huang, Bin Kang, Su Hwan Lee, Soo Jung Lee, Chuhee Bae, Yoe-Sik Lee, Jin-Gu Baek, Suk-Hwan TI RGS2 Suppresses Breast Cancer Cell Growth via a MCPIP1-Dependent Pathway SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE RGS2; MCPIP1; TSPYL5; GPCR; DUB ID PROTEIN SIGNALING 2; END RULE PATHWAY; MESSENGER-RNA; REGULATOR; EXPRESSION; DEGRADATION; ACTIVATION; PHOSPHORYLATION; RESISTANCE; APOPTOSIS AB Regulator of G protein signaling 2 (RGS2) is a member of a family of proteins that functions as a GTPase-activating protein (GAP) for G alpha subunits. RGS2 mRNA expression is lower in breast cancerous tissues than in normal tissues. In addition, expression of RGS2 is also lower in MCF7 (cancerous breast cells) than in MCF10A (normal breast cells). Here we investigated whether RGS2 inhibits growth of breast cancer cells. RGS2 overexpression in MCF7 cells inhibited epidermal growth factor- or serum-induced proliferation. In HEK293T cells expressing RGS2, cell growth was also significantly suppressed (In addition, exogenous expression of RGS2 in HEK293T cells resulted in the significant suppression of cell growth). These results suggest that RGS2 may have a tumor suppressor function. MG-132 treatment of MCF7 cells increased endogenous or exogenous RGS2 levels, suggesting a post-transcriptional regulatory mechanism that controls RGS2 protein levels. RGS2 protein was degraded polyubiquitinated the K71 residue, but stabilized by deubiquitinase monocyte chemotactic protein-induced protein 1 (MCPIP1), and not affected by dominant negative mutant (C157A) of MCPIP1. Gene expression profiling study showed that overexpression of RGS2 decreased levels of testis specific Y encoded like protein 5 (TSPYL5), which plays a causal role in breast oncogenesis. TSPYL5 protein expression was low in MCF10A and high in MCF7 cells, showing the opposite aspect to RGS2 expression. Additionally, RGS2 or MCPIP1 overexpression in MCF7 cells decreased TSPYL5 protein level, indicating that RGS2 stabilized by MCPIP1 have diminished TSPYL5 protein levels, thereby exerting an inhibitory effect of breast cancer cell growth. (C) 2014 Wiley Periodicals, Inc. C1 [Lyu, Ji Hyo; Park, Dae-Weon; Huang, Bin; Lee, Chuhee; Baek, Suk-Hwan] Aging Associated Vasc Dis Res Ctr, Dept Biochem & Mol Biol, Taegu 705802, South Korea. [Kang, Su Hwan; Lee, Soo Jung] Yeungnam Univ, Coll Med, Dept Surg, Taegu 705802, South Korea. [Bae, Yoe-Sik] Sungkyunkwan Univ, Dept Biol Sci, Suwon 440746, South Korea. [Lee, Jin-Gu] NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. RP Baek, SH (reprint author), Yeungnam Univ, Coll Med, Dept Biochem & Mol Biol, 210 Main Bldg,170 Hyeonchung Ro Daemyung 5 O Dong, Taegu 705802, South Korea. EM sbaek@med.yu.ac.kr FU Ministry of Science, ICT and Future Planning [2011-0013206] FX Grant sponsor: Ministry of Science, ICT and Future Planning; Grant number: 2011-0013206. NR 39 TC 8 Z9 8 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB PY 2015 VL 116 IS 2 BP 260 EP 267 DI 10.1002/jcb.24964 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AW4QM UT WOS:000346265700008 PM 25187114 ER PT J AU Cyphert, JM Carlin, DJ Nyska, A Schladweiler, MC Ledbetter, AD Shannahan, JH Kodavanti, UP Gavett, SH AF Cyphert, Jaime M. Carlin, Danielle J. Nyska, Abraham Schladweiler, Mette C. Ledbetter, Allen D. Shannahan, Jonathan H. Kodavanti, Urmila P. Gavett, Stephen H. TI Comparative Long-Term Toxicity of Libby Amphibole and Amosite Asbestos in Rats After Single or Multiple Intratracheal Exposures SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID FISCHER-344 RATS; MALIGNANT MESOTHELIOMA; MONTANA; VERMICULITE; DISEASE; LUNG; FERROACTINOLITE; CARCINOGENICITY; INSTILLATION; INHALATION AB In former mine workers of Libby, MT, exposure to amphibole-containing vermiculite was linked to increased rates of asbestosis, lung cancer, and mesothelioma. Although many studies showed adverse effects following exposure to Libby amphibole (LA; a mixture of winchite, richterite, and tremolite), little is known regarding the relative toxicity of LA compared to regulated asbestos, or regarding the risks associated with acute high-dose exposures relative to repeated low-dose exposures. In this study, pulmonary function, inflammation, and pathology were assessed after single or multiple intratracheal (IT) exposures of LA or a well-characterized amosite (AM) control fiber with equivalent fiber characteristics. Male F344 rats were exposed to an equivalent total mass dose (0.15, 0.5, 1.5, or 5 mg/rat) of LA or AM administered either as a single IT instillation, or as multiple IT instillations given every other week over a 13-wk period, and necropsied up to 20 mo after the initial IT. When comparing the two fiber types, in both studies LA resulted in greater acute neutrophilic inflammation and cellular toxicity than equal doses of AM, but long-term histopathological changes were approximately equivalent between fibers, suggesting that LA is at least as toxic as AM. In addition, although no dose-response relationship was discerned, mesothelioma or lung carcinomas were found after exposure to low and high dose levels of LA or AM in both studies. Conversely, when comparing studies, an equal mass dose given over multiple exposures instead of a single bolus resulted in greater chronic pathological changes in lung at lower doses, despite the initially weaker acute inflammatory response. Overall, these results suggest that there is a possibility of greater long-term pathological changes with repeated lower LA dose exposures, which more accurately simulates chronic environmental exposures. C1 [Cyphert, Jaime M.] Univ N Carolina, Sch Med, Curriculum Toxicol, Chapel Hill, NC USA. [Cyphert, Jaime M.; Carlin, Danielle J.; Nyska, Abraham] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Nyska, Abraham] Tel Aviv Univ, Sackler Sch Med, Timrat, Israel. [Schladweiler, Mette C.; Ledbetter, Allen D.; Kodavanti, Urmila P.; Gavett, Stephen H.] US EPA, Environm Publ Hlth Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Shannahan, Jonathan H.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO USA. RP Gavett, SH (reprint author), US EPA, DABT, Mail Drop B105-02,109 TW Alexander Dr, Res Triangle Pk, NC 27711 USA. EM Gavett.stephen@epa.gov FU U.S. EPA/University of North Carolina Toxicology Research Program Training Agreement [CR 933237, 83515201-0] FX This work was supported by a U.S. EPA/University of North Carolina Toxicology Research Program Training Agreement (CR 933237 and 83515201-0). The authors thank Judy Richards for assistance with biochemical analysis, and Drs. David Berry, Ian Gilmour, Maureen Gwinn, Gary Hatch, and Ronald Hines for manuscript review. NR 35 TC 7 Z9 7 U1 2 U2 18 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1528-7394 EI 1087-2620 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD FEB 1 PY 2015 VL 78 IS 3 BP 151 EP 165 DI 10.1080/15287394.2014.947455 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AW5YC UT WOS:000346345800001 PM 25506632 ER PT J AU Elliott, H Fischer, RS Myers, KA Desai, RA Gao, L Chen, CS Adelstein, RS Waterman, CM Danuser, G AF Elliott, Hunter Fischer, Robert S. Myers, Kenneth A. Desai, Ravi A. Gao, Lin Chen, Christopher S. Adelstein, Robert S. Waterman, Clare M. Danuser, Gaudenz TI Myosin II controls cellular branching morphogenesis and migration in three dimensions by minimizing cell-surface curvature SO NATURE CELL BIOLOGY LA English DT Article ID PHOSPHORYLATION; MUTATIONS; MATRICES; KINASE AB In many cases, cell function is intimately linked to cell shape control. We used endothelial cell branching morphogenesis as a model to understand the role of myosin II in shape control of invasive cells migrating in 3D collagen gels. We applied principles of differential geometry and mathematical morphology to 3D image sets to parameterize cell branch structure and local cell-surface curvature. We find that Rho/ROCK-stimulated myosin II contractility minimizes cell-scale branching by recognizing and minimizing local cell-surface curvature. Using microfabrication to constrain cell shape identifies a positive feedback mechanism in which low curvature stabilizes myosin II cortical association, where it acts to maintain minimal curvature. The feedback between regulation of myosin II by curvature and control of curvature by myosin II drives cycles of localized cortical myosin II assembly and disassembly. These cycles in turn mediate alternating phases of directionally biased branch initiation and retraction to guide 3D cell migration. C1 [Elliott, Hunter; Danuser, Gaudenz] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Fischer, Robert S.; Myers, Kenneth A.; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Myers, Kenneth A.] Univ Sci, Dept Biol Sci, Philadelphia, PA 19104 USA. [Desai, Ravi A.; Chen, Christopher S.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Gao, Lin; Chen, Christopher S.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Gao, Lin; Chen, Christopher S.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Adelstein, Robert S.] NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Fischer, RS (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM fischerr2@nhlbi.nih.gov; watermancm@nhlbi.nih.gov; gaudenz.danuser@utsouthwestern.edu OI Waterman, Clare/0000-0001-6142-6775; Desai, Ravi/0000-0002-4217-3351; Adelstein, Robert/0000-0002-8683-2144 FU NIH [R01 GM090317]; NHLBI Division of Intramural Research FX This work was initiated as a collaborative effort between R.S.E. and G.D. (NII I R2 1 CA124990). H.E. and G.D. are supported by NIH R01 GM090317. R.S.F, R.S.A., K.A.M. and C.M.W. are supported by the NHLBI Division of Intramural Research. NR 31 TC 16 Z9 16 U1 3 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2015 VL 17 IS 2 BP 137 EP + DI 10.1038/ncb3092 PG 22 WC Cell Biology SC Cell Biology GA CA8FI UT WOS:000349152400005 PM 25621949 ER PT J AU Lee, HK Finniss, S Cazacu, S Xiang, CL Poisson, LM Blumberg, PM Brodie, C AF Lee, Hae Kyung Finniss, Susan Cazacu, Simona Xiang, Cunli Poisson, Laila M. Blumberg, Peter M. Brodie, Chaya TI RasGRP3 regulates the migration of glioma cells via interaction with Arp3 SO ONCOTARGET LA English DT Article ID GROWTH-FACTOR RECEPTORS; HUMAN-BRAIN-TUMORS; EXCHANGE FACTORS; PHORBOL ESTERS; RAS ACTIVATION; STEM-CELLS; GLIOBLASTOMA; PHOSPHORYLATION; EXPRESSION; INVASION AB Glioblastoma (GBM), the most aggressive primary brain tumors, are highly infiltrative. Although GBM express high Ras activity and Ras proteins have been implicated in gliomagenesis, Ras-activating mutations are not frequent in these tumors. RasGRP3, an important signaling protein responsive to diacylglycerol (DAG), increases Ras activation. Here, we examined the expression and functions of RasGRP3 in GBM and glioma cells. RasGRP3 expression was upregulated in GBM specimens and glioma stem cells compared with normal brains and neural stem cells, respectively. RasGRP3 activated Ras and Rap1 in glioma cells and increased cell migration and invasion partially via Ras activation. Using pull-down assay and mass spectroscopy we identified the actin-related protein, Arp3, as a novel interacting protein of RasGRP3. The interaction of RasGRP3 and Arp3 was validated by immunofluorescence staining and co-immunoprecipitation, and PMA, which activates RasGRP3 and induces its translocation to the peri-nuclear region, increased the association of Arp3 and RasGRP3. Arp3 was upregulated in GBM, regulated cell spreading and migration and its silencing partially decreased these effects of RasGRP3 in glioma cells. In summary, RasGRP3 acts as an important integrating signaling protein of the DAG and Ras signaling pathways and actin polymerization and represents an important therapeutic target in GBM. C1 [Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Brodie, Chaya] Henry Ford Hosp, Dept Neurosurg, Hermelin Brain Tumor Ctr, Davidson Lab Cell Signaling & Tumorigenesis, Detroit, MI 48202 USA. [Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Poisson, Laila M.; Brodie, Chaya] Henry Ford Hosp, Hermelin Brain Tumor Ctr, Detroit, MI 48202 USA. [Poisson, Laila M.] Henry Ford Hosp, Ctr Bioinformat, Dept Publ Hlth Sci, Detroit, MI 48202 USA. [Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Brodie, Chaya] Bar Ilan Univ, Everard & Mina Goodman Fac Life Sci, Ramat Gan, Israel. RP Brodie, C (reprint author), Henry Ford Hosp, Dept Neurosurg, Hermelin Brain Tumor Ctr, Davidson Lab Cell Signaling & Tumorigenesis, Detroit, MI 48202 USA. EM cbrodie1@hfhs.org FU National Institutes of Health [R01-NS066303]; William and Karen Davidson Fund, Hermelin Brain Tumor Center; Center for Cancer Research, National Cancer Institute, NIH [ZIA BC 005270] FX We thank the late Dr. Patricia S. Lorenzo for helpful discussions and Prof. Ray Mattingly for providing the H-RasDN plasmid. This work is supported by National Institutes of Health Grant R01-NS066303 (C.B.), the William and Karen Davidson Fund, Hermelin Brain Tumor Center (C.B.) and in part by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, NIH (Project ZIA BC 005270). NR 51 TC 3 Z9 3 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN 30 PY 2015 VL 6 IS 3 BP 1850 EP 1864 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CF6TS UT WOS:000352689800042 PM 25682201 ER PT J AU Marioni, RE Shah, S McRae, AF Chen, BH Colicino, E Harris, SE Gibson, J Henders, AK Redmond, P Cox, SR Pattie, A Corley, J Murphy, L Martin, NG Montgomery, GW Feinberg, AP Fallin, MD Multhaup, ML Jaffe, AE Joehanes, R Schwartz, J Just, AC Lunetta, KL Murabito, JM Starr, JM Horvath, S Baccarelli, AA Levy, D Visscher, PM Wray, NR Deary, IJ AF Marioni, Riccardo E. Shah, Sonia McRae, Allan F. Chen, Brian H. Colicino, Elena Harris, Sarah E. Gibson, Jude Henders, Anjali K. Redmond, Paul Cox, Simon R. Pattie, Alison Corley, Janie Murphy, Lee Martin, Nicholas G. Montgomery, Grant W. Feinberg, Andrew P. Fallin, M. Daniele Multhaup, Michael L. Jaffe, Andrew E. Joehanes, Roby Schwartz, Joel Just, Allan C. Lunetta, Kathryn L. Murabito, Joanne M. Starr, John M. Horvath, Steve Baccarelli, Andrea A. Levy, Daniel Visscher, Peter M. Wray, Naomi R. Deary, Ian J. TI DNA methylation age of blood predicts all-cause mortality in later life SO GENOME BIOLOGY LA English DT Article ID TELOMERE LENGTH; HUMAN LONGEVITY; T-CELLS; INTELLIGENCE; ASSOCIATION; DEMENTIA; FAMILIES; DISEASE; TRAITS AB Background: DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age. Results: Here we test whether differences between people's chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Delta(age)) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Delta(age) and mortality. A 5-year higher Delta(age) is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Delta(age). A pedigree-based heritability analysis of Delta(age) was conducted in a separate cohort. The heritability of Delta(age) was 0.43. Conclusions: DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors. C1 [Marioni, Riccardo E.; Harris, Sarah E.; Cox, Simon R.; Starr, John M.; Visscher, Peter M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland. [Marioni, Riccardo E.; Harris, Sarah E.] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland. [Marioni, Riccardo E.; Shah, Sonia; McRae, Allan F.; Visscher, Peter M.; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Shah, Sonia; McRae, Allan F.; Visscher, Peter M.] Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld 4072, Australia. [Chen, Brian H.; Joehanes, Roby; Lunetta, Kathryn L.; Murabito, Joanne M.; Levy, Daniel] NHLBIs Framingham Heart Study, Framingham, MA 01702 USA. [Chen, Brian H.; Levy, Daniel] NHLBI, Div Intramural Res, Populat Sci Branch, Bethesda, MD 01702 USA. [Colicino, Elena; Schwartz, Joel; Just, Allan C.; Baccarelli, Andrea A.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Gibson, Jude; Murphy, Lee] Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH4 2XU, Midlothian, Scotland. [Henders, Anjali K.; Martin, Nicholas G.; Montgomery, Grant W.] Queensland Inst Med Res Berghofer Med Res Inst, Brisbane, Qld 4029, Australia. [Redmond, Paul; Cox, Simon R.; Pattie, Alison; Corley, Janie; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland. [Feinberg, Andrew P.; Fallin, M. Daniele; Multhaup, Michael L.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. [Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Mol Biol, Baltimore, MD 21205 USA. [Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Genet, Baltimore, MD 21205 USA. [Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Fallin, M. Daniele; Jaffe, Andrew E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA. [Jaffe, Andrew E.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Joehanes, Roby] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Joehanes, Roby] Hebrew Senior Life, Boston, MA 02131 USA. [Schwartz, Joel; Baccarelli, Andrea A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland. [Horvath, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Gonda Res Ctr, Human Genet, Los Angeles, CA 90095 USA. [Horvath, Steve] Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90095 USA. RP Wray, NR (reprint author), Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. EM naomi.wray@uq.edu.au; i.deary@ed.ac.uk RI Montgomery, Grant/B-7148-2008; Jaffe, Andrew/L-3089-2016; Colicino, Elena/Q-4973-2016; Shah, Sonia/N-7547-2013; Wray, Naomi/C-8639-2015; OI Visscher, Peter/0000-0002-2143-8760; Cox, Simon R./0000-0003-4036-3642; Montgomery, Grant/0000-0002-4140-8139; Jaffe, Andrew/0000-0001-6886-1454; Colicino, Elena/0000-0002-1875-8448; Shah, Sonia/0000-0001-5860-4526; Wray, Naomi/0000-0001-7421-3357; Murphy, Lee/0000-0001-6467-7449; Baccarelli, Andrea/0000-0002-3436-0640; Just, Allan/0000-0003-4312-5957 FU UK's Biotechnology and Biological Sciences Research Council (BBSRC); Royal Society; Chief Scientist Office of the Scottish Government; Age UK (The Disconnected Mind project); Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award); Age UK; Wellcome Trust Institutional Strategic Support Fund; University of Edinburgh; University of Queensland; BBSRC; Medical Research Council (MRC); University of Edinburgh as part of the cross-council Lifelong Health and Wellbeing initiative [MR/K026992/1]; National Health and Medical Research Council (NHMRC) [613608, APP496667, APP1010374, APP1046880]; NHMRC Fellowships [613602]; Australia Research Council (ARC) Future Fellowship [FT0991360]; National Institutes of Health [N01-HC-25195]; Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health; Division of Intramural Research, National Heart, Lung, and Blood Institute; Center for Information Technology, National Institutes of Health, Bethesda, MD, USA; U.S. National Institute of Environmental Health Sciences (NIEHS) [R01ES015172, R01ES021733]; Cooperative Studies Program/ERIC, US Department of Veterans Affairs; US Department of Agriculture, Agricultural Research Service [53-K06-510]; [R01AG029451] FX We thank the cohort participants and team members who contributed to these studies. This work was supported by numerous funding bodies. Phenotype collection in the Lothian Birth Cohort 1921 was supported by the UK's Biotechnology and Biological Sciences Research Council (BBSRC), The Royal Society and The Chief Scientist Office of the Scottish Government. Phenotype collection in the Lothian Birth Cohort 1936 was supported by Age UK (The Disconnected Mind project). Methylation typing was supported by the Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland. REM, SEH, SRC, JMS, PMV, and IJD are members of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE). CCACE is supported by funding from the BBSRC, the Medical Research Council (MRC), and the University of Edinburgh as part of the cross-council Lifelong Health and Wellbeing initiative (MR/K026992/1). Research reported in this publication was supported by National Health and Medical Research Council (NHMRC) project grants 613608, APP496667, APP1010374, and APP1046880. NHMRC Fellowships to GWM, PMV, and NRW (613602) and Australia Research Council (ARC) Future Fellowship to NRW (FT0991360). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NHMRC or ARC. The Framingham Heart Study is funded by National Institutes of Health contract N01-HC-25195. The laboratory work for this investigation was funded by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. The analytical component of this project was funded by the Division of Intramural Research, National Heart, Lung, and Blood Institute, and the Center for Information Technology, National Institutes of Health, Bethesda, MD, USA. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster (http://biowulf.nih.gov) and Helix Systems (http://helix.nih.gov) at the National Institutes of Health, Bethesda, MD, USA. JMM and KLL were supported by R01AG029451. The present work on the US Department of Veterans Affairs (VA) Normative Aging Study has been supported by funding from the U.S. National Institute of Environmental Health Sciences (NIEHS) (R01ES015172, R01ES021733). The VA Normative Aging Study is supported by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). Additional support to the VA Normative Aging Study was provided by the US Department of Agriculture, Agricultural Research Service (contract 53-K06-510). The views expressed in this paper are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. We thank Stuart J Ritchie for his helpful comments and suggestions on the initial draft of the manuscript. NR 50 TC 107 Z9 108 U1 18 U2 51 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PD JAN 30 PY 2015 VL 16 AR 25 DI 10.1186/s13059-015-0584-6 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CE4RO UT WOS:000351818000002 PM 25633388 ER PT J AU Tsoi, LC Iyer, MK Stuart, PE Swindell, WR Gudjonsson, JE Tejasvi, T Sarkar, MK Li, BS Ding, J Voorhees, JJ Kang, HM Nair, RP Chinnaiyan, AM Abecasis, GR Elder, JT AF Tsoi, Lam C. Iyer, Matthew K. Stuart, Philip E. Swindell, William R. Gudjonsson, Johann E. Tejasvi, Trilokraj Sarkar, Mrinal K. Li, Bingshan Ding, Jun Voorhees, John J. Kang, Hyun M. Nair, Rajan P. Chinnaiyan, Arul M. Abecasis, Goncalo R. Elder, James T. TI Analysis of long non-coding RNAs highlights tissue-specific expression patterns and epigenetic profiles in normal and psoriatic skin SO GENOME BIOLOGY LA English DT Article ID EPIDERMAL DIFFERENTIATION COMPLEX; GENE-EXPRESSION; HUMAN-DISEASE; SUSCEPTIBILITY LOCI; DISTINCT CLASSES; PROSTATE-CANCER; INNATE IMMUNITY; HUMAN GENOME; DATA SETS; REVEALS AB Background: Although analysis pipelines have been developed to use RNA-seq to identify long non-coding RNAs (lncRNAs), inference of their biological and pathological relevance remains a challenge. As a result, most transcriptome studies of autoimmune disease have only assessed protein-coding transcripts. Results: We used RNA-seq data from 99 lesional psoriatic, 27 uninvolved psoriatic, and 90 normal skin biopsies, and applied computational approaches to identify and characterize expressed lncRNAs. We detect 2,942 previously annotated and 1,080 novel lncRNAs which are expected to be skin specific. Notably, over 40% of the novel lncRNAs are differentially expressed and the proportions of differentially expressed transcripts among protein-coding mRNAs and previously-annotated lncRNAs are lower in psoriasis lesions versus uninvolved or normal skin. We find that many lncRNAs, in particular those that are differentially expressed, are co-expressed with genes involved in immune related functions, and that novel lncRNAs are enriched for localization in the epidermal differentiation complex. We also identify distinct tissue-specific expression patterns and epigenetic profiles for novel lncRNAs, some of which are shown to be regulated by cytokine treatment in cultured human keratinocytes. Conclusions: Together, our results implicate many lncRNAs in the immunopathogenesis of psoriasis, and our results provide a resource for lncRNA studies in other autoimmune diseases. C1 [Tsoi, Lam C.; Li, Bingshan; Ding, Jun; Kang, Hyun M.; Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA. [Iyer, Matthew K.; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. [Stuart, Philip E.; Swindell, William R.; Gudjonsson, Johann E.; Tejasvi, Trilokraj; Sarkar, Mrinal K.; Voorhees, John J.; Nair, Rajan P.; Elder, James T.] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. [Tejasvi, Trilokraj; Elder, James T.] Univ Michigan, Ann Arbor Vet Affairs Hosp, Ann Arbor, MI 48109 USA. [Li, Bingshan] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Quantitat Sci, Nashville, TN 37232 USA. [Ding, Jun] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. [Elder, James T.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. RP Abecasis, GR (reprint author), Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Dept Biostat, M4614 SPH I,Box 2029, Ann Arbor, MI 48109 USA. EM goncalo@umich.edu; jelder@umich.edu OI Tsoi, Lam Cheung/0000-0003-1627-5722; Sarkar, Mrinal/0000-0001-8505-4259 FU NIH [AR042742, AR050511, AR054966, AR062382, AR065183, K08 AR060802]; National Human Genome Research Institute [R01HG007022]; National Eye Institute [R01EY022005]; Ann Arbor Veterans Affairs Hospital; Doris Duke Charitable Foundation [2013106]; Taubman Medical Institute; Howard Hughes Medical Institute; Dawn and Dudley Holmes Memorial Fund; Babcock Endowment Fund FX We thank the many volunteers who provided skin biopsies for this study. This research was supported by NIH R01 grants AR042742, AR050511, AR054966, AR062382, and AR065183 to JTE, as well as K08 AR060802 to JEG. GRA is supported by research grants R01HG007022 from the National Human Genome Research Institute and R01EY022005 from the National Eye Institute. JTE and TT are supported by the Ann Arbor Veterans Affairs Hospital, and JEG is supported by the Doris Duke Charitable Foundation Grant No. 2013106 and Taubman Medical Institute (as Kenneth and Frances Eisenberg Emerging Scholar). AMC is supported by the Howard Hughes Medical Institute, and is also supported as a Taubman Scholar. We also acknowledge generous support from the Dawn and Dudley Holmes Memorial Fund and the Babcock Endowment Fund to the Department of Dermatology at the University of Michigan. NR 68 TC 31 Z9 33 U1 4 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PD JAN 30 PY 2015 VL 16 AR 24 DI 10.1186/s13059-014-0570-4 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CE4RO UT WOS:000351818000001 PM 25723451 ER PT J AU Ghose, S Min, YF Lin, PC AF Ghose, Sampa Min, Yongfen Lin, P. Charles TI delta-Catenin Activates Rho GTPase, Promotes Lymphangiogenesis and Growth of Tumor Metastases SO PLOS ONE LA English DT Article AB delta-catenin, an adherens junctions protein, is not only involved in early development, cell-cell adhesion and cell motility in neuronal cells, but it also plays an important role in vascular endothelial cell motility and pathological angiogenesis. In this study, we report a new function of delta-catenin in lymphangiogenesis. Consistent with expression of delta-catenin in vascular endothelial cells, we detected expression of the gene in lymphatic endothelial cells (LECs). Ectopic expression of delta-catenin in LECs increased cell motility and lymphatic vascular network formation in vitro and lymphangiogenesis in vivo in a Matrigel plug assay. Conversely, knockdown of delta-catenin in LECs impaired lymphangiogenesis in vitro and in vivo. Biochemical analysis shows that delta-catenin regulates activation of Rho family small GTPases, key mediators in cell motility. delta-catenin activates Rac1 and Cdc42 but inhibits RhoA in LECs. Notably, blocking of Rac1 activation impaired delta-catenin mediated lymphangiogenesis in a Matrigel assay. Consistently, loss of delta-catenin in mice inhibited the growth of tumor metastases. Taken together, these findings identify a new function of delta-catenin in lymphangiogenesis and tumor growth/metastasis, likely through modulation of small Rho GTPase activation. Targeting delta-catenin may offer a new way to control tumor metastasis. C1 [Ghose, Sampa] Jawaharlal Nehru Univ, Ctr Mol Med, New Delhi 110067, India. [Min, Yongfen; Lin, P. Charles] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Lin, PC (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. EM p.lin@NIH.gov FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH); NIH [CA108856, NS45888, AR053718] FX This work is supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH) and by the grants from NIH (CA108856, NS45888 and AR053718). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 12 TC 1 Z9 1 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 JAN 30 PY 2015 VL 10 IS 1 AR e0116338 DI 10.1371/journal.pone.0116338 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC9HX UT WOS:000350680700029 PM 25635825 ER PT J AU Hollister, JR Lee, KS Dorward, DW Baron, GS AF Hollister, Jason R. Lee, Kil Sun Dorward, David W. Baron, Gerald S. TI Efficient Uptake and Dissemination of Scrapie Prion Protein by Astrocytes and Fibroblasts from Adult Hamster Brain SO PLOS ONE LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; DENSITY-LIPOPROTEIN RECEPTOR; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; RAT HIPPOCAMPAL-NEURONS; SMOOTH-MUSCLE-CELLS; IN-VITRO; PRP; INFECTION; TISSUE; SHEEP AB Prion infections target neurons and lead to neuronal loss. However, the role of non-neuronal cells in the initiation and spread of infection throughout the brain remains unclear despite the fact these cells can also propagate prion infectivity. To evaluate how different brain cells process scrapie prion protein (PrPres) during acute infection, we exposed neuron-enriched and non-neuronal cell cultures from adult hamster brain to fluorescently-labeled purified PrPres and followed the cultures by live cell confocal imaging over time. Non-neuronal cells present in both types of cultures, specifically astrocytes and fibroblasts, internalized PrPres more efficiently than neurons. PrPres was trafficked to late endosomal/lysosomal compartments and rapidly transported throughout the cell bodies and processes of all cell types, including contacts between astrocytes and neurons. These observations suggest that astrocytes and meningeal fibroblasts play an as yet unappreciated role in prion infections via efficient uptake and dissemination of PrPres. C1 [Hollister, Jason R.; Lee, Kil Sun; Baron, Gerald S.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Dorward, David W.] NIAID, Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Baron, GS (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM gbaron@niaid.nih.gov RI Lee, Kil/D-3678-2012 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 75 TC 2 Z9 2 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 30 PY 2015 VL 10 IS 1 AR e0115351 DI 10.1371/journal.pone.0115351 PG 25 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC9HX UT WOS:000350680700008 PM 25635871 ER PT J AU Magnus, MC Stigum, H Haberg, SE Nafstad, P London, SJ Nystad, W AF Magnus, Maria C. Stigum, Hein Haberg, Siri E. Nafstad, Per London, Stephanie J. Nystad, Wenche TI Peak Weight and Height Velocity to Age 36 Months and Asthma Development: The Norwegian Mother and Child Cohort Study SO PLOS ONE LA English DT Article ID EUROPEAN BIRTH COHORTS; LUNG DEVELOPMENT; INFANT GROWTH; FETAL-GROWTH; GENERATION R; RISK; SYMPTOMS; NEWBORNS; GAIN; 1ST AB Background The immediate postnatal period is the period of the fastest growth in the entire life span and a critical period for lung development. Therefore, it is interesting to examine the association between growth during this period and childhood respiratory disorders. Methods We examined the association of peak weight and height velocity to age 36 months with maternal report of current asthma at 36 months (n = 50,311), recurrent lower respiratory tract infections (LRTIs) by 36 months (n = 47,905) and current asthma at 7 years (n = 24,827) in the Norwegian Mother and Child Cohort Study. Peak weight and height velocity was calculated using the Reed1 model through multilevel mixed-effects linear regression. Multivariable log-binomial regression was used to calculate adjusted relative risks (adj.RR) and 95% confidence intervals (CI). We also conducted a sibling pair analysis using conditional logistic regression. Results Peak weight velocity was positively associated with current asthma at 36 months [adj. RR 1.22 (95% CI: 1.18, 1.26) per standard deviation (SD) increase], recurrent LRTIs by 36 months [adj. RR 1.14 (1.10, 1.19) per SD increase] and current asthma at 7 years [adj. RR 1.13 (95% CI: 1.07, 1.19) per SD increase]. Peak height velocity was not associated with any of the respiratory disorders. The positive association of peak weight velocity and asthma at 36 months remained in the sibling pair analysis. Conclusions Higher peak weight velocity, achieved during the immediate postnatal period, increased the risk of respiratory disorders. This might be explained by an influence on neonatal lung development, shared genetic/epigenetic mechanisms and/or environmental factors. C1 [Magnus, Maria C.; Stigum, Hein; Nafstad, Per; Nystad, Wenche] Norwegian Inst Publ Hlth, Div Epidemiol, Dept Chron Dis, Oslo, Norway. [Stigum, Hein; Nafstad, Per] Univ Oslo, Fac Med, Dept Community Med, Oslo, Norway. [Haberg, Siri E.] Norwegian Inst Publ Hlth, Inst Management & Staff, Oslo, Norway. [London, Stephanie J.] NIEHS, Epidemiol Branch, Div Intramural Res, NIH,US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Magnus, MC (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, Dept Chron Dis, Oslo, Norway. EM Maria.Christine.Magnus@fhi.no OI London, Stephanie/0000-0003-4911-5290 FU National Institutes of Health (NIH) (NIH/National Institute of Environmental Health Sciences (NIEHS)) [N01-ES-75558]; National Institutes of Health (NIH) (NIH/National Institute of Neurological Disorders and Stroke) [1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1]; Norwegian Research Council/FUGE [151918/S10]; Division of Intramural Research, NIEHS, NIH; Norwegian Extra-Foundation for Health and Rehabilitation [2011.2.0218] FX The Norwegian Mother and Child Cohort Study is supported by National Institutes of Health (NIH) (NIH/National Institute of Environmental Health Sciences (NIEHS) contract number N01-ES-75558, NIH/National Institute of Neurological Disorders and Stroke grant no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1) and the Norwegian Research Council/FUGE (grant number 151918/S10). Supported in part by the Division of Intramural Research, NIEHS, NIH. Ms. Magnus is also supported by the Norwegian Extra-Foundation for Health and Rehabilitation (grant number 2011.2.0218). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 7 Z9 7 U1 0 U2 1 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 JAN 30 PY 2015 VL 10 IS 1 AR e0116362 DI 10.1371/journal.pone.0116362 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC9HX UT WOS:000350680700031 PM 25635872 ER PT J AU Sykora, P Misiak, M Wang, Y Ghosh, S Leandro, GS Liu, D Tian, J Baptiste, BA Cong, WN Brenerman, BM Fang, E Becker, KG Hamilton, RJ Chigurupati, S Zhang, YQ Egan, JM Croteau, DL Wilson, DM Mattson, MP Bohr, VA AF Sykora, Peter Misiak, Magdalena Wang, Yue Ghosh, Somnath Leandro, Giovana S. Liu, Dong Tian, Jane Baptiste, Beverly A. Cong, Wei-Na Brenerman, Boris M. Fang, Evandro Becker, Kevin G. Hamilton, Royce J. Chigurupati, Soumya Zhang, Yongqing Egan, Josephine M. Croteau, Deborah L. Wilson, David M., III Mattson, Mark P. Bohr, Vilhelm A. TI DNA polymerase beta deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BASE EXCISION-REPAIR; MILD COGNITIVE IMPAIRMENT; INCREASED OXIDATIVE DAMAGE; DOWNS-SYNDROME PATIENTS; TRANSGENIC MOUSE MODEL; DOUBLE-STRAND BREAKS; AMYLOID-BETA; A-BETA; MITOCHONDRIAL-DNA; SYNAPTIC DYSFUNCTION AB We explore the role of DNA damage processing in the progression of cognitive decline by creating a new mouse model. The new model is a cross of a common Alzheimer's disease (AD) mouse (3xTgAD), with a mouse that is heterozygous for the critical DNA base excision repair enzyme, DNA polymerase beta. A reduction of this enzyme causes neurodegeneration and aggravates the AD features of the 3xTgAD mouse, inducing neuronal dysfunction, cell death and impairing memory and synaptic plasticity. Transcriptional profiling revealed remarkable similarities in gene expression alterations in brain tissue of human AD patients and 3xTg/Pol beta(+/-) mice including abnormalities suggestive of impaired cellular bioenergetics. Our findings demonstrate that a modest decrement in base excision repair capacity can render the brain more vulnerable to AD-related molecular and cellular alterations. C1 [Sykora, Peter; Misiak, Magdalena; Ghosh, Somnath; Leandro, Giovana S.; Tian, Jane; Baptiste, Beverly A.; Brenerman, Boris M.; Fang, Evandro; Hamilton, Royce J.; Croteau, Deborah L.; Wilson, David M., III; Bohr, Vilhelm A.] NIA IRP, Lab Mol Gerontol, Biomed Res Ctr, Baltimore, MD 21224 USA. [Misiak, Magdalena; Wang, Yue; Liu, Dong; Chigurupati, Soumya; Mattson, Mark P.] NIA IRP, Lab Neurosci, Biomed Res Ctr, Baltimore, MD 21224 USA. [Leandro, Giovana S.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Ribeirao Preto, SP, Brazil. [Cong, Wei-Na; Egan, Josephine M.] NIA IRP, Lab Clin Invest, Biomed Res Ctr, Baltimore, MD 21224 USA. [Becker, Kevin G.] NIA IRP, Genet Lab, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA IRP, Lab Mol Gerontol, Biomed Res Ctr, Baltimore, MD 21224 USA. EM vbohr@nih.gov FU Intramural Research Program of the National Institutes of Health (NIH), National Institute on Aging [Z01-AG00735]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP [2013/11052-1]; NIH Intramural Program FX Intramural Research Program of the National Institutes of Health (NIH), National Institute on Aging [Z01-AG00735]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP [2013/11052-1 to G.L.]. Funding for open access charge: NIH Intramural Program. NR 103 TC 18 Z9 18 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 30 PY 2015 VL 43 IS 2 BP 943 EP 959 DI 10.1093/nar/gku1356 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2XR UT WOS:000350209000028 PM 25552414 ER PT J AU Singh, KK Lovren, F Pan, Y Quan, A Ramadan, A Matkar, PN Ehsan, M Sandhu, P Mantella, LE Gupta, N Teoh, H Parotto, M Tabuchi, A Kuebler, WM Al-Omran, M Finkel, T Verma, S AF Singh, Krishna K. Lovren, Fina Pan, Yi Quan, Adrian Ramadan, Azza Matkar, Pratiek N. Ehsan, Mehroz Sandhu, Paul Mantella, Laura E. Gupta, Nandini Teoh, Hwee Parotto, Matteo Tabuchi, Arata Kuebler, Wolfgang M. Al-Omran, Mohammed Finkel, Toren Verma, Subodh TI The Essential Autophagy Gene ATG7 Modulates Organ Fibrosis via Regulation of Endothelial-to-Mesenchymal Transition SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Autophagy; Autophagy-related Protein 7 (ATG7); Endothelial Cell; Gene Silencing; Pulmonary Fibrosis; Endothelial-to-mesenchymal Transition ID INDUCED PULMONARY-FIBROSIS; MOLECULAR-MECHANISMS; SIGNAL-TRANSDUCTION; SYSTEMIC-SCLEROSIS; CARDIAC FIBROSIS; SMAD PROTEINS; SHEAR-STRESS; BLEOMYCIN; CELLS; FIBROBLASTS AB Background: Endothelial-to-mesenchymal transition (EndMT) is implicated in the development of organ fibrosis. Results: Loss of the autophagy gene ATG7 promotes EndMT and up-regulates TGF signaling and the associated pro-fibrotic genes. Endothelial-specific ATG7 knock-out mice exhibited increased bleomycin-induced pulmonary fibrosis. Conclusion:ATG7 is a novel regulator of EndMT-induced organ fibrosis. Significance: Intact endothelial autophagy prevents aberrant EndMT and represents a potential target to limit organ fibrosis. Pulmonary fibrosis is a progressive disease characterized by fibroblast proliferation and excess deposition of collagen and other extracellular matrix components. Although the origin of fibroblasts is multifactorial, recent data implicate endothelial-to-mesenchymal transition as an important source of fibroblasts. We report herein that loss of the essential autophagy gene ATG7 in endothelial cells (ECs) leads to impaired autophagic flux accompanied by marked changes in EC architecture, loss of endothelial, and gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition. Loss of ATG7 also up-regulates TGF signaling and key pro-fibrotic genes in vitro. In vivo, EC-specific ATG7 knock-out mice exhibit a basal reduction in endothelial-specific markers and demonstrate an increased susceptibility to bleomycin-induced pulmonary fibrosis and collagen accumulation. Our findings help define the role of endothelial autophagy as a potential therapeutic target to limit organ fibrosis, a condition for which presently there are no effective available treatments. C1 [Singh, Krishna K.; Lovren, Fina; Pan, Yi; Quan, Adrian; Ramadan, Azza; Ehsan, Mehroz; Sandhu, Paul; Mantella, Laura E.; Gupta, Nandini; Teoh, Hwee; Verma, Subodh] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Div Cardiac Surg, Toronto, ON M5B 1W8, Canada. [Singh, Krishna K.; Al-Omran, Mohammed] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Div Vasc Surg, Toronto, ON M5B 1W8, Canada. [Matkar, Pratiek N.] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Div Cardiol, Toronto, ON M5B 1W8, Canada. [Teoh, Hwee] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Div Endocrinol & Metab, Toronto, ON M5B 1W8, Canada. [Singh, Krishna K.; Lovren, Fina; Pan, Yi; Quan, Adrian; Ramadan, Azza; Ehsan, Mehroz; Sandhu, Paul; Mantella, Laura E.; Gupta, Nandini; Teoh, Hwee; Tabuchi, Arata; Kuebler, Wolfgang M.; Al-Omran, Mohammed; Verma, Subodh] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Dept Surg, Toronto, ON M5B 1W8, Canada. [Matkar, Pratiek N.; Teoh, Hwee] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Dept Med, Toronto, ON M5B 1W8, Canada. [Matkar, Pratiek N.; Teoh, Hwee] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Singh, Krishna K.; Kuebler, Wolfgang M.; Al-Omran, Mohammed; Verma, Subodh] Univ Toronto, Dept Surg, Toronto, ON M5S 2J7, Canada. [Kuebler, Wolfgang M.] Univ Toronto, Dept Physiol, Toronto, ON M5S 2J7, Canada. [Parotto, Matteo] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON M5S 2J7, Canada. [Kuebler, Wolfgang M.] Charite, Inst Physiol, D-10117 Berlin, Germany. [Al-Omran, Mohammed; Verma, Subodh] King Saud Univ, Li Ka Shing Collaborat Res Program, Riyadh 12372, Saudi Arabia. [Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. RP Verma, S (reprint author), St Michaels Hosp, Div Cardiac Surg, 8th Floor,Bond Wing,30 Bond St, Toronto, ON M5B 1W8, Canada. EM vermasu@smh.ca OI Parotto, Matteo/0000-0003-1165-4264 FU Heart and Stroke Foundation of Canada [G-13-0003003] FX This work was supported by in part by the Heart and Stroke Foundation of Canada Grant G-13-0003003 (to S. V.). NR 70 TC 13 Z9 13 U1 1 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 30 PY 2015 VL 290 IS 5 BP 2547 EP 2559 DI 10.1074/jbc.M114.604603 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CB0JA UT WOS:000349310700003 PM 25527499 ER PT J AU Cong, WN Chadwick, W Wang, R Daimon, CM Cai, H Amma, J Wood, WH Becker, KG Martin, B Maudsley, S AF Cong, Wei-Na Chadwick, Wayne Wang, Rui Daimon, Caitlin M. Cai, Huan Amma, Jennifer Wood, William H., III Becker, Kevin G. Martin, Bronwen Maudsley, Stuart TI Amitriptyline Improves Motor Function via Enhanced Neurotrophin Signaling and Mitochondrial Functions in the Murine N171-82Q Huntington Disease Model SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Bioinformatics; Brain-derived Neurotrophic Factor (BDNF); Huntington Disease; Mitochondria; Neurodegenerative Disease; Amitriptyline; Motor Function; mHTT ID STRIATAL PROJECTION NEURONS; TRKB RECEPTOR; MOUSE MODEL; MUTANT HUNTINGTIN; UNCOUPLING PROTEIN-2; THERAPEUTIC TARGET; TRANSGENIC MOUSE; SLOWS DISEASE; HUMAN BRAIN; IN-VIVO AB Background: Etiology of Huntington disease (HD) is related to the overproduction of mutant huntingtin (mHTT) protein. Results: Amitriptyline improved motor symptoms via decreasing mHTT protein expression, improving neurotrophin signaling, and enhancing mitochondrial functions in HD mice. Conclusion: Amitriptyline demonstrated beneficial effects in HD mice. Significance: Amitriptyline has therapeutic potential in treating HD. Huntington disease (HD) is a neurodegenerative disorder characterized by progressive motor impairment and cognitive alterations. Hereditary HD is primarily caused by the expansion of a CAG trinucleotide repeat in the huntingtin (Htt) gene, which results in the production of mutant huntingtin protein (mHTT) with an expanded amino-terminal polyglutamine (poly(Q)) stretch. Besides pathological mHTT aggregation, reduced brain-derived neurotrophic factor (BDNF) levels, impaired neurotrophin signaling, and compromised mitochondrial functions also contribute to the deleterious progressive etiology of HD. As a well tolerated Food and Drug Administration-approved antidepressant, amitriptyline (AMI) has shown efficacy in treating neurodegenerative murine models via potentiation of BDNF levels and amelioration of alterations in neurotrophin signaling pathways. In this study, we observed profound improvements in the motor coordination of AMI-treated N171-82Q HD model mice. The beneficial effects of AMI treatment were associated with its ability to reduce mHTT aggregation, potentiation of the BDNF-TrkB signaling system, and support of mitochondrial integrity and functionality. Our study not only provides preclinical evidence for the therapeutic potency of AMI in treating HD, but it also represents an important example of the usefulness of additional pharmacogenomic profiling of pre-existing drugs for novel therapeutic effects with often intractable pathological scenarios. C1 [Cong, Wei-Na; Wang, Rui; Daimon, Caitlin M.; Cai, Huan; Amma, Jennifer; Martin, Bronwen] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA. [Chadwick, Wayne; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA. [Wood, William H., III; Becker, Kevin G.] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA. [Maudsley, Stuart] Univ Antwerp, Inst Born Bunge, Dept Mol Genet VIB, Neurogenet Lab, B-2000 Antwerp, Belgium. RP Martin, B (reprint author), NIA, Metab Unit, NIH, 251 Bayview Blvd,Ste 100, Baltimore, MD 21224 USA. EM bronwenmartin@gmail.com; stuart.maudsley@molgen.vib-ua.be RI Cai, Huan/B-6578-2016 OI Cai, Huan/0000-0001-7731-8891 FU National Institutes of Health Intramural Research Program of the NIA FX This work was supported, in whole or in part, by National Institutes of Health Intramural Research Program of the NIA. NR 87 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 30 PY 2015 VL 290 IS 5 BP 2728 EP 2743 DI 10.1074/jbc.M114.588608 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CB0JA UT WOS:000349310700016 PM 25505248 ER PT J AU Tanaka, N Takahashi, S Matsubara, T Jiang, CT Sakamoto, W Chanturiya, T Teng, RF Gavrilova, O Gonzalez, FJ AF Tanaka, Naoki Takahashi, Shogo Matsubara, Tsutomu Jiang, Changtao Sakamoto, Wataru Chanturiya, Tatyana Teng, Ruifeng Gavrilova, Oksana Gonzalez, Frank J. TI Adipocyte-specific Disruption of Fat-specific Protein 27 Causes Hepatosteatosis and Insulin Resistance in High-fat Diet-fed Mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Adipose Tissue; Diabetes; Hepatocyte; Insulin Resistance; Lipid; Mouse ID HEPATIC STEATOSIS; LIPID DROPLETS; GENERALIZED LIPODYSTROPHY; METABOLIC DISEASE; DEFICIENT MICE; FSP27; LIVER; SENSITIVITY; STORAGE; GENE AB Background: FSP27 contributes to unilocular lipid droplet formation in adipocytes. Results: Adipocyte-specific FSP27 disruption in mice produced small white adipose mass, hepatosteatosis, and insulin resistance upon high-fat diet feeding. Conclusion: Adipose FSP27 plays a critical role in minimizing ectopic fat accumulation. Significance: This mouse model is useful for understanding the significance of fat storage in adipose tissue. White adipose tissue (WAT) functions as an energy reservoir where excess circulating fatty acids are transported to WAT, converted to triglycerides, and stored as unilocular lipid droplets. Fat-specific protein 27 (FSP27, CIDEC in humans) is a lipid-coating protein highly expressed in mature white adipocytes that contributes to unilocular lipid droplet formation. However, the influence of FSP27 in adipose tissue on whole-body energy homeostasis remains unclear. Mice with adipocyte-specific disruption of the Fsp27 gene (Fsp27(Ad)) were generated using an aP2-Cre transgene with the Cre/LoxP system. Upon high-fat diet feeding, Fsp27(Ad) mice were resistant to weight gain. In the small WAT of these mice, small adipocytes containing multilocular lipid droplets were dispersed. The expression levels of the genes associated with mitochondrial abundance and brown adipocyte identity were increased, and basal lipolytic activities were significantly augmented in adipocytes isolated from Fsp27(Ad) mice compared with the Fsp27(F/F) counterparts. The impaired fat-storing function in Fsp27(Ad) adipocytes and the resultant lipid overflow from WAT led to marked hepatosteatosis, dyslipidemia, and systemic insulin resistance in high-fat diet-treated Fsp27(Ad) mice. These results demonstrate a critical role for FSP27 in the storage of excess fat in WAT with minimizing ectopic fat accumulation that causes insulin-resistant diabetes and non-alcoholic fatty liver disease. This mouse model may be useful for understanding the significance of fat-storing properties of white adipocytes and the role of local FSP27 in whole-body metabolism and estimating the pathogenesis of human partial lipodystrophy caused by CIDEC mutations. C1 [Tanaka, Naoki; Takahashi, Shogo; Matsubara, Tsutomu; Jiang, Changtao; Gonzalez, Frank J.] NCI, Ctr Canc Res, Lab Metab, NIH, Bethesda, MD 20892 USA. [Sakamoto, Wataru] NIDDK, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA. [Chanturiya, Tatyana; Teng, Ruifeng; Gavrilova, Oksana] NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Ctr Canc Res, Lab Metab, NIH, Bethesda, MD 20892 USA. EM gonzalef@mail.nih.gov FU National Institutes of Health Intramural Research Program (NCI) [U54 ES16015] FX This work was supported, in whole or in part, by National Institutes of Health Intramural Research Program (NCI) and Grant U54 ES16015 (to F. J. G.). NR 31 TC 10 Z9 11 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 30 PY 2015 VL 290 IS 5 BP 3092 EP 3105 DI 10.1074/jbc.M114.605980 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CB0JA UT WOS:000349310700045 PM 25477509 ER PT J AU Fukuda, Y Fukui, T Hikichi, C Ishikawa, T Murate, K Adachi, T Imai, H Fukuhara, K Ueda, A Kaplan, AP Mutoh, T AF Fukuda, Yu Fukui, Takao Hikichi, Chika Ishikawa, Tomomasa Murate, Kenichiro Adachi, Takeshi Imai, Hideki Fukuhara, Koki Ueda, Akihiro Kaplan, Allen P. Mutoh, Tatsuro TI Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells SO BRAIN RESEARCH LA English DT Article DE Neurotropin; NGF signaling; GM1 ganglioside; Trk tyrosine kinase ID NERVE GROWTH-FACTOR; PROTOONCOGENE PRODUCT; SENSORY-NEUROPATHY; NEURITE OUTGROWTH; PAIN THRESHOLD; LIPID RAFTS; TRANSDUCTION; ACTIVATION; PROTEIN; EXPRESSION AB Activation of the high-affinity nerve growth factor (NGF) receptor Trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. Here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin (R)) enhanced efficiency of NGF signaling. In rat pheochromocytoma PC12 cells overexpressing Trk (PCtrk cells), Neurotropin augmented insufficient neurite outgrowth observed at suboptimal concentration of NGF (2 ng/mL) in a manner depending on Trk kinase activity. Cellular exposure to Neurotropin resulted in an accumulation of Trk-GM1 complexes without affecting dimerization or phosphorylation states of Trk. Following NGF stimulation, Neurotropin significantly facilitated the time course of NGF-induced Trk autophosphorylation. These observations provide a unique mechanism controlling efficiency of NGF signaling, and raise the therapeutic potential of Neurotropin for various neurological conditions associated with neurotrophin dysfunction. (C) 2014 Elsevier B.V. All rights reserved. C1 [Fukuda, Yu; Fukui, Takao; Hikichi, Chika; Ishikawa, Tomomasa; Murate, Kenichiro; Ueda, Akihiro; Mutoh, Tatsuro] Fujita Hlth Univ, Sch Med, Dept Neurol, Toyoake, Aichi 4701192, Japan. [Fukuda, Yu; Kaplan, Allen P.] Med Univ S Carolina, Dept Med, Div Pulm & Crit Care Med, Charleston, SC 29425 USA. [Fukuhara, Koki] NINR, NIH, Bethesda, MD 20892 USA. [Fukuda, Yu; Adachi, Takeshi; Imai, Hideki; Fukuhara, Koki] Nippon Zoki Pharmaceut Co Ltd, Osaka 5640052, Japan. RP Mutoh, T (reprint author), Fujita Hlth Univ, Sch Med, Dept Neurol, 1-98 Dengakugakubo, Toyoake, Aichi 4701192, Japan. EM tmutoh@fujita-hu.ac.jp FU MUSC Foundation for Research Development (Charleston, SC, USA); MEXT; Ministry of Education, Culture, Sports, Science and Technology of Japan FX We are grateful to Dr. Irwin J. Kopin (National Institutes of Health, USA) for helpful discussions. We also thank Ms. Chieko Nishikawa for her excellent technical assistance. This work was supported by the MUSC Foundation for Research Development (Charleston, SC, USA) to A.P.K., and by MEXT-Supported Program for the Strategic Research Foundation at Private Universities 2010-2014 and a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan to T.M. NR 46 TC 4 Z9 4 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JAN 30 PY 2015 VL 1596 BP 13 EP 21 DI 10.1016/j.brainres.2014.11.041 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CA5LX UT WOS:000348951000002 PM 25454796 ER PT J AU Nussenzweig, SC Verma, S Finkel, T AF Nussenzweig, Samuel C. Verma, Subodh Finkel, Toren TI The Role of Autophagy in Vascular Biology SO CIRCULATION RESEARCH LA English DT Review DE aging; angiogenesis effect; autophagy; endothelial cells ID SMOOTH-MUSCLE-CELLS; NITRIC-OXIDE BIOAVAILABILITY; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; PULMONARY-HYPERTENSION; CARDIOVASCULAR-DISEASE; CALORIC RESTRICTION; MEDIATED AUTOPHAGY; IMPAIRED AUTOPHAGY; SHEAR-STRESS AB There is increasing interest in the role of autophagic flux in maintaining normal vessel wall biology and a growing suspicion that autophagic dysregulation may be a common pathway through which vascular aging and associated pathologies develop. Within endothelial and smooth muscle cells, diverse but important triggers that range from oxidized lipids to beta-amyloid seem to stimulate autophagosome formation potently. In addition, emerging evidence links autophagy to a wide array of vascular processes ranging from angiogenesis to calcification of the vessel wall. Alterations in autophagic flux are also increasingly being implicated in disease processes that include both atherosclerosis and pulmonary hypertension. Finally, recent insights point toward an important role of autophagy in the paracrine regulation of vasoactive substances from the endothelium. Here, we review the progress in understanding how autophagy can contribute to vascular biology and the emerging strategies to target this process for therapeutic benefit. C1 [Nussenzweig, Samuel C.; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. [Verma, Subodh] Univ Toronto, St Michaels Hosp, Div Cardiac Surg, Toronto, ON, Canada. RP Finkel, T (reprint author), NIH, Bldg 10 CRC 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@nih.gov FU Heart and Stroke Foundation of Canada; National Institutes of Health; Leducq Foundation FX This work was supported by the Heart and Stroke Foundation of Canada (S. Verma) and National Institutes of Health Intramural funds and the Leducq Foundation (T. Finkel). NR 84 TC 28 Z9 31 U1 4 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD JAN 30 PY 2015 VL 116 IS 3 BP 480 EP 488 DI 10.1161/CIRCRESAHA.116.303805 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA CA3IJ UT WOS:000348799500014 PM 25634971 ER PT J AU de Moraes, MC Santos, JB dos Anjos, DM Rangel, LP Vieira, TCRG Moaddel, R da Silva, JL AF de Moraes, Marcela Cristina Santos, Juliana Bosco dos Anjos, Daniel Meira Rangel, Luciana Pereira Ramos Goncalves Vieira, Tuane Cristine Moaddel, Ruin da Silva, Jerson Lima TI Prion protein-coated magnetic beads: Synthesis, characterization and development of a new ligands screening method SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Prion protein; Ligand fishing; Magnetic beads; Anti-prion compounds; Quinacrine; Screening method ID PURINE NUCLEOSIDE PHOSPHORYLASE; AGGREGATION; IDENTIFICATION; DERIVATIVES; INHIBITION; ACRIDINE; CHROMATOGRAPHY; NANOPARTICLES; CONFORMATION; BINDERS AB Prion diseases are characterized by protein aggregation and neurodegeneration. Conversion of the native prion protein (PrPc) into the abnormal scrapie PrP isoform (PrPsc), which undergoes aggregation and can eventually form amyloid fibrils, is a critical step leading to the characteristic path morphological hallmark of these diseases. However, the mechanism of conversion remains unclear. It is known that ligands can act as cofactors or inhibitors in the conversion mechanism of PrPc into PrPsc. Within this context, herein, we describe the immobilization of PrPc onto the surface of magnetic beads and the morphological characterization of PrPc-coated beads by fluorescence confocal microscopy. PrPc-coated magnetic beads were used to identify ligands from a mixture of compounds, which were monitored by UHPLC-ESI-MS/MS. This affinity-based method allowed the isolation of the anti-prion compound quinacrine, an inhibitor of PrP aggregation. The results indicate that this approach can be applied to not only "fish" for anti-prion compounds from complex matrixes, but also to screening for and identify possible cellular cofactors involved in the deflagration of prion diseases. (C) 2014 Elsevier B.V. All rights reserved. C1 [de Moraes, Marcela Cristina] Univ Fed Fluminense, Inst Quim, Dept Quim Organ, BR-24210141 Niteroi, RJ, Brazil. [de Moraes, Marcela Cristina; Santos, Juliana Bosco; dos Anjos, Daniel Meira; Ramos Goncalves Vieira, Tuane Cristine; da Silva, Jerson Lima] Univ Fed Rio de Janeiro, Inst Bioquim Med, BR-21941902 Rio De Janeiro, RJ, Brazil. [Rangel, Luciana Pereira; Ramos Goncalves Vieira, Tuane Cristine; da Silva, Jerson Lima] Inst Nacl Ciencia & Tecnol Biol Estrutural & Bioi, BR-21941902 Rio De Janeiro, RJ, Brazil. [Rangel, Luciana Pereira] Univ Fed Rio de Janeiro, Fac Farm, BR-21941902 Rio De Janeiro, RJ, Brazil. [Moaddel, Ruin] NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. RP de Moraes, MC (reprint author), Univ Fed Fluminense, Inst Quim, Dept Quim Organ, BR-24210141 Niteroi, RJ, Brazil. EM mcmoraes@id.uff.br RI Silva, Jerson/J-8984-2014 OI Silva, Jerson/0000-0001-9523-9441 FU National Council for Scientific and Technological Development (CNPq); Carlos Chagas Filho Foundation for Research in the State of Rio de Janeiro (FAPERJ); Intramural Research Program at National Institute on Aging FX This work was funded by grants from the National Council for Scientific and Technological Development (CNPq) and the Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro (FAPERJ). We also thank Eduardo R. dos Santos and Prof. Dr. Ronaldo da Silva Mohana Borges from CEMBIO-CCS-UFRJ for the UHPLC-MS/MS availability. This work was also supported in part by Intramural Research Program at National Institute on Aging (RM). NR 43 TC 1 Z9 1 U1 8 U2 27 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 JAN 30 PY 2015 VL 1379 BP 1 EP 8 DI 10.1016/j.chroma.2014.12.014 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CA8UV UT WOS:000349197300001 PM 25576041 ER PT J AU Doyle, SM Shastry, S Kravats, AN Shih, YH Miot, M Hoskins, JR Stan, G Wickner, S AF Doyle, Shannon M. Shastry, Shankar Kravats, Andrea N. Shih, Yu-Hsuan Miot, Marika Hoskins, Joel R. Stan, George Wickner, Sue TI Interplay between E. coli DnaK, ClpB and GrpE during Protein Disaggregation SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE GrpE; nucleotide exchange factor; Hsp40; protein disaggregation; molecular chaperone ID HEAT-SHOCK-PROTEIN; NUCLEOTIDE EXCHANGE FACTOR; MOLECULAR CHAPERONE DNAK; AAA PLUS DISAGGREGASE; ESCHERICHIA-COLI; HSP70 CHAPERONES; SUBSTRATE-BINDING; SYSTEM; HSP104; MECHANISM AB The DnaK/Hsp70 chaperone system and ClpB/Hsp104 collaboratively disaggregate protein aggregates and reactivate inactive proteins. The teamwork is specific: Escherichia coli DnaK interacts with E. coli ClpB and yeast Hsp70, Ssa1, interacts with yeast Hsp104. This interaction is between the middle domains of hexameric ClpB/Hsp104 and the DnaK/Hsp70 nucleotide-binding domain (NBD). To identify the site on E. coli DnaK that interacts with ClpB, we substituted amino acid residues throughout the DnaK NBD. We found that several variants with substitutions in subdomains IB and IIB of the DnaK NBD were defective in ClpB interaction in vivo in a bacterial two-hybrid assay and in vitro in a fluorescence anisotropy assay. The DnaK subdomain IIB mutants were also defective in the ability to disaggregate protein aggregates with ClpB, DnaJ and GrpE, although they retained some ability to reactivate proteins with DnaJ and GrpE in the absence of ClpB. We observed that GrpE, which also interacts with subdomains IB and IIB, inhibited the interaction between ClpB and DnaK in vitro, suggesting competition between ClpB and GrpE for binding DnaK. Computational modeling of the DnaK ClpB hexamer complex indicated that one DnaK monomer contacts two adjacent ClpB protomers simultaneously. The model and the experiments support a common and mutually exclusive GrpE and ClpB interaction region on DnaK. Additionally, homologous substitutions in subdomains IB and IIB of Ssa1 caused defects in collaboration between Ssa1 and Hsp104. Altogether, these results provide insight into the molecular mechanism of collaboration between the DnaK/Hsp70 system and ClpB/Hsp104 for protein disaggregation. Published by Elsevier Ltd. C1 [Doyle, Shannon M.; Shastry, Shankar; Kravats, Andrea N.; Miot, Marika; Hoskins, Joel R.; Wickner, Sue] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Shih, Yu-Hsuan; Stan, George] Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. RP Wickner, S (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Bldg 37,Room 5144, Bethesda, MD 20892 USA. EM wickners@mail.nih.gov FU National Science Foundation CAREER [MCB-0952082]; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the National Science Foundation CAREER grant number MCB-0952082 (to G.S.) and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 64 TC 7 Z9 7 U1 4 U2 21 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 30 PY 2015 VL 427 IS 2 BP 312 EP 327 DI 10.1016/j.jmb.2014.10.013 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CA4PX UT WOS:000348888200012 PM 25451597 ER PT J AU Nishi, H Demir, E Panchenko, AR AF Nishi, Hafumi Demir, Emek Panchenko, Anna R. TI Crosstalk between Signaling Pathways Provided by Single and Multiple Protein Phosphorylation Sites SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein phosphorylation; multiple phosphorylation sites; signaling pathway; pathway crosstalk ID POSTTRANSLATIONAL MODIFICATIONS; TYROSINE KINASES; IN-VIVO; MECHANISMS; STABILITY; EVOLUTION; BINDING; CONSERVATION; SPECIFICITY; ACTIVATION AB Cellular fate depends on the spatiotemporal separation and integration of signaling processes that can be provided by phosphorylation events. In this study, we identify the crucial points in signaling crosstalk that can be triggered by discrete phosphorylation events on a single target protein. We integrated the data on individual human phosphosites with the evidence on their corresponding kinases, the functional consequences of phosphorylation on activity of the target protein and corresponding pathways. Our results show that there is a substantial fraction of phosphosites that can play critical roles in crosstalk between alternative and redundant pathways and regulatory outcome of phosphorylation can be linked to a type of phosphorylated residue. These regulatory phosphosites can serve as hubs in the signal flow and their functional roles are directly connected to their specific properties. Namely, phosphosites with similar regulatory functions are phosphorylated by the same kinases and participate in regulation of similar biochemical pathways. Such sites are more likely to cluster in sequence and space unlike sites with antagonistic outcomes of their phosphorylation on a target protein. In addition, we found that in silico phosphorylation of sites with similar functional consequences has comparable outcomes on a target protein stability. An important role of phosphorylation sites in biological crosstalk is evident from the analysis of their evolutionary conservation. Published by Elsevier Ltd. C1 [Nishi, Hafumi; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Demir, Emek] Mem Sloan Kettering Res Ctr, Computat Biol Ctr, New York, NY 10065 USA. RP Panchenko, AR (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM panch@ncbi.nlm.nih.gov OI Demir, Emek/0000-0002-3663-7113 FU National Library of Medicine at the US National Institutes of Health; National Human Genome Research Institute, National Institutes of Health [5U41-HG006623-02] FX We thank Thomas Madej and Yuri Wolf for insightful discussions. This work was supported by the Intramural Research Program of the National Library of Medicine at the US National Institutes of Health. E.D. was supported by grant 5U41-HG006623-02 of the National Human Genome Research Institute, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 50 TC 6 Z9 7 U1 1 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 30 PY 2015 VL 427 IS 2 BP 511 EP 520 DI 10.1016/j.jmb.2014.11.001 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CA4PX UT WOS:000348888200026 PM 25451034 ER PT J AU Sengupta, S Nguyen, AM van Landingham, SW Solomon, SD Do, DV Ferrucci, L Friedman, DS Ramulu, PY AF Sengupta, Sabyasachi Nguyen, Angeline M. van Landingham, Suzanne W. Solomon, Sharon D. Do, Diana V. Ferrucci, Luigi Friedman, David S. Ramulu, Pradeep Y. TI Evaluation of real-world mobility in age-related macular degeneration SO BMC Ophthalmology LA English DT Article DE Age-related macular degeneration; Physical activity; Mobility ID PHYSICAL-ACTIVITY; UNITED-STATES; LIFE-SPACE; OLDER-ADULTS; VISION LOSS; ACCELEROMETER; RISK; ASSOCIATION; MORTALITY; HOME AB Background: Previous research has suggested an association between poor vision and decreased mobility, including restricted levels of physical activity and travel away from home. We sought to determine the impact of age-related macular degeneration (AMD) on these measures of mobility. Methods: Fifty-seven AMD patients with bilateral, or severe unilateral, visual impairment were compared to 59 controls with normal vision. All study subjects were between the ages of 60 and 80. Subjects wore accelerometers and cellular network-based tracking devices over 7 days of normal activity. Number of steps taken, time spent in moderate-to-vigorous physical activity (MVPA), number of excursions from home, and time spent away from home were the primary outcome measures. Results: In multivariate negative binomial regression models adjusted for age, gender, race, comorbidities, and education, AMD participants took fewer steps than controls (18% fewer steps per day, p = 0.01) and spent significantly less time in MVPA (35% fewer minutes, p < 0.001). In multivariate logistic regression models adjusting for age, sex, race, cognition, comorbidities, and grip strength, AMD subjects showed an increased likelihood of not leaving their home on a given day (odds ratio = 1.36, p = 0.04), but did not show a significant difference in the magnitude of time spent away from home (9% fewer minutes, p = 0.11). Conclusion: AMD patients with poorer vision engage in significantly less physical activity and take fewer excursions away from the home. Further studies identifying the factors mediating the relationship between vision loss and mobility are needed to better understand how to improve mobility among AMD patients. C1 [Sengupta, Sabyasachi; Nguyen, Angeline M.; van Landingham, Suzanne W.; Solomon, Sharon D.; Friedman, David S.; Ramulu, Pradeep Y.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21287 USA. [Do, Diana V.] Univ Nebraska Med Ctr, Truhlsen Eye Inst, Omaha, NE USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Bethesda, MD 20892 USA. [Friedman, David S.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Friedman, David S.; Ramulu, Pradeep Y.] Johns Hopkins Univ, Dana Ctr Prevent Ophthalmol, Baltimore, MD USA. RP Ramulu, PY (reprint author), Johns Hopkins Univ, Wilmer Eye Inst, 600 North Wolfe St,Maumenee B-110, Baltimore, MD 21287 USA. EM pramulu@jhmi.edu FU Dennis W. Jahnigen Memorial Award; NIH [EY018595, EY022976]; Research to Prevent Blindness Robert and Helen Schaub Special Scholar Award; Intramural Research Program of the NIH (National Institute on Aging); Doris Duke Charitable Research Foundation Clinical Research Fellowship FX This research was supported in part by the Dennis W. Jahnigen Memorial Award, NIH Grants EY018595 and EY022976, the Research to Prevent Blindness Robert and Helen Schaub Special Scholar Award, the Intramural Research Program of the NIH (National Institute on Aging), and the Doris Duke Charitable Research Foundation Clinical Research Fellowship. All funding organizations had no role in the design or conduct of this research. Sabyasachi Sengupta and Pradeep Ramulu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 37 TC 4 Z9 4 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2415 J9 BMC OPHTHALMOL JI BMC Ophthalmol. PD JAN 30 PY 2015 VL 15 AR 9 DI 10.1186/1471-2415-15-9 PG 11 WC Ophthalmology SC Ophthalmology GA CA6SG UT WOS:000349045300001 PM 25636376 ER PT J AU Liu, ZZ Roche, PA AF Liu, Zhenzhen Roche, Paul A. TI Macropinocytosis in phagocytes: regulation of MHC class-II-restricted antigen presentation in dendritic cells SO Frontiers in Physiology LA English DT Review DE dendritic cell; macropinocytosis; endocytosis; MHC class II; antigen presentation ID IN-VIVO; CROSS-PRESENTATION; MANNOSE RECEPTOR; CONSTITUTIVE MACROPINOCYTOSIS; INHIBITS MACROPINOCYTOSIS; DOWN-REGULATION; ENDOCYTOSIS; CAPTURE; MACROPHAGES; MATURATION AB Dendritic cells (DCs) are outstanding antigen presenting cells (APCs) due to their robust ability to internalize extracellular antigens using endocytic processes such as receptor-mediated endocytosis, phagocytosis, and macropinocytosis. Macropinocytosis mediates the non-specific uptake of soluble antigens and occurs in DCs constitutively. Macropinocytosis plays a key role in DC-mediated antigen presentation to T cells against pathogens and the efficiency of macropinocytosis in antigen capture is regulated during the process of DC maturation. Here, we review the methods to study macropinocytosis, describe our current knowledge of the regulatory mechanisms of antigen uptake via macropinocytosis and the intracellular trafficking route followed by macropinocytosed antigens, and discuss the significance of macropinocytosis for DC function. C1 [Liu, Zhenzhen; Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. EM paul.roche@nih.gov FU Intramural Research Program of the National Cancer Institute FX We acknowledge the many investigators whose important work could not be cited due to space limitations. The work was supported by the Intramural Research Program of the National Cancer Institute. NR 47 TC 17 Z9 18 U1 2 U2 16 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PD JAN 30 PY 2015 VL 6 AR 1 DI 10.3389/fphys.2015.00001 PG 6 WC Physiology SC Physiology GA CA2GN UT WOS:000348727000001 PM 25688210 ER PT J AU Korn, EL Dignam, JJ Freidlin, B AF Korn, Edward L. Dignam, James J. Freidlin, Boris TI Assessing treatment benefit with competing risks not affected by the randomized treatment SO STATISTICS IN MEDICINE LA English DT Article DE cause-specific survival; competing risks; cumulative incidence curves; death rates; randomized clinical trials; survival curves ID PROSTATE-CANCER AB The comparison of overall survival curves between treatment arms will always be of interest in a randomized clinical trial involving a life-shortening disease. In some settings, the experimental treatment is only expected to affect the deaths caused by the disease, and the proportion of deaths caused by the disease is relatively low. In these settings, the ability to assess treatment-effect differences between Kaplan-Meier survival curves can be hampered by the large proportion of deaths in both arms that are unrelated to the disease. To address this problem, frequently displayed are cause-specific survival curves or cumulative incidence curves, which respectively censor and immortalize events (deaths) not caused by the disease. However, the differences between the experimental and control treatment arms for these curves overestimate the difference between the overall survival curves for the treatment arms and thus could result in overestimation of the benefit of the experimental treatment for the patients. To address this issue, we propose new estimators of overall survival for the treatment arms that are appropriate when the treatment does not affect the non-disease-related deaths. These new estimators give a more precise estimate of the treatment benefit, potentially enabling future patients to make a more informed decision concerning treatment choice. We also consider the case where an exponential assumption allows the simple presentation of mortality rates as the outcome measures. Applications are given for estimating overall survival in a prostate-cancer treatment randomized clinical trial, and for estimating the overall mortality rates in a prostate-cancer screening trial. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Korn, Edward L.; Freidlin, Boris] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Dignam, James J.] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA. [Dignam, James J.] NRG Oncol Stat & Data Management, Philadelphia, PA 19103 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch MSC9735, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM korne@ctep.nci.nih.gov FU National Cancer Institute, NIH, US Department of Health and Human Services [U10 CA21661, U10 CA180822]; National Cancer Institute, NIH, US Department of Health and Human Services FX J. Dignam was supported by Public Health Service grants U10 CA21661 and U10 CA180822 from the National Cancer Institute, NIH, US Department of Health and Human Services. NR 12 TC 0 Z9 0 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2015 VL 34 IS 2 BP 265 EP 280 DI 10.1002/sim.6353 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA AW4ZT UT WOS:000346286700006 PM 25363739 ER PT J AU Murthy, M Ram, JL AF Murthy, Mahadev Ram, Jeffrey L. TI Invertebrates as model organisms for research on aging biology SO INVERTEBRATE REPRODUCTION & DEVELOPMENT LA English DT Editorial Material ID ASCIDIAN CIONA-INTESTINALIS; LIFE-SPAN; CAENORHABDITIS-ELEGANS; BOTRYLLUS-SCHLOSSERI; STEM-CELLS; LONGEVITY; NEMATODE; MUTANTS; DAPHNIA; NICHES AB Invertebrate model systems, such as nematodes and fruit flies, have provided valuable information about the genetics and cellular biology involved in aging. However, limitations of these simple, genetically tractable organisms suggest the need for other model systems, some of them invertebrate, to facilitate further advances in the understanding of mechanisms of aging and longevity in mammals, including humans. This paper introduces 10 review articles about the use of invertebrate model systems for the study of aging by authors who participated in an 'NIA-NIH symposium on aging in invertebrate model systems' at the 2013 International Congress for Invertebrate Reproduction and Development. In contrast to the highly derived characteristics of nematodes and fruit flies as members of the superphylum Ecdysozoa, cnidarians, such as Hydra, are more 'basal' organisms that have a greater number of genetic orthologs in common with humans. Moreover, some other new model systems, such as the urochordate Botryllus schlosseri, the tunicate Ciona, and the sea urchins (Echinodermata) are members of the Deuterostomia, the same superphylum that includes all vertebrates, and thus have mechanisms that are likely to be more closely related to those occurring in humans. Additional characteristics of these new model systems, such as the recent development of new molecular and genetic tools and a more similar pattern to humans of regeneration and stem cell function suggest that these new model systems may have unique advantages for the study of mechanisms of aging and longevity. C1 [Murthy, Mahadev] NIA, Div Aging Biol, NIH, Bethesda, MD 20892 USA. [Ram, Jeffrey L.] Wayne State Univ, Dept Physiol, Detroit, MI 48201 USA. RP Ram, JL (reprint author), Wayne State Univ, Dept Physiol, Detroit, MI 48201 USA. EM jeffram@wayne.edu NR 32 TC 3 Z9 3 U1 4 U2 89 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0792-4259 EI 2157-0272 J9 INVERTEBR REPROD DEV JI Invertebr. Reprod. Dev. PD JAN 30 PY 2015 VL 59 SU 1 SI SI BP 1 EP 4 DI 10.1080/07924259.2014.970002 PG 4 WC Reproductive Biology; Zoology SC Reproductive Biology; Zoology GA AW1SW UT WOS:000346071100001 ER PT J AU Shah, NN Baird, K Delbrook, CP Fleisher, TA Kohler, ME Rampertaap, S Lemberg, K Hurley, CK Kleiner, DE Merchant, MS Pittaluga, S Sabatino, M Stroncek, DF Wayne, AS Zhang, H Fry, TJ Mackall, CL AF Shah, Nirali N. Baird, Kristin Delbrook, Cynthia P. Fleisher, Thomas A. Kohler, Mark E. Rampertaap, Shakuntala Lemberg, Kimberly Hurley, Carolyn K. Kleiner, David E. Merchant, Melinda S. Pittaluga, Stefania Sabatino, Marianna Stroncek, David F. Wayne, Alan S. Zhang, Hua Fry, Terry J. Mackall, Crystal L. TI Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell-depleted stem cell transplantation SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; KIR-LIGAND INCOMPATIBILITY; RECEPTOR EXPRESSION; ADOPTIVE TRANSFER; INHIBITORY KIR; DONOR ORIGIN AB Natural killer (NK) cells can enhance engraftment and mediate graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT), but the potency of graft-versus-leukemia mediated by naturally reconstituting NK cells following HSCT is limited. Preclinical studies demonstrate that activation of NK cells using interleukin-15 (IL-15) plus 4-1BBL upregulates activating receptor expression and augments killing capacity. In an effort to amplify the beneficial effects of NK cells post-HSCT, we conducted a first-in-human trial of adoptive transfer of donor-derived IL-15/4-1BBL-activated NK cells (aNK-DLI) following HLA-matched, T-cell-depleted (1-2 x 10(4) T cells/kg) non-myeloablative peripheral blood stem cell transplantation in children and young adults with ultra-high-risk solid tumors. aNK-DLI were CD3(+)-depleted, CD56(+)-selected lymphocytes, cultured for 9 to 11 days with recombinant human IL-15 plus 4-1BBL(+) IL-15R alpha(+) artificial antigen-presenting cells. aNK-DLI demonstrated potent killing capacity and displayed high levels of activating receptor expression. Five of 9 transplant recipients experienced acute graft-versus-host disease (GVHD) following aNK-DLI, with grade 4 GVHD observed in 3 subjects. GVHD was more common in matched unrelated donor vs matched sibling donor recipients and was associated with higher donor CD3 chimerism. Given that the T-cell dose was below the threshold required for GVHD in this setting, we conclude that aNK-DLI contributed to the acute GVHD observed, likely by augmenting underlying T-cell alloreactivity. This trial was registered at www.clinicaltrials.gov as # NCT01287104. C1 [Shah, Nirali N.; Baird, Kristin; Delbrook, Cynthia P.; Kohler, Mark E.; Merchant, Melinda S.; Zhang, Hua; Fry, Terry J.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Fleisher, Thomas A.; Rampertaap, Shakuntala; Lemberg, Kimberly] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Kohler, Mark E.] Johns Hopkins Univ Hosp, Dept Pediat, Baltimore, MD 21287 USA. [Hurley, Carolyn K.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Kleiner, David E.; Pittaluga, Stefania] NIH, Dept Pathol, Ctr Canc Res, Bethesda, MD 20892 USA. [Sabatino, Marianna; Stroncek, David F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wayne, Alan S.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90033 USA. RP Mackall, CL (reprint author), 10 CRC,1W-3750,10 Ctr Dr,MSC 1104, Bethesda, MD 20892 USA. EM mackallc@mail.nih.gov FU Center for Cancer Research, Intramural Research Program of the National Institutes of Health FX This work was supported by the Center for Cancer Research, Intramural Research Program of the National Institutes of Health. NR 66 TC 37 Z9 40 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 29 PY 2015 VL 125 IS 5 BP 784 EP 792 DI 10.1182/blood-2014-07-592881 PG 9 WC Hematology SC Hematology GA CD1DR UT WOS:000350814900012 PM 25452614 ER PT J AU Balakumaran, A Mishra, PJ Pawelczyk, E Yoshizawa, S Sworder, BJ Cherman, N Kuznetsov, SA Bianco, P Giri, N Savage, SA Merlino, G Dumitriu, B Dunbar, CE Young, NS Alter, BP Robey, PG AF Balakumaran, Arun Mishra, Prasun J. Pawelczyk, Edyta Yoshizawa, Sayuri Sworder, Brian J. Cherman, Natasha Kuznetsov, Sergei A. Bianco, Paolo Giri, Neelam Savage, Sharon A. Merlino, Glenn Dumitriu, Bogdan Dunbar, Cynthia E. Young, Neal S. Alter, Blanche P. Robey, Pamela G. TI Bone marrow skeletal stem/progenitor cell defects in dyskeratosis congenita and telomere biology disorders SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELL; IN-SITU HYBRIDIZATION; PROGENITOR CELLS; APLASTIC-ANEMIA; STROMAL FIBROBLASTS; FIBROUS DYSPLASIA; FAILURE SYNDROMES; GROWTH-FACTOR; C-KIT; MICROENVIRONMENT AB Dyskeratosis congenita (DC) is an inherited multisystem disorder, characterized by oral leukoplakia, nail dystrophy, and abnormal skin pigmentation, as well as high rates of bone marrow (BM) failure, solid tumors, and other medical problems such as osteopenia. DC and telomere biology disorders (collectively referred to as TBD here) are caused by germline mutations in telomere biology genes leading to very short telomeres and limited proliferative potential of hematopoietic stem cells. We found that skeletal stem cells (SSCs) within the BM stromal cell population (BMSCs, also known as BM-derived mesenchymal stem cells), may contribute to the hematologic phenotype. TBD-BMSCs exhibited reduced clonogenicity, spontaneous differentiation into adipocytes and fibrotic cells, and increased senescence in vitro. Upon in vivo transplantation into mice, TBD-BMSCs failed to form bone or support hematopoiesis, unlike normal BMSCs. TERC reduction (a TBD-associated gene) in normal BMSCs by small interfering TERC-RNA (siTERC-RNA) recapitulated the TBD-BMSC phenotype by reducing proliferation and secondary colony-forming efficiency, and by accelerating senescence in vitro. Microarray profiles of control and siTERC-BMSCs showed decreased hematopoietic factors at the messenger RNA level and decreased secretion of factors at the protein level. These findings are consistent with defects in SSCs/BMSCs contributing to BM failure in TBD. C1 [Balakumaran, Arun; Yoshizawa, Sayuri; Sworder, Brian J.; Cherman, Natasha; Kuznetsov, Sergei A.; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Skeletal Biol Sect, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. [Mishra, Prasun J.; Merlino, Glenn] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Pawelczyk, Edyta] NIH, Lab Diagnost Radiol Res, Warren G Magnuson Clin Ctr, US Dept HHS, Bethesda, MD 20892 USA. [Bianco, Paolo] Univ Roma La Sapienza, Dept Mol Med, I-00185 Rome, Italy. [Giri, Neelam; Savage, Sharon A.; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Dumitriu, Bogdan; Dunbar, Cynthia E.; Young, Neal S.] NHLBI, Hematol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Robey, PG (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, US Dept HHS, 30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA. EM probey@dir.nidcr.nih.gov RI Savage, Sharon/B-9747-2015; Robey, Pamela/H-1429-2011; OI Savage, Sharon/0000-0001-6006-0740; Robey, Pamela/0000-0002-5316-5576; Sworder, Brian/0000-0002-5902-5507 FU Intramural Research Program of the NIH, DHHS (the National Institute of Dental and Craniofacial Research Division of Intramural Research); Intramural Research Program of the NIH, DHHS (National Cancer Institute Cancer Research Center); Intramural Research Program of the NIH, DHHS (National Cancer Institute Division of Cancer Epidemiology and Genetics); Intramural Research Program of the NIH, DHHS (National Heart, Lung, and Blood Institute Intramural Research Program); Telethon [GGP09227]; European Union Pluripotent Stem Cell Resources for Mesodermal Medicine [60243]; Ministry of Education, Universities and Research (PRIN) [20102M7T8X] FX This work was supported by the Intramural Research Program of the NIH, DHHS (the National Institute of Dental and Craniofacial Research Division of Intramural Research: A.B., S.Y., N.C., S.A.K., P.G.R.; the National Cancer Institute Cancer Research Center: P.J.M., G.M.; the National Cancer Institute Division of Cancer Epidemiology and Genetics: N.G., S.A.S., B.P.A.; the National Heart, Lung, and Blood Institute Intramural Research Program: B.D., C.E.D., N.S.Y.); and by GGP09227 Telethon, European Union Pluripotent Stem Cell Resources for Mesodermal Medicine 60243, Ministry of Education, Universities and Research (PRIN 2010-2011, 20102M7T8X; P.B.). NR 59 TC 9 Z9 9 U1 1 U2 7 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 JAN 29 PY 2015 VL 125 IS 5 BP 793 EP 802 DI 10.1182/blood-2014-06-566810 PG 10 WC Hematology SC Hematology GA CD1DR UT WOS:000350814900013 PM 25499762 ER PT J AU Lawrence, MS Sougnez, C Lichtenstein, L Cibulskisl, K Lander, E Gabriel, SB Getz, G Ally, A Balasundaram, M Birol, I Bowlby, R Brooks, D Butterfield, YSN Carlsen, R Cheng, D Chu, A Dhalla, N Guin, R Holt, RA Jones, SJM Lee, D Li, HYI Marra, MA Mayo, M Moore, RA Mungall, AJ Robertson, AG Schein, JE Sipahimalan, P Tam, A Thiessen, N Wong, T Protopopov, A Santoso, N Lee, S Parfenov, M Zhang, JH Mahadeshwar, HS Tang, JB Ren, XJ Seth, S Haseley, P Zeng, D Yang, LX Xu, AW Song, XZ Pantazi, A Bristow, CA Hadjipanayis, A Seidman, J Chin, L Park, PJ Kucherlapati, R Akbani, R Casasent, T Liu, WB Le, Y Mille, G Motter, T Weinstein, J Diao, LX Wang, J Fan, YH Lie, JZ Wang, K Auman, JT Balu, S Bodenheimer, T Buda, E Hayes, DN Hoadley, KA Hoyle, AP Jefferys, SR Jones, CD Kimes, PK Liu, YF Marron, JS Meng, SW Mieczkowski, PA Mose, LE Parker, JS Perou, CM Prins, JF Roach, J Shi, Y Simons, JV Singh, D Soloway, MG Tan, DH Veluvolu, U Walter, V Waring, S Wilkerson, MD Wu, JY Zhao, N Cherniack, AD Hammerman, PS Tward, AD Pedamallu, CS Saksena, G Jung, J Ojesina, AI Carter, SL Zack, TI Schumacher, SE Beroukhim, R Freeman, SS Meyerson, M Cho, J Chin, L Getz, G Noble, MS DiCara, D Zhang, H Heiman, DI Gehlenborg, N Voet, D Lin, P Frazer, S Stojanov, P Liu, YC Zou, LH Kim, J Sougnez, C Gabriel, SB Lawrence, MS Muzny, D Doddapaneni, H Kovar, C Reid, J Morton, D Han, Y Hale, W Chao, H Chang, K Drummond, JA Gibbs, RA Kakkar, N Wheeler, D Xi, L Ciriello, G Ladanyi, M Lee, W Ramirez, R Sander, C Shen, R Sinhal, R Weinhold, N Taylor, BS Aksoy, BA Dresdner, G Gao, JJ Gross, B Jacobsen, A Reva, B Schultz, N Sumer, SO Sun, YC Chan, TA Morris, LG Stuart, J Benz, S Ng, S Benz, C Yau, C Baylin, SB Cope, L Danilova, L Herman, JG Bootwalla, M Maglinte, DT Larid, PW Triche, T Weisenberger, DJ Van den Berg, DJ Agrawal, N Bishop, J Boutros, PC Bruce, JP Byers, LA Califano, J Carey, TE Chen, Z Cheng, H Chiosea, SI Cohen, E Diergaarde, B Egloff, AM El-Naggar, AK Ferris, RL Frederick, MJ Grandis, JR Guo, Y Haddad, RI Hammerman, PS Harris, T Hayes, DN Hui, ABY Lee, JJ Lippman, SM Liu, FF McHugh, JB Myers, J Ng, PKS Perez-Ordonez, B Pickering, CR Prystowsky, M Romkes, M Saleh, AD Sartor, MA Seethala, R Seiwert, TY Si, H Tward, AD Van Waes, C Waggott, DM Wiznerowicz, M Yarbrough, WG Zhang, JX Zuo, ZX Burnett, K Crain, D Gardner, J Lau, K Mallery, D Morris, S Lauskis, JP Penny, R Shelton, C Shelton, T Sherman, M Yena, P Black, AD Bowen, J Frick, J Gastier-Foster, JM Harper, HA Leraas, K Lichtenberg, TM Ramirez, NC Wise, L Zmuda, E Baboud, J Jensen, MA Kahn, AB Pihl, TD Pot, DA Srinivasan, D Walton, JS Wan, YH Burton, RA Davidsen, T Demchok, JA Eley, G Ferguson, ML Shaw, KRM Ozenberger, BA Sheth, M Sofia, HJ Tarnuzzer, R Wang, ZN Yang, LM Zenklusen, JC Saller, C Tarvi, K Chen, C Bollag, R Weinberger, P Golusinski, W Golusinski, P Ibbs, M Korski, K Mackiewicz, A Suchorska, W Szybiak, B Wiznerowicz, M Burnett, K Curley, E Gardner, J Mallery, D Penny, R Shelton, T Yena, P Beard, C Mitchell, C Sandusky, G Agrawal, N Ahn, J Bishop, J Califano, J Khan, Z Bruce, JP Hui, ABY Irish, J Liu, FF Perez-Ordonez, B Waldron, J Boutros, PC Waggott, DM Myers, J William, WN Lippman, SM Egea, S Gomez-Fernandez, C Herbert, L Bradford, CR Carey, TE Chepeha, DB Haddad, AS Jones, TR Komarck, CM Malakh, M McHugh, JB Moyer, JS Nguyen, A Peterson, LA Prince, ME Rozek, LS Sartor, MA Taylor, EG Walline, HM Wolf, GT Boice, L Chera, BS Funkhouser, WK Gulley, ML Hackman, TG Hayes, DN Hayward, MC Huang, M Rathmell, WK Salazar, AH Shockley, WW Shores, CG Thorne, L Weissler, MC Wrenn, S Zanation, AM Chiosea, SI Diergaarde, B Egloff, AM Ferris, RL Romkes, M Seethala, R Brown, BT Guo, Y Pham, M Yarbrough, WG AF Lawrence, Michael S. Sougnez, Carrie Lichtenstein, Lee Cibulskisl, Kristian Lander, Eric Gabriel, Stacey B. Getz, Gad Ally, Adrian Balasundaram, Miruna Birol, Inanc Bowlby, Reanne Brooks, Denise Butterfield, Yaron S. N. Carlsen, Rebecca Cheng, Dean Chu, Andy Dhalla, Noreen Guin, Ranabir Holt, Robert A. Jones, Steven J. M. Lee, Darlene Li, Haiyan I. Marra, Marco A. Mayo, Michael Moore, Richard A. Mungall, Andrew J. Robertson, A. Gordon Schein, Jacqueline E. Sipahimalan, Payal Tam, Angela Thiessen, Nina Wong, Tina Protopopov, Alexei Santoso, Netty Lee, Semin Parfenov, Michael Zhang, Jianhua Mahadeshwar, Harshad S. Tang, Jiabin Ren, Xiaojia Seth, Sahil Haseley, Psalm Zeng, Dong Yang, Lixing Xu, Andrew W. Song, Xingzhi Pantazi, Angeliki Bristow, Christopher A. Hadjipanayis, Angela Seidman, Jonathan Chin, Lynda Park, Peter J. Kucherlapati, Raju Akbani, Rehan Casasent, Tod Liu, Wenbin Le, Yiling Mille, Gordon Motter, Thomas Weinstein, John Diao, Lixia Wang, Jing Fan, You Hong Lie, Jinze Wang, Kai Auman, J. Todd Balu, Saianand Bodenheimer, Thomas Buda, Elizabeth Hayes, D. Neil Hoadley, Katherine A. Hoyle, Alan P. Jefferys, Stuart R. Jones, Corbin D. Kimes, Patrick K. Liu, Yufeng Marron, J. S. Meng, Shaowu Mieczkowski, Piotr A. Mose, Lisle E. Parker, Joel S. Perou, Charles M. Prins, Jan F. Roach, Jeffrey Shi, Yan Simons, Janae V. Singh, Darshan Soloway, Matthew G. Tan, Donghui Veluvolu, Umadevi Walter, Vonn Waring, Scot Wilkerson, Matthew D. Wu, Junyuan Zhao, Ni Cherniack, Andrew D. Hammerman, Peter S. Tward, Aaron D. Pedamallu, Chandra Sekhar Saksena, Gordon Jung, Joonil Ojesina, Akinyemi I. Carter, Scott L. Zack, Travis I. Schumacher, Steven E. Beroukhim, Rameen Freeman, Samuel S. Meyerson, Matthew Cho, Juok Chin, Lynda Getz, Gad Noble, Michael S. DiCara, Daniel Zhang, Hailei Heiman, David I. Gehlenborg, Nils Voet, Doug Lin, Pei Frazer, Scott Stojanov, Petar Liu, Yingchun Zou, Lihua Kim, Jaegil Sougnez, Carrie Gabriel, Stacey B. Lawrence, Michael S. Muzny, Donna Doddapaneni, HarshaVardhan Kovar, Christie Reid, Jeff Morton, Donna Han, Yi Hale, Walker Chao, Hsu Chang, Kyle Drummond, Jennifer A. Gibbs, Richard A. Kakkar, Nipun Wheeler, David Xi, Liu Ciriello, Giovanni Ladanyi, Marc Lee, William Ramirez, Ricardo Sander, Chris Shen, Ronglai Sinhal, Rileen Weinhold, Nils Taylor, Barry S. Aksoy, B. Arman Dresdner, Gideon Gao, Jianjiong Gross, Benjamin Jacobsen, Anders Reva, Boris Schultz, Nikolaus Sumer, S. Onur Sun, Yichao Chan, Timothy A. Morris, Luc G. Stuart, Joshua Benz, Stephen Ng, Sam Benz, Christopher Yau, Christina Baylin, Stephen B. Cope, Leslie Danilova, Ludmila Herman, James G. Bootwalla, Moiz Maglinte, Dennis T. Larid, Peter W. Triche, Timothy, Jr. Weisenberger, Daniel J. Van den Berg, David J. Agrawal, Nishant Bishop, Justin Boutros, Paul C. Bruce, Jeff P. Byers, Lauren Averett Califano, Joseph Carey, Thomas E. Chen, Zhong Cheng, Hui Chiosea, Simion I. Cohen, Ezra Diergaarde, Brenda Egloff, Ann Marie El-Naggar, Adel K. Ferris, Robert L. Frederick, Mitchell J. Grandis, Jennifer R. Guo, Yan Haddad, Robert I. Hammerman, Peter S. Harris, Thomas Hayes, D. Neil Hui, Angela B. Y. Lee, J. Jack Lippman, Scott M. Liu, Fei-Fei McHugh, Jonathan B. Myers, Jeff Ng, Patrick Kwok Shing Perez-Ordonez, Bayardo Pickering, Curtis R. Prystowsky, Michael Romkes, Marjorie Saleh, Anthony D. Sartor, Maureen A. Seethala, Raja Seiwert, Tanguy Y. Si, Han Tward, Aaron D. Van Waes, Carter Waggott, Daryl M. Wiznerowicz, Maciej Yarbrough, Wendell G. Zhang, Jiexin Zuo, Zhixiang Burnett, Ken Crain, Daniel Gardner, Johanna Lau, Kevin Mallery, David Morris, Scott Lauskis, Joseph Pau Penny, Robert Shelton, Candace Shelton, Troy Sherman, Mark Yena, Peggy Black, Aaron D. Bowen, Jay Frick, Jessica Gastier-Foster, Julie M. Harper, Hollie A. Leraas, Kristen Lichtenberg, Tara M. Ramirez, Nilsa C. Wise, Lisa Zmuda, Erik Baboud, Julien Jensen, Mark A. Kahn, An B. Pihl, Todd D. Pot, David A. Srinivasan, Deepak Walton, Jessica S. Wan, Yunhu Burton, Robert A. Davidsen, Tanja Demchok, John A. Eley, Greg Ferguson, Martin L. Shaw, Kenna R. Mills Ozenberger, Bradley A. Sheth, Margi Sofia, Heidi J. Tarnuzzer, Roy Wang, Zhining Yang, Liming Zenklusen, Jean Claude Saller, Charles Tarvi, Katherine Chen, Chu Bollag, Roni Weinberger, Paul Golusinski, Wojciech Golusinski, Pawel Ibbs, Matthew Korski, Konstanty Mackiewicz, Andrzej Suchorska, Wiktoria Szybiak, Bartosz Wiznerowicz, Maciej Burnett, Ken Curley, Erin Gardner, Johanna Mallery, David Penny, Robert Shelton, Troy Yena, Peggy Beard, Christina Mitchell, Colleen Sandusky, George Agrawal, Nishant Ahn, Julie Bishop, Justin Califano, Joseph Khan, Zubair Bruce, Jeff P. Hui, Angela B. Y. Irish, Jonathan Liu, Fei-Fei Perez-Ordonez, Bayardo Waldron, John Boutros, Paul C. Waggott, Daryl M. Myers, Jeff William, William N., Jr. Lippman, Scott M. Egea, Sophie Gomez-Fernandez, Carmen Herbert, Lynn Bradford, Carol R. Carey, Thomas E. Chepeha, Douglas B. Haddad, Andrea S. Jones, Tamara R. Komarck, Christine M. Malakh, Mayya McHugh, Jonathan B. Moyer, Jeffrey S. Nguyen, Ariane Peterson, Lisa A. Prince, Mark E. Rozek, Laura S. Sartor, Maureen A. Taylor, Evan G. Walline, Heather M. Wolf, Gregory T. Boice, Lori Chera, Bhishamjit S. Funkhouser, William K. Gulley, Margaret L. Hackman, Trevor G. Hayes, D. Neil Hayward, Michele C. Huang, Mei Rathmell, W. Kimryn Salazar, Ashley H. Shockley, William W. Shores, Carol G. Thorne, Leigh Weissler, Mark C. Wrenn, Sylvia Zanation, Adam M. Chiosea, Simion I. Diergaarde, Brenda Egloff, Ann Marie Ferris, Robert L. Romkes, Marjorie Seethala, Raja Brown, Brandee T. Guo, Yan Pham, Michelle Yarbrough, Wendell G. CA Canc Genome Atlas Network TI Comprehensive genomic characterization of head and neck squamous cell carcinomas SO NATURE LA English DT Article ID NF-KAPPA-B; GROWTH-FACTOR-RECEPTOR; AJUBA FAMILY PROTEINS; CANCER GROWTH; ACTIVATION; EXPRESSION; TRAF3; EGFR; CLASSIFICATION; RESISTANCE AB The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs. C1 [Lichtenstein, Lee; Cibulskisl, Kristian; Lander, Eric; Gabriel, Stacey B.; Cherniack, Andrew D.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Jung, Joonil; Ojesina, Akinyemi I.; Carter, Scott L.; Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Freeman, Samuel S.; Meyerson, Matthew; Cho, Juok; Noble, Michael S.; DiCara, Daniel; Zhang, Hailei; Heiman, David I.; Gehlenborg, Nils; Voet, Doug; Lin, Pei; Frazer, Scott; Stojanov, Petar; Liu, Yingchun; Zou, Lihua; Kim, Jaegil] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Cheng, Dean; Chu, Andy; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J. M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalan, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada. [Protopopov, Alexei; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Seth, Sahil; Zeng, Dong; Song, Xingzhi; Bristow, Christopher A.; Akbani, Rehan; Casasent, Tod; Liu, Wenbin; Le, Yiling; Mille, Gordon; Motter, Thomas; Weinstein, John; Diao, Lixia; Wang, Jing; Fan, You Hong; Byers, Lauren Averett; El-Naggar, Adel K.; Frederick, Mitchell J.; Lee, J. Jack; Myers, Jeff; Ng, Patrick Kwok Shing; Pickering, Curtis R.; Zhang, Jiexin; William, William N., Jr.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Santoso, Netty; Lee, Semin; Parfenov, Michael; Ren, Xiaojia; Haseley, Psalm; Yang, Lixing; Xu, Andrew W.; Pantazi, Angeliki; Hadjipanayis, Angela; Seidman, Jonathan; Park, Peter J.; Kucherlapati, Raju; Beroukhim, Rameen; Meyerson, Matthew; Tward, Aaron D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hadjipanayis, Angela; Park, Peter J.; Kucherlapati, Raju] Brigham & Womens Hosp, Boston, MA 02115 USA. [Park, Peter J.] Boston Childrens Hosp, Boston, MA 02115 USA. [Lie, Jinze; Wang, Kai] Univ Kentucky, Lexington, KY 40506 USA. [Auman, J. Todd; Balu, Saianand; Bodenheimer, Thomas; Buda, Elizabeth; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Kimes, Patrick K.; Liu, Yufeng; Marron, J. S.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Parker, Joel S.; Perou, Charles M.; Prins, Jan F.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Singh, Darshan; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Walter, Vonn; Waring, Scot; Wilkerson, Matthew D.; Wu, Junyuan; Zhao, Ni; Boice, Lori; Chera, Bhishamjit S.; Funkhouser, William K.; Gulley, Margaret L.; Hackman, Trevor G.; Hayward, Michele C.; Huang, Mei; Rathmell, W. Kimryn; Salazar, Ashley H.; Shockley, William W.; Shores, Carol G.; Thorne, Leigh; Weissler, Mark C.; Wrenn, Sylvia; Zanation, Adam M.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Pedamallu, Chandra Sekhar; Ojesina, Akinyemi I.; Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Meyerson, Matthew; Stojanov, Petar; Haddad, Robert I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zack, Travis I.] Harvard Univ, Boston, MA 02115 USA. [Muzny, Donna; Doddapaneni, HarshaVardhan; Kovar, Christie; Reid, Jeff; Morton, Donna; Han, Yi; Hale, Walker; Chao, Hsu; Chang, Kyle; Drummond, Jennifer A.; Gibbs, Richard A.; Kakkar, Nipun; Wheeler, David; Xi, Liu] Baylor Coll Med, Houston, TX 77030 USA. [Ciriello, Giovanni; Ladanyi, Marc; Lee, William; Ramirez, Ricardo; Sander, Chris; Shen, Ronglai; Sinhal, Rileen; Weinhold, Nils; Taylor, Barry S.; Aksoy, B. Arman; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Reva, Boris; Schultz, Nikolaus; Sumer, S. Onur; Sun, Yichao; Chan, Timothy A.; Morris, Luc G.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Stuart, Joshua; Benz, Stephen; Ng, Sam; Benz, Christopher; Yau, Christina] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. [Baylin, Stephen B.; Cope, Leslie; Danilova, Ludmila; Herman, James G.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Bootwalla, Moiz; Maglinte, Dennis T.; Larid, Peter W.; Triche, Timothy, Jr.; Weisenberger, Daniel J.; Van den Berg, David J.] Univ So Calif, Los Angeles, CA 90033 USA. [Agrawal, Nishant; Bishop, Justin; Califano, Joseph; Ahn, Julie; Khan, Zubair] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Boutros, Paul C.; Waggott, Daryl M.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada. [Bruce, Jeff P.; Hui, Angela B. Y.] Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. [Carey, Thomas E.; McHugh, Jonathan B.; Sartor, Maureen A.; Bradford, Carol R.; Chepeha, Douglas B.; Haddad, Andrea S.; Jones, Tamara R.; Komarck, Christine M.; Malakh, Mayya; Moyer, Jeffrey S.; Nguyen, Ariane; Peterson, Lisa A.; Prince, Mark E.; Rozek, Laura S.; Taylor, Evan G.; Walline, Heather M.; Wolf, Gregory T.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Chen, Zhong; Cheng, Hui; Saleh, Anthony D.; Si, Han; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. [Chiosea, Simion I.; Diergaarde, Brenda; Egloff, Ann Marie; Ferris, Robert L.; Grandis, Jennifer R.; Romkes, Marjorie; Seethala, Raja] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Cohen, Ezra; Seiwert, Tanguy Y.; Zuo, Zhixiang] Univ Chicago, Chicago, IL 60637 USA. [Guo, Yan; Brown, Brandee T.; Pham, Michelle] Vanderbilt Univ, Med Ctr, Med Ctr East 7209, Nashville, TN 37232 USA. [Harris, Thomas; Prystowsky, Michael] Albert Einstein Coll Med, Bronx, NY 10461 USA. [Lippman, Scott M.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Liu, Fei-Fei; Irish, Jonathan; Waldron, John] Univ Toronto, Toronto, ON M5G 2M9, Canada. [Perez-Ordonez, Bayardo] Univ Hlth Network, Toronto, ON M5G 2C4, Canada. [Wiznerowicz, Maciej; Golusinski, Wojciech; Golusinski, Pawel; Ibbs, Matthew; Korski, Konstanty; Mackiewicz, Andrzej; Suchorska, Wiktoria; Szybiak, Bartosz] Greater Poland Canc Ctr, PL-61866 Poznan, Poland. [Yarbrough, Wendell G.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Burnett, Ken; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Lauskis, Joseph Pau; Shelton, Candace; Shelton, Troy; Sherman, Mark; Yena, Peggy; Curley, Erin] Int Genom Consortium, Phoenix, AZ 85004 USA. [Black, Aaron D.; Bowen, Jay; Frick, Jessica; Gastier-Foster, Julie M.; Harper, Hollie A.; Leraas, Kristen; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA. [Baboud, Julien; Jensen, Mark A.; Kahn, An B.; Pihl, Todd D.; Pot, David A.; Srinivasan, Deepak; Walton, Jessica S.; Wan, Yunhu] SRA Int, Fairfax, VA 22033 USA. [Burton, Robert A.] Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Davidsen, Tanja; Demchok, John A.; Ferguson, Martin L.; Shaw, Kenna R. Mills; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude] NCI, Bethesda, MD 20892 USA. [Eley, Greg] Scimentis LLC, Atlanta, GA 30666 USA. [Ozenberger, Bradley A.; Sofia, Heidi J.] NHGRI, NIH, Bethesda, MD 20892 USA. [Saller, Charles; Tarvi, Katherine] Analyt Biol Serv Inc, St Petersburg 198013, Russia. [Chen, Chu] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Bollag, Roni; Weinberger, Paul] Georgia Regents Univ, Augusta, GA 30912 USA. [Beard, Christina; Mitchell, Colleen; Sandusky, George] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46202 USA. [Egea, Sophie; Gomez-Fernandez, Carmen; Herbert, Lynn] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. RP Hayes, DN (reprint author), Univ N Carolina, Chapel Hill, NC 27599 USA. EM hayes@med.unc.edu; anaggar@mdanderson.org; grandisjr@upmc.edu RI Schein, Jacquie/G-3674-2015; Weinberger, Paul/B-7007-2008; Holt, Robert/C-3303-2009; Zhao, Ni/P-9086-2014; Marra, Marco/B-5987-2008; Jones, Steven/C-3621-2009; Zuo, Zhixiang/M-4441-2016; Lee, Semin/S-2629-2016; Birol, Inanc/G-5440-2011; OI Benz, Stephen/0000-0002-4067-0602; Spence, Tara/0000-0001-7098-4103; Weinberger, Paul/0000-0002-5885-2631; Zhao, Ni/0000-0002-7762-3949; Zuo, Zhixiang/0000-0002-2492-2689; Lee, Semin/0000-0002-9015-6046; Birol, Inanc/0000-0003-0950-7839; Ojesina, Akinyemi/0000-0003-0755-3639; Schultz, Nikolaus/0000-0002-0131-4904; Diergaarde, Brenda/0000-0002-3578-6547; Carey, Thomas/0000-0002-5202-7518; Seth, Sahil/0000-0003-4579-3959; Pot, David/0000-0002-1480-9826; Jacobsen, Anders/0000-0001-6847-4980; Sinha, Rileen/0000-0001-5497-5055; Perou, Charles/0000-0001-9827-2247; Gehlenborg, Nils/0000-0003-0327-8297 FU National Institutes of Health (NIH) [P50CA097190, P50CA16672, U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, RO1 CA 095419]; Bobby F. Garrett Fund for Head and Neck Cancer Research; NIDCD Intramural Projects [ZIA-DC-000016, 73, 74] FX This study was supported by National Institutes of Health (NIH) grants: P50CA097190, P50CA16672, U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025 and RO1 CA 095419. Supported by The Bobby F. Garrett Fund for Head and Neck Cancer Research and NIDCD Intramural Projects ZIA-DC-000016, 73 and 74. NR 45 TC 226 Z9 227 U1 26 U2 103 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 JAN 29 PY 2015 VL 517 IS 7536 BP 576 EP 582 DI 10.1038/nature14129 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA2ZL UT WOS:000348775000035 ER PT J AU Freudenthal, BD Beard, WA Perera, L Shock, DD Kim, T Schlick, T Wilson, SH AF Freudenthal, Bret D. Beard, William A. Perera, Lalith Shock, David D. Kim, Taejin Schlick, Tamar Wilson, Samuel H. TI Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide SO NATURE LA English DT Article ID EMPIRICAL FORCE-FIELD; BASE EXCISION-REPAIR; MOLECULAR-DYNAMICS; OXIDATIVE STRESS; ACTIVE-SITE; KINETIC-ANALYSIS; STRUCTURAL BASIS; NUCLEIC-ACIDS; DNTP POOL; DNA AB Oxidative stress promotes genomic instability and humandiseases(1). A common oxidized nucleoside is 8-oxo-7,8-dihydro-2'-deoxyguanosine, which is found both in DNA (8-oxo-G) and as a free nucleotide (8-oxo- dGTP)(2,3). Nucleotide pools are especially vulnerable to oxidative damage(4). Therefore cells encodeanenzyme(MutT/MTH1) that removes free oxidized nucleotides. This cleansing function is required for cancer cell survival(5,6) and to modulate Escherichia coli antibiotic sensitivity in a DNA polymerase (pol)-dependent manner(7). How polymerases discriminate between damaged and non-damaged nucleotides is not well understood. This analysis is essential given the role of oxidized nucleotides in mutagenesis, cancer therapeutics, and bacterial antibiotics(8). Even with cellular sanitizing activities, nucleotide pools contain enough 8-oxo-dGTP to promote mutagenesis(9,10). This arises from the dual coding potential where 8-oxo-dGTP(anti) base pairs with cytosine and 8-oxo-dGTP(syn) uses its Hoogsteen edge to base pair with adenine(11). Here we use time-lapse crystallography to follow 8-oxo-dGTP insertion opposite adenine or cytosine with human pol beta, to reveal that insertion is accommodated in either the syn-oranti-conformation, respectively. For 8-oxo-dGTP(anti) insertion, a novel divalent metal relieves repulsive interactions between the adducted guanine base and the triphosphate of the oxidized nucleotide. With either templating base, hydrogen-bonding interactions between the bases are lost as the enzyme reopens after catalysis, leading to a cytotoxic nicked DNA repair intermediate. Combining structural snapshots with kinetic and computational analysis reveals how 8-oxo-dGTP uses charge modulation during insertion that can lead to a blocked DNA repair intermediate. C1 [Freudenthal, Bret D.; Beard, William A.; Perera, Lalith; Shock, David D.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kim, Taejin; Schlick, Tamar] NYU, Dept Chem, New York, NY 10003 USA. [Kim, Taejin; Schlick, Tamar] NYU Shanghai, NYU ECNU Ctr Computat Chem, New York, NY 10003 USA. [Kim, Taejin; Schlick, Tamar] NYU, Courant Inst Math Sci, New York, NY 10012 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01-E5050158, Z01-ES050161, ZIC-ES043010]; National Institutes of Health [1U19CA105010]; Philip Morris USA Inc.; Philip Morris International FX We thank the Collaborative Crystallography group at the National Institute of Environmental Health Sciences for help with data collection and analysis. We thank L. Pedersen for discussions. Use of the advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract W-31-109-Eng-38. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (project numbers Z01-E5050158 (to SW.), Z01-ES050161 (to S.W.), and ZIC-ES043010 (to L.P.)) and in association with National Institutes of Health grant 1U19CA105010. We are grateful for computational support for the molecular dynamics simulations from the HPC clusters at NYU as well as the Blue Gene at CCNI. Support from Philip Morris USA Inc. and Philip Morris International to T.S. is gratefully acknowledged. NR 48 TC 24 Z9 24 U1 4 U2 50 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 JAN 29 PY 2015 VL 517 IS 7536 BP 635 EP U261 DI 10.1038/nature13886 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA2ZL UT WOS:000348775000048 PM 25409153 ER PT J AU Hofmann, JW Zhao, XA De Cecco, M Peterson, AL Pagliaroli, L Manivannan, J Hubbard, GB Ikeno, Y Zhang, YQ Feng, B Li, XX Serre, T Qi, WB Van Remmen, H Miller, RA Bath, KG de Cabo, R Xu, HY Neretti, N Sedivy, JM AF Hofmann, Jeffrey W. Zhao, Xiaoai De Cecco, Marco Peterson, Abigail L. Pagliaroli, Luca Manivannan, Jayameenakshi Hubbard, Gene B. Ikeno, Yuji Zhang, Yongqing Feng, Bin Li, Xiaxi Serre, Thomas Qi, Wenbo Van Remmen, Holly Miller, Richard A. Bath, Kevin G. de Cabo, Rafael Xu, Haiyan Neretti, Nicola Sedivy, John M. TI Reduced Expression of MYC Increases Longevity and Enhances Healthspan SO CELL LA English DT Article ID AMES DWARF MICE; LIFE-SPAN; C-MYC; CALORIC RESTRICTION; DIETARY RESTRICTION; OXIDATIVE STRESS; MODEL ORGANISMS; DNA-DAMAGE; CANCER; MITOCHONDRIA AB MYC is a highly pleiotropic transcription factor whose deregulation promotes cancer. In contrast, we find that Myc haploinsufficient (Myc(+/-)) mice exhibit increased lifespan. They show resistance to several age-associated pathologies, including osteoporosis, cardiac fibrosis, and immunosenescence. They also appear to be more active, with a higher metabolic rate and healthier lipid metabolism. Transcriptomic analysis reveals a gene expression signature enriched for metabolic and immune processes. The ancestral role of MYC as a regulator of ribosome biogenesis is reflected in reduced protein translation, which is inversely correlated with longevity. We also observe changes in nutrient and energy sensing pathways, including reduced serum IGF-1, increased AMPK activity, and decreased AKT, TOR, and S6K activities. In contrast to observations in other longevity models, Myc(+/-) mice do not show improvements in stress management pathways. Our findings indicate that MYC activity has a significant impact on longevity and multiple aspects of mammalian healthspan. C1 [Hofmann, Jeffrey W.; Zhao, Xiaoai; De Cecco, Marco; Peterson, Abigail L.; Pagliaroli, Luca; Manivannan, Jayameenakshi; Neretti, Nicola; Sedivy, John M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. [Hubbard, Gene B.; Ikeno, Yuji; Qi, Wenbo; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Zhang, Yongqing; de Cabo, Rafael] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Feng, Bin; Xu, Haiyan] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Hallett Ctr Diabet & Endocrinol, Providence, RI 02903 USA. [Li, Xiaxi; Serre, Thomas; Bath, Kevin G.] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA. [Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA. RP Sedivy, JM (reprint author), Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. EM john_sedivy@brown.edu RI de Cabo, Rafael/J-5230-2016; FENG, BIN/E-9505-2017; OI de Cabo, Rafael/0000-0002-3354-2442; FENG, BIN/0000-0001-6258-2729; pagliaroli, luca/0000-0001-5539-4789; , rafael/0000-0003-2830-5693 FU NIH [R37 AG016694, P42 ES013660, P30 GM103410]; Intramural Research Program of the National Institute on Aging (NIH); [F30 AG035592] FX This work was supported by NIH grant R37 AG016694 to J.M.S. J.W.H. was supported in part by grant F30 AG035592. J.M.S. was a Senior Scholar of the Ellison Medical Foundation and a recipient of the Glenn Award for Research on the Biological Mechanisms of Aging. The Brown Molecular Pathology and Genomics core facilities were supported by NIH grants P42 ES013660 and P30 GM103410. R.dC. is funded by the Intramural Research Program of the National Institute on Aging (NIH). NR 47 TC 33 Z9 33 U1 6 U2 38 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 29 PY 2015 VL 160 IS 3 BP 477 EP 488 DI 10.1016/j.cell.2014.12.016 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CA8YX UT WOS:000349208000013 PM 25619689 ER PT J AU Wheatley, LM Togias, A AF Wheatley, Lisa M. Togias, Alkis TI Allergic Rhinitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NUTRITION EXAMINATION SURVEY; RANDOMIZED CONTROLLED-TRIAL; SUBLINGUAL IMMUNOTHERAPY; NONALLERGIC RHINITIS; UNITED-STATES; HAY-FEVER; SUBCUTANEOUS IMMUNOTHERAPY; GENERAL-PRACTICE; NATIONAL-HEALTH; ASTHMA AB A 35-year-old woman has a history of nasal congestion on most days of the year, dating back to her late teens. She has chronic nasal drainage, which is clear and thick. Her congestion is worst in the late summer and early fall and again in the early spring; at these times, she also has sneezing, nasal itching, and cough. Five years ago, she had an episode of shortness of breath with wheezing on a day when her nasal symptoms were severe, but this episode resolved spontaneously and has not recurred. Her eyes do not bother her. Over-the-counter oral antihistamines help her symptoms a little, as do nasal decongestants, which she uses occasionally. Her 6-year-old son has similar symptoms. How should this case be managed? C1 [Wheatley, Lisa M.; Togias, Alkis] NIAID, Allergy Asthma & Airway Biol Branch, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. RP Wheatley, LM (reprint author), NIH, 5601 Fishers Ln,Rm 6B56, Bethesda, MD 20892 USA. EM lisa.wheatley@nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 50 TC 34 Z9 39 U1 5 U2 22 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 29 PY 2015 VL 372 IS 5 BP 456 EP 463 DI 10.1056/NEJMcp1412282 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CA1CD UT WOS:000348649700010 PM 25629743 ER PT J AU Keasey, SL Natesan, M Pugh, C Kamata, T Wuchty, S Ulrich, RG AF Keasey, Sarah L. Natesan, Mohan Pugh, Christine Kamata, Teddy Wuchty, Stefan Ulrich, Robert G. TI The road to linking genomics and proteomics of pathogenic bacteria: from binary protein complexes to interaction pathways SO BMC BIOINFORMATICS LA English DT Meeting Abstract CT 10th Student Council Symposium of the International-Society-for-Computational-Biology (ISCB) held in conjunction with the Intelligent Systems for Molecular Biology (ISMB) CY JUL 11, 2014 CL Boston, MA SP Int Soc Computat Biol C1 [Keasey, Sarah L.; Natesan, Mohan; Pugh, Christine; Kamata, Teddy; Ulrich, Robert G.] US Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Frederick, MD 21702 USA. [Wuchty, Stefan] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JAN 28 PY 2015 VL 16 SU 2 AR A9 DI 10.1186/1471-2105-16-S2-A9 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA CH4BE UT WOS:000353975100010 ER PT J AU Agarwala, R Barrett, T Beck, J Benson, DA Bollin, C Bolton, E Bourexis, D Brister, JR Bryant, SH Canese, K Clark, K DiCuccio, M Dondoshansky, I Federhen, S Feolo, M Funk, K Geer, LY Gorelenkov, V Hoeppner, M Holmes, B Johnson, M Khotomlianski, VE Kimchi, A Kimelman, M Kitts, P Klimke, W Krasnov, S Kuznetsov, A Landrum, MJ Landsman, D Lee, JM Lipman, DJ Lu, ZY Madden, TL Madej, T Marchler-Bauer, A Karsch-Mizrachi, I Murphy, T Orris, R Ostell, J O'Sullivan, C Panchenko, A Phan, L Preuss, D Pruitt, KD Rubinstein, W Sayers, EW Schneider, V Schuler, GD Sherry, ST Sirotkin, K Siyan, K Slotta, D Soboleva, A Soussov, V Starchenko, G Tatusova, TA Trawick, BW Vakatov, D Wang, YL Ward, M Wilbur, WJ Yaschenko, E Zbicz, K AF Agarwala, Richa Barrett, Tanya Beck, Jeff Benson, Dennis A. Bollin, Colleen Bolton, Evan Bourexis, Devon Brister, J. Rodney Bryant, Stephen H. Canese, Kathi Clark, Karen DiCuccio, Michael Dondoshansky, Ilya Federhen, Scott Feolo, Michael Funk, Kathryn Geer, Lewis Y. Gorelenkov, Viatcheslav Hoeppner, Marilu Holmes, Brad Johnson, Mark Khotomlianski, Viatch-Eslav Kimchi, Avi Kimelman, Michael Kitts, Paul Klimke, William Krasnov, Sergey Kuznetsov, Anatoliy Landrum, Melissa J. Landsman, David Lee, Jennifer M. Lipman, David J. Lu, Zhiyong Madden, Thomas L. Madej, Tom Marchler-Bauer, Aron Karsch-Mizrachi, Ilene Murphy, Terence Orris, Rebecca Ostell, James O'Sullivan, Christopher Panchenko, Anna Phan, Lon Preuss, Don Pruitt, Kim D. Rubinstein, Wendy Sayers, Eric W. Schneider, Valerie Schuler, Gregory D. Sherry, Stephen T. Sirotkin, Karl Siyan, Karanjit Slotta, Douglas Soboleva, Alexandra Soussov, Vladimir Starchenko, Grigory Tatusova, Tatiana A. Trawick, Bart W. Vakatov, Denis Wang, Yanli Ward, Minghong Wilbur, W. John Yaschenko, Eugene Zbicz, Kerry CA NCBI Resource Coordinators TI Database resources of the National Center for Biotechnology Information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BIOLOGICAL PATHWAYS; GENE ONTOLOGY; NCBI; SEQUENCE; TOOL; GENOMES; ARCHIVE; ANNOTATION; FEATURES; SEARCH AB The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank (R) nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. Additional NCBI resources focus on literature (Bookshelf, PubMed Central (PMC) and PubReader); medical genetics (ClinVar, dbMHC, the Genetic Testing Registry, HIV-1/Human Protein Interaction Database and MedGen); genes and genomics (BioProject, BioSample, dbSNP, dbVar, Epigenomics, Gene, Gene Expression Omnibus (GEO), Genome, HomoloGene, the Map Viewer, Nucleotide, PopSet, Probe, RefSeq, Sequence Read Archive, the Taxonomy Browser, Trace Archive and UniGene); and proteins and chemicals (Biosystems, COBALT, the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), the Molecular Modeling Database (MMDB), Protein Clusters, Protein and the PubChem suite of small molecule databases). The Entrez system provides search and retrieval operations for many of these databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. C1 [Sayers, Eric W.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Sayers, EW (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM say-ers@ncbi.nlm.nih.gov OI Trawick, Bart/0000-0002-3635-3508; Landsman, David/0000-0002-9819-6675 FU National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 68 TC 111 Z9 112 U1 3 U2 54 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D6 EP D17 DI 10.1093/nar/gku1130 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400002 ER PT J AU Ako-Adjei, D Fu, W Wallin, C Katz, KS Song, G Darji, D Brister, JR Ptak, RG Pruitt, KD AF Ako-Adjei, Danso Fu, William Wallin, Craig Katz, Kenneth S. Song, Guangfeng Darji, Dakshesh Brister, J. Rodney Ptak, Roger G. Pruitt, Kim D. TI HIV-1, human interaction database: current status and new features SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; NONCODING RNAS; CELLS; INFORMATION; EXPRESSION; CHROMATIN; NETWORKS; PATHWAYS; REVEALS; GENES AB The 'Human Immunodeficiency Virus Type 1 (HIV-1), Human Interaction Database', available through the National Library of Medicine at http://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses/hiv-1/interactions, serves the scientific community exploring the discovery of novel HIV vaccine candidates and therapeutic targets. Each HIV-1 human protein interaction can be retrieved without restriction by web-based downloads and ftp protocols and includes: Reference Sequence (RefSeq) protein accession numbers, National Center for Biotechnology Information Gene identification numbers, brief descriptions of the interactions, searchable keywords for interactions and PubMed identification numbers (PMIDs) of journal articles describing the interactions. In addition to specific HIV-1 protein-human protein interactions, included are interaction effects upon HIV-1 replication resulting when individual human gene expression is blocked using siRNA. A total of 3142 human genes are described participating in 12 786 protein-protein interactions, along with 1316 replication interactions described for each of 1250 human genes identified using small interfering RNA (siRNA). Together the data identifies 4006 human genes involved in 14 102 interactions. With the inclusion of siRNA interactions we introduce a redesigned web interface to enhance viewing, filtering and downloading of the combined data set. C1 [Ako-Adjei, Danso; Wallin, Craig; Katz, Kenneth S.; Song, Guangfeng; Darji, Dakshesh; Brister, J. Rodney; Pruitt, Kim D.] Natl Lib Med, Natl Inst Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Fu, William; Ptak, Roger G.] So Res Inst, Dept Infect Dis Res, Frederick, MD 21701 USA. RP Pruitt, KD (reprint author), Natl Lib Med, Natl Inst Biotechnol Informat, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM pruitt@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine; Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases, National Institutes of Health [HHSN272200700042C] FX Intramural Research Program of the National Institutes of Health, National Library of Medicine. Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases, National Institutes of Health [HHSN272200700042C] entitled 'In Vitro Testing Resources for AIDS Therapeutic Development, PART B: Specialized In Vitro Virological Assays for HIV Therapeutics and Topical Microbicides' under the direction of Dr. Roger Miller (DHHS, NIH, NIAID, DAIDS, BSP). Funding for open access charge: The Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 35 TC 14 Z9 14 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D566 EP D570 DI 10.1093/nar/gku1126 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400084 PM 25378338 ER PT J AU Benson, DA Clark, K Karsch-Mizrachi, I Lipman, DJ Ostell, J Sayers, EW AF Benson, Dennis A. Clark, Karen Karsch-Mizrachi, Ilene Lipman, David J. Ostell, James Sayers, Eric W. TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE; ANNOTATION; ARCHIVE; GROWTH; BLAST AB GenBank (R) (http://www.ncbi.nlm.nih.gov/genbank/) is a comprehensive databases contains publicly available nucleotide sequences for over 300 000 formally described species. These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and GenBank staff assign accession numbers upon data receipt. Daily data exchange with the European Nucleotide Archive and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. C1 [Benson, Dennis A.; Clark, Karen; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Sayers, EW (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM sayers@ncbi.nlm.nih.gov FU National Institutes of Health, National Library of Medicine FX Intramural Research Program of the National Institutes of Health, National Library of Medicine. Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 16 TC 109 Z9 111 U1 7 U2 54 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D30 EP D35 DI 10.1093/nar/gku1216 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400005 PM 25414350 ER PT J AU Brister, JR Ako-adjei, D Bao, YM Blinkova, O AF Brister, J. Rodney Ako-adjei, Danso Bao, Yiming Blinkova, Olga TI NCBI Viral Genomes Resource SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RESPIRATORY SYNDROME CORONAVIRUS; REFERENCE SEQUENCES REFSEQ; HEPATITIS-C VIRUS; NATIONAL-CENTER; BIOTECHNOLOGY-INFORMATION; STANDARDIZED NOMENCLATURE; FAMILY FILOVIRIDAE; COMPARISON PASC; SPECIES LEVEL; ANNOTATION AB Recent technological innovations have ignited an explosion in virus genome sequencing that promises to fundamentally alter our understanding of viral biology and profoundly impact public health policy. Yet, any potential benefits from the billowing cloud of next generation sequence data hinge upon well implemented reference resources that facilitate the identification of sequences, aid in the assembly of sequence reads and provide reference annotation sources. The NCBI Viral Genomes Resource is a reference resource designed to bring order to this sequence shockwave and improve usability of viral sequence data. The resource can be accessed at http://www.ncbi.nlm.nih.gov/genome/viruses/ and catalogs all publicly available virus genome sequences and curates reference genome sequences. As the number of genome sequences has grown, so too have the difficulties in annotating and maintaining reference sequences. The rapid expansion of the viral sequence universe has forced a recalibration of the data model to better provide extant sequence representation and enhanced reference sequence products to serve the needs of the various viral communities. This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets. C1 [Brister, J. Rodney; Ako-adjei, Danso; Bao, Yiming; Blinkova, Olga] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Brister, JR (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM jamesbr@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. Funding for open access charge: Intramural Research Program of National Institutes of Health, National Library of Medicine. NR 57 TC 16 Z9 16 U1 3 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D571 EP D577 DI 10.1093/nar/gku1207 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400085 PM 25428358 ER PT J AU Brown, GR Hem, V Katz, KS Ovetsky, M Wallin, C Ermolaeva, O Tolstoy, I Tatusova, T Pruitt, KD Maglott, DR Murphy, TD AF Brown, Garth R. Hem, Vichet Katz, Kenneth S. Ovetsky, Michael Wallin, Craig Ermolaeva, Olga Tolstoy, Igor Tatusova, Tatiana Pruitt, Kim D. Maglott, Donna R. Murphy, Terence D. TI Gene: a gene-centered information resource at NCBI SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE; REFSEQ; GENOMES AB The National Center for Biotechnology Information's (NCBI) Gene database (www.ncbi.nlm.nih.gov/gene) integrates gene-specific information from multiple data sources. NCBI Reference Sequence (RefSeq) genomes for viruses, prokaryotes and eukaryotes are the primary foundation for Gene records in that they form the critical association between sequence and a tracked gene upon which additional functional and descriptive content is anchored. Additional content is integrated based on the genomic location and RefSeq transcript and protein sequence data. The content of a Gene record represents the integration of curation and automated processing from RefSeq, collaborating model organism databases, consortia such as Gene Ontology, and other databases within NCBI. Records in Gene are assigned unique, tracked integers as identifiers. The content (citations, nomenclature, genomic location, gene products and their attributes, phenotypes, sequences, interactions, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities and Entrez Direct) and for bulk transfer by FTP. C1 [Brown, Garth R.; Hem, Vichet; Katz, Kenneth S.; Ovetsky, Michael; Wallin, Craig; Ermolaeva, Olga; Tolstoy, Igor; Tatusova, Tatiana; Pruitt, Kim D.; Maglott, Donna R.; Murphy, Terence D.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Murphy, TD (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. EM murphyte@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Intramural Research Program of the National Institutes of Health, National Library of Medicine. Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 19 TC 68 Z9 69 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D36 EP D42 DI 10.1093/nar/gku1055 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400006 PM 25355515 ER PT J AU Eicher, JD Landowski, C Stackhouse, B Sloan, A Chen, WJ Jensen, N Lien, JP Leslie, R Johnson, AD AF Eicher, John D. Landowski, Christa Stackhouse, Brian Sloan, Arielle Chen, Wenjie Jensen, Nicole Lien, Ju-Ping Leslie, Richard Johnson, Andrew D. TI GRASP v2.0: an update on the Genome-Wide Repository of Associations between SNPs and phenotypes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SEQUENCING DATA; HUMAN-DISEASES; DNA ELEMENTS; DATABASE; RESOURCE; BROWSER; PROJECT; TRAITS; TISSUE AB Here, we present an update on the Genome-Wide Repository of Associations between SNPs and Phenotypes (GRASP) database version 2.0 (http://apps.nhlbi.nih.gov/Grasp/Overview.aspx). GRASP is a centralized repository of publically available genome-wide association study (GWAS) results. GRASP v2.0 contains similar to 8.87 million SNP associations reported in 2082 studies, an increase of similar to 2.59 million SNP associations (41.4% increase) and 693 studies (48.9% increase) from our previous version. Our goal in developing and maintaining GRASP is to provide a user-friendly means for diverse sets of researchers to query reported SNP associations (P <= 0.05) with human traits, including methylation and expression quantitative trait loci (QTL) studies. Therefore, in addition to making the full database available for download, we developed a user-friendly web interface that allows for direct querying of GRASP. We provide details on the use of this web interface and what information may be gleaned from using this interactive option. Additionally, we describe potential uses of GRASP and how the scientific community may benefit from the convenient availability of all SNP association results from GWAS (P <= 0.05). We plan to continue updating GRASP with newly published GWAS and increased annotation depth. C1 [Eicher, John D.; Landowski, Christa; Stackhouse, Brian; Sloan, Arielle; Chen, Wenjie; Jensen, Nicole; Lien, Ju-Ping; Leslie, Richard; Johnson, Andrew D.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Framingham Heart Study, Framingham, MA 01702 USA. [Leslie, Richard] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. RP Johnson, AD (reprint author), NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Framingham Heart Study, Framingham, MA 01702 USA. EM johnsonad2@nhlbi.nih.gov RI Johnson, Andrew/G-6520-2013 FU National Heart, Lung, and Blood Institute (NHLBI) intramural program; National Institutes of Health/NHLBI FX National Heart, Lung, and Blood Institute (NHLBI) intramural program. Funding for open access charge: National Institutes of Health/NHLBI. NR 22 TC 25 Z9 25 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D799 EP D804 DI 10.1093/nar/gku1202 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400116 PM 25428361 ER PT J AU Federhen, S AF Federhen, Scott TI Type material in the NCBI Taxonomy Database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID 16S RIBOSOMAL-RNA; GENETIC SEQUENCES; SP-NOV; NOMENCLATURE; NAMES; HETEROGENEITY; PROKARYOTES; KLEBSIELLA; STRAIN; ONLINE AB Type material is the taxonomic device that ties formal names to the physical specimens that serve as exemplars for the species. For the prokaryotes these are strains submitted to the culture collections; for the eukaryotes they are specimens submitted to museums or herbaria. The NCBI Taxonomy Database ( ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov/taxonomy" xlink:type="simple">http://www.ncbi.nlm.nih.gov/taxonomy) now includes annotation of type material that we use to flag sequences from type in GenBank and in Genomes. This has important implications for many NCBI resources, some of which are outlined below. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Federhen, S (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM federhen@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Intramural Research Program of the National Institutes of Health, National Library of Medicine. Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 46 TC 22 Z9 22 U1 3 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D1086 EP D1098 DI 10.1093/nar/gku1127 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400159 PM 25398905 ER PT J AU Galperin, MY Rigden, DJ Fernandez-Suarez, XM AF Galperin, Michael Y. Rigden, Daniel J. Fernandez-Suarez, Xose M. TI The 2015 Nucleic Acids Research Database Issue and Molecular Biology Database Collection SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The 2015 Nucleic Acids Research Database Issue contains 172 papers that include descriptions of 56 new molecular biology databases, and updates on 115 databases whose descriptions have been previously published in NAR or other journals. Following the classification that has been introduced last year in order to simplify navigation of the entire issue, these articles are divided into eight subject categories. This year's highlights include RNA-central, an international community portal to various databases on noncoding RNA; ValidatorDB, a validation database for protein structures and their ligands; SASBDB, a primary repository for small-angle scattering data of various macromolecular complexes; MoonProt, a database of 'moonlighting' proteins, and two new databases of protein-protein and other macromolecular complexes, ComPPI and the Complex Portal. This issue also includes an unusually high number of cancer-related databases and other databases dedicated to genomic basics of disease and potential drugs and drug targets. The size of NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/a/, remained approximately the same, following the addition of 74 new resources and removal of 77 obsolete web sites. The entire Database Issue is freely available online on the Nucleic Acids Research web site (http://nar.oxfordjournals.org/). C1 [Galperin, Michael Y.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Rigden, Daniel J.] Univ Liverpool, Inst Integrat Biol, Liverpool L69 7ZB, Merseyside, England. [Fernandez-Suarez, Xose M.] Thermo Fisher Sci, Paisley PA4 9RF, Renfrew, Scotland. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM nardatabase@gmail.com OI Rigden, Daniel/0000-0002-7565-8937 FU NIH Intramural Research Program at the National Library of Medicine; Oxford University Press FX The NIH Intramural Research Program at the National Library of Medicine [to M.Y.G.]. Funding for open access charge: Oxford University Press. NR 50 TC 26 Z9 26 U1 1 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D1 EP D5 DI 10.1093/nar/gku1241 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400001 PM 25593347 ER PT J AU Galperin, MY Makarova, KS Wolf, YI Koonin, EV AF Galperin, Michael Y. Makarova, Kira S. Wolf, Yuri I. Koonin, Eugene V. TI Expanded microbial genome coverage and improved protein family annotation in the COG database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PEPTIDOGLYCAN SYNTHESIS; ORTHOLOGOUS GENES; RNA MODIFICATION; EVOLUTION; COMPLEX; CLASSIFICATION; SPORULATION; SEQUENCE; ARCHAEA; CYANOBACTERIAL AB Microbial genome sequencing projects produce numerous sequences of deduced proteins, only a small fraction of which have been or will ever be studied experimentally. This leaves sequence analysis as the only feasible way to annotate these proteins and assign to them tentative functions. The Clusters of Orthologous Groups of proteins (COGs) database (http://www.ncbi.nlm.nih.gov/COG/), first created in 1997, has been a popular tool for functional annotation. Its success was largely based on (i) its reliance on complete microbial genomes, which allowed reliable assignment of orthologs and paralogs for most genes; (ii) orthology-based approach, which used the function(s) of the characterized member(s) of the protein family (COG) to assign function(s) to the entire set of carefully identified orthologs and describe the range of p otential functions when there were more than one; and (iii) careful manual curation of the annotation of the COGs, aimed at detailed prediction of the biological function(s) for each COG while avoiding annotation errors and overprediction. Here we present an update of the COGs, the first since 2003, and a comprehensive revision of the COG annotations and expansion of the genome coverage to include representative complete genomes from all bacterial and archaeal lineages down to the genus level. This re-analysis of the COGs shows that the original COG assignments had an error rate below 0.5% and allows an assessment of the progress in functional genomics in the past 12 years. During this time, functions of many previously uncharacterized COGs have been elucidated and tentative functional assignments of many COGs have been validated, either by targeted experiments or through the use of high-throughput methods. A particularly important development is the assignment of functions to several widespread, conserved proteins many of which turned out to participate in translation, in particular rRNA maturation and tRNA modification. The new version of the COGs is expected to become an important tool for microbial genomics. C1 [Galperin, Michael Y.; Makarova, Kira S.; Wolf, Yuri I.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU Intramural Research Program of the U.S. National Institutes of Health at the National Library of Medicine; U.S. Department of Health and Human Services FX Intramural Research Program of the U.S. National Institutes of Health at the National Library of Medicine. Funding for open access charge: Intramural funds of the U.S. Department of Health and Human Services [to the National Library of Medicine, National Institutes of Health]. NR 70 TC 85 Z9 88 U1 4 U2 20 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D261 EP D269 DI 10.1093/nar/gku1223 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400041 PM 25428365 ER PT J AU Howe, EA de Souza, A Lahr, DL Chatwin, S Montgomery, P Alexander, BR Nguyen, DT Cruz, Y Stonich, DA Walzer, G Rose, JT Picard, SC Liu, Z Rose, JN Xiang, X Asiedu, J Durkin, D Levine, J Yang, JJ Schurer, SC Braisted, JC Southall, N Southern, MR Chung, TDY Brudz, S Tanega, C Schreiber, SL Bittker, JA Guha, R Clemons, PA AF Howe, E. A. de Souza, A. Lahr, D. L. Chatwin, S. Montgomery, P. Alexander, B. R. Nguyen, D. -T. Cruz, Y. Stonich, D. A. Walzer, G. Rose, J. T. Picard, S. C. Liu, Z. Rose, J. N. Xiang, X. Asiedu, J. Durkin, D. Levine, J. Yang, J. J. Schuerer, S. C. Braisted, J. C. Southall, N. Southern, M. R. Chung, T. D. Y. Brudz, S. Tanega, C. Schreiber, S. L. Bittker, J. A. Guha, R. Clemons, P. A. TI BioAssay Research Database (BARD): chemical biology and probe-development enabled by structured metadata and result types SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RESOURCE; ONTOLOGY AB BARD, the BioAssay Research Database (https://bard.nih.gov/) is a public database and suite of tools developed to provide access to bioassay data produced by the NIH Molecular Libraries Program (MLP). Data from 631 MLP projects were migrated to a new structured vocabulary designed to capture bioassay data in a formalized manner, with particular emphasis placed on the description of assay protocols. New data can be submitted to BARD with a user-friendly set of tools that assist in the creation of appropriately formatted datasets and assay definitions. Data published through the BARD application program interface (API) can be accessed by researchers using web-based query tools or a desktop client. Third-party developers wishing to create new tools can use the API to produce stand-alone tools or new plug-ins that can be integrated into BARD. The entire BARD suite of tools therefore supports three classes of researcher: those who wish to publish data, those who wish to mine data for testable hypotheses, and those in the developer community who wish to build tools that leverage this carefully curated chemical biology resource. C1 [Howe, E. A.; de Souza, A.; Lahr, D. L.; Chatwin, S.; Montgomery, P.; Alexander, B. R.; Walzer, G.; Rose, J. T.; Picard, S. C.; Liu, Z.; Rose, J. N.; Xiang, X.; Asiedu, J.; Durkin, D.; Levine, J.; Brudz, S.; Schreiber, S. L.; Bittker, J. A.; Clemons, P. A.] Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA. [Nguyen, D. -T.; Braisted, J. C.; Southall, N.; Tanega, C.; Guha, R.] NIH, NCATS, Rockville, MD 20850 USA. [Cruz, Y.; Southern, M. R.] Scripps Res Inst, Translat Res Inst, Jupiter, FL 33458 USA. [Stonich, D. A.; Chung, T. D. Y.] Sanford Burnham Med Res Inst, Conrad Prebys Ctr Chem Genom, La Jolla, CA 92037 USA. [Yang, J. J.] Univ New Mexico, Hlth Sci Ctr, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Schuerer, S. C.] Univ Miami, Ctr Computat Sci, Coral Gables, FL 33146 USA. RP Clemons, PA (reprint author), Broad Inst, Ctr Sci Therapeut, 415 Main St, Cambridge, MA 02142 USA. EM Andrea.desouza@sloan.mit.edu; guhar@mail.nih.gov; pclemons@broadinstitute.org RI Alexander, Benjamin/M-7471-2015; Southall, Noel/H-8991-2012 OI Alexander, Benjamin/0000-0002-0960-6119; Southall, Noel/0000-0003-4500-880X FU National Institutes of Health Common Fund through Molecular Libraries Probe Production Center Network [RFA-RM-08-005]; Broad Institute Comprehensive Screening Center [U54-HG005032] FX National Institutes of Health Common Fund through its Molecular Libraries Probe Production Center Network [RFA-RM-08-005 to BARD] as an administrative supplement directly to the centers following receipt and review of center proposals in response to a request for proposal crafted by Dr. Ajay Pillai (National Human Genome Research Institute). Funding for open access charge: Broad Institute Comprehensive Screening Center (U54-HG005032). NR 13 TC 7 Z9 7 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D1163 EP D1170 DI 10.1093/nar/gku1244 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400170 PM 25477388 ER PT J AU Kibbe, WA Arze, C Felix, V Mitraka, E Bolton, E Fu, G Mungall, CJ Binder, JX Malone, J Vasant, D Parkinson, H Schriml, LM AF Kibbe, Warren A. Arze, Cesar Felix, Victor Mitraka, Elvira Bolton, Evan Fu, Gang Mungall, Christopher J. Binder, Janos X. Malone, James Vasant, Drashtti Parkinson, Helen Schriml, Lynn M. TI Disease Ontology 2015 update: an expanded and updated database of human diseases for linking biomedical knowledge through disease data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID INFORMATION; SPECIFICATIONS; TERMINOLOGY; SYSTEM; MODEL AB The current version of the Human Disease Ontology (DO) ( ext-link-type="uri" xlink:href="http://www.disease-ontology.org" xlink:type="simple">http://www.disease-ontology.org) database expands the utility of the ontology for the examination and comparison of genetic variation, phenotype, protein, drug and epitope data through the lens of human disease. DO is a biomedical resource of standardized common and rare disease concepts with stable identifiers organized by disease etiology. The content of DO has had 192 revisions since 2012, including the addition of 760 terms. Thirty-two percent of all terms now include definitions. DO has expanded the number and diversity of research communities and community members by 50+ during the past two years. These community members actively submit term requests, coordinate biomedical resource disease representation and provide expert curation guidance. Since the DO 2012 NAR paper, there have been hundreds of term requests and a steady increase in the number of DO listserv members, twitter followers and DO website usage. DO is moving to a multi-editor model utilizing Prot,g, to curate DO in web ontology language. This will enable closer collaboration with the Human Phenotype Ontology, EBI's Ontology Working Group, Mouse Genome Informatics and the Monarch Initiative among others, and enhance DO's current asserted view and multiple inferred views through reasoning. C1 [Kibbe, Warren A.] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20850 USA. [Arze, Cesar; Felix, Victor; Mitraka, Elvira; Schriml, Lynn M.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Bolton, Evan; Fu, Gang] NIH, PubChem, Natl Ctr Biotechnol Informat, Natl Lib Med,Dept Hlth & Human Serv, Bethesda, MD 20894 USA. [Mungall, Christopher J.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA. [Binder, Janos X.] European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany. [Binder, Janos X.] Univ Luxembourg, LCSB, Bioinformat Core Facil, L-4362 Luxembourg, Luxembourg. [Malone, James; Vasant, Drashtti; Parkinson, Helen] EBI, EMBL, Cambridge CB10 1SD, England. [Schriml, Lynn M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. RP Schriml, LM (reprint author), Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. EM lschriml@som.umaryland.edu RI Fu, Gang/F-8837-2016; OI Fu, Gang/0000-0002-4860-8539; Mitraka, Elvira/0000-0003-0719-3485; Malone, James Robert/0000-0002-1615-2899; Parkinson, Helen/0000-0003-3035-4195; Schriml, Lynn/0000-0001-8910-9851 FU National Institutes of Health-National Center for Research Resources [R01RR025341]; EMBL Core funds; WT HIPSCI [098503/D/12/Z]; NHGRI; NHLBI; NIH Common Fund [U54-HG004028]; NIH [R24OD011883]; Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy [DE-AC02-05CH11231]; University of Maryland, Institute for Genome Sciences FX National Institutes of Health-National Center for Research Resources (R01RR025341); EMBL Core funds and WT HIPSCI [098503/D/12/Z]; NHGRI, NHLBI and NIH Common Fund under U54-HG004028. NIH R24OD011883 (to C.J.M.); Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231 (to C.J.M.). Funding for open access charge: University of Maryland, Institute for Genome Sciences. NR 32 TC 48 Z9 48 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D1071 EP D1078 DI 10.1093/nar/gku1011 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400157 PM 25348409 ER PT J AU Marchler-Bauer, A Derbyshire, MK Gonzales, NR Lu, SN Chitsaz, F Geer, LY Geer, RC He, J Gwadz, M Hurwitz, DI Lanczycki, CJ Lu, F Marchler, GH Song, JS Thanki, N Wang, ZX Yamashita, RA Zhang, DC Zheng, CJ Bryant, SH AF Marchler-Bauer, Aron Derbyshire, Myra K. Gonzales, Noreen R. Lu, Shennan Chitsaz, Farideh Geer, Lewis Y. Geer, Renata C. He, Jane Gwadz, Marc Hurwitz, David I. Lanczycki, Christopher J. Lu, Fu Marchler, Gabriele H. Song, James S. Thanki, Narmada Wang, Zhouxi Yamashita, Roxanne A. Zhang, Dachuan Zheng, Chanjuan Bryant, Stephen H. TI CDD: NCBI's conserved domain database SO NUCLEIC ACIDS RESEARCH LA English DT Article AB NCBI's CDD, the Conserved Domain Database, enters its 15(th) year as a public resource for the annotation of proteins with the location of conserved domain footprints. Going forward, we strive to improve the coverage and consistency of domain annotation provided by CDD. We maintain a live search system as well as an archive of pre-computed domain annotation for sequences tracked in NCBI's Entrez protein database, which can be retrieved for single sequences or in bulk. We also maintain import procedures so that CDD contains domain models and domain definitions provided by several collections available in the public domain, as well as those produced by an in-house curation effort. The curation effort aims at increasing coverage and providing finer-grained classifications of common protein domains, for which a wealth of functional and structural data has become available. CDD curation generates alignment models of representative sequence fragments, which are in agreement with domain boundaries as observed in protein 3D structure, and which model the structurally conserved cores of domain families as well as annotate conserved features. C1 [Marchler-Bauer, Aron; Derbyshire, Myra K.; Gonzales, Noreen R.; Lu, Shennan; Chitsaz, Farideh; Geer, Lewis Y.; Geer, Renata C.; He, Jane; Gwadz, Marc; Hurwitz, David I.; Lanczycki, Christopher J.; Lu, Fu; Marchler, Gabriele H.; Song, James S.; Thanki, Narmada; Wang, Zhouxi; Yamashita, Roxanne A.; Zhang, Dachuan; Zheng, Chanjuan; Bryant, Stephen H.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Marchler-Bauer, A (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 38 A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA. EM bauer@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Intramural Research Program of the National Institutes of Health, National Library of Medicine. Funding open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 13 TC 542 Z9 558 U1 16 U2 74 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D222 EP D226 DI 10.1093/nar/gku1221 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400035 PM 25414356 ER PT J AU Peng, XX Thierry-Mieg, J Thierry-Mieg, D Nishida, A Pipes, L Bozinoski, M Thomas, MJ Kelly, S Weiss, JM Raveendran, M Muzny, D Gibbs, RA Rogers, J Schroth, GP Katze, MG Mason, CE AF Peng, Xinxia Thierry-Mieg, Jean Thierry-Mieg, Danielle Nishida, Andrew Pipes, Lenore Bozinoski, Marjan Thomas, Matthew J. Kelly, Sara Weiss, Jeffrey M. Raveendran, Muthuswamy Muzny, Donna Gibbs, Richard A. Rogers, Jeffrey Schroth, Gary P. Katze, Michael G. Mason, Christopher E. TI Tissue-specific transcriptome sequencing analysis expands the non-human primate reference transcriptome resource (NHPRTR) SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA-SEQ; EVOLUTIONARY DYNAMICS; RHESUS MACAQUE; GENE; INSIGHTS; GENOME AB The non-human primate reference transcriptome resource (NHPRTR, available online at http://nhprtr.org/)aims to generate comprehensive RNA-seq data from a wide variety of non-human primates (NHPs), from lemurs to hominids. In the 2012 Phase I of the NHPRTR project, 19 billion fragments or 3.8 terabases of transcriptome sequences were collected from pools of similar to 20 tissues in 15 species and subspecies. Here we describe a major expansion of NHPRTR by adding 10.1 billion fragments of tissue-specific RNA-seq data. For this effort, we selected 11 of the original 15 NHP species and subspecies and constructed total RNA libraries for the same similar to 15 tissues in each. The sequence quality is such that 88% of the reads align to human reference sequences, allowing us to compute the full list of expression abundance across all tissues for each species, using the reads mapped to human genes. This update also includes improved transcript annotations derived from RNA-seq data for rhesus and cynomolgus macaques, two of the most commonly used NHP models and additional RNA-seq data compiled from related projects. Together, these comprehensive reference transcriptomes from multiple primates serve as a valuable community resource for genome annotation, gene dynamics and comparative functional analysis. C1 [Peng, Xinxia; Nishida, Andrew; Thomas, Matthew J.; Kelly, Sara; Weiss, Jeffrey M.; Katze, Michael G.] Univ Washington, Dept Microbiol, Seattle, WA 98109 USA. [Peng, Xinxia; Nishida, Andrew; Thomas, Matthew J.; Kelly, Sara; Weiss, Jeffrey M.; Katze, Michael G.] Washington Natl Primate Res Ctr, Seattle, WA 98109 USA. [Thierry-Mieg, Jean; Thierry-Mieg, Danielle] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Pipes, Lenore; Bozinoski, Marjan; Mason, Christopher E.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA. [Pipes, Lenore; Bozinoski, Marjan; Mason, Christopher E.] Weill Cornell Med Coll, ICB, New York, NY 10065 USA. [Raveendran, Muthuswamy; Muzny, Donna; Gibbs, Richard A.; Rogers, Jeffrey] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Schroth, Gary P.] Illumina Inc, San Diego, CA 92122 USA. [Mason, Christopher E.] Weill Cornell Med Coll, Feil Family Brain & Mind Res Inst BMRI, New York, NY 10065 USA. RP Thierry-Mieg, J (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM Jean.Thierry-Mieg@nih.gov RI THIERRY-MIEG, Jean/F-1975-2017 OI THIERRY-MIEG, Jean/0000-0002-0396-6789 FU National Institutes of Health, Office of Research Infrastructure Programs [R24OD011172, R24OD010445, P51OD010425]; National Institute of Neurological Disorders and Stroke [1R01NS076465-02]; XSEDE [MCB120116]; National Human Genome Research Institute [U54-HG003273]; Intramural Research Program of the NIH, National Library of Medicine; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272201300010C]; NIH FX National Institutes of Health, Office of Research Infrastructure Programs [R24OD011172, R24OD010445, P51OD010425 to M.G.K.]; National Institute of Neurological Disorders and Stroke [1R01NS076465-02 to C.E.M.]; XSEDE [MCB120116]; National Human Genome Research Institute [U54-HG003273 to R.A.G.]. Intramural Research Program of the NIH, National Library of Medicine (in part). Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272201300010C, in part]. Funding for open access charge: NIH. NR 17 TC 8 Z9 8 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D737 EP D742 DI 10.1093/nar/gku1110 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400107 PM 25392405 ER PT J AU Petrov, AI Kay, SJE Gibson, R Kulesha, E Staines, D Bruford, EA Wright, MW Burge, S Finn, RD Kersey, PJ Cochrane, G Bateman, A Griffiths-Jones, S Harrow, J Chan, PP Lowe, TM Zwieb, CW Wower, J Williams, KP Hudson, CM Gutell, R Clark, MB Dinger, M Quek, XC Bujnicki, JM Chua, NH Liu, J Wang, H Skogerbo, G Zhao, Y Chen, RS Zhu, WM Cole, JR Chai, BL Huang, HD Huang, HY Cherry, JM Hatzigeorgiou, A Pruitt, KD AF Petrov, Anton I. Kay, Simon J. E. Gibson, Richard Kulesha, Eugene Staines, Dan Bruford, Elspeth A. Wright, Mathew W. Burge, Sarah Finn, Robert D. Kersey, Paul J. Cochrane, Guy Bateman, Alex Griffiths-Jones, Sam Harrow, Jennifer Chan, Patricia P. Lowe, Todd M. Zwieb, Christian W. Wower, Jacek Williams, Kelly P. Hudson, Corey M. Gutell, Robin Clark, Michael B. Dinger, Marcel Quek, Xiu Cheng Bujnicki, Janusz M. Chua, Nam-Hai Liu, Jun Wang, Huan Skogerbo, Geir Zhao, Yi Chen, Runsheng Zhu, Weimin Cole, James R. Chai, Benli Huang, Hsien-Da Huang, His-Yuan Cherry, J. Michael Hatzigeorgiou, Artemis Pruitt, Kim D. CA RNAcent Consortium TI RNAcentral: an international database of ncRNA sequences SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA GENES; EVOLUTION; PROJECT; ARCHIVE; GENCODE; UPDATE AB The field of non-coding RNA biology has been hampered by the lack of availability of a comprehensive, up-to-date collection of accessioned RNA sequences. Here we present the first release of RNAcentral, a database that collates and integrates information from an international consortium of established RNA sequence databases. The initial release contains over 8.1 million sequences, including representatives of all major functional classes. A web portal (http://rnacentral.org) provides free access to data, search functionality, cross-references, source code and an integrated genome browser for selected species. C1 [Petrov, Anton I.; Kay, Simon J. E.; Gibson, Richard; Kulesha, Eugene; Staines, Dan; Bruford, Elspeth A.; Wright, Mathew W.; Burge, Sarah; Finn, Robert D.; Kersey, Paul J.; Cochrane, Guy; Bateman, Alex] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England. [Griffiths-Jones, Sam] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. [Harrow, Jennifer] Wellcome Trust Sanger Inst, Cambridge CB10 1SD, England. [Chan, Patricia P.; Lowe, Todd M.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. [Zwieb, Christian W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Wower, Jacek] Auburn Univ, Dept Anim Sci, Auburn, AL 36849 USA. [Williams, Kelly P.; Hudson, Corey M.] Sandia Natl Labs, Livermore, CA 94551 USA. [Gutell, Robin] Univ Texas Austin, Dept Integrat Biol, Austin, TX 78712 USA. [Clark, Michael B.] Univ Oxford, Dept Physiol Anat & Genet, MRC, Funct Genom Unit, Oxford OX1 3PT, England. [Dinger, Marcel; Quek, Xiu Cheng] St Vincents Hosp, Garvan Inst Med Res, Kinghorn Ctr Clin Genom, Darlinghurst, NSW 2010, Australia. [Bujnicki, Janusz M.] Int Inst Mol & Cell Biol Warsaw, Lab Bioinformat & Prot Engn, PL-02109 Warsaw, Poland. [Bujnicki, Janusz M.] Adam Mickiewicz Univ, Inst Mol Biol & Biotechnol, Fac Biol, Lab Bioinformat, PL-61614 Poznan, Poland. [Chua, Nam-Hai; Liu, Jun; Wang, Huan] Rockefeller Univ, Plant Mol Biol Lab, New York, NY 10065 USA. [Skogerbo, Geir; Zhao, Yi; Chen, Runsheng] Chinese Acad Sci, Inst Biophys, Lab Noncoding RNA, Beijing 100101, Peoples R China. [Skogerbo, Geir; Zhao, Yi; Chen, Runsheng] Chinese Acad Sci, Inst Comp Technol, Beijing 100190, Peoples R China. [Skogerbo, Geir; Zhao, Yi; Chen, Runsheng] Chinese Acad Med Sci, Inst Basic Med Sci, Beijing, Peoples R China. [Zhu, Weimin] Peking Union Med Coll, Sch Basic Med, Beijing 100005, Peoples R China. [Zhu, Weimin] Taicang Inst Life Sci Informat, Suzhou 215400, Peoples R China. [Cole, James R.; Chai, Benli] Michigan State Univ, E Lansing, MI 48824 USA. [Huang, Hsien-Da; Huang, His-Yuan] Natl Chiao Tung Univ, Dept Biol Sci & Technol, Inst Bioinformat & Syst Biol, Hsinchu, Taiwan. [Cherry, J. Michael] Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA. [Hatzigeorgiou, Artemis] Univ Thessaly, Dept Comp & Commun Engn, Volos 38221, Greece. [Pruitt, Kim D.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Petrov, AI (reprint author), European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England. EM agb@ebi.ac.uk OI Kay, Simon/0000-0001-7690-2711; Clark, Michael/0000-0002-2903-9537; Cochrane, Guy/0000-0001-7954-7057; Gibson, Richard Charles/0000-0001-5412-1965; Finn, Robert/0000-0001-8626-2148; Petrov, Anton/0000-0001-7279-2682; Wright, Matt/0000-0002-2650-2426; Bateman, Alex/0000-0002-6982-4660; Staines, Daniel/0000-0002-7564-9125; Bruford, Elspeth/0000-0002-8380-5247; Kersey, Paul/0000-0002-7054-800X FU Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J019232/1, BB/J019321/1]; Intramural Research Program of the National Institutes of Health, National Library of Medicine; European Bioinformatics Institute FX Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J019232/1, BB/J019321/1]; Intramural Research Program of the National Institutes of Health, National Library of Medicine. Funding for open access charge: European Bioinformatics Institute. NR 23 TC 13 Z9 13 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D123 EP D129 DI 10.1093/nar/gku991 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400020 ER PT J AU Tatusova, T Ciufo, S Federhen, S Fedorov, B McVeigh, R O'Neill, K Tolstoy, I Zaslavsky, L AF Tatusova, Tatiana Ciufo, Stacy Federhen, Scott Fedorov, Boris McVeigh, Richard O'Neill, Kathleen Tolstoy, Igor Zaslavsky, Leonid TI Update on RefSeq microbial genomes resources SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE AB NCBI RefSeq genome collection ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov/genome" xlink:type="simple">http://www.ncbi.nlm.nih.gov/genome represents all three major domains of life: Eukarya, Bacteria and Archaea as well as Viruses. Prokaryotic genome sequences are the most rapidly growing part of the collection. During the year of 2014 more than 10 000 microbial genome assemblies have been publicly released bringing the total number of prokaryotic genomes close to 30 000. We continue to improve the quality and usability of the microbial genome resources by providing easy access to the data and the results of the pre-computed analysis, and improving analysis and visualization tools. A number of improvements have been incorporated into the Prokaryotic Genome Annotation Pipeline. Several new features have been added to RefSeq prokaryotic genomes data processing pipeline including the calculation of genome groups (clades) and the optimization of protein clusters generation using pan-genome approach. C1 [Tatusova, Tatiana; Ciufo, Stacy; Federhen, Scott; Fedorov, Boris; McVeigh, Richard; O'Neill, Kathleen; Tolstoy, Igor; Zaslavsky, Leonid] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Tatusova, T (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A 8600 Rockville Pike, Bethesda, MD 20894 USA. EM tatiana@ncbi.nlm.nih.gov FU National Library of Medicine; National Center for Biotechnology Information; National Institutes of Health FX Funding for open access charge: Intramural Research Program of the National Institutes of Health; National Library of Medicine; National Center for Biotechnology Information; National Institutes of Health. NR 14 TC 30 Z9 30 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 28 PY 2015 VL 43 IS D1 BP D599 EP D605 DI 10.1093/nar/gku1062 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CC2YF UT WOS:000350210400090 PM 25510495 ER PT J AU Gautam, A Arpa, PD Donohue, DE Muhie, S Chakraborty, N Luke, BT Grapov, D Carroll, EE Meyerhoff, JL Hammamleh, R Jett, M AF Gautam, Aartl Arpa, Peter D' Donohue, Duncan E. Muhie, Seid Chakraborty, Nabarun Luke, Brian T. Grapov, Dmitry Carroll, Erica E. Meyerhoff, James L. Hammamleh, Rasha Jett, Marti TI Acute and Chronic Plasma Metabolomic and Liver Transcriptomic Stress Effects in a Mouse Model with Features of Post-Traumatic Stress Disorder SO PLOS ONE LA English DT Article ID GUT MICROBIOTA; PSYCHOSOCIAL STRESS; ACID-METABOLISM; MALE-MICE; DISEASE; HEALTH; INJURY; PHASE; PTSD; MATRIX-METALLOPROTEINASE-9 AB Acute responses to intense stressors can give rise to post-traumatic stress disorder (PTSD). PTSD diagnostic criteria include trauma exposure history and self-reported symptoms. Individuals who meet PTSD diagnostic criteria often meet criteria for additional psychiatric diagnoses. Biomarkers promise to contribute to reliable phenotypes of PTSD and comorbidities by linking biological system alterations to behavioral symptoms. Here we have analyzed unbiased plasma metabolomics and other stress effects in a mouse model with behavioral features of PTSD. In this model, C57BL/6 mice are repeatedly exposed to a trained aggressor mouse (albino SJL) using a modified, resident-intruder, social defeat paradigm. Our recent studies using this model found that aggressor-exposed mice exhibited acute stress effects including changed behaviors, body weight gain, increased body temperature, as well as inflammatory and fibrotic histopathologies and transcriptomic changes of heart tissue. Some of these acute stress effects persisted, reminiscent of PTSD. Here we report elevated proteins in plasma that function in inflammation and responses to oxidative stress and damaged tissue at 24 hrs post-stressor. Additionally at this acute time point, transcriptomic analysis indicated liver inflammation. The unbiased metabolomics analysis showed altered metabolites in plasma at 24 hrs that only partially normalized toward control levels after stress-withdrawal for 1.5 or 4 wks. In particular, gut-derived metabolites were altered at 24 hrs post-stressor and remained altered up to 4 wks after stress-withdrawal. Also at the 4 wk time point, hyperlipidemia and suppressed metabolites of amino acids and carbohydrates in plasma coincided with transcriptomic indicators of altered liver metabolism (activated xenobiotic and lipid metabolism). Collectively, these system-wide sequelae to repeated intense stress suggest that the simultaneous perturbed functioning of multiple organ systems (e.g., brain, heart, intestine and liver) can interact to produce injuries that lead to chronic metabolic changes and disorders that have been associated with PTSD. C1 [Gautam, Aartl; Arpa, Peter D'; Donohue, Duncan E.; Chakraborty, Nabarun; Meyerhoff, James L.; Hammamleh, Rasha; Jett, Marti] US Army Ctr Environm Hlth Res, Ft Detrick, MD 21702 USA. [Gautam, Aartl; Arpa, Peter D'; Donohue, Duncan E.; Chakraborty, Nabarun; Meyerhoff, James L.] Geneva Fdn, Tacoma, WA 98402 USA. [Muhie, Seid; Luke, Brian T.] Adv Biomed Comp Ctr, Frederick Natl Lab Canc Res, Frederick, MD USA. [Grapov, Dmitry] Univ Calif Davis, NIH, West Coast Metabol Ctr, Davis, CA USA. [Carroll, Erica E.] Army Inst Publ Hlth, Aberdeen Proving Ground, MD 21010 USA. RP Jett, M (reprint author), US Army Ctr Environm Hlth Res, Ft Detrick, Ft Detrick, MD 21702 USA. EM marti.jett-tilton.civ@mail.mil FU Office of the Assistant Secretary of Defense for Health Affairs; Military Operational Medicine Research Program (MOMRP); NIH [1 U24 DK097154]; [09284002] FX This project is supported by the Office of the Assistant Secretary of Defense for Health Affairs and the Military Operational Medicine Research Program (MOMRP), and the support of grant #USAMRMC NO: 09284002 is highly acknowledged. DG was supported by NIH 1 U24 DK097154. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 89 TC 6 Z9 6 U1 1 U2 13 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 JAN 28 PY 2015 VL 10 IS 1 AR e0117092 DI 10.1371/journal.pone.0117092 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA2IM UT WOS:000348732100063 PM 25629821 ER PT J AU Chan, AWY Baker, CI AF Chan, Annie W. -Y. Baker, Chris I. TI Seeing Is Not Feeling: Posterior Parietal But Not Somatosensory Cortex Engagement During Touch Observation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE action; empathy; hands; human fMRI; touch; vision ID HUMAN BRAIN; SOMATOTOPIC ORGANIZATION; CORTICAL REPRESENTATIONS; FUSIFORM GYRUS; MIRROR NEURONS; BODY AREAS; FMRI; ACTIVATION; RESPONSES; HUMANS AB Observing touch has been reported to elicit activation in human primary and secondary somatosensory cortices and is suggested to underlie our ability to interpret other's behavior and potentially empathy. However, despite these reports, there are a large number of inconsistencies in terms of the precise topography of activation, the extent of hemispheric lateralization, and what aspects of the stimulus are necessary to drive responses. To address these issues, we investigated the localization and functional properties of regions responsive to observed touch in a large group of participants (n = 40). Surprisingly, even with a lenient contrast of hand brushing versus brushing alone, we did not find any selective activation for observed touch in the hand regions of somatosensory cortex but rather in superior and inferior portions of neighboring posterior parietal cortex, predominantly in the left hemisphere. These regions in the posterior parietal cortex required the presence of both brush and hand to elicit strong responses and showed some selectivity for the form of the object or agent of touch. Furthermore, the inferior parietal region showed nonspecific tactile and motor responses, suggesting some similarity to area PFG in the monkey. Collectively, our findings challenge the automatic engagement of somatosensory cortex when observing touch, suggest mislocalization in previous studies, and instead highlight the role of posterior parietal cortex. C1 [Chan, Annie W. -Y.; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Chan, AWY (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Neurol, 415 Link Bldg, Memphis, TN 38163 USA. EM wchan2@uthsc.edu OI Baker, Chris/0000-0001-6861-8964 FU Intramural NIH HHS; PHS HHS [NCT00001360] NR 53 TC 4 Z9 4 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 28 PY 2015 VL 35 IS 4 BP 1468 EP 1480 DI 10.1523/JNEUROSCI.3621-14.2015 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CB5LU UT WOS:000349669600014 PM 25632124 ER PT J AU Pretegiani, E Astefanoaei, C Daye, PM FitzGibbon, EJ Creanga, DE Rufa, A Optican, LM AF Pretegiani, Elena Astefanoaei, Corina Daye, Pierre M. FitzGibbon, Edmond J. Creanga, Dorina-Emilia Rufa, Alessandra Optican, Lance M. TI Action and Perception Are Temporally Coupled by a Common Mechanism That Leads to a Timing Misperception SO JOURNAL OF NEUROSCIENCE LA English DT Article DE attention; gap effect; model; saccades; superior colliculus ID MONKEY SUPERIOR COLLICULUS; SACCADIC EYE-MOVEMENTS; CONTRAST SENSITIVITY; INTERMEDIATE LAYERS; TARGET SELECTION; ARM MOVEMENTS; ATTENTION; FIXATION; CONNECTIONS; SUPPRESSION AB We move our eyes to explore the world, but visual areas determining where to look next (action) are different from those determining what we are seeing (perception). Whether, or how, action and perception are temporally coordinated is not known. The preparation time course of an action (e.g., a saccade) has been widely studied with the gap/overlap paradigm with temporal asynchronies (TA) between peripheral target onset and fixation point offset (gap, synchronous, or overlap). However, whether the subjects perceive the gap or overlap, and when they perceive it, has not been studied. We adapted the gap/overlap paradigm to study the temporal coupling of action and perception. Human subjects made saccades to targets with different TAs with respect to fixation point offset and reported whether they perceived the stimuli as separated by a gap or overlapped in time. Both saccadic and perceptual report reaction times changed in the same way as a function of TA. The TA dependencies of the time change for action and perception were very similar, suggesting a common neural substrate. Unexpectedly, in the perceptual task, subjects misperceived lights overlapping by less than similar to 100 ms as separated in time (overlap seen as gap). Wepresent an attention-perception model with amapof prominence in the superior colliculus that modulates the stimulus signal's effectiveness in the action and perception pathways. This common source of modulation determines how competition between stimuli is resolved, causes the TA dependence of action and perception to be the same, and causes the misperception. C1 [Pretegiani, Elena; Daye, Pierre M.; FitzGibbon, Edmond J.; Optican, Lance M.] NEI, Sensorimotor Res Lab, NIH, DHHS, Bethesda, MD 20892 USA. [Pretegiani, Elena; Rufa, Alessandra] Univ Siena, EVA Lab, I-53100 Siena, Italy. [Astefanoaei, Corina; Creanga, Dorina-Emilia] Alexandru Ioan Cuza Univ, Fac Phys, Iasi 700506, Romania. [Daye, Pierre M.] Inst Cerveau & Moelle Epiniere ICM, INSERM UMRS 975, F-75013 Paris, France. RP Pretegiani, E (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA. EM elena.pretegiani@nih.gov FU Intramural NIH HHS NR 73 TC 0 Z9 0 U1 10 U2 20 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 JAN 28 PY 2015 VL 35 IS 4 BP 1493 EP 1504 DI 10.1523/JNEUROSCI.2054-14.2015 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CB5LU UT WOS:000349669600016 PM 25632126 ER PT J AU Aldworth, ZN Stopfer, MA AF Aldworth, Zane N. Stopfer, Mark A. TI Trade-Off between Information Format and Capacity in the Olfactory System SO JOURNAL OF NEUROSCIENCE LA English DT Article DE information theory; neural coding; oscillations; synchrony ID EVOKED NEURAL OSCILLATIONS; RETINAL GANGLION-CELLS; LOCUST ANTENNAL LOBE; ODOR REPRESENTATIONS; LOCAL INTERNEURONS; NETWORK DYNAMICS; POPULATION CODES; SPIKE TRAINS; DISCRIMINATION; ASSEMBLIES AB As information about the sensory environment passes between layers within the nervous system, the format of the information often changes. To examine how information format affects the capacity of neurons to represent stimuli, we measured the rate of information transmission in olfactory neurons in intact, awake locusts (Schistocerca americana) while pharmacologically manipulating patterns of correlated neuronal activity. Blocking the periodic inhibition underlying odor-elicited neural oscillatory synchronization increased information transmission rates. This suggests oscillatory synchrony, which serves other information processing roles, comes at a cost to the speed with which neurons can transmit information. Our results provide an example of a trade-off between benefits and costs in neural information processing. C1 [Aldworth, Zane N.; Stopfer, Mark A.] NICHD, NIH, Lab Cellular & Synapt Physiol, Bethesda, MD 20892 USA. RP Aldworth, ZN (reprint author), NICHD, NIH, Lab Cellular & Synapt Physiol, Bethesda, MD 20892 USA. EM zane.aldworth@nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [R01 DC012943] NR 48 TC 2 Z9 2 U1 1 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 28 PY 2015 VL 35 IS 4 BP 1521 EP 1529 DI 10.1523/JNEUROSCI.3562-14.2015 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CB5LU UT WOS:000349669600019 PM 25632129 ER PT J AU Brachman, RA Lehmann, ML Maric, D Herkenham, M AF Brachman, Rebecca A. Lehmann, Michael L. Maric, Dragan Herkenham, Miles TI Lymphocytes from Chronically Stressed Mice Confer Antidepressant-Like Effects to Naive Mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE adaptive immune system; cytokines; depression; hippocampal neurogenesis; lymphocytes; stress ID IMMUNE-SYSTEM; T-CELLS; PSYCHOLOGICAL STRESS; ADULT NEUROGENESIS; DEPRESSION; BEHAVIOR; PROLIFERATION; MEMORY; BRAIN; INFLAMMATION AB We examined whether cells of the adaptive immune system retain the memory of psychosocial stress and thereby alter mood states and CNS function in the host. Lymphocytes from mice undergoing chronic social defeat stress or from unstressed control mice were isolated and adoptively transferred into naive lymphopenic Rag2(-/-) mice. Changes in affective behavior, hippocampal cell proliferation, microglial activation states, and blood cytokine levels were examined in reconstituted stress-naive mice. The mice receiving lymphocytes from defeated donors showed less anxiety, more social behavior, and increased hippocampal cell proliferation compared with those receiving no cells or cells from unstressed donors. Mice receiving stressed immune cells had reduced pro-inflammatory cytokine levels in the blood relative to the other groups, an effect opposite to the elevated donor pro-inflammatory cytokine profile. Furthermore, mice receiving stressed immune cells had microglia skewed toward an anti-inflammatory, neuroprotective M2-like phenotype, an effect opposite the stressed donors' M1-like pro-inflammatory profile. However, stress had no effect on lymphocyte surface marker profiles in both donor and recipient mice. The data suggest that chronic stress-induced changes in the adaptive immune system, contrary to conferring anxiety and depressive behavior, protect against the deleterious effects of stress. Improvement in affective behavior is potentially mediated by reduced peripheral pro-inflammatory cytokine load, protective microglial activity, and increased hippocampal cell proliferation. The data identify the peripheral adaptive immune system as putatively involved in the mechanisms underlying stress resilience and a potential basis for developing novel rapid-acting antidepressant therapies. C1 [Brachman, Rebecca A.; Lehmann, Michael L.; Herkenham, Miles] NIMH, Funct Neuroanat Sect, LCMR, Bethesda, MD 20892 USA. [Maric, Dragan] NINDS, Flow Cytometry Core Facil, NIH, DHHS, Bethesda, MD 20892 USA. RP Herkenham, M (reprint author), NIMH, Funct Neuroanat Sect, LCMR, Bldg 35,Room 1C913, Bethesda, MD 20892 USA. EM herkenh@mail.nih.gov OI Brachman, Rebecca/0000-0002-1221-0414; Lehmann, Michael/0000-0003-4476-8268 FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH001090, Z01MH001090] NR 43 TC 20 Z9 20 U1 3 U2 18 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 28 PY 2015 VL 35 IS 4 BP 1530 EP 1538 DI 10.1523/JNEUROSCI.2278-14.2015 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CB5LU UT WOS:000349669600020 PM 25632130 ER PT J AU Meirovitch, Y Harris, H Dayan, E Arieli, A Flash, T AF Meirovitch, Yaron Harris, Hila Dayan, Eran Arieli, Amos Flash, Tamar TI Alpha and Beta Band Event-Related Desynchronization Reflects Kinematic Regularities SO JOURNAL OF NEUROSCIENCE LA English DT Article DE 2/ 3 power law; action-perception coupling; biological motion; event-related desynchronization; motion perception; movement kinematics ID PRIMARY MOTOR CORTEX; ARM MOVEMENTS; DRAWING MOVEMENTS; EEG EVIDENCE; DYNAMICS; MODULATION; RHYTHMS; IMAGERY; BRAIN; LAW AB The short-lasting attenuation of brain oscillations is termed event-related desynchronization (ERD). It is frequently found in the alpha and beta bands in humans during generation, observation, and imagery of movement and is considered to reflect cortical motor activity and action-perception coupling. The shared information driving ERD in all these motor-related behaviors is unknown. We investigated whether particular laws governing production and perception of curved movement may account for the attenuation of alpha and beta rhythms. Human movement appears to be governed by relatively few kinematic laws of motion. One dominant law in biological motion kinematics is the 2/3 power law (PL), which imposes a strong dependency of movement speed on curvature and is prominent in action-perception coupling. Here we directly examined whether the 2/3 PL elicits ERD during motion observation by characterizing the spatiotemporal signature of ERD. ERDs were measured while human subjects observed a cloud of dots moving along elliptical trajectories either complying with or violating the 2/3 PL. We found that ERD within both frequency bands was consistently stronger, arose faster, and was more widespread while observing motion obeying the 2/3 PL. An activity pattern showing clear 2/3 PL preference and lying within the alpha band was observed exclusively above central motor areas, whereas 2/3 PL preference in the beta band was observed in additional prefrontal-central cortical sites. Our findings reveal that compliance with the 2/3 PL is sufficient to elicit a selective ERD response in the human brain. C1 [Meirovitch, Yaron; Flash, Tamar] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel. [Harris, Hila; Arieli, Amos] Weizmann Inst Sci, Dept Neurobiol Brain Res, IL-76100 Rehovot, Israel. [Dayan, Eran] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. RP Meirovitch, Y (reprint author), Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel. EM yaron.mr@gmail.com FU European Union [FP7-ICT-248311, EC-ICT-257695, EC FP7-ICT-249858]; Planning and Budgeting Committee I-CORE Program; Israel Science Foundation [51/11]; Azrieli Foundation FX This work was supported by the European Union projects FP7-ICT-248311 AMARSi, EC-ICT-257695 Vere, and EC FP7-ICT-249858 TANGO, Planning and Budgeting Committee I-CORE Program, and Israel Science Foundation Grant 51/11. H.H. is supported by the Azrieli Foundation. T.F. is an incumbent of the Dr. Moross Professorial chair. We thank Prof. Dov Sagi for supporting this work; Dr. Simon Israeli-Korn, Dr. Shlomit Ben Ami, Irit Sella, and Prof. Martin Giese, Prof. Daniel Bennequin, Prof. Alain Berthoz, and Prof. Moshe Abeles for useful discussions; and Dr. Jenny Kien for editorial help. NR 61 TC 8 Z9 8 U1 1 U2 9 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 JAN 28 PY 2015 VL 35 IS 4 BP 1627 EP 1637 DI 10.1523/JNEUROSCI.5371-13.2015 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CB5LU UT WOS:000349669600028 PM 25632138 ER PT J AU Singh, SR Tan, M Rameshwar, P AF Singh, Shree Ram Tan, Ming Rameshwar, Pranela TI Featuring the guest editor: Special issue cancer metabolism SO CANCER LETTERS LA English DT Editorial Material C1 [Singh, Shree Ram] NCI, Mouse Canc Genet Program, Stem Cell Regulat & Anim Aging Sect, Frederick, MD 21702 USA. [Singh, Shree Ram] NCI, Basic Res Lab, Frederick, MD 21702 USA. [Tan, Ming] Univ S Alabama, Mitchell Canc Inst, Dept Oncol Sci, Mobile, AL 36688 USA. [Rameshwar, Pranela] Rutgers State Univ, New Jersey Med Sch, Div Hematol & Oncol, Newark, NJ 07103 USA. RP Singh, SR (reprint author), NCI, Mouse Canc Genet Program, Stem Cell Regulat & Anim Aging Sect, Frederick, MD 21702 USA. EM singhshr@mail.nih.gov; mtan@health.southalabama.edu; rameshwa@njms.rutgers.edu RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X NR 0 TC 0 Z9 0 U1 0 U2 4 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 JAN 28 PY 2015 VL 356 IS 2 SI SI BP 145 EP 146 DI 10.1016/j.canlet.2014.02.007 PN A PG 2 WC Oncology SC Oncology GA AY7XX UT WOS:000347770200001 ER PT J AU Singh, SR Tan, M Rameshwar, P AF Singh, Shree Ram Tan, Ming Rameshwar, Pranela TI Cancer Metabolism: Targeting metabolic pathways in cancer therapy SO CANCER LETTERS LA English DT Editorial Material C1 [Singh, Shree Ram] NCI, Stein Cell Regulat & Anim Aging Sect, Basic Res Lab, Frederick, MD 21702 USA. [Tan, Ming] Univ S Alabama, Mitchell Canc Inst, Dept Oncol Sci, Mobile, AL 36688 USA. [Rameshwar, Pranela] Rutgers State Univ, Div Hematol & Oncol, Newark, NJ 07103 USA. RP Singh, SR (reprint author), NCI, Stein Cell Regulat & Anim Aging Sect, Basic Res Lab, Frederick, MD 21702 USA. EM singhshr@mail.nih.gov; mtan@health.southalabama.edu; rameshwa@njms.rutgers.edu RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU Intramural NIH HHS [Z99 CA999999] NR 10 TC 4 Z9 4 U1 1 U2 10 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 JAN 28 PY 2015 VL 356 IS 2 SI SI BP 147 EP 148 DI 10.1016/j.canlet.2014.06.002 PN A PG 2 WC Oncology SC Oncology GA AY7XX UT WOS:000347770200002 PM 24956174 ER PT J AU Zeng, W Liu, PY Pan, WM Singh, SR Wei, YY AF Zeng, Wen Liu, Peiyi Pan, Weimin Singh, Shree Ram Wei, Yiyong TI Hypoxia and hypoxia inducible factors in tumor metabolism SO CANCER LETTERS LA English DT Review DE Hypoxia; HIFs; Tumor; Metabolism; Tumor microenvironment; Apoptosis ID SELECTIVE CANCER-THERAPY; MULTIDRUG-RESISTANCE; GLUCOSE-METABOLISM; DNA-REPAIR; AEROBIC GLYCOLYSIS; CELL-METABOLISM; GENE-EXPRESSION; SOLID TUMORS; LDH-A; MECHANISMS AB Because of the abnormal vasculature, most growing solid tumors contain regions that experience either acute or chronic hypoxia. However, tumor cells can maintain a high glycolytic rate even when there is enough oxygen supply. Hypoxia-inducible factors (HIFs) play crucial role in the response of tumor cells to this distinct microenvironment by shifting energy production from mitochondria towards glycolysis. In this review, we focus on the metabolism of tumor cell survival in hypoxic microenvironments. Furthermore, we also emphasize the mechanisms by which hypoxia and HIFs regulate tumor metabolism. Published by Elsevier Ireland Ltd. C1 [Zeng, Wen; Liu, Peiyi; Wei, Yiyong] Shanghai Jiao Tong Univ, Shanghai Key Lab Prevent & Treatment Bone & Joint, Shanghai Inst Traumatol & Orthopaed, Ruijin Hosp,Sch Med, Shanghai 20025, Peoples R China. [Zeng, Wen] Tongji Univ, Sch Med, Shanghai East Hosp, Dept Joint & Bone Dis, Shanghai 200120, Peoples R China. [Liu, Peiyi; Wei, Yiyong] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Orthopaed, Shanghai 20025, Peoples R China. [Pan, Weimin] Xian Phys Educ Univ, Dept Human Movement Studies, Xian 710068, Peoples R China. [Singh, Shree Ram] NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Wei, YY (reprint author), Shanghai Jiao Tong Univ, Shanghai Key Lab Prevent & Treatment Bone & Joint, Shanghai Inst Traumatol & Orthopaed, Ruijin Hosp,Sch Med, Shanghai 20025, Peoples R China. EM singhshr@mail.nih.gov; dr.yiyongwei@yahoo.com RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU Intramural NIH HHS [Z99 CA999999] NR 71 TC 16 Z9 17 U1 6 U2 47 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 JAN 28 PY 2015 VL 356 IS 2 SI SI BP 263 EP 267 DI 10.1016/j.canlet.2014.01.032 PN A PG 5 WC Oncology SC Oncology GA AY7XX UT WOS:000347770200018 PM 24508030 ER PT J AU Chan, B Manley, J Lee, J Singh, SR AF Chan, Brian Manley, Jacob Lee, Jae Singh, Shree Ram TI The emerging roles of microRNAs in cancer metabolism SO CANCER LETTERS LA English DT Review DE Cancer; Metabolism; MicroRNAs; Glycolysis; TCA cycle; Cancer therapy ID SQUAMOUS-CELL CARCINOMA; HEPATOCELLULAR-CARCINOMA; C-MYC; TUMOR-SUPPRESSOR; MITOCHONDRIAL METABOLISM; GLUTAMINE-METABOLISM; REGULATES GLYCOLYSIS; PANCREATIC-CANCER; COLORECTAL-CANCER; PYRUVATE-KINASE AB The major goal of cancer therapy is to destroy cancer cells without harming normal cells. However, because cancer cells have incredible heterogeneity and adaptability, it is difficult to target them therapeutically. Metabolic reprogramming has emerged as a common feature of cancer. Ever since microRNAs (miRNAs) have been found to influence metabolism, researchers have been trying to address the connection between cancer cells and specific miRNAs. Many of the well-known miRNAs relate to crucial genes that can impact metabolic pathways, both negatively and positively. With a better understanding of how different pathways are affected, the roles of miRNAs will be more transparent, which could lead to the discovery of new ideas about the concept of tumorigenesis and other cancer-related topics. Published by Elsevier Ireland Ltd. C1 [Chan, Brian; Manley, Jacob; Lee, Jae; Singh, Shree Ram] NCI, Basic Res Lab, Stem Cell Regulat & Anim Aging Sect, Frederick, MD 21702 USA. RP Singh, SR (reprint author), NCI, Basic Res Lab, Stem Cell Regulat & Anim Aging Sect, Frederick, MD 21702 USA. EM singhshr@mail.nih.gov RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU Intramural Research Program of the National Cancer Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. We apologize to all colleagues whose work we could not cite due to space constraints. NR 135 TC 22 Z9 24 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 JAN 28 PY 2015 VL 356 IS 2 SI SI BP 301 EP 308 DI 10.1016/j.canlet.2014.10.011 PN A PG 8 WC Oncology SC Oncology GA AY7XX UT WOS:000347770200023 PM 25451319 ER PT J AU Kaiser, E Schroeder, L Wiesen, K Wess, J Tian, QH Kaestner, L Lipp, P AF Kaiser, Elisabeth Schroeder, Laura Wiesen, Kathrina Wess, Juergen Tian, Qinghai Kaestner, Lars Lipp, Peter TI Novel Roles of Gq-Dependent Signal Transduction for Cardiac Pace-making and Cardiac Impulse Propagation Studied by Gq-KO and a DREADD SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Kaiser, Elisabeth; Schroeder, Laura; Wiesen, Kathrina; Tian, Qinghai; Kaestner, Lars; Lipp, Peter] Univ Saarland, Inst Mol Cell Biol, Homburg, Germany. [Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RI Kaestner, Lars/P-6988-2016 NR 0 TC 2 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 656-Pos BP 131A EP 132A PG 2 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700657 ER PT J AU Alexander, SJ Gawrisch, K Pastor, RW Lyman, ER AF Alexander, Sodt J. Gawrisch, Klaus Pastor, Richard W. Lyman, Edward R. TI Nanoscale Structure and Dynamics of the Liquid Ordered Phase SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Alexander, Sodt J.; Pastor, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA. [Gawrisch, Klaus] NIAAA, NIH, Bethesda, MD USA. [Lyman, Edward R.] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA. NR 1 TC 0 Z9 0 U1 4 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 5-Subg BP 1A EP 1A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700006 ER PT J AU Kraft, ML Frisz, JF Klitzing, HA Wilson, RL Yeager, A Lizunov, V Zimmerberg, JJ Weber, PK AF Kraft, Mary L. Frisz, Jessica F. Klitzing, Haley A. Wilson, Robert L. Yeager, Ashley Lizunov, Vladimir Zimmerberg, Joshua J. Weber, Peter K. TI Investigating the Mechanisms of Non-Random Sphingolipid Organization in the Plasma Membranes of Fibroblast Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kraft, Mary L.; Yeager, Ashley] Univ Illinois, Chem & Biomol Engr, Urbana, IL 61801 USA. [Frisz, Jessica F.; Klitzing, Haley A.; Wilson, Robert L.] Univ Illinois, Chem, Urbana, IL 61801 USA. [Lizunov, Vladimir; Zimmerberg, Joshua J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD USA. [Weber, Peter K.] Lawrence Livermore Natl Lab, Glenn T Seaborg Inst, Livermore, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 4-Subg BP 1A EP 1A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700005 ER PT J AU Bassereau, P Prevost, C Simunovic, M Aimon, S Toombes, G Callan-Jones, A AF Bassereau, Patricia Prevost, Coline Simunovic, Mijo Aimon, Sophie Toombes, Gilman Callan-Jones, Andrew TI Protein Spatial Distribution Depends on Membrane Curvature SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Bassereau, Patricia] Inst Curie, Paris, France. [Prevost, Coline; Simunovic, Mijo; Aimon, Sophie] Inst Curie, PhysicoChim Curie, Paris, France. [Simunovic, Mijo] Univ Chicago, Dept Chem, Chicago, IL 60637 USA. [Aimon, Sophie] Univ Calif San Diego, Kavli Inst Brain & Mind, San Diego, CA 92103 USA. [Toombes, Gilman] NIH, Mol Physiol & Biophys Sect, Bethesda, MD 20892 USA. [Callan-Jones, Andrew] Univ Paris 07, Lab Matiere & Syst Complexes, Paris, France. OI Bassereau, Patricia/0000-0002-8544-6778 NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 9-Subg BP 2A EP 2A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700010 ER PT J AU Larson, D AF Larson, Daniel TI Understanding Gene Expression Heterogeneity in Living Cells with Single-Molecule Fluorescence Microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Larson, Daniel] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 38-Subg BP 8A EP 8A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700039 ER PT J AU Ortega-Arroyo, J Andrecka, J Takagi, Y Sellers, JR Kukura, P AF Ortega-Arroyo, Jaime Andrecka, Joanna Takagi, Yasuharu Sellers, James R. Kukura, Philipp TI Myosin 5 Side Steps along Actin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Ortega-Arroyo, Jaime; Andrecka, Joanna; Kukura, Philipp] Univ Oxford, Phys & Theoret Chem Lab, Oxford, England. [Takagi, Yasuharu; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 122-Plat BP 25A EP 25A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700123 ER PT J AU Fitzgerald, GA Mulligan, C Mindell, JA AF Fitzgerald, Gabriel A. Mulligan, Christopher Mindell, Joseph A. TI Transport Coupling Stoichiometry Determination of Electrogenic Secondary Transporters SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Fitzgerald, Gabriel A.; Mulligan, Christopher; Mindell, Joseph A.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 137-Plat BP 28A EP 28A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700138 ER PT J AU Parmeswaran, H Dhandayuthapani, B Peterkofsky, A Kaback, RH Guan, L AF Parmeswaran, Hariharan Dhandayuthapani, Balasubramaniam Peterkofsky, Alan Kaback, Ronald H. Guan, Lan TI Thermodynamic Features of IIA(Glc) Inhibition of Sugar Symporters SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Parmeswaran, Hariharan; Guan, Lan] Texas Tech Univ, Hlth Sci Ctr, Ctr Membrane Prot Res, Cell Physiol & Mol Biophys, Lubbock, TX 79430 USA. [Dhandayuthapani, Balasubramaniam; Kaback, Ronald H.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. [Peterkofsky, Alan] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 136-Plat BP 28A EP 28A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700137 ER PT J AU Fenollar-Ferrer, C Patti, M Werner, A Knoepfel, T Forster, IC Forrest, LR AF Fenollar-Ferrer, Cristina Patti, Monica Werner, Andreas Knoepfel, Thomas Forster, Ian C. Forrest, Lucy R. TI The Na1 Binding Site in the Human Sodium-Phosphate Cotransporter NaPi-IIa SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Fenollar-Ferrer, Cristina; Forrest, Lucy R.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. [Patti, Monica; Knoepfel, Thomas; Forster, Ian C.] Univ Zurich, Inst Physiol, Zurich, Switzerland. [Werner, Andreas] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 140-Plat BP 29A EP 29A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700141 ER PT J AU Patti, M Fenollar-Ferrer, C Werner, A Knopfel, T Forrest, L Forster, I AF Patti, Monica Fenollar-Ferrer, Cristina Werner, Andreas Knoepfel, Thomas Forrest, Lucy Forster, Ian TI Functional Identification of the Na1 Site of the Phosphate Cotransporter NaPi-IIa SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Patti, Monica] Univ Zurich, Physiol, Zurich, Switzerland. [Fenollar-Ferrer, Cristina; Forrest, Lucy] NIH, Computat Struct Biol, Rockville, MD 20852 USA. [Werner, Andreas] Newcastle Univ, Inst Cell & Mol Biosci, Sch Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Knoepfel, Thomas; Forster, Ian] Univ Zurich, Inst Physiol, Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 141-Plat BP 29A EP 29A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700142 ER PT J AU Bae, C Jara-Oseguera, A Krepkiy, DV Ryu, J Kim, JI Swartz, KJ AF Bae, Chanhyung Jara-Oseguera, Andres Krepkiy, Dmitriy V. Ryu, Jaeha Kim, Jae Il Swartz, Kenton J. TI Surface Characterization and Membrane Interaction of Double-Knot Toxin, an Activator of TRPV1 Channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Bae, Chanhyung; Jara-Oseguera, Andres; Krepkiy, Dmitriy V.; Swartz, Kenton J.] NIH, Bethesda, MD 20892 USA. [Ryu, Jaeha; Kim, Jae Il] GIST, Gwangju, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 177-Plat BP 36A EP 36A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700178 ER PT J AU Damjanovic, A Miller, BT Okur, A Garcia-Moreno, B Brooks, BR AF Damjanovic, Ana Miller, Benjamin T. Okur, Asim Garcia-Moreno, Bertrand Brooks, Bernard R. TI Constant pH Simulations with the Double Reservoir pH Replica Exchange SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Damjanovic, Ana; Garcia-Moreno, Bertrand] Johns Hopkins Univ, Biophys, Baltimore, MD USA. [Damjanovic, Ana; Miller, Benjamin T.; Okur, Asim; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 233-Pos BP 47A EP 47A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700234 ER PT J AU Nestorovich, EM Bezrukov, SM AF Nestorovich, Ekaterina M. Bezrukov, Sergey M. TI Specific or General - It is All About Solute Interactions with the Pore SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Nestorovich, Ekaterina M.] Catholic Univ Amer, Biol, Washington, DC 20064 USA. [Bezrukov, Sergey M.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 281-Pos BP 56A EP 56A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700282 ER PT J AU Xu, L Margittai, M Nussinov, R Ma, BY AF Xu, Liang Margittai, Martin Nussinov, Ruth Ma, Buyong TI Simulation of the Distribution of Disordered Tau Proteins Around Its Amyloid Fibrils Core SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Xu, Liang] Dalian Univ Technol, Sch Chem, Dalian, Peoples R China. [Margittai, Martin] Univ Denver, Dept Chem & Biochem, Dever, CO USA. [Nussinov, Ruth; Ma, Buyong] NCI, Leidos Biomed, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 310-Pos BP 62A EP 62A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700311 ER PT J AU Xu, L Ma, BY AF Xu, Liang Ma, Buyong TI From Monomers, Dimers to Oligomers: How Metal Ions Regulate Amyloid Beta Porteins in Amyloid Formation? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Xu, Liang] Dalian Univ Technol, Dept Chem, Dalian, Peoples R China. [Ma, Buyong] NCI, Leidos Biomed, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 321-Pos BP 64A EP 64A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700322 ER PT J AU Shaytan, AK Armeev, GA Zhurkin, VB Landsman, D Panchenko, AR AF Shaytan, Alexey K. Armeev, Grigory A. Zhurkin, Victor B. Landsman, David Panchenko, Anna R. TI Polymorphism of Histone Tail Interactions in Nucleosome SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Shaytan, Alexey K.; Landsman, David; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Armeev, Grigory A.] Moscow MV Lomonosov State Univ, Fac Biol, Moscow, Russia. [Zhurkin, Victor B.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RI Shaytan, Alexey/D-7306-2012 OI Shaytan, Alexey/0000-0003-0312-938X NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 368-Pos BP 72A EP 72A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700369 ER PT J AU Hutchison, JM Ritchie, J Rau, DC AF Hutchison, James M. Ritchie, James Rau, Donald C. TI Elucidation of DNA Packaging and Mispackaging in Sperm Nuclei by X-Ray Scattering SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Hutchison, James M.; Ritchie, James; Rau, Donald C.] NICHD, SMRA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 376-Pos BP 74A EP 74A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700377 ER PT J AU Zamanian, M Bae, C Gupta, K Milescu, M Krepkiy, D Tilley, D Sack, J Yarov-Yarovoy, V Kim, JII Swartz, K AF Zamanian, Maryam Bae, Chanhyung Gupta, Kanchan Milescu, Mirela Krepkiy, Dmitriy Tilley, Drew Sack, Jon Yarov-Yarovoy, Vladimir Kim, Jae I. I. Swartz, Kenton TI Tarantula Toxins use Common Surfaces for Interacting with Kv and ASIC Ion Channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Zamanian, Maryam; Bae, Chanhyung; Gupta, Kanchan; Krepkiy, Dmitriy; Swartz, Kenton] NINDS, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA. [Milescu, Mirela] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. [Tilley, Drew; Sack, Jon; Yarov-Yarovoy, Vladimir] Univ Calif Davis, Dept Physiol & Membrane Biol, Davis, CA 95616 USA. [Kim, Jae I. I.] Gwangju Inst Sci & Technol, Dept Life Sci, Gwangju, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 415-Pos BP 82A EP 82A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700416 ER PT J AU Gershfeld, NL Nossal, R AF Gershfeld, Norman L. Nossal, Ralph TI Temperature-Dependent Lipid Phase Transitions Occurring in Higher Organisms SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Gershfeld, Norman L.; Nossal, Ralph] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 449-Pos BP 88A EP 88A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700450 ER PT J AU Domanski, J Sansom, M Stansfeld, P Best, R AF Domanski, Jan Sansom, Mark Stansfeld, Philip Best, Robert TI Studying Membrane Protein Folding by Molecular Dynamics Simulations SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Domanski, Jan; Sansom, Mark; Stansfeld, Philip] Univ Oxford, Oxford, England. [Best, Robert] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 467-Pos BP 92A EP 92A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700468 ER PT J AU Jang, H Lu, SY Chakrabarti, M Khavrutskii, L Tarasova, NI Gaponenko, V Nussinov, R AF Jang, Hyunbum Lu, Shaoyong Chakrabarti, Mayukh Khavrutskii, Lyuba Tarasova, Nadya I. Gaponenko, Vadim Nussinov, Ruth TI Nucleotide-Dependent Membrane Interaction and Dimerization of K-Ras4B SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Jang, Hyunbum; Khavrutskii, Lyuba; Nussinov, Ruth] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab, Frederick, MD USA. [Jang, Hyunbum; Lu, Shaoyong; Chakrabarti, Mayukh; Khavrutskii, Lyuba; Tarasova, Nadya I.; Nussinov, Ruth] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Lu, Shaoyong] Shanghai Jiao Tong Univ, Shanghai 200030, Peoples R China. [Chakrabarti, Mayukh] Johns Hopkins Univ, Dept Biotechnol, Baltimore, MD USA. [Gaponenko, Vadim] Univ Illinois, Dept Med Chem, Chicago, IL USA. [Gaponenko, Vadim] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 475-Pos BP 93A EP 94A PG 2 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700476 ER PT J AU Shin, WC Chiang, HC Wen, PJ Sheng, JS Wu, LG AF Shin, Wonchul Chiang, Hsueh-Cheng Wen, Peter J. Sheng, Jiansong Wu, Ling-Gang TI Closure of Pre-Existing Omega Profiles Mediates Compensatory Endocytosis, Endocytosis Overshoot and Bulk Endocytosis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Shin, Wonchul; Chiang, Hsueh-Cheng; Wen, Peter J.; Sheng, Jiansong; Wu, Ling-Gang] NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 501-Pos BP 99A EP 99A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700502 ER PT J AU Ahuja, M Park, S Kim, M Brailoiu, E Muallem, S AF Ahuja, Malini Park, Soonhong Kim, MinSeuk Brailoiu, Eugen Muallem, Shmuel TI Fusion of Lysosomes with Secretory Vesicle Leads to Excessive Uncontrolled Exocytosis in Mucolipidosis Type IV SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Ahuja, Malini; Muallem, Shmuel] NIDCR, Bethesda, MD USA. [Park, Soonhong] Yonsei Univ, Seoul 120749, South Korea. [Kim, MinSeuk] Wokwang Univ, Iksan, South Korea. [Brailoiu, Eugen] Temple Univ, Philadelphia, PA 19122 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 508-Pos BP 101A EP 101A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700509 ER PT J AU Ha, J Sherman, A AF Ha, Joon Sherman, Arthur TI Ethnic Differences in Insulin Granule Exocytosis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Ha, Joon; Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 512-Pos BP 102A EP 102A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700513 ER PT J AU Bird, GS Putney, JW AF Bird, Gary S. Putney, James W., Jr. TI Differential Effects of PLC-Coupled Receptors on Intracellular Calcium Oscillations in HEK293 Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Bird, Gary S.; Putney, James W., Jr.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 528-Pos BP 105A EP 105A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700529 ER PT J AU Sirenko, S Zahanich, I Tarasova, Y Riordon, DR Chen, WQ Chen, WSR Lakatta, EG AF Sirenko, Syevda Zahanich, Ihor Tarasova, Yelena Riordon, Daniel R. Chen, Wenqian Chen, Wayne S. R. Lakatta, Edward G. TI Reduced Heart Rate in Mice Harboring an SR Luminal Ca2+ Sensor Mutation (E4872Q) is Linked to Abnormal Ca2+ Release and Pacemaker Function in Isolated Cardiocytes Derived from the Mutant RyR Clone SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Sirenko, Syevda; Zahanich, Ihor; Tarasova, Yelena; Riordon, Daniel R.; Lakatta, Edward G.] NIA, LCS, Baltimore, MD 21224 USA. [Chen, Wenqian; Chen, Wayne S. R.] Univ Calgary, Dept Physiol & Pharmacol, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 537-Pos BP 107A EP 107A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700538 ER PT J AU Yang, DM Lyashkov, AE Yaniv, Y Ziman, BD Lakatta, EG AF Yang, Dongmei Lyashkov, Alexey E. Yaniv, Yael Ziman, Bruce D. Lakatta, Edward G. TI Phosphorylation-Dependent Synchronization of Random Spontaneous Local Diastolic Ca2+ Releases Regulates Action Potential Firing Rhythmicity of Pacemaker Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Yang, Dongmei; Lyashkov, Alexey E.; Yaniv, Yael; Ziman, Bruce D.; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 538-Pos BP 107A EP 107A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700539 ER PT J AU Liu, XB Gong, BJ Ong, HL Cheng, KT Muniswamy, M Ambudkar, IS AF Liu, Xibao Gong, Baijuan Ong, Hwei Ling Cheng, Kwong Tai Muniswamy, Madesh Ambudkar, Indu S. TI Role of Mitochondrial Ca2+ Uniporter in Radiation-Induced Cell Damage SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Liu, Xibao; Gong, Baijuan; Ong, Hwei Ling; Cheng, Kwong Tai; Ambudkar, Indu S.] NIDCR, MPTB, NIH, Bethesda, MD USA. [Muniswamy, Madesh] Temple Univ, Dept Biochem, Sch Med, Philadelphia, PA 19122 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 545-Pos BP 108A EP 109A PG 2 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700546 ER PT J AU Muallem, S Maleth, J Choi, S Ahuja, M AF Muallem, Shmuel Maleth, Jozsef Choi, Seok Ahuja, Malini TI Translocation between PI(4,5)P-2-Poor and PI(4,5)P-2-Rich Microdomains During Store Depletion Determines STIM1 Conformation and Gating of Orai1 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Muallem, Shmuel; Maleth, Jozsef; Choi, Seok; Ahuja, Malini] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 551-Pos BP 110A EP 110A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700552 ER PT J AU Matt, MG Ahmet, I Monfredi, O Tsutsui, K Lakatta, EG AF Matt, Michael G. Ahmet, Ismayil Monfredi, Oliver Tsutsui, Kenta Lakatta, Edward G. TI Overexpression of Adenylyl Cyclase 8 (AC8) in Mice Increases Intrinsic Heart Rate (IHR) and Reduces Heart Rate Variability (HRV), and Detaches HR and HRV from Autonomic Modulation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Matt, Michael G.; Ahmet, Ismayil; Tsutsui, Kenta; Lakatta, Edward G.] NIA, Baltimore, MD 21224 USA. [Monfredi, Oliver] Univ Manchester, Manchester, Lancs, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 567-Pos BP 113A EP 113A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700568 ER PT J AU Bocksteins, E Snyders, DJ Holmgren, M AF Bocksteins, Elke Snyders, Dirk J. Holmgren, Miguel TI Movements of the Kv2.1 and Kv6.4 S4 Segments in Heterotetrameric Kv2.1/Kv6.4 Channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Bocksteins, Elke; Snyders, Dirk J.] Univ Antwerp, Biomed Sci, B-2020 Antwerp, Belgium. [Bocksteins, Elke; Holmgren, Miguel] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 583-Pos BP 117A EP 117A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700584 ER PT J AU Miranda, P Giraldez, T Holmgren, M AF Miranda, Pablo Giraldez, Teresa Holmgren, Miguel TI Voltage Dependence of BK Channels Gating Ring Motion Studied by State Dependent FRET SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Miranda, Pablo; Holmgren, Miguel] NINDS, Mol Neurophysiol Sect, NIH, Bethesda, MD 20892 USA. [Giraldez, Teresa] Univ La Laguna, Ctr Biomed Res Canary Isl CIBICAN, Sch Med, Biomed Sci, E-38207 San Cristobal la Laguna, Spain. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 593-Pos BP 119A EP 119A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700594 ER PT J AU Jara-Oseguera, A Swartz, KJ AF Jara-Oseguera, Andres Swartz, Kenton J. TI Unraveling Allosteric Coupling Mechanisms in the TRPV1 Channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Jara-Oseguera, Andres; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 621-Pos BP 124A EP 124A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700622 ER PT J AU Okamoto, Y Tarasov, KV Ziman, BD Lee, J Lakatta, EG AF Okamoto, Yosuke Tarasov, Kirill V. Ziman, Bruce D. Lee, Joonho Lakatta, Edward G. TI The Large Scale Transcriptome Analysis of Mouse Sinoatrial Node (SAN) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Okamoto, Yosuke; Tarasov, Kirill V.; Ziman, Bruce D.; Lee, Joonho; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 657-Pos BP 132A EP 132A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700658 ER PT J AU Cartagena-Rivera, AX Logue, JS Waterman, CM Chadwick, RS AF Cartagena-Rivera, Alexander X. Logue, Jeremy S. Waterman, Clare M. Chadwick, Richard S. TI Cortical Actin Tension, Elastic Modulus and Cytosolic Pressure in Fibroblasts Determined using Atomic Force Microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Cartagena-Rivera, Alexander X.; Logue, Jeremy S.; Chadwick, Richard S.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. [Logue, Jeremy S.; Waterman, Clare M.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 697-Pos BP 140A EP 140A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700698 ER PT J AU Sanchez-Rodriguez, JE Miranda-Fernandez, P Holmgren, M Bezanilla, F AF Sanchez-Rodriguez, Jorge E. Miranda-Fernandez, Pablo Holmgren, Miguel Bezanilla, Francisco TI Voltage Dependent Conformational Changes of the Na+/K+-ATPase Revealed by Site Directed Fluorometry SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Sanchez-Rodriguez, Jorge E.; Bezanilla, Francisco] Univ Chicago, Biochem & Mol Biol, Chicago, IL 60637 USA. [Miranda-Fernandez, Pablo; Holmgren, Miguel] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 716-Pos BP 144A EP 144A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700717 ER PT J AU Liu, HY Rao, DK Ambudkar, SV Mayer, M AF Liu, Haiyan Rao, Divya K. Ambudkar, Suresh V. Mayer, Michael TI A Combination of Curcumin with Either Gramicidin or Ouabain Selectively Kills Cells that Express the Multidrug Resistance-Linked ABCG2 Transporter SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Liu, Haiyan; Rao, Divya K.; Mayer, Michael] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. [Ambudkar, Suresh V.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 722-Pos BP 145A EP 145A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700723 ER PT J AU Elliott, AD Diao, FC Waller, BF Wu, YC York, AG Shroff, H White, BH AF Elliott, Amicia D. Diao, Feici Waller, Brianna F. Wu, Yicong York, Andrew G. Shroff, Hari White, Benjamin H. TI Imaging Calcium Activity Patterns in the Drosophila Pupal Ecdysis Neural Circuit SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Elliott, Amicia D.; Diao, Feici; Waller, Brianna F.; White, Benjamin H.] NIMH, NIH, Bethesda, MD 20892 USA. [Wu, Yicong; York, Andrew G.; Shroff, Hari] NIBIB, NIH, Bethesda, MD USA. RI Shroff, Hari/E-7247-2016 OI Shroff, Hari/0000-0003-3613-8215 NR 0 TC 0 Z9 0 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 760-Pos BP 153A EP 153A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700761 ER PT J AU Petukh, M Morrison, J Li, M Panchenko, A Alexov, E AF Petukh, Marharyta Morrison, Jacon Li, Minghui Panchenko, Anna Alexov, Emil TI SAMBE: The New Webserver for Predicting the Effect of nssNP on the Protein-Protein Binding Free Energy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Petukh, Marharyta; Alexov, Emil] Clemson Univ, Dept Phys, Computat Biophys & Bioinformat, Clemson, SC USA. [Morrison, Jacon] Clemson Univ, Dept Elect & Comp Engn, Comp Engn, Clemson, SC USA. [Li, Minghui; Panchenko, Anna] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 785-Pos BP 157A EP 158A PG 2 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700786 ER PT J AU Marinelli, F Faraldo-Gomez, JD AF Marinelli, Fabrizio Faraldo-Gomez, Jose D. TI Minimally-Biased Metadynamics Method to Sample Conformational Ensembles Compatible with Experimental Measurements SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Marinelli, Fabrizio; Faraldo-Gomez, Jose D.] NHLBI, Theoret Mol Biophys Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 791-Pos BP 158A EP 158A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700792 ER PT J AU Shao, Y Simmonett, A Pickard, F Koenig, G Brooks, B AF Shao, Yihan Simmonett, Andrew Pickard, Frank Koenig, Gerhard Brooks, Bernard TI Quantum Mechanical Molecular Mechanical Calculations using AMOEBA Force Fields SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Shao, Yihan; Simmonett, Andrew; Pickard, Frank; Koenig, Gerhard; Brooks, Bernard] NHLBI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 789-Pos BP 158A EP 158A PG 1 WC Biophysics SC Biophysics GA CO9DB UT WOS:000359471700790 ER PT J AU Pickard, FC Simmonett, AC Brooks, BR AF Pickard, Frank C. Simmonett, Andrew Craig Brooks, Bernard Rigoberto TI Efficient High Accuracy Non-Bonded Interactions in the CHARMM Simulation Package SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Pickard, Frank C.; Simmonett, Andrew Craig; Brooks, Bernard Rigoberto] NIH, Lab Computat Biol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 792-Pos BP 159A EP 159A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100002 ER PT J AU Zhang, DM Winter, PW Roess, DA Barisas, BG AF Zhang, Dongmei Winter, Peter W. Roess, Deborah A. Barisas, B. George TI Blinking of Quantum Dot Probes in Single Membrane Molecule Rotation Measurements SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Zhang, Dongmei; Barisas, B. George] Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA. [Winter, Peter W.] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, Bethesda, MD USA. [Roess, Deborah A.] Colorado State Univ, Dept Biomed Sci, Ft Collins, CO 80523 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 811-Pos BP 162A EP 162A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100021 ER PT J AU Smirnov, AV Combs, C Lee, J Knutson, JR AF Smirnov, Aleksandr V. Combs, Christian Lee, Justin Knutson, Jay R. TI Total Emission Detection for Efficient and Affordable Two-Photon Fluctuation Correlation Spectroscopy (2P-Fcs) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Smirnov, Aleksandr V.; Combs, Christian; Knutson, Jay R.] NHLBI, NIH, Bethesda, MD 20892 USA. [Lee, Justin] Duke Univ, Bioengn, Durham, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 817-Pos BP 163A EP 163A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100027 ER PT J AU Wu, ZH Plotnikov, SV Waterman, CM Liu, J AF Wu, Zhanghan Plotnikov, Sergey V. Waterman, Clare M. Liu, Jian TI Two Distinct Actin Networks Mediate Traction Oscillations to Confer Mechanosensitivity of Focal Adhesions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Wu, Zhanghan; Plotnikov, Sergey V.; Waterman, Clare M.; Liu, Jian] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 902-Plat BP 179A EP 179A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100112 ER PT J AU Sodt, AJ Venable, RM Lyman, E Pastor, RW AF Sodt, Alexander J. Venable, Richard M. Lyman, Edward Pastor, Richard W. TI Lipid-Lipid Interactions Determine the Membrane Spontaneous Curvature SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Sodt, Alexander J.; Venable, Richard M.; Pastor, Richard W.] NIH, Lab Computat Biol, Bethesda, MD 20892 USA. [Lyman, Edward] Univ Delaware, Phys, Newark, DE USA. NR 0 TC 1 Z9 1 U1 4 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 913-Plat BP 181A EP 181A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100123 ER PT J AU Lee, J Miller, T Damjanovic, A Brooks, BR AF Lee, Juyong Miller, Tim Damjanovic, Ana Brooks, Bernard R. TI Constant pH Molecular Dynamics in Explicit Solvent with Enveloping Distribution Sampling and Hamiltonian Exchange SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Lee, Juyong; Miller, Tim; Damjanovic, Ana; Brooks, Bernard R.] NHLBI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 921-Plat BP 183A EP 183A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100131 ER PT J AU Hoogerheide, DP Gurnev, PA Rostovtseva, TK Bezrukov, SM AF Hoogerheide, David P. Gurnev, Philip A. Rostovtseva, Tatiana K. Bezrukov, Sergey M. TI Probing the Motion of the Intrinsically Disordered Neuronal Protein Alpha-Synuclein through the VDAC Pore using a Single-Molecule Approach SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Hoogerheide, David P.; Gurnev, Philip A.; Rostovtseva, Tatiana K.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Hoogerheide, David P.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Gurnev, Philip A.] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 933-Plat BP 185A EP 185A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100143 ER PT J AU Veshaguri, S Christensen, SM Moller, MP Ghale, G Lohr, C Christensen, AL Tutkus, M Kemmer, G Jorgensen, IL Justesen, BH Curran, P Pomorski, TG Mindell, J Stamou, D AF Veshaguri, Salome Christensen, Sune M. Moller, Mads P. Ghale, Garima Lohr, Christina Christensen, Andreas L. Tutkus, Marijonas Kemmer, Gerdi Jorgensen, Ida L. Justesen, Bo H. Curran, Patricia Pomorski, Thomas G. Mindell, Joseph Stamou, Dimitrios TI Development of a Fluorescence-Based Assay for Functional Studies of Transporter Proteins on the Single Molecule Level SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Veshaguri, Salome; Christensen, Sune M.; Moller, Mads P.; Ghale, Garima; Lohr, Christina; Christensen, Andreas L.; Tutkus, Marijonas; Stamou, Dimitrios] Univ Copenhagen, Dept Chem, Lundbeck Fdn Ctr Biomembranes Nanomed, Bionanotechnol Lab, DK-2100 Copenhagen, Denmark. [Kemmer, Gerdi; Jorgensen, Ida L.; Justesen, Bo H.; Pomorski, Thomas G.] Univ Copenhagen, Dept Plant & Environm Sci, Copenhagen, Denmark. [Curran, Patricia; Mindell, Joseph] NINDS, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RI Ghale, Garima/E-9016-2016; Veshaguri, Salome/F-8052-2016 OI Veshaguri, Salome/0000-0002-7439-6373 NR 5 TC 0 Z9 0 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 940-Plat BP 187A EP 187A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100150 ER PT J AU Rostovtseva, TK Gurnev, PA Hoogerheide, DP Maldonado, EN Lemasters, JJ Protchenko, O Lee, JC Bezrukov, SM AF Rostovtseva, Tatiana K. Gurnev, Philip A. Hoogerheide, David P. Maldonado, Eduardo N. Lemasters, John J. Protchenko, Olga Lee, Jennifer C. Bezrukov, Sergey M. TI High-Affinity Interaction with VDAC Links Cytosolic Proteins to Mitochondrial Regulation in Health, Cancer, and Neurodegeneration SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Rostovtseva, Tatiana K.; Bezrukov, Sergey M.] NICHD, Program Phys Biol, NIH, Bethesda, MD USA. [Gurnev, Philip A.] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA. [Hoogerheide, David P.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Maldonado, Eduardo N.] Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Lemasters, John J.] Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Bethesda, SC USA. [Protchenko, Olga] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 952-Symp BP 189A EP 189A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100162 ER PT J AU Calco, GN Hoyne, JD Kuo, BC Aronova, MA Zhang, GF Shomorony, A Pfeifer, CR Cai, T Xu, HY Notkins, AL Leapman, RD AF Calco, Gina N. Hoyne, Jake D. Kuo, Bryan C. Aronova, Maria A. Zhang, Guofeng Shomorony, Andre Pfeifer, Charlotte R. Cai, Tao Xu, Huanyu Notkins, Abner L. Leapman, Richard D. TI 3D Ultrastructural Investigation of Entire Pancreatic Islets of Langerhans by Serial Block Face Scanning Electron Microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Calco, Gina N.; Hoyne, Jake D.; Kuo, Bryan C.; Aronova, Maria A.; Zhang, Guofeng; Shomorony, Andre; Pfeifer, Charlotte R.; Leapman, Richard D.] NIBIB, NIH, Bethesda, MD USA. [Cai, Tao; Xu, Huanyu; Notkins, Abner L.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 957-Plat BP 190A EP 190A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100167 ER PT J AU Matthies, D Bartesaghi, A Merk, A Banerjee, S Subramaniam, S AF Matthies, Doreen Bartesaghi, Alberto Merk, Alan Banerjee, Soojay Subramaniam, Sriram TI Residue Specific Radiation Damage of Protein Structures using High-Resolution Cryo-Electron Microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Matthies, Doreen; Bartesaghi, Alberto; Merk, Alan; Banerjee, Soojay; Subramaniam, Sriram] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 956-Plat BP 190A EP 190A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100166 ER PT J AU Hoppe, TA Best, R AF Hoppe, Travis A. Best, Robert TI Combinational Evidence that Intrinsic Disorder Provides Broad Association Profiles SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Hoppe, Travis A.; Best, Robert] NIDDKD, NIH, Bethesda, MD USA. OI Hoppe, Travis/0000-0002-4694-3050 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 970-Plat BP 193A EP 193A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100180 ER PT J AU Li, MF Toombes, G Silberberg, SD Swartz, KJ AF Li, Mufeng Toombes, Gilman Silberberg, Shai D. Swartz, Kenton J. TI Rapid Activation of Distinct Conducting States in P2X Receptor Channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Li, Mufeng; Toombes, Gilman; Silberberg, Shai D.; Swartz, Kenton J.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 968-Plat BP 193A EP 193A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100178 ER PT J AU Tolchard, JL Hackstadt, T Blumenschein, TMA AF Tolchard, James L. Hackstadt, Ted Blumenschein, Tharin M. A. TI The Intrinsically Disordered C. Trachomatis Tarp Binds Actin with a Partially Preformed Helix SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Tolchard, James L.; Blumenschein, Tharin M. A.] Univ E Anglia, Sch Chem, Norwich NR4 7TJ, Norfolk, England. [Hackstadt, Ted] NIAID, Intracellular Parasites Lab, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 971-Plat BP 193A EP 193A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100181 ER PT J AU Zerze, GH Best, RB Mittal, J AF Zerze, Guel H. Best, Robert B. Mittal, Jeetain TI Molecular Simulations of Unfolded and Intrinsically Disordered Proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Zerze, Guel H.; Mittal, Jeetain] Lehigh Univ, Chem & Biomol Engn, Bethlehem, PA 18015 USA. [Best, Robert B.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Best, Robert/H-7588-2016 OI Best, Robert/0000-0002-7893-3543 NR 0 TC 0 Z9 0 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 974-Plat BP 194A EP 194A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100184 ER PT J AU Leone, V Grell, E Pogoryelov, D Meier, T Faraldo-Gomez, JD AF Leone, Vanessa Grell, Ernst Pogoryelov, Denys Meier, Thomas Faraldo-Gomez, Jose D. TI On the Na+/H+ Selectivity of Membrane Transporters and Enzymes: Experimental and Theoretical Studies of an ATP-Synthase Rotor Ring SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Leone, Vanessa; Faraldo-Gomez, Jose D.] NHLBI, Theoret Mol Biophys Sect, NIH, Bethesda, MD 20892 USA. [Grell, Ernst; Pogoryelov, Denys; Meier, Thomas] Max Planck Inst Biophys, Frankfurt, Germany. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 985-Plat BP 196A EP 197A PG 2 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100195 ER PT J AU Chufan, EE Kapoor, K Ambudkar, SV AF Chufan, Eduardo E. Kapoor, Khyati Ambudkar, Suresh V. TI Identification of Structural Motifs in P-Glycoprotein Responsible for the Drug-Mediated Inhibition of ATP Hydrolysis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Chufan, Eduardo E.; Kapoor, Khyati; Ambudkar, Suresh V.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 989-Plat BP 197A EP 197A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100199 ER PT J AU Roche, J Louis, JM Bax, A AF Roche, Julien Louis, John M. Bax, Ad TI Solution Conformation of the Unbound HIV-1 Protease Derived from Residual Dipolar Couplings Measured at Ambient and High-Pressure Conditions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Roche, Julien; Louis, John M.; Bax, Ad] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1017-Plat BP 203A EP 203A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100227 ER PT J AU Naufer, MN Furano, AV Williams, MC AF Naufer, M. Nabuan Furano, Anthony V. Williams, Mark C. TI Oligomerization Kinetics of ORF1p is Correlated with Line1 Retrotransposition SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Naufer, M. Nabuan; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Furano, Anthony V.] NIDDK, Lab Mol & Cellular Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1025-Plat BP 204A EP 205A PG 2 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100235 ER PT J AU Tofoleanu, F Brooks, B AF Tofoleanu, Florentina Brooks, Bernard TI Computational Studies on the cAMP Modulation of the HCN2 Channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Tofoleanu, Florentina; Brooks, Bernard] NHLBI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1041-Plat BP 208A EP 208A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100251 ER PT J AU Beaven, AH Sodt, AJ Andersen, OS Pastor, RW Im, W AF Beaven, Andrew H. Sodt, Alexander J. Andersen, Olaf S. Pastor, Richard W. Im, Wonpil TI Ion Channel Regulation by Lipid Bilayers: Theory & Simulation of Deformed Membranes around Gramicidin A SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Beaven, Andrew H.] Univ Kansas, Dept Chem, Lawrence, KS 66045 USA. [Sodt, Alexander J.; Pastor, Richard W.] NIH, Lab Computat Biol, Rockville, MD USA. [Andersen, Olaf S.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY USA. [Im, Wonpil] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. [Im, Wonpil] Univ Kansas, Ctr Bioinformat, Lawrence, KS 66045 USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1047-Plat BP 209A EP 209A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100257 ER PT J AU Chakrabarti, M Lu, SY Jang, H Khavrutskii, L Tarasova, NI Gaponenko, V Nussinov, R AF Chakrabarti, Mayukh Lu, Shaoyong Jang, Hyunbum Khavrutskii, Lyuba Tarasova, Nadya I. Gaponenko, Vadim Nussinov, Ruth TI Elucidating the Functional Significance of the C-Terminal Hypervariable Region (HVR) in K-Ras4A SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Chakrabarti, Mayukh] Johns Hopkins Univ, Dept Biotechnol, Baltimore, MD USA. [Chakrabarti, Mayukh; Jang, Hyunbum; Khavrutskii, Lyuba; Tarasova, Nadya I.; Nussinov, Ruth] NCI, Canc & Inflammat Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Lu, Shaoyong] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China. [Jang, Hyunbum; Nussinov, Ruth] NCI, Basic Sci Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Gaponenko, Vadim] Univ Illinois, Dept Med Chem, Chicago, IL USA. [Gaponenko, Vadim] Univ Illinois, Dept Biochem, Chicago, IL 60612 USA. [Gaponenko, Vadim] Univ Illinois, Dept Mol Genet, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1055-Pos BP 210A EP 211A PG 2 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100265 ER PT J AU Busse, B Blank, P Bezrukov, L Zimmerberg, J AF Busse, Brad Blank, Paul Bezrukov, Ludmila Zimmerberg, Joshua TI Resin-Embedded Multicycle Imaging of Cells and Isolated Plasma Membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Busse, Brad; Blank, Paul; Bezrukov, Ludmila; Zimmerberg, Joshua] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1110-Pos BP 221A EP 221A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100320 ER PT J AU Schuck, P Metrick, M Zhao, HY AF Schuck, Peter Metrick, Michael Zhao, Huaying TI Sedimentation in a Time-Varying Centrifugal Field for Rapid Attainment of Sedimentation Equilibrium SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Schuck, Peter; Metrick, Michael; Zhao, Huaying] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1115-Pos BP 222A EP 222A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100325 ER PT J AU Hoppe, T Minton, AP AF Hoppe, Travis Minton, Allen P. TI An Equilibrium Model for the Combined Effect of Macromolecular Crowding and Surface Adsorption on the Formation of Linear Protein SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Hoppe, Travis; Minton, Allen P.] NIH, Bethesda, MD 20892 USA. OI Hoppe, Travis/0000-0002-4694-3050 NR 0 TC 0 Z9 0 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1117-Pos BP 223A EP 223A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100327 ER PT J AU Best, R Zheng, WW Mittal, JT AF Best, Robert Zheng, Wenwei Mittal, Jeetain TI Optimized Force Fields for Simulations of Intrinsically Disordered Proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Best, Robert; Zheng, Wenwei] NIH, Chem Phys Lab, Bethesda, MD 20892 USA. [Mittal, Jeetain] Lehigh Univ, Dept Chem Engn, Bethlehem, PA 18015 USA. NR 0 TC 0 Z9 0 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1137-Pos BP 227A EP 227A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100347 ER PT J AU Kasprzak, WK Dinman, JD Shapiro, BA AF Kasprzak, Wojciech K. Dinman, Jonathan D. Shapiro, Bruce A. TI A Ribosomal Frameshifting Structure in the CCR5 mRNA Leads to Mirna-Stimulated Nonsense-Mediated mRNA Decay SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kasprzak, Wojciech K.] Leidos Biomed Res Inc, Basic Res Program, Frederick, MD USA. [Dinman, Jonathan D.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. [Shapiro, Bruce A.] NCI, Basic Res Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1200-Pos BP 238A EP 238A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100410 ER PT J AU Kimura, T Vukoti, K Lynch, DL Hurst, DP Grossfield, A Pitman, MC Reggio, PH Yeliseev, AA Gawrisch, K AF Kimura, Tomohiro Vukoti, Krishna Lynch, Diane L. Hurst, Dow P. Grossfield, Alan Pitman, Michael C. Reggio, Patricia H. Yeliseev, Alexei A. Gawrisch, Klaus TI Global Fold of Human Cannabinoid Type 2 Receptor Probed by Solid-State NMR and Molecular Dynamics Simulations SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kimura, Tomohiro; Vukoti, Krishna; Yeliseev, Alexei A.; Gawrisch, Klaus] NIAAA, Lab Membrane Biochem Biophys, NIH, Bethesda, MD USA. [Lynch, Diane L.; Hurst, Dow P.; Reggio, Patricia H.] Univ N Carolina, Dept Chem Biochem, Greensboro, NC 27412 USA. [Grossfield, Alan] Univ Rochester, Med Ctr, Dept Biochem Biophys, Rochester, NY 14642 USA. [Pitman, Michael C.] IBM Thomas J Watson Res Ctr, Computat Biol Ctr, Yorktown Hts, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1271-Pos BP 251A EP 251A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100481 ER PT J AU Tian, Y Schwieters, C Opella, S Marassi, F AF Tian, Ye Schwieters, Charles Opella, Stanley Marassi, Francesca TI NMR-Restrained Structure Calculations of Membrane Proteins in Implicit Lipid Bilayer Membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Tian, Ye; Marassi, Francesca] Sanford Burnham Med Res Inst, La Jolla, CA 92093 USA. [Schwieters, Charles] NIH, Bethesda, MD USA. [Opella, Stanley] UCSD, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1270-Pos BP 251A EP 251A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100480 ER PT J AU Tyndall, ER Gill, RL Ramamurthi, KS Tian, F AF Tyndall, Erin R. Gill, Richard L., Jr. Ramamurthi, Kumaran S. Tian, Fang TI Membrane Insertion Depth and Curvature Sensing SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Tyndall, Erin R.; Gill, Richard L., Jr.; Tian, Fang] Penn State Univ, Biochem, Hershey, PA USA. [Ramamurthi, Kumaran S.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1279-Pos BP 253A EP 253A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100489 ER PT J AU Kobrinsky, E Tarasov, KV Tarasova, YS Maltsev, V Sollott, SJ Lakatta, EG AF Kobrinsky, Evgeny Tarasov, Kirill V. Tarasova, Yelena S. Maltsev, Victor Sollott, Steven J. Lakatta, Edward G. TI FRET Measurements of cAMP Dynamics in HL1 Cells Support the Key Role of Constitutive AC Activity in Cardiac Pacemaking SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kobrinsky, Evgeny; Tarasov, Kirill V.; Tarasova, Yelena S.; Maltsev, Victor; Sollott, Steven J.; Lakatta, Edward G.] NIA, LCS, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1377-Pos BP 274A EP 274A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100587 ER PT J AU Kilfoil, P Barski, OA Bhatnagar, A AF Kilfoil, Peter Barski, Oleg A. Bhatnagar, Aruni TI Modulation of Pancreatic Islet Electrophysiology and Insulin Release by Potassium Channel Subunit Kvbeta2 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kilfoil, Peter] Univ Louisville, Biochem, Louisville, KY 40292 USA. [Barski, Oleg A.] NIH, Bethesda, MD 20892 USA. [Bhatnagar, Aruni] Univ Louisville, Med, Louisville, KY 40292 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1396-Pos BP 278A EP 278A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100606 ER PT J AU Meyerson, JR Kumar, J Chittori, S Rao, P Pierson, J Bartesaghi, A Mayer, ML Subramaniam, S AF Meyerson, Joel R. Kumar, Janesh Chittori, Sagar Rao, Prashant Pierson, Jason Bartesaghi, Alberto Mayer, Mark L. Subramaniam, Sriram TI Structural Mechanism of Glutamate Receptor Activation and Desensitization SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Meyerson, Joel R.; Rao, Prashant; Bartesaghi, Alberto; Subramaniam, Sriram] NCI, NIH, Bethesda, MD 20892 USA. [Kumar, Janesh] Wellcome Trust Res Labs, Natl Ctr Cell Sci, Ganeshkhind, India. [Chittori, Sagar; Mayer, Mark L.] NICHHD, NIH, Bethesda, MD 20892 USA. [Pierson, Jason] FEI Co, Hillsboro, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1441-Pos BP 287A EP 287A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100651 ER PT J AU Harnish, E AF Harnish, Emily TI Controlled Activation of Heteromeric P2X Receptors by ATP and Magnesium SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Harnish, Emily] NINDS, Membrane Physiol & Biophys Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1447-Pos BP 288A EP 288A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100657 ER PT J AU Toombes, GES Li, MF Silberberg, SD Swartz, KJ AF Toombes, Gilman E. S. Li, Mufeng Silberberg, Shai D. Swartz, Kenton J. TI Ion Accumulation and Depletion in Patch Clamp Experiments SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Toombes, Gilman E. S.; Li, Mufeng; Silberberg, Shai D.; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1449-Pos BP 289A EP 289A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100659 ER PT J AU Sulbaran, G Mun, JY Lee, KH Alamo, L Pinto, A Sato, O Ikebe, M Liu, X Korn, ED Padron, R Craig, R AF Sulbaran, Guidenn Mun, Ji Young Lee, Kyoung Hwan Alamo, Lorenzo Pinto, Antonio Sato, Osamu Ikebe, Mitsuo Liu, Xiong Korn, Edward D. Padron, Raul Craig, Roger TI The Inhibited, Interacting-Heads Motif Characterizes Myosin II from the Earliest Animals with Muscles SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Sulbaran, Guidenn; Alamo, Lorenzo; Pinto, Antonio; Padron, Raul] IVIC, Caracas, Venezuela. [Mun, Ji Young] Eulji Univ, Gyeonggi Do, South Korea. [Lee, Kyoung Hwan; Craig, Roger] UMass Med Sch, Worcester, MA USA. [Sato, Osamu; Ikebe, Mitsuo] Univ Texas Hlth Sci Ctr Northeast, Tyler, TX USA. [Liu, Xiong; Korn, Edward D.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1508-Pos BP 301A EP 301A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100718 ER PT J AU Arroyo, JO Andrecka, J de Wit, G Takagi, Y Sellers, JR Kukura, P AF Arroyo, Jaime Ortega Andrecka, Joanna de Wit, Gabrielle Takagi, Yasuharu Sellers, James R. Kukura, Philipp TI Myosin Steps Symmetrically along Actin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Arroyo, Jaime Ortega; Andrecka, Joanna; de Wit, Gabrielle; Kukura, Philipp] Univ Oxford, Phys & Theoret Chem Lab, Oxford, England. [Takagi, Yasuharu; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1511-Pos BP 302A EP 302A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100721 ER PT J AU Afasizheva, A Kotobuki, Y Tillman, H Vieira, W Fung, KL Chen, E Tanner, K AF Afasizheva, Anna Kotobuki, Yorihisa Tillman, Heather Vieira, Wilfred Fung, King Leung Chen, Emily Tanner, Kandice TI Malignant Melanoma Cells Assemble a Tumor Biofilm that Promotes Survival and Resistance in Response to External Stresses SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Afasizheva, Anna; Kotobuki, Yorihisa; Tillman, Heather; Vieira, Wilfred; Fung, King Leung; Tanner, Kandice] NCI, Bethesda, MD 20892 USA. [Chen, Emily] SUNY Stony Brook, Sch Med, Prote Ctr, Stony Brook, NY 11794 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1526-Pos BP 305A EP 305A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100736 ER PT J AU Szatmary, AC AF Szatmary, Alex C. TI The Effect of P-Selectin Dimers on Neutrophil Rolling on Endothelium SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Szatmary, Alex C.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1536-Pos BP 307A EP 307A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100746 ER PT J AU Lioi, SB Weston, MR Mindell, JA AF Lioi, Sara B. Weston, Mary R. Mindell, Joseph A. TI Sirna Knockdown of ClC-7 Produces a Lysosomal pH Increase SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Lioi, Sara B.; Weston, Mary R.; Mindell, Joseph A.] NINDS, NIH, Bethesda, MD 20892 USA. [Weston, Mary R.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1561-Pos BP 312A EP 312A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100771 ER PT J AU Shcheynikov, N Son, A Yamazaki, O Muallem, S Ohana, E Hong, JH Kurtz, I Shin, DM AF Shcheynikov, Nikolay Son, Aran Yamazaki, Osamu Muallem, Shmuel Ohana, Ehud Hong, Jeong Hee Kurtz, Ira Shin, Dong Min TI Intracellular C1 as a Signaling Molecule that Potently Regulates Na and HCO3 Transporters SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Shcheynikov, Nikolay; Son, Aran; Yamazaki, Osamu; Muallem, Shmuel] NIH, Mol Physiol & Therapeut Branch, Bethesda, MD 20892 USA. [Ohana, Ehud] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. [Hong, Jeong Hee] Gachon Univ, Songnam, South Korea. [Kurtz, Ira] Univ Calif Los Angeles, Los Angeles, CA USA. [Shin, Dong Min] Yonsei Univ, Seoul 120749, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1560-Pos BP 312A EP 312A PG 1 WC Biophysics SC Biophysics GA CT5KR UT WOS:000362849100770 ER PT J AU Anderluh, A Klotzsch, E Kumar, V Newman, AH Sitte, HH Schuetz, GJ AF Anderluh, Andreas Klotzsch, Enrico Kumar, Vivek Newman, Amy H. Sitte, Harald H. Schuetz, Gerhard J. TI Single Molecule Analysis Reveals Coexistence of Stable Serotonin Transporter Monomers and Oligomers in the Live Cell Plasma Membrane SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Anderluh, Andreas; Klotzsch, Enrico; Schuetz, Gerhard J.] Vienna Univ Technol, Inst Appl Phys, A-1040 Vienna, Austria. [Kumar, Vivek; Newman, Amy H.] NIDA, Med Chem Sect, Baltimore, MD USA. [Sitte, Harald H.] Med Univ Vienna, Ctr Biomol Med & Pharmacol, Vienna, Austria. RI Klotzsch, Enrico/J-8831-2012 OI Klotzsch, Enrico/0000-0002-7577-9042 NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1617-Pos BP 322A EP 322A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400031 ER PT J AU Mayer, M AF Mayer, Mark TI Conformational Changes Underlying Glutamate Receptor Gating SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Mayer, Mark] NIH, LCMN, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1688-Symp BP 335A EP 335A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400103 ER PT J AU Kimura, A Pekkurnaz, G Kimura, T Germeyan, SC Zimmerberg-Helms, J Loewke, J Blank, PS Reese, TS Gawrisch, K Bezrukov, L Zimmerberg, J AF Kimura, Atsuko Pekkurnaz, Gulcin Kimura, Tomohiro Germeyan, Sierra C. Zimmerberg-Helms, Jessica Loewke, James Blank, Paul S. Reese, Thomas S. Gawrisch, Klaus Bezrukov, Ludmila Zimmerberg, Joshua TI Phase Behavior of Synaptosomal Membranes: The Effect of Lipid Composition and Temperature SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Kimura, Atsuko; Kimura, Tomohiro; Germeyan, Sierra C.; Zimmerberg-Helms, Jessica; Loewke, James; Blank, Paul S.; Reese, Thomas S.; Gawrisch, Klaus; Bezrukov, Ludmila; Zimmerberg, Joshua] NIH, Bethesda, MD 20892 USA. [Pekkurnaz, Gulcin] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1722-Plat BP 342A EP 342A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400137 ER PT J AU Koefinger, J Ragusa, MJ Hummer, G Hurley, JH AF Koefinger, Juergen Ragusa, Michael J. Hummer, Gerhard Hurley, James H. TI Autophagy: Solution Structure of the Atg17-Atg29-Atg31-Atg1-Atg13 Complex SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Koefinger, Juergen; Hummer, Gerhard] Max Planck Inst Biophys, Dept Theoret Biophys, Frankfurt, Germany. [Ragusa, Michael J.; Hurley, James H.] Univ Calif Berkeley, Dept Mol & Cell Biol, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA. [Ragusa, Michael J.] NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1727-Plat BP 343A EP 343A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400142 ER PT J AU Chung, HS Piana-Agostinetti, S Shaw, DE Eaton, WA AF Chung, Hoi Sung Piana-Agostinetti, Stefano Shaw, David E. Eaton, William A. TI Structural Origin of Landscape Roughness in Protein Folding from Single-Molecule FRET and All-Atom Molecular Dynamics Simulations SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Chung, Hoi Sung; Eaton, William A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Piana-Agostinetti, Stefano; Shaw, David E.] DE Shaw Res, New York, NY USA. NR 0 TC 1 Z9 1 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1744-Plat BP 347A EP 347A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400159 ER PT J AU Evilevitch, A Sae-Ueng, U Li, D Zuo, XB Huffman, J Homa, F Rau, D AF Evilevitch, Alex Sae-Ueng, Udom Li, Dong Zuo, Xiaobing Huffman, Jamie Homa, Fred Rau, Donald TI Solid-To-Fluid DNA Transition Inside HSV-1 Capsid Close to the Temperature of Infection SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Evilevitch, Alex; Sae-Ueng, Udom; Li, Dong] Carnegie Mellon Univ, Phys, Pittsburgh, PA 15213 USA. [Zuo, Xiaobing] Argonne Natl Lab, Argonne, IL 60439 USA. [Huffman, Jamie; Homa, Fred] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Rau, Donald] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1764-Plat BP 351A EP 351A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400179 ER PT J AU Chlanda, P Mekhedov, E Waters, H Blank, PS Zimmerberg, J AF Chlanda, Petr Mekhedov, Elena Waters, Hang Blank, Paul S. Zimmerberg, Josh TI Role of Hemagglutinin Palmitoylation in Assembly and Fusion of Influenza Virus-Like Particles SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Chlanda, Petr; Mekhedov, Elena; Waters, Hang; Blank, Paul S.; Zimmerberg, Josh] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1775-Plat BP 353A EP 354A PG 2 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400190 ER PT J AU Trexler, AJ Taraska, J AF Trexler, Adam J. Taraska, Justin TI Temporally Resolving Protein and Lipid Colocalization at Exocytic Sites in INS-1 Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Trexler, Adam J.; Taraska, Justin] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1778-Plat BP 354A EP 354A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400193 ER PT J AU Sochacki, KA Shtengel, G Hess, HF Taraska, JW AF Sochacki, Kem A. Shtengel, Gleb Hess, Harald F. Taraska, Justin W. TI Correlative iPALM and Platinum Replica Electron Tomography Pinpoints Endocytic Proteins on the Mammalian Cell Cortex in 3D SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Sochacki, Kem A.; Taraska, Justin W.] NHLBI, Bethesda, MD 20892 USA. [Shtengel, Gleb; Hess, Harald F.] Janelia Farm Howard Hughes Med Inst, Ashburn, VA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1810-Plat BP 360A EP 360A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400225 ER PT J AU Munro, JB Gorman, J Ma, XC Zhou, Z Arthos, J Burton, D Koff, W Courter, J Smith, A Kwong, P Blanchard, S Mothes, W AF Munro, James B. Gorman, Jason Ma, Xiaochu Zhou, Zhou Arthos, James Burton, Dennis Koff, Wayne Courter, Joel Smith, Amos Kwong, Peter Blanchard, Scott Mothes, Walther TI Conformational Dynamics of Single HIV-1 Envelope Proteins on the Surface of Native Virions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Munro, James B.] Tufts Univ, Mol Biol & Microbiol, Boston, MA 02111 USA. [Gorman, Jason; Kwong, Peter] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Ma, Xiaochu; Mothes, Walther] Yale Univ, Microbial Pathogenesis, New Haven, CT USA. [Zhou, Zhou; Blanchard, Scott] Weill Cornell Med Coll, Physiol & Biophys, New York, NY USA. [Arthos, James] NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. [Burton, Dennis] Scripps Res Inst, Immunol & Microbial Sci, La Jolla, CT USA. [Koff, Wayne] Int AIDS Vaccine Initiat, New York, NY USA. [Courter, Joel; Smith, Amos] Univ Penn, Chem, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1820-Plat BP 362A EP 363A PG 2 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400235 ER PT J AU Dittmore, A Silver, J Marmer, B Goldberg, GI Neuman, KC AF Dittmore, Andrew Silver, Jonathan Marmer, Barry Goldberg, Gregory I. Neuman, Keir C. TI Super-Resolution Mapping of the Dynamics of Periodic Structural Defects in Collagen Fibrils SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Dittmore, Andrew; Silver, Jonathan; Neuman, Keir C.] NIH, Lab Mol Biophys, Bethesda, MD 20892 USA. [Marmer, Barry; Goldberg, Gregory I.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. [Marmer, Barry; Goldberg, Gregory I.] Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USA. RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1827-Plat BP 364A EP 364A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400242 ER PT J AU Gahl, RF He, Y Yu, SQ Tjandra, N AF Gahl, Robert F. He, Yi Yu, Shiqin Tjandra, Nico TI Live-Cell Measurements of the Conformational Rearrangements in Bax at the Initiation of Apoptosis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Gahl, Robert F.; He, Yi; Yu, Shiqin; Tjandra, Nico] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1876-Pos BP 374A EP 374A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400291 ER PT J AU de Messieres, M Ng, A Duarte, CJ Remaley, AT Lee, JC AF de Messieres, Michel Ng, Abby Duarte, Cornelio J. Remaley, Alan T. Lee, Jennifer C. TI Monitoring Apolipoprotein Binding to Single Lipoproteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [de Messieres, Michel; Ng, Abby; Duarte, Cornelio J.; Remaley, Alan T.; Lee, Jennifer C.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1929-Pos BP 384A EP 384A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400344 ER PT J AU Miller, M AF Miller, Maria TI C/EBPb: Case Study for the Importance of Intrinsic Disorder for Protein Function SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Miller, Maria] NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1948-Pos BP 388A EP 388A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400363 ER PT J AU Marzahn, MR Lee, J Marada, S Nourse, A Zhao, HY Schuck, P Ogden, SK Mittag, T AF Marzahn, Melissa R. Lee, Jihun Marada, Suresh Nourse, Amanda Zhao, Huaying Schuck, Peter Ogden, Stacey K. Mittag, Tanja TI The Role of Higher-Order SPOP Oligomers for Localization to Cellular "Bodies'' and Ubiquitination Activity SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Marzahn, Melissa R.; Lee, Jihun; Nourse, Amanda; Mittag, Tanja] St Jude Childrens Res Hosp, Struct Biol, Memphis, TN 38105 USA. [Marada, Suresh; Ogden, Stacey K.] St Jude Childrens Res Hosp, Cell & Mol Biol, Memphis, TN 38105 USA. [Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1957-Pos BP 390A EP 390A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400372 ER PT J AU Howell, SC Meng, W Andresen, K Mendonca, A Yuan, CL Zhou, BR Bai, YW Curtis, JE Qiu, XY AF Howell, Steven C. Meng, Wei Andresen, Kurt Mendonca, Agnes Yuan, Chongli Zhou, Bing-Rui Bai, Yawen Curtis, Joseph E. Qiu, Xiangyun TI Ensemble Models of Nucleosome Arrays Constrained by Small-Angle X-Ray Scattering SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Howell, Steven C.; Meng, Wei; Qiu, Xiangyun] George Washington Univ, Phys, Washington, DC USA. [Andresen, Kurt] Gettysburg Coll, Phys, Gettysburg, PA 17325 USA. [Mendonca, Agnes; Yuan, Chongli] Purdue Univ, Chem Engn, W Lafayette, IN 47907 USA. [Zhou, Bing-Rui; Bai, Yawen] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA. [Curtis, Joseph E.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 1980-Pos BP 394A EP 394A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400395 ER PT J AU Wen, P AF Wen, Peter TI Actin and Dynamin Control the Fate of the Fusion Intermediate - the gamma-Profile SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Wen, Peter] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2039-Pos BP 405A EP 405A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400454 ER PT J AU Babikow, E Papp, F Lomash, S Smith, J Swartz, K AF Babikow, Erika Papp, Ferenc Lomash, Suvendu Smith, Jamie Swartz, Kenton TI Investigating the Function of a Novel Voltage-Sensing Protein SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Babikow, Erika; Papp, Ferenc; Lomash, Suvendu; Smith, Jamie; Swartz, Kenton] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2140-Pos BP 425A EP 426A PG 2 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400555 ER PT J AU Vadrevu, S Ren, JH Zhang, M Glynn, EJ Sherman, A Satin, LS AF Vadrevu, Suryakiran Ren, Jinhua Zhang, Min Glynn, Eric J. Sherman, Arthur Satin, Leslie S. TI Kir2.1 Channels Compensate for the Loss of KATP Channels in SUR1 Null Islets SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Vadrevu, Suryakiran; Ren, Jinhua; Glynn, Eric J.; Satin, Leslie S.] Univ Michigan, Pharmacol, Ann Arbor, MI 48109 USA. [Zhang, Min] Virginia Commonwealth Univ, Pharmacol & Toxicol, Richmond, VA USA. [Sherman, Arthur] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2185-Pos BP 435A EP 435A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400600 ER PT J AU Roll-Mecak, A Szyk, A Deaconescu, A Spector, J Valenstein, M Grigorieff, N AF Roll-Mecak, Antonina Szyk, Agnieszka Deaconescu, Alexandra Spector, Jeffrey Valenstein, Max Grigorieff, Niko TI Molecular Basis for Age-Dependent Microtubule Acetylation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Roll-Mecak, Antonina; Szyk, Agnieszka; Spector, Jeffrey; Valenstein, Max] NIH, Bethesda, MD 20892 USA. [Deaconescu, Alexandra] Brown Univ, Providence, RI 02912 USA. [Grigorieff, Niko] HHMI Janelia Farm, Ashburn, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2254-Pos BP 448A EP 448A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400669 ER PT J AU Spector, J Szyk, A Deaconescu, AM Valenstein, M Goodman, B Kormendi, V Grigorieff, N Roll-Mecak, A AF Spector, Jeffrey Szyk, Agnieszka Deaconescu, Alexandra M. Valenstein, Max Goodman, Benjamin Kormendi, Vasilisa Grigorieff, Nikolaus Roll-Mecak, Antonina TI Molecular Basis for Age-Dependent Acetylation by Tubulin Acetyltransferase SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Spector, Jeffrey; Szyk, Agnieszka; Valenstein, Max; Goodman, Benjamin; Kormendi, Vasilisa; Roll-Mecak, Antonina] NINDS, NIH, Bethesda, MD 20892 USA. [Deaconescu, Alexandra M.; Grigorieff, Nikolaus] HHMI Janelia Farm, Ashburn, VA USA. [Deaconescu, Alexandra M.] Brown Univ, Providence, RI 02912 USA. [Roll-Mecak, Antonina] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2256-Pos BP 449A EP 449A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400671 ER PT J AU Vemu, A AF Vemu, Annapurna TI Generation of Differentially Modified Microtubules using in vitro Enzymatic Approaches SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Vemu, Annapurna] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2260-Pos BP 450A EP 450A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400675 ER PT J AU Chen, J Liu, J AF Chen, Jing Liu, Jian TI Spatio-Temporal Model for Silencing of the Mitotic Spindle Assembly Checkpoint SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Chen, Jing; Liu, Jian] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2270-Pos BP 451A EP 451A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400685 ER PT J AU Vemu, A Garnham, CP Lee, DY Roll-Mecak, A AF Vemu, Annapurna Garnham, Christopher P. Lee, Duck-Yeon Roll-Mecak, Antonina TI Generation of Differentially Modified Microtubules using in vitro Enzymatic Approaches SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Vemu, Annapurna; Garnham, Christopher P.; Roll-Mecak, Antonina] NINDS, Cell Biol & Biophys Unit, Bethesda, MD 20892 USA. [Lee, Duck-Yeon] NHLBI, Biochem Core, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2266-Pos BP 451A EP 451A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400681 ER PT J AU Devine, A Tanner, K AF Devine, Alexus Tanner, Kandice TI The Interplay between Cell Motility and Proteolysis in the Establishment of Brain Metastasis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Devine, Alexus; Tanner, Kandice] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2296-Pos BP 456A EP 456A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400711 ER PT J AU Salazar, DT Garcia-Olivares, J Amara, SG AF Salazar, Delany Torres Garcia-Olivares, Jennie Amara, Susan G. TI A Mutation in TM7 of Excitatory Amino Acid Transporters Disrupts the Substrate-Dependent Gating of the Intrinsic Anion Conductance and Drives the Channel into a Constitutively Open State SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Salazar, Delany Torres; Garcia-Olivares, Jennie; Amara, Susan G.] NIH, Lab Celullar & Mol Neurobiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2316-Pos BP 460A EP 460A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400731 ER PT J AU Mulligan, C Fitzgerald, GA Mindell, JA AF Mulligan, Christopher Fitzgerald, Gabriel A. Mindell, Joseph A. TI Assessing Protomer Independence of the Dimeric C4-Dicarboxylate Transporter, Vcindy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Mulligan, Christopher; Fitzgerald, Gabriel A.; Mindell, Joseph A.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2319-Pos BP 461A EP 461A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400734 ER PT J AU Ohana, E Shcheynikov, N Muallem, S AF Ohana, Ehud Shcheynikov, Nikolay Muallem, Shmuel TI Physiological Implications of Transepithelial Carboxylic Acid Absorption and Regulation by Slc26a6 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Ohana, Ehud] Ben Gurion Univ Negev, Clin Biochem & Pharmacol, IL-84105 Beer Sheva, Israel. [Shcheynikov, Nikolay; Muallem, Shmuel] NIDCR, MPTB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2318-Pos BP 461A EP 461A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400733 ER PT J AU Vergara-Jaque, A Yaffe, D Shuster, Y Listov, D Meena, S Singh, SK Schuldiner, S Forrest, LR AF Vergara-Jaque, Ariela Yaffe, Dana Shuster, Yonatan Listov, Dina Meena, Sitaram Singh, Satinder K. Schuldiner, Shimon Forrest, Lucy R. TI Carboxyl Residues Required for Transport by a Vesicular Monoamine Transporter Homolog from Brevibacillus Brevis (BbMAT) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Vergara-Jaque, Ariela; Forrest, Lucy R.] NINDS, Computat Struct Biol Sect, NIH, Rockville, MD USA. [Yaffe, Dana; Shuster, Yonatan; Listov, Dina; Schuldiner, Shimon] Hebrew Univ Jerusalem, Dept Biol Chem, Jerusalem, Israel. [Meena, Sitaram; Singh, Satinder K.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2326-Pos BP 462A EP 462A PG 1 WC Biophysics SC Biophysics GA CT5KU UT WOS:000362849400741 ER PT J AU Blehm, BH Jiang, N Kotobuki, Y Tanner, K AF Blehm, Benjamin H. Jiang, Nancy Kotobuki, Yorihisa Tanner, Kandice TI Deconstructing the Role of the Microenvironment on Drug Efficacy in a Brain-Mimetic Platform for Cutaneous Metastatic Melanoma SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Blehm, Benjamin H.; Jiang, Nancy; Kotobuki, Yorihisa; Tanner, Kandice] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2456-Pos BP 486A EP 486A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600064 ER PT J AU Hinshaw, JE Sundborger, AC Fang, SM Heymann, JA Ray, P Chappie, JS AF Hinshaw, Jenny E. Sundborger, Anna C. Fang, Shunming Heymann, Jurgen A. Ray, Pampa Chappie, Joshua S. TI Dynamin at the Brink of Fission SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Hinshaw, Jenny E.; Sundborger, Anna C.; Fang, Shunming; Heymann, Jurgen A.; Ray, Pampa] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. [Chappie, Joshua S.] Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2469-Symp BP 489A EP 489A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600077 ER PT J AU Bachir, AI Zareno, J Kubow, KE Han, S Moissoglu, K Danuser, G Gratton, E Plow, E Horwitz, AR AF Bachir, Alexia I. Zareno, Jessica Kubow, Kristopher E. Han, Sangyoon Moissoglu, Kostadinos Danuser, Gaudenz Gratton, Enrico Plow, Edward Horwitz, Alan R. TI Correlative Traction Force Microscopy and Fluorescence Fluctuation Analysis of Molecular Aggregation and Complex Formation in Cell Adhesions in Distinct Microenvironments SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Bachir, Alexia I.; Zareno, Jessica; Horwitz, Alan R.] Univ Virginia, Cell Biol, Charlottesville, VA USA. [Kubow, Kristopher E.] James Madison Univ, Biol, Harrisonburg, VA 22807 USA. [Han, Sangyoon; Danuser, Gaudenz] UT Southwestern, Cell Biol, Dallas, TX USA. [Moissoglu, Kostadinos] NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Gratton, Enrico] UC Irvine, Biomed Engn, Irvine, CA USA. [Plow, Edward] Cleveland Clin, Mol Cardiol, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2492-Plat BP 493A EP 494A PG 2 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600100 ER PT J AU Hategan, AP Steiner, J Bianchet, MA Karnaukhova, E Dimitriadis, EK Nath, A AF Hategan, Alina Popescu Steiner, Joseph Bianchet, Mario A. Karnaukhova, Elena Dimitriadis, Emilios K. Nath, Avindra TI HIV-Tat Protein-Amyloid Beta Complex: From Molecular Interaction to Increased Neurotoxicity SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Hategan, Alina Popescu; Steiner, Joseph; Nath, Avindra] NINDS, NIH, Bethesda, MD 20892 USA. [Bianchet, Mario A.] Johns Hopkins Sch Med, Baltimore, MD USA. [Karnaukhova, Elena] US FDA, CBER, Silver Spring, MD USA. [Dimitriadis, Emilios K.] NIBIB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2505-Plat BP 496A EP 496A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600113 ER PT J AU Perrin, BS Sodt, AJ Cotten, ML Pastor, RW AF Perrin, Bradley S. Sodt, Alexander J. Cotten, Myriam L. Pastor, Richard W. TI The Curvature Induction of Surface-Bound Antimicrobial Peptides Piscidin 1 and Piscidin 3 Varies with Lipid Chain Length SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Perrin, Bradley S.; Sodt, Alexander J.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Rockville, MD USA. [Cotten, Myriam L.] Hamilton Coll, Dept Chem, Clinton, NY 13323 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2513-Plat BP 498A EP 498A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600121 ER PT J AU Borgia, A Kemplen, KR Borgia, MB Best, RB Soranno, A Nettels, D Wunderlich, B Clarke, J Schuler, B AF Borgia, Alessandro Kemplen, Katherine R. Borgia, Madeleine B. Best, Robert B. Soranno, Andrea Nettels, Daniel Wunderlich, Bengt Clarke, Jane Schuler, Benjamin TI Surprising Abundance of Misfolding during Refolding of Multidomain Proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Borgia, Alessandro; Borgia, Madeleine B.; Soranno, Andrea; Nettels, Daniel; Wunderlich, Bengt; Clarke, Jane; Schuler, Benjamin] Univ Zurich, Biochem, Zurich, Switzerland. [Kemplen, Katherine R.] Univ Cambridge, Chem, Cambridge, England. [Best, Robert B.] NIKKD, NIH, Bethesda, MD USA. RI Best, Robert/H-7588-2016; Schuler, Benjamin/E-7342-2011 OI Best, Robert/0000-0002-7893-3543; Schuler, Benjamin/0000-0002-5970-4251 NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2532-Plat BP 501A EP 501A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600140 ER PT J AU Liu, XP Pan, BF Asai, Y Kurima, K Griffith, AJ Holt, JR AF Liu, Xiao-Ping Pan, Bifeng Asai, Yukako Kurima, Kyoto Griffith, Andrew J. Holt, Jeffrey R. TI Probing the Structure and Function of TMC1 in Sensory Hair Cells using Mutagenesis and Cysteine Modification SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Liu, Xiao-Ping; Pan, Bifeng; Asai, Yukako; Holt, Jeffrey R.] Boston Childrens Hosp, Boston, MA USA. [Kurima, Kyoto; Griffith, Andrew J.] NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2554-Plat BP 506A EP 506A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600162 ER PT J AU Mills, M Seol, Y Neuman, K AF Mills, Maria Seol, Yeonee Neuman, Keir TI Functional Implications of the RecQ Helicase - Topoisomerase III - SSB Complex: Insights from Single Molecule Measurements SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Mills, Maria; Seol, Yeonee; Neuman, Keir] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 NR 0 TC 0 Z9 0 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2559-Plat BP 507A EP 507A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600167 ER PT J AU Thompson, PM Lee, HT Kim, L Ramachandran, S Tandon, A Mendez-Giraldez, R Alushin, GM Dokholyan, NV Campbell, SL AF Thompson, Peter M. Lee, Hyunna T. Kim, Laura Ramachandran, Srinivas Tandon, Arpit Mendez-Giraldez, Raul Alushin, Gregory M. Dokholyan, Nikolay V. Campbell, Sharon L. TI New Models for Regulation of Vinculin by Actin and Phospholipids SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Thompson, Peter M.; Lee, Hyunna T.; Ramachandran, Srinivas; Tandon, Arpit; Mendez-Giraldez, Raul; Dokholyan, Nikolay V.; Campbell, Sharon L.] Univ N Carolina, Biochem & Biophys, Chapel Hill, NC USA. [Kim, Laura; Alushin, Gregory M.] NHLBI, Lab Macromol Interact, Bethesda, MD 20892 USA. [Ramachandran, Srinivas] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. OI Thompson, Peter/0000-0001-7562-6049 NR 0 TC 0 Z9 0 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2566-Plat BP 508A EP 509A PG 2 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600174 ER PT J AU Borgnia, MJ Banerjee, S Rao, P Bartesaghi, A Merk, A Pierson, J Subramaniam, S Milne, J AF Borgnia, Mario J. Banerjee, Soojay Rao, Prashant Bartesaghi, Alberto Merk, Allan Pierson, Jason Subramaniam, Sriram Milne, Jacqueline TI Localization of Small Ligands in a Metabolic Protein Complex using Cryo-Electron Microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Borgnia, Mario J.; Banerjee, Soojay; Rao, Prashant; Bartesaghi, Alberto; Merk, Allan; Subramaniam, Sriram; Milne, Jacqueline] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Pierson, Jason] FEI Co, Hillsboro, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2599-Pos BP 514A EP 514A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600207 ER PT J AU Zheng, WW de Sancho, D Hoppe, T Best, RB AF Zheng, Wenwei de Sancho, David Hoppe, Travis Best, Robert B. TI Dependence of Internal Friction on Native Topology SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Zheng, Wenwei; Hoppe, Travis; Best, Robert B.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [de Sancho, David] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. RI De Sancho, David/C-4995-2009; Best, Robert/H-7588-2016 OI De Sancho, David/0000-0002-8985-2685; Best, Robert/0000-0002-7893-3543 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2620-Pos BP 518A EP 518A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600228 ER PT J AU Frank, GA Narayan, K Bess, JW Del Prete, GQ Wu, XW Moran, A Hartnell, L Earl, LA Lifson, JD Subramaniam, S AF Frank, Gabriel A. Narayan, Kedar Bess, Julian W., Jr. Del Prete, Gregory Q. Wu, Xiongwu Moran, Amy Hartnell, Lisa Earl, Lesley A. Lifson, Jeffrey D. Subramaniam, Sriram TI Paradigm Shift in the Mechanism of HIV-1 Core Biogenesis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Frank, Gabriel A.; Narayan, Kedar; Hartnell, Lisa; Earl, Lesley A.; Subramaniam, Sriram] NCI, LCB, NIH, Bethessda, MD USA. [Bess, Julian W., Jr.; Del Prete, Gregory Q.; Lifson, Jeffrey D.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick, MD USA. [Wu, Xiongwu] NHLBI, Lab Computat Biol, Bethessda, MD USA. [Moran, Amy] NIH, NLM, Bethessda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2666-Pos BP 527A EP 527A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600274 ER PT J AU Lu, SY Huang, WK Wang, Q Shen, QC Li, S Nussinov, R Zhang, J AF Lu, Shaoyong Huang, Wenkang Wang, Qi Shen, Qiancheng Li, Shuai Nussinov, Ruth Zhang, Jian TI The Structural Basis of ATP as an Allosteric Modulator SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Lu, Shaoyong; Huang, Wenkang; Wang, Qi; Shen, Qiancheng; Li, Shuai; Zhang, Jian] Shanghai Jiao Tong Univ, Pathophysiol, Sch Med, Shanghai 200030, Peoples R China. [Nussinov, Ruth] Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick Natl Lab, NCI, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2671-Pos BP 528A EP 528A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600279 ER PT J AU Coulon, A Lenstra, TL Chow, CC Larson, DR AF Coulon, Antoine Lenstra, Tineke L. Chow, Carson C. Larson, Daniel R. TI Live-Cell Single-Molecule Imaging of Sense and Antisense Transcription of a Yeast Gene SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Coulon, Antoine; Chow, Carson C.] NIDDK, NIH, Bethesda, MD 20892 USA. [Lenstra, Tineke L.; Larson, Daniel R.] NCI, NIH, Bethesda, MD 20892 USA. RI Coulon, Antoine/A-9006-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2712-Pos BP 536A EP 536A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600320 ER PT J AU Chereji, RV Clark, DD AF Chereji, Razvan V. Clark, David D. TI Biophysical Models of Nucleosome Positioning SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Chereji, Razvan V.; Clark, David D.] NICHD, NIH, Bethesda, MD USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2720-Pos BP 537A EP 537A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600328 ER PT J AU Norouzi, D Zhurkin, VB AF Norouzi, Davood Zhurkin, Victor B. TI Topological Polymorphism of Two-Start Nucleosome Fibers: A Stereochemical Analysis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Norouzi, Davood; Zhurkin, Victor B.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2724-Pos BP 538A EP 538A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600332 ER PT J AU Zhao, HQ Dalal, Y Papoian, GA AF Zhao, Haiqing Dalal, Yamini Papoian, Garegin A. TI The Binding Landscapes of the H3/H4 and CENP-A/H4 Dimers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Zhao, Haiqing; Papoian, Garegin A.] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA. [Dalal, Yamini] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2723-Pos BP 538A EP 538A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600331 ER PT J AU Hu, LH Liu, J AF Hu, Longhua Liu, Jian TI Mechanochemistry of Persistent Plasmid Movement SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Hu, Longhua; Liu, Jian] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2730-Pos BP 539A EP 539A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600338 ER PT J AU Katebi, AR Norouzi, D Cui, F Zhurkin, V AF Katebi, Ataur R. Norouzi, Davood Cui, Feng Zhurkin, Victor TI Nucleosome Repeat Length Relates to the Gene Expression Level in Yeast SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Katebi, Ataur R.; Norouzi, Davood; Zhurkin, Victor] NCI, NIH, Bethesda, MD 20892 USA. [Cui, Feng] Rochester Inst Technol, Coll Sci, Rochester, NY 14623 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2731-Pos BP 539A EP 539A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600339 ER PT J AU Vlijm, R Dalal, Y Dekker, C AF Vlijm, Rifka Dalal, Yamini Dekker, Cees TI Torque Mediated Kinetics of CENP-A Nucleosomes Reveals Resilience to Tension SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Vlijm, Rifka; Dekker, Cees] Delft Univ Technol, Kavli Inst Nanosci, Dept Bionanosci, Delft, Netherlands. [Dalal, Yamini] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2728-Pos BP 539A EP 539A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600336 ER PT J AU Haldar, S Blank, PS Zimmerberg, J Rau, DC AF Haldar, Sourav Blank, Paul S. Zimmerberg, Joshua Rau, Donald C. TI Effect of Phosphatidylinositol-Bisphosphate (PIP2) Lipids on Membrane Structure and Forces SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Haldar, Sourav; Blank, Paul S.; Zimmerberg, Joshua; Rau, Donald C.] NICHHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2754-Pos BP 543A EP 544A PG 2 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600362 ER PT J AU Humphrey, G Backlund, PS Blank, PS Zimmerberg, J AF Humphrey, Glen Backlund, Peter S. Blank, Paul S. Zimmerberg, Joshua TI Ion-Mobility Mass Spectrometry Assay for Incorporation of Phytanic Acid into Muscle Phospholipids SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Humphrey, Glen; Blank, Paul S.; Zimmerberg, Joshua] NICHD, PPB, NIH, Bethesda, MD USA. [Backlund, Peter S.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2752-Pos BP 543A EP 543A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600360 ER PT J AU Hoogerheide, DP Hermida, OT Rostovtseva, TK Bezrukov, SM Nanda, H AF Hoogerheide, David P. Hermida, Oscar Teijido Rostovtseva, Tatiana K. Bezrukov, Sergey M. Nanda, Hirsh TI Effect of Lipid Composition on the Affinity and Binding of Dimeric Tubulin to Membranes Studied using Surface Plasmon Resonance, Neutron Reflectivity, Electrophysiology, and AC Electrical Methods SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Hoogerheide, David P.; Nanda, Hirsh] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Hoogerheide, David P.; Hermida, Oscar Teijido; Rostovtseva, Tatiana K.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Nanda, Hirsh] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2823-Pos BP 557A EP 557A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600431 ER PT J AU Barros, M Dick, RA Datta, SAK Vogt, VM Rein, A Losche, M Nanda, H AF Barros, Marilia Dick, Robert A. Datta, Siddhartha A. K. Vogt, Volker M. Rein, Alan Loesche, Mathias Nanda, Hirsh TI Structural Comparison of Membrane-Bound Retroviral Gag Proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Barros, Marilia; Loesche, Mathias; Nanda, Hirsh] Carnegie Mellon Univ, Phys, Pittsburgh, PA 15213 USA. [Dick, Robert A.; Vogt, Volker M.] Cornell Univ, Mol Biol & Genet, Ithaca, NY USA. [Datta, Siddhartha A. K.; Rein, Alan] NCI, HIV Drug Resitance Program, NIH, Frederick, MD USA. [Loesche, Mathias] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Nanda, Hirsh] NIST, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2835-Pos BP 559A EP 559A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600443 ER PT J AU Plummer, AM Bernstein, HD Fleming, KG AF Plummer, Ashlee M. Bernstein, Harris D. Fleming, Karen G. TI Evolutionary Avoidance of Transmembrane Embedded Arginines is due to Slowed Folding Kinetics SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Plummer, Ashlee M.; Fleming, Karen G.] Johns Hopkins Univ, Biophys, Baltimore, MD USA. [Bernstein, Harris D.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2832-Pos BP 559A EP 559A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600440 ER PT J AU de Souza, L Lockwich, T Ong, HL Cheng, KT Ambudkar, IS AF de Souza, Lorena Lockwich, Timothy Ong, Hwei Ling Cheng, Kwong Tai Ambudkar, Indu S. TI Remodeling of the Cytoskeleton and Regulation of Store-Operated Calcium Entry SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [de Souza, Lorena; Lockwich, Timothy; Ong, Hwei Ling; Cheng, Kwong Tai; Ambudkar, Indu S.] NIDCR, MPTB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2866-Pos BP 566A EP 566A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600474 ER PT J AU Subedi, K Ong, HL Ambudkar, I AF Subedi, Krishna Ong, Hwei Ling Ambudkar, Indu TI STIM1-STIM2 Interactions Modulate Store-Operated Calcium Entry SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Subedi, Krishna; Ong, Hwei Ling; Ambudkar, Indu] NIH, MPTB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2865-Pos BP 566A EP 566A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600473 ER PT J AU Maltsev, AV Stern, MD AF Maltsev, Alexander V. Stern, Michael D. TI Filling the Gap Between Calcium Sparks and Waves: Automatic Detection and Classification of Local Calcium Releases in Cardiac Pacemaker Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Maltsev, Alexander V.; Stern, Michael D.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2879-Pos BP 568A EP 569A PG 2 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600487 ER PT J AU Bychkov, R Sirenko, S Yaniv, Y Maltsev, VA Lakatta, EG AF Bychkov, Rostislav Sirenko, Syevda Yaniv, Yael Maltsev, Victor A. Lakatta, Edward G. TI Glycoside-Induced Collapse of the Sodium and Calcium Gradients Leads to a Biphasic Effect on Cardiac Cell Pacemaker Function SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Bychkov, Rostislav] Univ Cent Caribe, Pharmacol, Bayamon, PR USA. [Bychkov, Rostislav; Sirenko, Syevda; Maltsev, Victor A.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Yaniv, Yael] Technion IIT, Biomed Engn Fac, Haifa, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2882-Pos BP 569A EP 569A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600490 ER PT J AU Maltsev, VA Monfredi, O Shroff, H York, AG Maltsev, AV Lakatta, EG Stern, MD AF Maltsev, Victor A. Monfredi, Oliver Shroff, Hari York, Andrew G. Maltsev, Anna V. Lakatta, Edward G. Stern, Michael D. TI A New Simplified 3D Model of Cardiac Pacemaker Cell Based on Super-resolution Structured Illumination Microscopy (SIM) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Maltsev, Victor A.; Monfredi, Oliver; Lakatta, Edward G.; Stern, Michael D.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Monfredi, Oliver] Univ Manchester, Inst Cardiovasc Sci, Manchester, Lancs, England. [Shroff, Hari; York, Andrew G.] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD USA. [Maltsev, Anna V.] Univ Bristol, Dept Math, Bristol BS8 1TW, Avon, England. RI Shroff, Hari/E-7247-2016 OI Shroff, Hari/0000-0003-3613-8215 NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2881-Pos BP 569A EP 569A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600489 ER PT J AU Monfredi, OJ Lakatta, EG Maltsev, VA AF Monfredi, Oliver J. Lakatta, Edward G. Maltsev, Victor A. TI Autonomic Stimulation Modulates Action Potential Firing Rate in Cardiac Pacemaker Cells via Synchronization of Local Calcium Pumping and Release SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Monfredi, Oliver J.] Univ Manchester, Inst Cardiovasc Sci, Manchester, Lancs, England. [Lakatta, Edward G.; Maltsev, Victor A.] NIA, Cardiovasc Sci Lab, IRP, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2883-Pos BP 569A EP 570A PG 2 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600491 ER PT J AU Vinogradova, TM Tarasov, KV Lakatta, EG AF Vinogradova, Tatiana M. Tarasov, Kirill V. Lakatta, Edward G. TI Basal Activity of Epidermal Growth Factor Receptor (EGFR) and Phospholipase C (PLC) are Required to Sustain Spontaneous Beating of Cardiac Pacemaker Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Vinogradova, Tatiana M.; Tarasov, Kirill V.; Lakatta, Edward G.] NIA, BRC, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2880-Pos BP 569A EP 569A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600488 ER PT J AU Jha, A Ahuja, M Muallem, S AF Jha, Archana Ahuja, Malini Muallem, Shmuel TI Similarities and Differences in Gating of the Two-Pore Channels TPC1 and TPC2 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Jha, Archana; Ahuja, Malini; Muallem, Shmuel] Nidcr, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 2885-Pos BP 570A EP 570A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600493 ER PT J AU Petrashevskaya, N Tae, HJ Marshall, S Krawczyk, M Talan, M AF Petrashevskaya, Natalia Tae, Hyun-Jin Marshall, Shanon Krawczyk, Melissa Talan, Mark TI Cardiac Remodeling in the Mouse Model of Marfan Syndrome Develops Independently from Aortic and Valvular Abnormalities SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Petrashevskaya, Natalia; Tae, Hyun-Jin; Marshall, Shanon; Krawczyk, Melissa; Talan, Mark] NIA, LCS, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3001-Pos BP 595A EP 595A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600609 ER PT J AU Hammer, JA Wu, XS AF Hammer, John A. Wu, Xufeng S. TI Visualizing Melanosome Transfer in vivo SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Hammer, John A.; Wu, Xufeng S.] NIH, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3016-Pos BP 598A EP 598A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600624 ER PT J AU Vecchiarelli, A Hwang, LC Li, M Seol, Y Mizuuchi, M Neuman, K Mizuuchi, K AF Vecchiarelli, Anthony Hwang, Ling Chin Li, Min Seol, Yeonee Mizuuchi, Michiyo Neuman, Keir Mizuuchi, Kiyoshi TI Spatial Regulators for Bacterial Cell Division Self-Organize into an Oscillator on a Flat Bilayer SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Vecchiarelli, Anthony; Hwang, Ling Chin; Li, Min; Seol, Yeonee; Mizuuchi, Michiyo; Neuman, Keir; Mizuuchi, Kiyoshi] NIDDK, NIH, Bethesda, MD 20892 USA. RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 NR 0 TC 0 Z9 0 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3021-Pos BP 599A EP 599A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600629 ER PT J AU Gurnev, PA Rostovtseva, TK Hoogerheide, DP Protchenko, O Yap, TL Lee, JC Bezrukov, SM AF Gurnev, Philip A. Rostovtseva, Tatiana K. Hoogerheide, David P. Protchenko, Olga Yap, Thai Leong Lee, Jennifer C. Bezrukov, Sergey M. TI Alpha-Synuclein Blocks VDAC Suggesting Mechanism of Mitochondrial Regulation and Toxicity in Parkinson Disease SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Gurnev, Philip A.] UMass Amherst, Dept Phys, Amherst, MA USA. [Gurnev, Philip A.; Rostovtseva, Tatiana K.; Hoogerheide, David P.; Bezrukov, Sergey M.] NICHD, Sect Mol Transport, PPB, NIH, Bethesda, MD USA. [Hoogerheide, David P.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Protchenko, Olga] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Yap, Thai Leong; Lee, Jennifer C.] NHLBI, Lab Prot Conformat & Dynam, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3064-Pos BP 607A EP 607A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600672 ER PT J AU Hermida, OT Kuszak, AJ Buchanan, SK Bezrukov, SM Rostovtseva, TK AF Hermida, Oscar Teijido Kuszak, Adam J. Buchanan, Susan K. Bezrukov, Sergey M. Rostovtseva, Tatiana K. TI VDAC3 Forms Typical Voltage-Gated, Anion-Selective, and Tubulin-Sensitive Channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Hermida, Oscar Teijido; Bezrukov, Sergey M.; Rostovtseva, Tatiana K.] NICHD, Program Phys Biol, NIH, Bethesda, MD USA. [Kuszak, Adam J.] NIDDK, NIH, Bethesda, MD 20892 USA. [Buchanan, Susan K.] NICHD, Program Phys Biol, NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3062-Pos BP 607A EP 607A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600670 ER PT J AU Sousa, T Coutinho, A Banerjee, S Castro, R Youle, R Rodrigues, C Prieto, M Fernandes, F AF Sousa, Tania Coutinho, Ana Banerjee, Soojay Castro, Rui Youle, Richard Rodrigues, Cecilia Prieto, Manuel Fernandes, Fabio TI Binding of Pro-Apoptotic Protein Bax to Cytoprotective UDCA and TUDCA SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Sousa, Tania; Prieto, Manuel; Fernandes, Fabio] Univ Lisbon, Ctr Quim Fis Mol, P-1699 Lisbon, Portugal. [Sousa, Tania; Prieto, Manuel; Fernandes, Fabio] Univ Lisbon, Inst Super Tecn, Inst Nanosci & Nanotechnol, P-1699 Lisbon, Portugal. [Coutinho, Ana] Univ Lisbon, Ins, Fac Ciencias, Dept Quim & Bioquim, P-1699 Lisbon, Portugal. [Banerjee, Soojay; Youle, Richard] NINDS, NIH, Bethesda, MD 20892 USA. [Castro, Rui; Rodrigues, Cecilia] Univ Lisbon, Fac Farm, P-1699 Lisbon, Portugal. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3070-Pos BP 608A EP 609A PG 2 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600678 ER PT J AU Peixoto, PM Teijido, OH Dejean, LM Pavlov, E Antonsson, B Kinnally, KW AF Peixoto, Pablo M. Teijido, Oscar H. Dejean, Laurent M. Pavlov, Evgeny Antonsson, Bruno Kinnally, Kathleen W. TI MAC Inhibitors Neutralize the Pro-Apoptotic Effects of Tbid SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Peixoto, Pablo M.] CUNY, Baruch Coll, Nat Sci, New York, NY 10021 USA. [Teijido, Oscar H.] NICHHD, Baltimore, MD USA. [Dejean, Laurent M.] Calif State Univ Fresno, Chem, Fresno, CA 93740 USA. [Pavlov, Evgeny; Kinnally, Kathleen W.] NYU, Coll Dent, New York, NY USA. [Antonsson, Bruno] Merck Serono, Geneva Res Ctr, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3071-Pos BP 609A EP 609A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600679 ER PT J AU Lizunov, VA Blank, PS Stenkula, KG Skarulis, M Cushman, S Zimmerberg, J AF Lizunov, Vladimir A. Blank, Paul S. Stenkula, Karin G. Skarulis, Monica Cushman, Samuel Zimmerberg, Joshua TI Human Adipose Cell Response to Insulin: Analysis of Cellular Switch-Like Transformations and Distributions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Lizunov, Vladimir A.; Blank, Paul S.; Zimmerberg, Joshua] NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD USA. [Stenkula, Karin G.] Lund Univ, Expt Med Sci, Lund, Sweden. [Skarulis, Monica] NIDDK, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA. [Cushman, Samuel] NIDDK, Expt Diabet Metab & Nutr Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3093-Pos BP 613A EP 613A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600701 ER PT J AU Peercy, BE Bertram, R Sherman, A AF Peercy, Bradford E. Bertram, Richard Sherman, Arthur TI Glucose-Induced Cyclic-AMP Oscillations: Modeling Incretin Impact on Pancreatic Beta Cell Secretion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Peercy, Bradford E.] UMBC, Math & Stat, Baltimore, MD USA. [Bertram, Richard] Florida State Univ, Tallahassee, FL 32306 USA. [Sherman, Arthur] NIH, Lab Biol Modeling, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3098-Pos BP 614A EP 614A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600706 ER PT J AU Bai, RL Basser, PJ AF Bai, Ruiliang Basser, Peter J. TI Multi-Component Water Dynamics and Exchange in Brain Cortical Tissue Probed via In-Vitro D-T2 2D Correlation NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Bai, Ruiliang; Basser, Peter J.] NIH, Bethesda, MD 20892 USA. [Bai, Ruiliang] Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3101-Pos BP 615A EP 615A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600709 ER PT J AU Hayakawa, EH Tokumasu, F Usukura, J Matsuoka, H Tsuboi, T Wellems, TE AF Hayakawa, Eri H. Tokumasu, Fuyuki Usukura, Jiro Matsuoka, Hiroyuki Tsuboi, Takafumi Wellems, Thomas E. TI The Steric Fine Structure of Maurer's Cleft in "Unroofed" Plasmodium Falciparum-Infected Erythrocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Hayakawa, Eri H.; Matsuoka, Hiroyuki] Jichi Med Univ, Dept Infect & Immun, Lab Med Zool & Parasitol, Shimotsuke, Japan. [Tokumasu, Fuyuki] Univ Tokyo, Grad Sch Med, Dept Lipid, Tokyo, Japan. [Usukura, Jiro] Nagoya Univ, EcoTopia Sci Inst, Div Integrated Project, Nagoya, Aichi 4648601, Japan. [Tsuboi, Takafumi] Ehime Univ, Cell Free Sci & Technol Res Ctr, Malaria Res Unit, Matsuyama, Ehime, Japan. [Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3119-Pos BP 618A EP 618A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600727 ER PT J AU Hoyne, JD Calco, GN Kuo, BC Aronova, MA Sousa, AA He, QP Zhang, GF Pokrovskaya, ID MacDonald, L Prince, AA Storrie, B Leapman, RD AF Hoyne, Jake D. Calco, Gina N. Kuo, Bryan C. Aronova, Maria A. Sousa, Alioscka A. He, Qianping Zhang, Guofeng Pokrovskaya, Irina D. MacDonald, Laura Prince, Andrew A. Storrie, Brian Leapman, Richard D. TI Scanning Transmission Electron Tomography of Blood Platelets in Thick Sections SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Hoyne, Jake D.; Calco, Gina N.; Kuo, Bryan C.; Aronova, Maria A.; Sousa, Alioscka A.; He, Qianping; Zhang, Guofeng; Leapman, Richard D.] NIBIB, NIH, Bethesda, MD USA. [Pokrovskaya, Irina D.; MacDonald, Laura; Prince, Andrew A.; Storrie, Brian] Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3116-Pos BP 618A EP 618A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600724 ER PT J AU He, QP Aronova, MA Joy, DC Zhang, GF Leapman, RD AF He, Qianping Aronova, Maria A. Joy, David C. Zhang, Guofeng Leapman, Richard D. TI Sub-Surface Serial Block Face Scanning Electron Microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [He, Qianping; Aronova, Maria A.; Zhang, Guofeng; Leapman, Richard D.] NIBIB, NIH, Bethesda, MD USA. [Joy, David C.] Univ Tennessee, Dept Mat Sci & Engn, Knoxville, TN 37996 USA. [Joy, David C.] Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Oak Ridge, TN USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3125-Pos BP 619A EP 620A PG 2 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600733 ER PT J AU Ma, J Zhao, HY Schuck, P AF Ma, Jia Zhao, Huaying Schuck, Peter TI Sedimentation Velocity Analysis of the EGFPs in E. coli Whole Cell Extracts using Fluorescence Detection System SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Ma, Jia; Zhao, Huaying; Schuck, Peter] NIBIB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3146-Pos BP 624A EP 624A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600754 ER PT J AU Zhao, HY Ma, J Ingaramo, M Andrade, E MacDonald, J Ramsay, G Piszczek, G Patterson, G Schuck, P AF Zhao, Huaying Ma, Jia Ingaramo, Maria Andrade, Eric MacDonald, Jeff Ramsay, Glen Piszczek, Grzegorz Patterson, George Schuck, Peter TI Accounting for Photophysical Processes and Specific Signal Intensity Change in Fluorescence-Detected Sedimentation Velocity Analytical Ultracentrifugation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Zhao, Huaying; Ma, Jia; Ingaramo, Maria; Andrade, Eric; Patterson, George; Schuck, Peter] NIBIB, NIH, Bethesda, MD USA. [MacDonald, Jeff; Ramsay, Glen] Aviv Biomed Inc, Lakewood, NJ USA. [Piszczek, Grzegorz] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3145-Pos BP 624A EP 624A PG 1 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600753 ER PT J AU Hamilla, SM Mili, S Aranda-Espinoza, H AF Hamilla, Susan M. Mili, Stavroula Aranda-Espinoza, Helim TI Mechanobiology of mRNA Localization in Breast Cancer Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 59th Annual Meeting of the Biophysical-Society CY FEB 07-11, 2015 CL Baltimore, MD SP Biophys Soc C1 [Hamilla, Susan M.; Aranda-Espinoza, Helim] Univ Maryland, College Pk, MD 20742 USA. [Mili, Stavroula] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN 27 PY 2015 VL 108 IS 2 SU 1 MA 3168-Pos BP 628A EP 629A PG 2 WC Biophysics SC Biophysics GA CT5KV UT WOS:000362849600776 ER PT J AU Cooper, LL Rong, J Benjamin, EJ Larson, MG Levy, D Vita, JA Hamburg, NM Vasan, RS Mitchell, GF AF Cooper, Leroy L. Rong, Jian Benjamin, Emelia J. Larson, Martin G. Levy, Daniel Vita, Joseph A. Hamburg, Naomi M. Vasan, Ramachandran S. Mitchell, Gary F. TI Components of Hemodynamic Load and Cardiovascular Events The Framingham Heart Study SO CIRCULATION LA English DT Article DE cardiovascular diseases; hemodynamics; pulsatile flow ID ISOLATED SYSTOLIC HYPERTENSION; PULSE-WAVE VELOCITY; LEFT-VENTRICULAR FUNCTION; HIGH BLOOD-PRESSURE; ARTERIAL STIFFNESS; AORTIC STIFFNESS; MYOCARDIAL-INFARCTION; AUGMENTATION INDEX; RISK; DISEASE AB Background-Elevated blood pressure is the leading modifiable risk factor for cardiovascular disease (CVD) and premature death. The blood pressure waveform consists of discrete hemodynamic components, derived from measured central pressure and flow, which may contribute separately to risk for an adverse outcome. However, pressure-flow measures have not been studied in a large, community-based sample. Methods and Results-We used proportional hazards models to examine the association of incident CVD with forward pressure wave amplitude, mean arterial pressure, and global reflection coefficient derived from wave separation analysis and echocardiography in 2492 participants (mean age 66 +/- 9 years, 56% women) in the Framingham Heart Study. During follow-up (0.04-6.8 years), 149 participants (6%) had a CVD event. In multivariable models adjusting for age, sex, antihypertensive therapy, body mass index, heart rate, total and high-density lipoprotein cholesterol concentrations, smoking, and the presence of diabetes mellitus, forward pressure wave amplitude (hazard ratio, 1.40; 95% confidence interval, 1.16-1.67; P=0.0003) was associated with incident CVD, whereas mean arterial pressure (hazard ratio, 1.10; 95% confidence interval, 0.94-1.29; P=0.25) and global wave reflection (hazard ratio, 0.93; 95% confidence interval, 0.78-1.12; P=0.58) were not. After adding systolic blood pressure and carotid-femoral pulse wave velocity to the model, forward pressure wave amplitude persisted as a correlate of events (hazard ratio, 1.33; 95% confidence interval, 1.05-1.68; P=0.02). Conclusions-Higher forward pressure wave amplitude (a measure of proximal aortic geometry and stiffness) was associated with increased risk for incident CVD, whereas mean arterial pressure and relative wave reflection (correlates of resistance vessel structure and function) were not associated with increased risk for incident CVD. C1 [Cooper, Leroy L.; Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA 02062 USA. [Cooper, Leroy L.] Brown Univ, Rhode Isl Hosp, W Alpert Med Sch, Cardiovasc Res Ctr, Providence, RI 02903 USA. [Rong, Jian; Benjamin, Emelia J.; Larson, Martin G.; Levy, Daniel] Boston Univ, Framingham, MA USA. [Rong, Jian; Benjamin, Emelia J.; Larson, Martin G.; Levy, Daniel] NHLBIs Framingham Study, Framingham, MA USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Larson, Martin G.; Vasan, Ramachandran S.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Vita, Joseph A.; Hamburg, Naomi M.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Vita, Joseph A.; Hamburg, Naomi M.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, 1 Edgewater Dr,Suite 201A, Norwood, MA 02062 USA. EM GaryFMitchell@mindspring.com OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; NIH [5T32HL094300-05]; [HL076784]; [AG028321]; [HL070100]; [HL060040]; [HL080124]; [HL071039]; [HL077447]; [HL107385]; [2-K24-HL04334] FX This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and by HL076784, AG028321, HL070100, HL060040, HL080124, HL071039, HL077447, HL107385, and 2-K24-HL04334. Dr Cooper is also supported by NIH grant 5T32HL094300-05. NR 50 TC 17 Z9 17 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 27 PY 2015 VL 131 IS 4 BP 354 EP U1157 DI 10.1161/CIRCULATIONAHA.114.011357 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AZ7YR UT WOS:000348432100012 PM 25416177 ER PT J AU Mozaffarian, D Benjamin, EJ Go, AS Arnett, DK Blaha, MJ Cushman, M de Ferranti, S Despres, JP Fullerton, HJ Howard, VJ Huffman, MD Judd, SE Kissela, BM Lackland, DT Lichtman, JH Lisabeth, LD Liu, SM Mackey, RH Matchar, DB McGuire, DK Mohler, ER Moy, CS Muntner, P Mussolino, ME Nasir, K Neumar, RW Nichol, G Palaniappan, L Pandey, DK Reeves, MJ Rodriguez, CJ Sorlie, PD Stein, J Towfighi, A Turan, TN Virani, SS Willey, JZ Woo, D Yeh, RW Turner, MB AF Mozaffarian, Dariush Benjamin, Emelia J. Go, Alan S. Arnett, Donna K. Blaha, Michael J. Cushman, Mary de Ferranti, Sarah Despres, Jean-Pierre Fullerton, Heather J. Howard, Virginia J. Huffman, Mark D. Judd, Suzanne E. Kissela, Brett M. Lackland, Daniel T. Lichtman, Judith H. Lisabeth, Lynda D. Liu, Simin Mackey, Rachel H. Matchar, David B. McGuire, Darren K. Mohler, Emile R., III Moy, Claudia S. Muntner, Paul Mussolino, Michael E. Nasir, Khurram Neumar, Robert W. Nichol, Graham Palaniappan, Latha Pandey, Dilip K. Reeves, Mathew J. Rodriguez, Carlos J. Sorlie, Paul D. Stein, Joel Towfighi, Amytis Turan, Tanya N. Virani, Salim S. Willey, Joshua Z. Woo, Daniel Yeh, Robert W. Turner, Melanie B. CA Amer Heart Assoc Stat Comm Stroke Stat Subcomm TI Executive Summary: Heart Disease and Stroke Statistics-2015 Update A Report From the American Heart Association SO CIRCULATION LA English DT Article C1 [Mozaffarian, Dariush] Tufts Univ, Medford, MA 02155 USA. [Arnett, Donna K.; Howard, Virginia J.; Judd, Suzanne E.; Muntner, Paul] Univ Alabama Birmingham, Birmingham, AL USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Blaha, Michael J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Cushman, Mary] Univ Vermont, Burlington, VT 05405 USA. [de Ferranti, Sarah] Childrens Hosp Boston, Boston, MA USA. [Despres, Jean-Pierre] Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada. [Fullerton, Heather J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Go, Alan S.] Kaiser Permanente, Oakland, CA USA. [Huffman, Mark D.] Northwestern Univ, Evanston, IL 60208 USA. [Kissela, Brett M.] Univ Cincinnati, Acad Hlth Ctr, Cincinnati, OH 45221 USA. [Lackland, Daniel T.; Turan, Tanya N.] Med Univ S Carolina, Charleston, SC USA. [Lichtman, Judith H.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Lisabeth, Lynda D.; Neumar, Robert W.] Univ Michigan, Ann Arbor, MI 48109 USA. [Liu, Simin] Brown Univ, Providence, RI 02912 USA. [Mackey, Rachel H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Matchar, David B.] Duke Univ, Durham, NC 27706 USA. [McGuire, Darren K.] Univ Texas Southwestern Med Ctr, Houston, TX USA. [Mohler, Emile R., III] Univ Penn, Philadelphia, PA 19104 USA. [Moy, Claudia S.; Mussolino, Michael E.] NIH, Washington, DC USA. [Nasir, Khurram] Baptist Hlth Med Grp, New York, NY USA. [Nichol, Graham] Univ Washington, Seattle, WA 98195 USA. [Palaniappan, Latha] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Pandey, Dilip K.] Univ Illinois, Chicago, IL USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Rodriguez, Carlos J.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Sorlie, Paul D.] NHLBI, Washington, DC USA. [Stein, Joel; Willey, Joshua Z.] Columbia Univ, New York, NY 10027 USA. [Towfighi, Amytis] Univ So Calif, Los Angeles, CA 90089 USA. [Turner, Melanie B.] Amer Heart Assoc, Bethesda, MD USA. [Virani, Salim S.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Innovat, Methodist DeBakey Heart & Vasc Ctr,Michael E DeBa, Houston, TX 77030 USA. [Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mozaffarian, D (reprint author), Tufts Univ, Medford, MA 02155 USA. OI Mackey, Rachel/0000-0001-6088-2664; Turan, Tanya/0000-0001-5399-8845; Huffman, Mark/0000-0001-7412-2519; Benjamin, Emelia/0000-0003-4076-2336; Virani, Salim/0000-0001-9541-6954; Kissela, Brett/0000-0002-9773-4013 FU NIH/NHLBI; Canadian Institutes of Health Research (CIHR); European Foundation for the Study of Diabetes (EFSD); Fondation de l'IUCPQ; Canadian Partnership Against Cancer (CPAC); Heart & Stroke Foundation of Canada (HSFC); Fonds de la recherche en sante du Quebec; Heart and Stroke Foundation of Canada (HSFC); Diabete Quebec; Ministere de la Sante et des Services sociaux du Quebec; Ministere des Finances et de l'Economie du Quebec; Conseil franco-quebecois de cooperation universitaire (CFQCU); Astra-Zeneca; NHLBI; National Institute of Diabetes, Digestive and Kidney Diseases; Sanofi; World Heart Federation; JR Alberts Foundation; Eisenberg Foundation; Stanford University; GlaxoSmithKline; Takeda; Orexigen; Janssen; Eli Lilly; Bristol Myers Squibb; AstraZeneca; Boehringer Ingelheim; Merck; Novo Nordisk; Lexicon; Amgen Inc.; Nexstim; Tyromotion; Myomo; Department of Veterans Affairs; American Heart Association; American Diabetes Association; NIH FX Emelia J. Benjamin Boston University School of Medicine NIH/NHLBI dagger None None None None AHA, Circulation Associate Editor dagger None; Jean-Pierre Despres Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Quebec Canadian Institutes of Health Research (CIHR)dagger; European Foundation for the Study of Diabetes (EFSD)dagger; Fondation de l'IUCPQ dagger; Fondation de l'IUCPQ dagger; Canadian Partnership Against Cancer (CPAC) and Heart & Stroke Foundation of Canada (HSFC)dagger; Canadian Institutes of Health Research (CIHR)dagger; Canadian Institutes of Health Research (CIHR)dagger; Canadian Institutes of Health Research (CIHR)dagger; Fonds de la recherche en sante du Quebec dagger; Canadian Institutes of Health Research (CIHR)dagger; Canadian Institutes of Health Research (CIHR)dagger; Heart and Stroke Foundation of Canada (HSFC)dagger; Canadian Institutes of Health Research (CIHR)dagger; Canadian Institutes of Health Research (CIHR)dagger; Diabete Quebec*; Ministere de la Sante et des Services sociaux du Quebec dagger; Ministere des Finances et de l'Economie du Quebec dagger; Conseil franco-quebecois de cooperation universitaire (CFQCU)dagger; Heart and Stroke Foundation of Canada (HSFC)dagger; Heart and Stroke Foundation of Canada (HSFC)dagger; Heart and Stroke Foundation of Canada (HSFC)dagger None Pfizer Canada dagger; Merck dagger None None Abbott Laboratories dagger; Torrent Pharmaceuticals dagger None; Alan S. Go Kaiser Permanente Astra-Zeneca dagger; NHLBI dagger; National Institute of Diabetes, Digestive and Kidney Diseases dagger; Sanofi dagger None None None None None None; Mark D. Huffman Northwestern University World Heart Federation dagger; JR Alberts Foundation dagger; Eisenberg Foundation dagger None None None None None None; Simin Liu Brown University Stanford University dagger None None None None None None; Darren K. McGuire University of Texas-Southwestern Med Ctr GlaxoSmithKline*; Takeda*; Orexigen dagger; Janssen dagger; Eli Lilly*; Bristol Myers Squibb dagger; AstraZeneca dagger; Boehringer Ingelheim dagger; Merck dagger; Novo Nordisk dagger; Lexicon dagger None None Takeda dagger None Novo Nordisk dagger; Boehringer Ingelheim dagger; Merck*; Regeneron* None; Paul Muntner University of Alabama at Birmingham Amgen Inc. (research grant to study cardiovascular disease prevention, diagnosis and treatment)dagger None None None None None None; Joel Stein Columbia University Nexstim*; Tyromotion*; Myomo* None None None None Myomo* None; Salim S. Virani Michael E. DeBakey VA Medical Center Health Services Research and Development Center for Innovations, Baylor College of Medicine, Michael E. DeBakey VAMC, Methodist DeBakey Heart and Vascular Center Department of Veterans Affairs dagger; American Heart Association dagger; American Diabetes Association dagger None None None None None None; Joshua Z. Willey Columbia University NIH dagger None None None None None None NR 0 TC 80 Z9 84 U1 5 U2 73 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 27 PY 2015 VL 131 IS 4 BP 434 EP 441 DI 10.1161/CIR.0000000000000157 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AZ7YR UT WOS:000348432100023 ER PT J AU Mozaffarian, D Benjamin, EJ Go, AS Arnett, DK Blaha, MJ Cushman, M de Ferranti, S Despres, JP Fullerton, HJ Howard, VJ Huffman, MD Judd, SE Kissela, BM Lackland, DT Lichtman, JH Lisabeth, LD Liu, SM Mackey, RH Matchar, DB McGuire, DK Mohler, ER Moy, CS Muntner, P Mussolino, ME Nasir, K Neumar, RW Nichol, G Palaniappan, L Pandey, DK Reeves, MJ Rodriguez, CJ Sorlie, PD Stein, J Towfighi, A Turan, TN Virani, SS Willey, JZ Woo, D Yeh, RW Turner, MB AF Mozaffarian, Dariush Benjamin, Emelia J. Go, Alan S. Arnett, Donna K. Blaha, Michael J. Cushman, Mary de Ferranti, Sarah Despres, Jean-Pierre Fullerton, Heather J. Howard, Virginia J. Huffman, Mark D. Judd, Suzanne E. Kissela, Brett M. Lackland, Daniel T. Lichtman, Judith H. Lisabeth, Lynda D. Liu, Simin Mackey, Rachel H. Matchar, David B. McGuire, Darren K. Mohler, Emile R., III Moy, Claudia S. Muntner, Paul Mussolino, Michael E. Nasir, Khurram Neumar, Robert W. Nichol, Graham Palaniappan, Latha Pandey, Dilip K. Reeves, Mathew J. Rodriguez, Carlos J. Sorlie, Paul D. Stein, Joel Towfighi, Amytis Turan, Tanya N. Virani, Salim S. Willey, Joshua Z. Woo, Daniel Yeh, Robert W. Turner, Melanie B. CA Amer Heart Assoc Stat Comm Stroke Stat Subcomm TI Heart Disease and Stroke Statistics-2015 Update A Report From the American Heart Association SO CIRCULATION LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; CHRONIC KIDNEY-DISEASE; BODY-MASS INDEX; NUTRITION-EXAMINATION-SURVEY; ACUTE MYOCARDIAL-INFARCTION; SUDDEN CARDIAC DEATH; CARDIOVASCULAR RISK-FACTORS; TYPE-2 DIABETES-MELLITUS; TRANSIENT ISCHEMIC ATTACK; ALL-CAUSE MORTALITY C1 [Mozaffarian, Dariush] Tufts Univ, Medford, MA 02155 USA. [Arnett, Donna K.; Howard, Virginia J.; Judd, Suzanne E.; Muntner, Paul] Univ Alabama Birmingham, Birmingham, AL USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Blaha, Michael J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Cushman, Mary] Univ Vermont, Burlington, VT 05405 USA. [de Ferranti, Sarah] Childrens Hosp Boston, Boston, MA USA. [Despres, Jean-Pierre] Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada. [Fullerton, Heather J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Go, Alan S.] Kaiser Permanente, Oakland, CA USA. [Huffman, Mark D.] Northwestern Univ, Evanston, IL 60208 USA. [Kissela, Brett M.] Univ Cincinnati, Acad Hlth Ctr, Cincinnati, OH 45221 USA. [Lackland, Daniel T.; Turan, Tanya N.] Med Univ S Carolina, Charleston, SC USA. [Lichtman, Judith H.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Lisabeth, Lynda D.; Neumar, Robert W.] Univ Michigan, Ann Arbor, MI 48109 USA. [Liu, Simin] Brown Univ, Providence, RI 02912 USA. [Mackey, Rachel H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Matchar, David B.] Duke Univ, Durham, NC 27706 USA. [McGuire, Darren K.] Univ Texas Southwestern Med Ctr, Houston, TX USA. [Mohler, Emile R., III] Univ Penn, Philadelphia, PA 19104 USA. [Mussolino, Michael E.] NIH, Bethesda, MD USA. [Nasir, Khurram] Baptist Hlth Med Grp, Houston, TX USA. [Nichol, Graham] Univ Washington, Seattle, WA 98195 USA. [Palaniappan, Latha] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Pandey, Dilip K.] Univ Illinois, Chicago, IL USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Rodriguez, Carlos J.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Sorlie, Paul D.] NHLBI, Bethesda, MD USA. [Stein, Joel; Willey, Joshua Z.] Columbia Univ, New York, NY 10027 USA. [Towfighi, Amytis] Univ So Calif, Los Angeles, CA 90089 USA. [Turner, Melanie B.] Amer Heart Assoc, Houston, TX USA. [Virani, Salim S.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Innovat, Methodist DeBakey Heart & Vasc Ctr,Michael E DeBa, Houston, TX 77030 USA. [Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mozaffarian, D (reprint author), Tufts Univ, Medford, MA 02155 USA. OI Mackey, Rachel/0000-0001-6088-2664; Turan, Tanya/0000-0001-5399-8845; Huffman, Mark/0000-0001-7412-2519; Benjamin, Emelia/0000-0003-4076-2336; Virani, Salim/0000-0001-9541-6954; Kissela, Brett/0000-0002-9773-4013 FU NCATS NIH HHS [UL1 TR000077, UL1 TR001425]; NHLBI NIH HHS [R01 HL104199]; NINDS NIH HHS [K23 NS073104] NR 1605 TC 1928 Z9 1977 U1 79 U2 326 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 27 PY 2015 VL 131 IS 4 BP E29 EP E322 DI 10.1161/CIR.0000000000000152 PG 294 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AZ7YR UT WOS:000348432100002 PM 25520374 ER PT J AU Ann, J Yoon, S Baek, J Kim, DH Lewin, NE Hill, CS Blumberg, PM Lee, J AF Ann, Jihyae Yoon, Suyoung Baek, Jisoo Kim, Da Hye Lewin, Nancy E. Hill, Colin S. Blumberg, Peter M. Lee, Jeewoo TI Design and synthesis of protein kinase C epsilon selective diacylglycerol lactones (DAG-lactones) SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Protein kinase C; Diacylglycerol lactone; PKC-epsilon ID CONFORMATIONALLY CONSTRAINED ANALOGS; PKC-EPSILON; BINDING-SITE; RESPONSES; ISOZYMES; NEURONS; TARGET; UNIQUE; DOMAIN AB DAG-lactones afford a synthetically accessible, high affinity platform for probing structure activity relationships at the Cl regulatory domain of protein kinase C (PKC). Given the central role of PKC isoforms in cellular signaling, along with their differential biological activities, a critical objective is the design of isoform selective ligands. Here, we report the synthesis of a series of DAG-lactones varying in their side chains, with a particular focus on linoleic acid derivatives. We evaluated their selectivity for PKC epsilon versus PKC alpha both under standard lipid conditions (100% phosphatidylserine, PS) as well as in the presence of a nuclear membrane mimetic lipid mixture (NML). We find that selectivity for PKC epsilon versus PKC alpha tended to be enhanced in the presence of the nuclear membrane mimetic lipid mixture and, for our lead compound, report a selectivity of 32-fold. (C) 2014 Elsevier Masson SAS. All rights reserved. C1 [Ann, Jihyae; Yoon, Suyoung; Baek, Jisoo; Kim, Da Hye; Lee, Jeewoo] Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Med Chem Lab, Seoul 151742, South Korea. [Lewin, Nancy E.; Hill, Colin S.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Med Chem Lab, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr FU National Research Foundation of Korea [R11-2007-107-02001-0]; Intramural Research Program of the National Institutes of Health, Center for Cancer Research, NCI [Z1A BC 005270] FX This research was supported by research grants from the National Research Foundation of Korea (R11-2007-107-02001-0) and by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, NCI (Project Z1A BC 005270). NR 24 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 EI 1768-3254 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD JAN 27 PY 2015 VL 90 BP 332 EP 341 DI 10.1016/j.ejmech.2014.11.025 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CA5MG UT WOS:000348951900027 PM 25437619 ER PT J AU Hudson, KL Collins, FS AF Hudson, Kathy L. Collins, Francis S. TI Sharing and Reporting the Results of Clinical Trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Hudson, Kathy L.; Collins, Francis S.] NIH, Bethesda, MD 20814 USA. RP Hudson, KL (reprint author), NIH, 1 Ctr Dr,Bldg 1,Room 109, Bethesda, MD 20814 USA. EM kathy.hudson@nih.gov NR 6 TC 30 Z9 30 U1 2 U2 4 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 JAN 27 PY 2015 VL 313 IS 4 BP 355 EP 356 DI 10.1001/jama.2014.10716 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CA7BS UT WOS:000349072600012 PM 25408371 ER PT J AU Fauci, AS Marston, HD AF Fauci, Anthony S. Marston, Hilary D. TI Focusing to Achieve a World Without AIDS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HIV C1 [Fauci, Anthony S.; Marston, Hilary D.] NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Bldg 31,Room 7A-03,31 Ctr Dr,MSC 2520, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 7 TC 0 Z9 0 U1 2 U2 2 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 JAN 27 PY 2015 VL 313 IS 4 BP 357 EP 358 DI 10.1001/jama.2014.17454 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CA7BS UT WOS:000349072600013 PM 25626032 ER PT J AU Siddiqui, MM Rais-Bahrami, S Turkbey, B George, AK Rothwax, J Shakir, N Okoro, C Raskolnikov, D Parnes, HL Linehan, WM Merino, MJ Simon, RM Choyke, PL Wood, BJ Pinto, PA AF Siddiqui, M. Minhaj Rais-Bahrami, Soroush Turkbey, Baris George, Arvin K. Rothwax, Jason Shakir, Nabeel Okoro, Chinonyerem Raskolnikov, Dima Parnes, Howard L. Linehan, W. Marston Merino, Maria J. Simon, Richard M. Choyke, Peter L. Wood, Bradford J. Pinto, Peter A. TI Comparison of MR/Ultrasound Fusion-Guided Biopsy With Ultrasound-Guided Biopsy for the Diagnosis of Prostate Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TARGETED BIOPSY; RADICAL PROSTATECTOMY; ACTIVE SURVEILLANCE; RESONANCE; MRI; RISK; LOCALIZATION; RECURRENCE; OUTCOMES; SCORE AB IMPORTANCE Targeted magnetic resonance (MR)/ultrasound fusion prostate biopsy has been shown to detect prostate cancer. The implications of targeted biopsy alone vs standard extended-sextant biopsy or the 2 modalities combined are not well understood. OBJECTIVE To assess targeted vs standard biopsy and the 2 approaches combined for the diagnosis of intermediate-to high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 1003 men undergoing both targeted and standard biopsy concurrently from 2007 through 2014 at the National Cancer Institute in the United States. Patients were referred for elevated level of prostate-specific antigen (PSA) or abnormal digital rectal examination results, often with prior negative biopsy results. Risk categorization was compared among targeted and standard biopsy and, when available, whole-gland pathology after prostatectomy as the "gold standard." INTERVENTIONS Patients underwent multiparametric prostate magnetic resonance imaging to identify regions of prostate cancer suspicion followed by targeted MR/ultrasound fusion biopsy and concurrent standard biopsy. MAIN OUTCOMES AND MEASURES The primary objective was to compare targeted and standard biopsy approaches for detection of high-risk prostate cancer (Gleason score >= 4 + 3); secondary end points focused on detection of low-risk prostate cancer (Gleason score 3 + 3 or low-volume 3 + 4) and the biopsy ability to predict whole-gland pathology at prostatectomy. RESULTS Targeted MR/ultrasound fusion biopsy diagnosed 461 prostate cancer cases, and standard biopsy diagnosed 469 cases. There was exact agreement between targeted and standard biopsy in 690 men (69%) undergoing biopsy. Targeted biopsy diagnosed 30% more high-risk cancers vs standard biopsy (173 vs 122 cases, P < .001) and 17% fewer low-risk cancers (213 vs 258 cases, P < .001). When standard biopsy cores were combined with the targeted approach, an additional 103 cases (22%) of mostly low-risk prostate cancer were diagnosed (83% low risk, 12% intermediate risk, and 5% high risk). The predictive ability of targeted biopsy for differentiating low-risk from intermediate-and high-risk disease in 170 men with whole-gland pathology after prostatectomy was greater than that of standard biopsy or the 2 approaches combined (area under the curve, 0.73, 0.59, and 0.67, respectively; P < .05 for all comparisons). CONCLUSIONS AND RELEVANCE Among men undergoing biopsy for suspected prostate cancer, targeted MR/ultrasound fusion biopsy, compared with standard extended-sextant ultrasound-guided biopsy, was associated with increased detection of high-risk prostate cancer and decreased detection of low-risk prostate cancer. Future studies will be needed to assess the ultimate clinical implications of targeted biopsy. C1 [Siddiqui, M. Minhaj; Rais-Bahrami, Soroush; George, Arvin K.; Rothwax, Jason; Shakir, Nabeel; Okoro, Chinonyerem; Raskolnikov, Dima; Linehan, W. Marston; Wood, Bradford J.; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Parnes, Howard L.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Simon, Richard M.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Wood, Bradford J.; Pinto, Peter A.] NIH, Ctr Intervent Oncol, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Wood, Bradford J.; Pinto, Peter A.] NCI, NIH, Bethesda, MD 20892 USA. RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210,Bldg 10 CRC,Room 2W-5940, Bethesda, MD 20892 USA. EM pintop@mail.nih.gov OI Shakir, Nabeel/0000-0002-9066-3670; Siddiqui, Mohummad/0000-0002-4484-6820; Rais-Bahrami, Soroush/0000-0001-9466-9925 FU Intramural Research Program of the National Institutes of Health (NIH); National Cancer Institute; Center for Cancer Research; Center for Interventional Oncology; NIH; Foundation for the NIH from Pfizer; Leona M. and Harry B. Helmsley Charitable Trust; Howard Hughes Medical Institute FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research, and Center for Interventional Oncology. The NIH, Philips Healthcare, and Invivo have a cooperative research and development agreement. The NIH, Philips Healthcare, and Invivo share intellectual property in the field. This research was also 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, 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, visit the foundation website at http://www.fnih.org. NR 31 TC 233 Z9 241 U1 12 U2 31 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 JAN 27 PY 2015 VL 313 IS 4 BP 390 EP 397 DI 10.1001/jama.2014.17942 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CA7BS UT WOS:000349072600021 PM 25626035 ER PT J AU Tomlinson, T De Vries, R Ryan, K Kim, HM Lehpamer, N Kim, SYH AF Tomlinson, Tom De Vries, Raymond Ryan, Kerry Kim, Hyungjin Myra Lehpamer, Nicole Kim, Scott Y. H. TI Moral Concerns and the Willingness to Donate to a Research Biobank SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Tomlinson, Tom] Michigan State Univ, Ctr Eth & Humanities Life Sci, E Lansing, MI 48824 USA. [De Vries, Raymond; Ryan, Kerry] Univ Michigan, Sch Med, Ctr Bioeth & Social Sci Med, Ann Arbor, MI USA. [Kim, Hyungjin Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. [Lehpamer, Nicole] Michigan State Univ, Dept Sociol, E Lansing, MI 48824 USA. [Kim, Scott Y. H.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Tomlinson, T (reprint author), Michigan State Univ, Ctr Eth & Humanities Life Sci, 965 Fee Rd, E Lansing, MI 48824 USA. EM tom.tomlinson@ht.msu.edu OI Ryan, Kerry/0000-0002-0582-3693; De Vries, Raymond/0000-0003-3087-3040 FU NHGRI NIH HHS [R01 HG007172] NR 5 TC 11 Z9 11 U1 0 U2 16 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 JAN 27 PY 2015 VL 313 IS 4 BP 417 EP 419 DI 10.1001/jama.2014.16363 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CA7BS UT WOS:000349072600026 PM 25626040 ER PT J AU Yang, CZ Wang, HH Zhu, DW Hong, CS Dmitriev, P Zhang, C Li, Y Ikejiri, B Brady, RO Zhuang, ZP AF Yang, Chunzhang Wang, Herui Zhu, Dongwang Hong, Christopher S. Dmitriev, Pauline Zhang, Chao Li, Yan Ikejiri, Barbara Brady, Roscoe O. Zhuang, Zhengping TI Mutant glucocerebrosidase in Gaucher disease recruits Hsp27 to the Hsp90 chaperone complex for proteasomal degradation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Gaucher disease; heat shock protein; hsp27; hsp90; molecular chaperone ID HISTONE DEACETYLASE INHIBITORS; MOLECULAR CHAPERONES; MISSENSE MUTATIONS; PROTEIN; UBIQUITINATION; TANESPIMYCIN; VARIANTS; PARKIN; CELLS AB Gaucher disease is caused by mutations of the GBA1 gene, which encodes the lysosomal anchored gluococerebrosidase (GCase). GBA1 mutations commonly result in protein misfolding, abnormal chaperone recognition, and premature degradation, but are less likely to affect catalytic activity. In the present study, we demonstrate that the Hsp90/HOP/Cdc37 complex recruits Hsp27 after recognition of GCase mutants with subsequent targeting of GCase mutant peptides to degradation mechanisms such as VCP and the 26S proteasome. Inhibition of Hsp27 not only increased the quantity of enzyme but also enhanced GCase activity in fibroblasts derived from patients with Gaucher disease. These findings provide insight into a possible therapeutic strategy for protein misfolding diseases by correcting chaperone binding and altering subsequent downstream patterns of protein degradation. C1 [Yang, Chunzhang; Wang, Herui; Zhu, Dongwang; Hong, Christopher S.; Dmitriev, Pauline; Zhang, Chao; Li, Yan; Ikejiri, Barbara; Brady, Roscoe O.; Zhuang, Zhengping] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Brady, RO (reprint author), NINDS, Surg Neurol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM yangc2@ninds.nih.gov; bradyr@ninds.nih.gov; zhuangp@ninds.nih.gov FU Intramural Research Program at the National Institutes of Health (NIH) FX The authors thank James A. Shayman, M.D., for his critical suggestions in the preparation of this manuscript. This work was supported by the Intramural Research Program at the National Institutes of Health (NIH). NR 26 TC 6 Z9 6 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 27 PY 2015 VL 112 IS 4 BP 1137 EP 1142 DI 10.1073/pnas.1424288112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ7SB UT WOS:000348417000052 PM 25583479 ER PT J AU Kusumoto-Yoshida, I Liu, HX Chen, BT Fontanini, A Bonci, A AF Kusumoto-Yoshida, Ikue Liu, Haixin Chen, Billy T. Fontanini, Alfredo Bonci, Antonello TI Central role for the insular cortex in mediating conditioned responses to anticipatory cues SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE insular cortex; reward; anticipation; cue; learning ID ORBITOFRONTAL CORTEX; INGESTIVE BEHAVIOR; NUCLEUS-ACCUMBENS; INCENTIVE MEMORY; GUSTATORY CORTEX; TASTE-AVERSIONS; REWARD; RATS; NEURONS; MOTIVATION AB Reward-related circuits are fundamental for initiating feeding on the basis of food-predicting cues, whereas gustatory circuits are believed to be involved in the evaluation of food during consumption. However, accumulating evidence challenges such a rigid separation. The insular cortex (IC), an area largely studied in rodents for its role in taste processing, is involved in representing anticipatory cues. Although IC responses to anticipatory cues are well established, the role of IC cue-related activity in mediating feeding behaviors is poorly understood. Here, we examined the involvement of the IC in the expression of cue-triggered food approach in mice trained with a Pavlovian conditioning paradigm. We observed a significant change in neuronal firing during presentation of the cue. Pharmacological silencing of the IC inhibited food port approach. Such a behavior could be recapitulated by temporally selective inactivation during the cue. These findings represent the first evidence, to our knowledge, that cue-evoked neuronal activity in the mouse IC modulates behavioral output, and demonstrate a causal link between cue responses and feeding behaviors. C1 [Kusumoto-Yoshida, Ikue; Chen, Billy T.; Bonci, Antonello] NIDA, Intramural Res Program, Baltimore, MD 21224 USA. [Liu, Haixin; Fontanini, Alfredo] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Solomon H Snyder Neurosci Inst, Baltimore, MD 21205 USA. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. RP Fontanini, A (reprint author), SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA. EM alfredo.fontanini@stonybrook.edu; antonello.bonci@nih.gov FU Rotary Foundation; Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH; NIDA IRP and National Institute of Deafness and Other Communication Disorders-National Institutes of Health [R01 - DC012543] FX We thank K. Deisseroth for providing the NpHR3.0 vectors and the National Institute on Drug Abuse (NIDA) Intramural Research Program (IRP) Optogenetics and Transgenic Technology Core for assistance with the AAV vectors. We thank Joo J. and Goddard S. for technical support. We also thank members of the Synaptic Plasticity Section in NIDA IRP for discussion. This work was supported by funds from the Rotary Foundation (I.K.-Y.), Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH (I.K.-Y.), and NIDA IRP and National Institute of Deafness and Other Communication Disorders-National Institutes of Health Grant R01 - DC012543 (to A.F.). NR 46 TC 11 Z9 11 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 27 PY 2015 VL 112 IS 4 BP 1190 EP 1195 DI 10.1073/pnas.1416573112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ7SB UT WOS:000348417000061 PM 25583486 ER PT J AU Koroshetz, W AF Koroshetz, Walter TI A core set of trial outcomes for every medical discipline? SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Editorial Material C1 NINDS, Bethesda, MD 20892 USA. RP Koroshetz, W (reprint author), NINDS, Bethesda, MD 20892 USA. EM koroshetzw@ninds.nih.gov NR 1 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 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD JAN 26 PY 2015 VL 350 AR h85 DI 10.1136/bmj.h85 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CA2ZM UT WOS:000348775100018 PM 25623113 ER PT J AU Church, DM Schneider, VA Steinberg, KM Schatz, MC Quinlan, AR Chin, CS Kitts, PA Aken, B Marth, GT Hoffman, MM Herrero, J Mendoza, MLZ Durbin, R Flicek, P AF Church, Deanna M. Schneider, Valerie A. Steinberg, Karyn Meltz Schatz, Michael C. Quinlan, Aaron R. Chin, Chen-Shan Kitts, Paul A. Aken, Bronwen Marth, Gabor T. Hoffman, Michael M. Herrero, Javier Mendoza, M. Lisandra Zepeda Durbin, Richard Flicek, Paul TI Extending reference assembly models SO GENOME BIOLOGY LA English DT Editorial Material ID COPY-NUMBER VARIATION; HUMAN-GENOME; EVOLUTION; SEQUENCE; PROJECT; FORMAT; GENES AB The human genome reference assembly is crucial for aligning and analyzing sequence data, and for genome annotation, among other roles. However, the models and analysis assumptions that underlie the current assembly need revising to fully represent human sequence diversity. Improved analysis tools and updated data reporting formats are also required. C1 [Church, Deanna M.] Personalis Inc, Menlo Pk, CA 94025 USA. [Schneider, Valerie A.; Kitts, Paul A.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Steinberg, Karyn Meltz] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA. [Schatz, Michael C.] Simons Ctr Quantitat Biol, Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Quinlan, Aaron R.] Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. [Quinlan, Aaron R.] Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. [Chin, Chen-Shan] Pacific Biosci Inc, Menlo Pk, CA 94025 USA. [Aken, Bronwen; Flicek, Paul] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England. [Marth, Gabor T.] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84132 USA. [Marth, Gabor T.] Univ Utah, Sch Med, USTAR Ctr Genet Discovery, Salt Lake City, UT 84132 USA. [Hoffman, Michael M.] Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada. [Hoffman, Michael M.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada. [Hoffman, Michael M.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3G4, Canada. [Herrero, Javier] UCL, UCL Canc Inst, Bill Lyons Informat Ctr, London WC1E 6BT, England. [Mendoza, M. Lisandra Zepeda] Univ Copenhagen, Nat Hist Museum, Ctr GeoGenet, Menlo Park, CA, Denmark. [Durbin, Richard] Wellcome Trust Sanger Inst, Cambridge CB10 1SD, England. RP Church, DM (reprint author), Personalis Inc, Menlo Pk, CA 94025 USA. EM deanna.church@personalis.com; schneiva@ncbi.nlm.nih.gov; rd@sanger.ac.uk; flicek@ebi.ac.uk RI Hoffman, Michael/I-1924-2012; OI Hoffman, Michael/0000-0002-4517-1562; Durbin, Richard/0000-0002-9130-1006; Aken, Bronwen/0000-0002-3032-4095; Schatz, Michael/0000-0002-4118-4446; Herrero, Javier/0000-0001-7313-717X; Flicek, Paul/0000-0002-3897-7955; Meltz Steinberg, Karyn/0000-0002-8676-3337 FU Intramural NIH HHS; NHGRI NIH HHS [U41 HG007234, U41 HG007635, U41HG007234]; Wellcome Trust [095908] NR 22 TC 23 Z9 23 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PD JAN 24 PY 2015 VL 16 AR 13 DI 10.1186/s13059-015-0587-3 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CE4QW UT WOS:000351816100002 PM 25651527 ER PT J AU Kellman, P Xue, H Spottiswoode, BS Sandino, CM Hansen, MS Abdel-Gadir, A Treibel, TA Rosmini, S Mancini, C Bandettini, WP McGill, LA Gatehouse, P Moon, JC Pennell, DJ Arai, AE AF Kellman, Peter Xue, Hui Spottiswoode, Bruce S. Sandino, Christopher M. Hansen, Michael S. Abdel-Gadir, Amna Treibel, Thomas A. Rosmini, Stefania Mancini, Christine Bandettini, W. Patricia McGill, Laura-Ann Gatehouse, Peter Moon, James C. Pennell, Dudley J. Arai, Andrew E. TI Free-breathing T2*mapping using respiratory motion corrected averaging SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE T2*; R2*; Motion correction; Iron; Mapping; Hemochromatosis; Thalassemia; Cardiovascular magnetic resonance ID T2-ASTERISK-CARDIOVASCULAR MAGNETIC-RESONANCE; MYOCARDIAL IRON OVERLOAD; IMAGE-RECONSTRUCTION; HUMAN HEART; THALASSEMIA; DIAGNOSIS AB Background: Pixel-wise T2* maps based on breath-held segmented image acquisition are prone to ghost artifacts in instances of poor breath-holding or cardiac arrhythmia. Single shot imaging is inherently immune to ghost type artifacts. We propose a free-breathing method based on respiratory motion corrected single shot imaging with averaging to improve the signal to noise ratio. Methods: Images were acquired using a multi-echo gradient recalled echo sequence and T2* maps were calculated at each pixel by exponential fitting. For 40 subjects (2 cohorts), two acquisition protocols were compared: (1) a breath-held, segmented acquisition, and (2) a free-breathing, single-shot multiple repetition respiratory motion corrected average. T2* measurements in the interventricular septum and liver were compared for the 2-methods in all studies with diagnostic image quality. Results: In cohort 1 (N = 28) with age 51.4 +/- 17.6 (m +/- SD) including 1 subject with severe myocardial iron overload, there were 8 non-diagnostic breath-held studies due to poor image quality resulting from ghost artifacts caused by respiratory motion or arrhythmias. In cohort 2 (N = 12) with age 30.9 +/- 7.5 (m +/- SD), including 7 subjects with severe myocardial iron overload and 4 subjects with mild iron overload, a single subject was unable to breath-hold. Free-breathing motion corrected T2* maps were of diagnostic quality in all 40 subjects. T2* measurements were in excellent agreement (In cohort #1, T2(FB)*= 0.95 x T2(BH)* + 0.41, r(2) = 0.93, N = 39 measurements, and in cohort #2, T2(FB)* = 0.98 x T2(BH)* + 0.05, r(2) > 0.99, N = 22 measurements). Conclusions: A free-breathing approach to T2* mapping is demonstrated to produce consistently good quality maps in the presence of respiratory motion and arrhythmias. C1 [Kellman, Peter; Xue, Hui; Sandino, Christopher M.; Hansen, Michael S.; Mancini, Christine; Bandettini, W. Patricia; Arai, Andrew E.] NHLBI, NIH, DHHS, Bethesda, MD 20892 USA. [Spottiswoode, Bruce S.] Siemens Med Solut USA Inc, Chicago, IL USA. [Abdel-Gadir, Amna; Treibel, Thomas A.; Rosmini, Stefania; Moon, James C.] Heart Hosp, London W1G 8PH, England. [McGill, Laura-Ann; Gatehouse, Peter; Pennell, Dudley J.] Royal Brompton Hosp, Cardiovasc Biomed Res Unit, London SW3 6NP, England. RP Kellman, P (reprint author), NHLBI, NIH, DHHS, 10 Ctr Dr MSC 1061, Bethesda, MD 20892 USA. EM kellman@nih.gov RI Hansen, Michael/J-5391-2015; OI Hansen, Michael/0000-0002-8087-8731; Gatehouse, Peter/0000-0002-0260-4719; moon, james/0000-0001-8071-1491 FU National Heart, Lung and Blood Institute, National Institutes of Health by the Division of Intramural Research, NHLBI, NIH, DHHS [HL004607-14CPB]; UK National Institute for Health Research Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS foundation Trust; Imperial College FX Supported by the National Heart, Lung and Blood Institute, National Institutes of Health by the Division of Intramural Research, NHLBI, NIH, DHHS (HL004607-14CPB), and from the UK National Institute for Health Research Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS foundation Trust and Imperial College. NR 14 TC 6 Z9 6 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 EI 1532-429X J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD JAN 24 PY 2015 VL 17 AR 3 DI 10.1186/s12968-014-0106-9 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CB9IG UT WOS:000349944600001 PM 25616857 ER PT J AU Dora, C Haines, A Balbus, J Fletcher, E Adair-Rohani, H Alabaster, G Hossain, R de Onis, M Branca, F Neira, M AF Dora, Carlos Haines, Andy Balbus, John Fletcher, Elaine Adair-Rohani, Heather Alabaster, Graham Hossain, Rifat de Onis, Mercedes Branca, Francesco Neira, Maria TI Indicators linking health and sustainability in the post-2015 development agenda SO LANCET LA English DT Review ID RED MEAT CONSUMPTION; CLIMATE-CHANGE; CHILD UNDERNUTRITION; PUBLIC-HEALTH; URBAN SPRAWL; RISK-FACTOR; BENEFITS; STRATEGIES; EMISSIONS; DISEASE AB The UN-led discussion about the post-2015 sustainable development agenda provides an opportunity to develop indicators and targets that show the importance of health as a precondition for and an outcome of policies to promote sustainable development. Health as a precondition for development has received considerable attention in terms of achievement of health-related Millennium Development Goals (MDGs), addressing growing challenges of non-communicable diseases, and ensuring universal health coverage. Much less attention has been devoted to health as an outcome of sustainable development and to indicators that show both changes in exposure to health-related risks and progress towards environmental sustainability. We present a rationale and methods for the selection of health-related indicators to measure progress of post-2015 development goals in non-health sectors. The proposed indicators show the ancillary benefits to health and health equity (co-benefits) of sustainable development policies, particularly those to reduce greenhouse gas emissions and increase resilience to environmental change. We use illustrative examples from four thematic areas: cities, food and agriculture, energy, and water and sanitation. Embedding of a range of health-related indicators in the post-2015 goals can help to raise awareness of the probable health gains from sustainable development policies, thus making them more attractive to decision makers and more likely to be implemented than before. C1 [Dora, Carlos; Fletcher, Elaine; Adair-Rohani, Heather; Hossain, Rifat; Neira, Maria] WHO, Dept Publ Hlth & Environm, CH-1211 Geneva 27, Switzerland. [de Onis, Mercedes; Branca, Francesco] WHO, Dept Nutr Hlth & Dev, CH-1211 Geneva 27, Switzerland. [Haines, Andy] London Sch Hyg & Trop Med, Dept Social & Environm Hlth Res, London WC1, England. [Haines, Andy] London Sch Hyg & Trop Med, Dept Populat Hlth, London WC1, England. [Balbus, John] NIEHS, NIH, Durham, NC USA. [Alabaster, Graham] UN Human Settlements Programme, Urban Basic Serv Branch, Nairobi, Kenya. RP Dora, C (reprint author), WHO, Dept Publ Hlth & Environm, 20 Ave Appia, CH-1211 Geneva 27, Switzerland. EM dorac@who.int FU USA National Institute of Environmental Health Sciences (NIEHS) FX For contributions to the discussions that informed this paper, we thank participants of the June, 2012, workshop Health Indicators of Sustainable Development, hosted by the WHO and funded partly by the USA National Institute of Environmental Health Sciences (NIEHS). We also thank contributors to the scoping reviews of the WHO's Health in a Green Economy series, funded partly by a contribution from the UK of UK's Department for International Development (DFID). We also thankfully acknowledge the work of Jamie Hosking and Nathalie Roebbel, as lead authors of reports on transport and on housing respectively, part of the WHO Health in Green Economy series that outline linkages between health and climate change mitigation policies proposed by the Intergovernmental Panel on Climate Change (IPCC) in their fourth assessment report in certain sectors of the economy. We thank Nana L Wenz for technical assistance with the preparation of this paper. We thank Tara Garnett for advice and comment on the food and agriculture section. NR 115 TC 11 Z9 14 U1 7 U2 47 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JAN 24 PY 2015 VL 385 IS 9965 BP 380 EP 391 DI 10.1016/S0140-6736(14)60605-X PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AZ9CN UT WOS:000348509000031 PM 24923529 ER PT J AU Miras, AD Mogford, JT Wright, J Mendoza, NN Xekouki, P Lakhani, A Pellegata, NS Stratakis, CA Roncaroli, F Russell-Jones, D AF Miras, Alexander D. Mogford, Julianne T. Wright, John Mendoza, Nigel N. Xekouki, Paraskevi Lakhani, Amish Pellegata, Natalia S. Stratakis, Costantine A. Roncaroli, Federico Russell-Jones, David TI Ovarian hyperstimulation from ectopic hypersecretion of follicle stimulating hormone SO LANCET LA English DT Editorial Material C1 [Miras, Alexander D.; Mogford, Julianne T.; Wright, John; Russell-Jones, David] Royal Surrey Cty Hosp, Cedar Ctr, Guildford GU2 7XX, Surrey, England. [Mendoza, Nigel N.; Lakhani, Amish; Roncaroli, Federico] Univ London Imperial Coll Sci Technol & Med, London, England. [Xekouki, Paraskevi; Stratakis, Costantine A.] NIH, Sect Endocrinol & Genet, Bethesda, MD 20892 USA. [Pellegata, Natalia S.] Helmholtz Zentrum Munchen, Inst Pathol, Neuherberg, Germany. RP Wright, J (reprint author), Royal Surrey Cty Hosp, Cedar Ctr, Guildford GU2 7XX, Surrey, England. EM john.wright5@nhs.net NR 4 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JAN 24 PY 2015 VL 385 IS 9965 BP 392 EP 392 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AZ9CN UT WOS:000348509000032 PM 25706853 ER PT J AU Bang, J Jang, M Huh, JH Na, JW Shim, M Carlson, BA Tobe, R Tsuji, PA Gladyshev, VN Hatfield, DL Lee, BJ AF Bang, Jeyoung Jang, Mihyun Huh, Jang Hoe Na, Ji-Woon Shim, Myoungsup Carlson, Bradley A. Tobe, Ryuta Tsuji, Petra A. Gladyshev, Vadim N. Hatfield, Dolph L. Lee, Byeong Jae TI Deficiency of the 15-kDa selenoprotein led to cytoskeleton remodeling and non-apoptotic membrane blebbing through a RhoA/ROCK pathway SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE 15-kDa selenoprotein; Membrane blebbing; Apoptosis; Cytoskeletal protein; Selenium ID HUMAN HEALTH; SELENIUM; SEP15; PROTEIN; BLEBS; CELLS; LAMELLIPODIA; CLEAVAGE; SEQUENCE; BINDING AB The 15-kDa selenoprotein (Sep15) has been implicated in etiology of some types of cancer. Herein, inducible RNAi cell lines were established and cell morphology and motility were analyzed. The majority of Sep15-deficient cells (>95%) formed membrane blebs in a dynamic manner. Blebbing cells transformed cell morphology from a normal flat spindle shape to a spherical morphology. In blebbing cells, actin fibers moved to the cell periphery, covering and obscuring visualization of ot-tubulin. Bleb formation was suppressed by the inhibitors of Rho-associated protein kinase (ROCK), RhoA or myosin light chain (MLC), restoring blebbing cells to wild-type morphology. RhoA activation and phosphorylation of myosin phosphatase target subunit 1 was induced by Sep15 knockdown. Sep15-deficient cells were non-apoptotic, and displayed a distinct relative localization of F-actin and alpha-tubulin from typical apoptotic blebbing cells. Our data suggest that Sep15 in Chang liver cells regulates the pathway that antagonizes RhoA/ROCK/MLC-dependent non-apoptotic bleb formation. (C) 2014 Elsevier Inc. All rights reserved. C1 [Bang, Jeyoung; Jang, Mihyun; Huh, Jang Hoe; Na, Ji-Woon; Shim, Myoungsup; Lee, Byeong Jae] Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. [Bang, Jeyoung; Lee, Byeong Jae] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul 151742, South Korea. [Shim, Myoungsup; Lee, Byeong Jae] Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea. [Carlson, Bradley A.; Tobe, Ryuta; Hatfield, Dolph L.] NCI, Mouse Canc Genet Program, NIH, Bethesda, MD 20892 USA. [Tsuji, Petra A.] Towson Univ, Dept Biol Sci, Towson, MD 21252 USA. [Gladyshev, Vadim N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Lee, BJ (reprint author), Seoul Natl Univ, Coll Nat Sci, Sch Biol Sci, Seoul 151742, South Korea. EM imbglmg@snu.ac.kr FU Priority Research Centers Program [2010-0029694]; Basic Science Research Program through the National Research Foundation (NRF) - Ministry of Education, Science and Technology - Korea [2011-0012947]; Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Ministry of Science, ICT & Future Planning - Korea [2012M3A9D1054622]; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research - United States; Brain Korea 21 Research Fellowship from the Ministry of Education and Human Resources Development - Korea FX This work was supported by the Priority Research Centers Program (Grant No. 2010-0029694) and Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Education, Science and Technology - Korea (Grant No. 2011-0012947), the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning - Korea (2012M3A9D1054622) to BJL, and in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research - United States to DLH. JB, MJ, JHH, JN and MS were supported by the Brain Korea 21 Research Fellowship from the Ministry of Education and Human Resources Development - Korea. NR 32 TC 3 Z9 3 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 24 PY 2015 VL 456 IS 4 BP 884 EP 890 DI 10.1016/j.bbrc.2014.12.059 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CA1UF UT WOS:000348696100009 PM 25529450 ER PT J AU Ursea, R De Castro, D Bowen, TJ Chan, CC AF Ursea, Roxana De Castro, Dawn Bowen, Trent J. Chan, Chi-Chao TI The role of conjunctival biopsy in the diagnosis of granulomatosis with polyangiitis SO JOURNAL OF OPHTHALMIC INFLAMMATION AND INFECTION LA English DT Article DE Conjunctivitis; Cornea; Ulceration; Biopsy; Granulomatosis with polyangiitis ID WEGENERS-GRANULOMATOSIS; PRESENTING FEATURE; LIMITED FORMS; MANIFESTATIONS AB Background: The purpose of this study is to describe a patient who was diagnosed with granulomatosis with polyangiitis based on conjunctival biopsy. This study is a case report and review of the literature. Findings: A 48-year-old Caucasian woman presented with a 2-week history of a left eye peripheral corneal ulcer with adjacent conjunctivitis and a 4-month history of a non-resolving productive cough. Given her elevated serum perinuclear antineutrophil cytoplasmic antibody (P-ANCA) and erythrocyte sedimentation rate (ESR) levels as well as a chest computed topography (CT) that showed bilateral patchy infiltrates, suspicion of limited granulomatosis with polyangiitis with lung and ocular involvement was high. Because bronchoalveolar lavage was nondiagnostic for granulomatous disease, conjunctival biopsy was initially attempted in order to avoid a more invasive lung biopsy. The conjunctival biopsy revealed mixed subacute inflammatory mediators and vasculitis consistent with granulomatosis with polyangiitis. Conclusions: Conjunctival biopsy may be a valuable, minimally invasive method for diagnosing systemic granulomatosis with polyangiitis. C1 [Ursea, Roxana] Univ Arizona, Dept Ophthalmol & Vis Sci, Coll Med, Tucson, AZ 85711 USA. [De Castro, Dawn] Massachusetts Eye & Ear Infirm, Oculoplast Serv, Boston, MA 02114 USA. [Bowen, Trent J.] Univ Arizona, Coll Med, Tucson, AZ 85711 USA. [Chan, Chi-Chao] NEI, Immunopathol Sect, Bethesda, MD 20892 USA. RP Ursea, R (reprint author), Univ Arizona, Dept Ophthalmol & Vis Sci, Coll Med, Tucson, AZ 85711 USA. EM roxanaursea@hotmail.com NR 26 TC 2 Z9 2 U1 0 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1869-5760 J9 J OPHTHALMIC INFLAMM JI J. Ophthalmic Inflamm. Infect. PD JAN 23 PY 2015 VL 5 AR 1 DI 10.1186/s12348-014-0033-9 PG 5 WC Ophthalmology SC Ophthalmology GA CZ2JP UT WOS:000366931600001 PM 25632308 ER PT J AU Moulaei, T Alexandre, KB Shenoy, SR Meyerson, JR Krumpe, LRH Constantine, B Wilson, J Buckheit, RW McMahon, JB Subramaniam, S Wlodawer, A O'Keefe, BR AF Moulaei, Tinoush Alexandre, Kabamba B. Shenoy, Shilpa R. Meyerson, Joel R. Krumpe, Lauren R. H. Constantine, Brian Wilson, Jennifer Buckheit, Robert W., Jr. McMahon, James B. Subramaniam, Sriram Wlodawer, Alexander O'Keefe, Barry R. TI Griffithsin tandemers: flexible and potent lectin inhibitors of the human immunodeficiency virus SO RETROVIROLOGY LA English DT Article DE Lectins; HIV; Griffithsin ID ANTIVIRAL PROTEIN GRIFFITHSIN; HIV-1 ENVELOPE GLYCOPROTEINS; CARBOHYDRATE-BINDING AGENTS; IN-VITRO; ANTIBODY; GP120; GLYCOSYLATION; TYPE-1; SITES; NEUTRALIZATION AB Background: The lectin griffithsin (GRFT) is a potent antiviral agent capable of prevention and treatment of infections caused by a number of enveloped viruses and is currently under development as an anti-HIV microbicide. In addition to its broad antiviral activity, GRFT is stable at high temperature and at a broad pH range, displays little toxicity and immunogenicity, and is amenable to large-scale manufacturing. Native GRFT is a domain-swapped homodimer that binds to viral envelope glycoproteins and has displayed mid-picomolar activity in cell-based anti-HIV assays. Previously, we have engineered and analyzed several monomeric forms of this lectin (mGRFT) with anti-HIV EC50 values ranging up to 323 nM. Based on our previous analysis of mGRFT, we hypothesized that the orientation and spacing of the carbohydrate binding domains GRFT were key to its antiviral activity. Results: Here we present data on engineered tandem repeats of mGRFT (mGRFT tandemers) with antiviral activity at concentrations as low as one picomolar in whole-cell anti-HIV assays. mGRFT tandemers were analyzed thermodynamically, both individually and in complex with HIV-1 gp120. We also demonstrate by dynamic light scattering and cryo-electron microscopy that mGRFT tandemers do not aggregate HIV virions. This establishes that, although the intra-virion crosslinking of HIV envelope glycoproteins is likely integral to their activity, the antiviral activity of these lectins is not due to virus aggregation caused by inter-virion crosslinking. Conclusions: The engineered tandemer constructs of mGRFT may provide novel and powerful agents for prevention of infection by HIV and other enveloped viruses. C1 [Moulaei, Tinoush; Alexandre, Kabamba B.; Shenoy, Shilpa R.; Krumpe, Lauren R. H.; Constantine, Brian; Wilson, Jennifer; McMahon, James B.; O'Keefe, Barry R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Moulaei, Tinoush; Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. [Moulaei, Tinoush] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20740 USA. [Shenoy, Shilpa R.; Krumpe, Lauren R. H.] Leidos Biomed Res Inc, Frederick Natl Lab, Basic Sci Program, Frederick, MD 21702 USA. [Meyerson, Joel R.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Buckheit, Robert W., Jr.] Imquest BioSci, Frederick, MD 21704 USA. RP Moulaei, T (reprint author), NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM tinoush@umd.edu; wlodawer@nih.gov; okeefeba@mail.nih.gov FU NIH Intramural AIDS Targeted Antiviral Program and Center for Cancer Research at the National Cancer Institute; NIH Intramural AIDS Research Fellowship; National Cancer Institute, National Institutes of Health [HHSN26120080001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX We thank Nicole LaRonde (University of Maryland) and Maria Miller (NCI-Frederick) for helpful discussions regarding experimental design. We thank Steven Fellini, Susan Chacko, and colleagues for support with our use of the Biowulf Linux cluster (National Institutes of Health, Bethesda, MD 20814, USA, http://biowulf.nih.gov); Jeffrey D. Lifson and Julian W. Bess for providing purified, AT-2 treated HIV-1 virions (AIDS and Cancer Virus Program, Leidos Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA); David Schauder (now of Medical College of Wisconsin) for assistance with cryo-electron microscopy and analysis; and Grzegorz Piszczek for assistance with the dynamic light scattering experiments (National Institutes of Health, National Heart, Lung and Blood Institute, Biophysics Facility, Bethesda, MD 20814, USA). This work was supported in part by funds from the NIH Intramural AIDS Targeted Antiviral Program and Center for Cancer Research at the National Cancer Institute (to B.O, A.W. and S.S.), and an NIH Intramural AIDS Research Fellowship (to J.R.M.). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E, and supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 50 TC 4 Z9 4 U1 4 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JAN 23 PY 2015 VL 12 DI 10.1186/s12977-014-0127-3 PG 14 WC Virology SC Virology GA CH7WS UT WOS:000354247900001 PM 25613831 ER PT J AU Englert, NA Luo, G Goldstein, JA Surapureddi, S AF Englert, Neal A. Luo, George Goldstein, Joyce A. Surapureddi, Sailesh TI Epigenetic Modification of Histone 3 Lysine 27 MEDIATOR SUBUNIT MED25 IS REQUIRED FOR THE DISSOCIATION OF POLYCOMB REPRESSIVE COMPLEX 2 FROM THE PROMOTER OF CYTOCHROME P450 2C9 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONSTITUTIVE ANDROSTANE RECEPTOR; RNA-POLYMERASE-II; HEPATIC NUCLEAR FACTOR-4-ALPHA; REPRESSIVE COMPLEX 2; GENOME-WIDE ANALYSIS; PREGNANE-X-RECEPTOR; TRANSCRIPTIONAL REGULATION; GENE-EXPRESSION; HUMAN HEPATOCYTES; MEDIATOR COMPLEX AB The Mediator complex is vital for the transcriptional regulation of eukaryotic genes. Mediator binds to nuclear receptors at target response elements and recruits chromatin-modifying enzymes and RNA polymerase II. Here, we examine the involvement of Mediator subunit MED25 in the epigenetic regulation of human cytochrome P450 2C9 (CYP2C9). MED25 is recruited to the CYP2C9 promoter through association with liver-enriched HNF4 alpha, and we show that MED25 influences the H3K27 status of the HNF4 alpha binding region. This region was enriched for the activating marker H3K27ac and histone acetyltransferase CREBBP after MED25 overexpression but was trimethylated when MED25 expression was silenced. The epigenetic regulator Polycomb repressive complex (PRC2), which represses expression by methylating H3K27, plays an important role in target gene regulation. Silencing MED25 correlated with increased association of PRC2 not only with the promoter region chromatin but with HNF4 alpha itself. We confirmed the involvement of MED25 for fully functional preinitiation complex recruitment and transcriptional output in vitro. Formaldehyde-assisted isolation of regulatory elements (FAIRE) revealed chromatin conformation changes that were reliant on MED25, indicating that MED25 induced a permissive chromatin state that reflected increases in CYP2C9 mRNA. For the first time, we showed evidence that a functionally relevant human gene is transcriptionally regulated by HNF4 alpha via MED25 and PRC2. CYP2C9 is important for the metabolism of many exogenous chemicals including pharmaceutical drugs as well as endogenous substrates. Thus, MED25 is important for regulating the epigenetic landscape resulting in transcriptional activation of a highly inducible gene, CYP2C9. C1 [Englert, Neal A.; Luo, George; Goldstein, Joyce A.; Surapureddi, Sailesh] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. RP Goldstein, JA (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov FU National Institutes of Health Intramural Research Program, NIEHS [ES021024-32] FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program, NIEHS Project ES021024-32. NR 62 TC 1 Z9 1 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 23 PY 2015 VL 290 IS 4 BP 2264 EP 2278 DI 10.1074/jbc.M114.579474 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CA0EH UT WOS:000348588000030 PM 25391650 ER PT J AU Lu, ZP Chen, Y Aponte, AM Battaglia, V Gucek, M Sack, MN AF Lu, Zhongping Chen, Yong Aponte, Angel M. Battaglia, Valentina Gucek, Marjan Sack, Michael N. TI Prolonged Fasting Identifies Heat Shock Protein 10 as a Sirtuin 3 Substrate ELUCIDATING A NEW MECHANISM LINKING MITOCHONDRIAL PROTEIN ACETYLATION TO FATTY ACID OXIDATION ENZYME FOLDING AND FUNCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACYL-COA DEHYDROGENASE; MUSCLE INSULIN-RESISTANCE; ACID OXIDATION; SKELETAL-MUSCLE; LYSINE ACETYLATION; UREA CYCLE; DEACETYLATION; DEGRADATION; HSP60; METABOLISM AB Although Sirtuin 3 (SIRT3), a mitochondrially enriched deacetylase and activator of fat oxidation, is down-regulated in response to high fat feeding, the rate of fatty acid oxidation and mitochondrial protein acetylation are invariably enhanced in this dietary milieu. These paradoxical data implicate that additional acetylation modification-dependent levels of regulation may be operational under nutrient excess conditions. Because the heat shock protein (Hsp) Hsp10-Hsp60 chaperone complex mediates folding of the fatty acid oxidation enzyme mediumchain acyl-CoA dehydrogenase, we tested whether acetylation-dependent mitochondrial protein folding contributes to this regulatory discrepancy. We demonstrate that Hsp10 is a functional SIRT3 substrate and that, in response to prolonged fasting, SIRT3 levels modulate mitochondrial protein folding. Acetyl mutagenesis of Hsp10 lysine 56 alters Hsp10-Hsp60 binding, conformation, and protein folding. Consistent with Hsp10-Hsp60 regulation of fatty acid oxidation enzyme integrity, medium-chain acyl-CoA dehydrogenase activity and fat oxidation are elevated by Hsp10 acetylation. These data identify acetyl modification of Hsp10 as a nutrient-sensing regulatory node controlling mitochondrial protein folding and metabolic function. C1 [Lu, Zhongping; Sack, Michael N.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Chen, Yong; Aponte, Angel M.; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. [Lu, Zhongping; Battaglia, Valentina] George Washington Univ, Dept Biochem & Mol Med, Washington, DC 20052 USA. [Lu, Zhongping; Battaglia, Valentina] Vet Affairs Med Ctr, Washington, DC 20422 USA. RP Lu, ZP (reprint author), George Washington Univ, Vet Affairs Med Ctr, Washington, DC 20052 USA. EM luz@gwu.edu RI chen, yong/E-2432-2011 FU NHLBI/National Institutes of Health Intramural Research Program [HL006047-01]; NHLBI/National Institutes of Health K22 Award [K22HL109236] FX This work was supported, in whole or in part, by NHLBI/National Institutes of Health Intramural Research Program HL006047-01 and by NHLBI/National Institutes of Health K22 Award K22HL109236. NR 44 TC 12 Z9 12 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 23 PY 2015 VL 290 IS 4 BP 2466 EP 2476 DI 10.1074/jbc.M114.606228 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CA0EH UT WOS:000348588000048 PM 25505263 ER PT J AU Tian, E Stevens, SR Guan, Y Springer, DA Anderson, SA Starost, MF Patel, V Ten Hagen, KG Tabak, LA AF Tian, E. Stevens, Sharon R. Guan, Yu Springer, Danielle A. Anderson, Stasia A. Starost, Matthew F. Patel, Vyomesh Ten Hagen, Kelly G. Tabak, Lawrence A. TI Galnt1 Is Required for Normal Heart Valve Development and Cardiac Function SO PLOS ONE LA English DT Article ID EXTRACELLULAR-MATRIX; O-GLYCOSYLATION; PROTEOLYTIC CLEAVAGE; VERSICAN CLEAVAGE; TGF-BETA; MICE; DISEASE; ADAMTS5; FAMILY; DIFFERENTIATION AB Congenital heart valve defects in humans occur in approximately 2% of live births and are a major source of compromised cardiac function. In this study we demonstrate that normal heart valve development and cardiac function are dependent upon Galnt1, the gene that encodes a member of the family of glycosyltransferases (GalNAc- Ts) responsible for the initiation of mucin-type O-glycosylation. In the adult mouse, compromised cardiac function that mimics human congenital heart disease, including aortic and pulmonary valve stenosis and regurgitation; altered ejection fraction; and cardiac dilation, was observed in Galnt1 null animals. The underlying phenotype is aberrant valve formation caused by increased cell proliferation within the outflow tract cushion of developing hearts, which is first detected at developmental stage E11.5. Developing valves from Galnt1 deficient animals displayed reduced levels of the proteases ADAMTS1 and ADAMTS5, decreased cleavage of the proteoglycan versican and increased levels of other extracellular matrix proteins. We also observed increased BMP and MAPK signaling. Taken together, the ablation of Galnt1 appears to disrupt the formation/ remodeling of the extracellular matrix and alters conserved signaling pathways that regulate cell proliferation. Our study provides insight into the role of this conserved protein modification in cardiac valve development and may represent a new model for idiopathic valve disease. C1 [Tian, E.; Ten Hagen, Kelly G.] Natl Inst Dent & Craniofacial Res, Dev Glycobiol Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [Stevens, Sharon R.; Guan, Yu; Tabak, Lawrence A.] Natl Inst Dent & Craniofacial Res, Sect Biol Chem, NIH, Bethesda, MD 20892 USA. [Springer, Danielle A.; Anderson, Stasia A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Starost, Matthew F.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. [Patel, Vyomesh] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Tabak, LA (reprint author), Natl Inst Dent & Craniofacial Res, Sect Biol Chem, NIH, Bethesda, MD 20892 USA. EM Lawrence.Tabak@nih.gov FU Intramural Research Programs of the National Institutes of Health FX This work was supported by the Intramural Research Programs of the National Institutes of Health. NR 32 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 JAN 23 PY 2015 VL 10 IS 1 AR e0115861 DI 10.1371/journal.pone.0115861 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA7UF UT WOS:000349122100020 PM 25615642 ER PT J AU Yao, YW Chen, PR Li, S Wang, LJ Zhang, JT Yip, SW Chen, G Deng, LY Liu, QX Fang, XY AF Yao, Yuan-Wei Chen, Pin-Ru Li, Song Wang, Ling-Jiao Zhang, Jin-Tao Yip, Sarah W. Chen, Gang Deng, Lin-Yuan Liu, Qin-Xue Fang, Xiao-Yi TI Decision-Making for Risky Gains and Losses among College Students with Internet Gaming Disorder SO PLOS ONE LA English DT Article ID ALCOHOL DEPENDENCE; DIAGNOSTIC-CRITERIA; ADDICTION; REWARD; SENSITIVITY; ACTIVATION; DEFICITS; CORTEX; USERS; FMRI AB Individuals with Internet gaming disorder (IGD) tend to exhibit disadvantageous risky decision-making not only in their real life but also in laboratory tasks. Decision-making is a complex multifaceted function and different cognitive processes are involved in decision-making for gains and losses. However, the relationship between impaired decision-making and gain versus loss processing in the context of IGD is poorly understood. The main aim of the present study was to separately evaluate decision-making for risky gains and losses among college students with IGD using the Cups task. Additionally, we further examined the effects of outcome magnitude and probability level on decision-making related to risky gains and losses respectively. Sixty college students with IGD and 42 matched healthy controls (HCs) participated. Results indicated that IGD subjects exhibited generally greater risk taking tendencies than HCs. In comparison to HCs, IGD subjects made more disadvantageous risky choices in the loss domain (but not in the gain domain). Follow-up analyses indicated that the impairment was associated to insensitivity to changes in outcome magnitude and probability level for risky losses among IGD subjects. In addition, higher Internet addiction severity scores were associated with percentage of disadvantageous risky options in the loss domain. These findings emphasize the effect of insensitivity to losses on disadvantageous decisions under risk in the context of IGD, which has implications for future intervention studies. C1 [Yao, Yuan-Wei; Chen, Pin-Ru] Beijing Normal Univ, Sch Psychol, Beijing 100875, Peoples R China. [Li, Song] Beijing Normal Univ, Sch Math Sci, Beijing 100875, Peoples R China. [Wang, Ling-Jiao; Zhang, Jin-Tao; Fang, Xiao-Yi] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. [Wang, Ling-Jiao; Zhang, Jin-Tao; Fang, Xiao-Yi] Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China. [Zhang, Jin-Tao] Beijing Normal Univ, Ctr Collaborat & Innovat Brain & Learning Sci, Beijing 100875, Peoples R China. [Yip, Sarah W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Deng, Lin-Yuan] Beijing Normal Univ, Fac Educ, Beijing 100875, Peoples R China. [Liu, Qin-Xue] Cent China Normal Univ, Sch Psychol, Wuhan, Peoples R China. [Liu, Qin-Xue] Minist Educ, Key Lab Adolescent Cyberpsychol & Behav CCNU, Wuhan, Peoples R China. [Fang, Xiao-Yi] Beijing Normal Univ, Inst Dev Psychol, Beijing 100875, Peoples R China. [Fang, Xiao-Yi] Tianjin Normal Univ, Acad Psychol & Behav, Tianjin, Peoples R China. RP Zhang, JT (reprint author), Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. EM zhangjintao@bnu.edu.cn; fangxy@bnu.edu.cn OI Yao, Yuan-Wei/0000-0002-9635-7826 FU National Natural Science Foundation of China [31170990, 81100992]; fundamental research funds for the central universities [2012WYB01]; National Innovative Foundation Programs for College Students of China [201310027028]; NIDA [T32 DA007238-23] FX This study was supported by the National Natural Science Foundation of China (No. 31170990 and No. 81100992), the fundamental research funds for the central universities (No. 2012WYB01), and the National Innovative Foundation Programs for College Students of China (No. 201310027028). SWY received salary support from the grant from NIDA (T32 DA007238-23). The funders had no role in the study design, collection and analysis of the data, or preparation of the manuscript. NR 50 TC 9 Z9 9 U1 3 U2 26 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 JAN 23 PY 2015 VL 10 IS 1 AR e0116471 DI 10.1371/journal.pone.0116471 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA7UF UT WOS:000349122100028 PM 25615595 ER PT J AU Straimer, J Gnadig, NF Witkowski, B Amaratunga, C Duru, V Ramadani, AP Dacheux, M Khim, N Zhang, L Lam, S Gregory, PD Urnov, FD Mercereau-Puijalon, O Benoit-Vical, F Fairhurst, RM Menard, D Fidock, DA AF Straimer, Judith Gnaedig, Nina F. Witkowski, Benoit Amaratunga, Chanaki Duru, Valentine Ramadani, Arba Pramundita Dacheux, Melanie Khim, Nimol Zhang, Lei Lam, Stephen Gregory, Philip D. Urnov, Fyodor D. Mercereau-Puijalon, Odile Benoit-Vical, Francoise Fairhurst, Rick M. Menard, Didier Fidock, David A. TI K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates SO SCIENCE LA English DT Article ID DIHYDROARTEMISININ-PIPERAQUINE; MALARIA PARASITES; WESTERN CAMBODIA; IN-VITRO; CLEARANCE; POPULATIONS; DERIVATIVES; MECHANISM AB The emergence of artemisinin resistance in Southeast Asia imperils efforts to reduce the global malaria burden. We genetically modified the Plasmodium falciparum K13 locus using zinc-finger nucleases and measured ring-stage survival rates after drug exposure in vitro; these rates correlate with parasite clearance half-lives in artemisinin-treated patients. With isolates from Cambodia, where resistance first emerged, survival rates decreased from 13 to 49% to 0.3 to 2.4% after the removal of K13 mutations. Conversely, survival rates in wild-type parasites increased from <= 0.6% to 2 to 29% after the insertion of K13 mutations. These mutations conferred elevated resistance to recent Cambodian isolates compared with that of reference lines, suggesting a contemporary contribution of additional genetic factors. Our data provide a conclusive rationale for worldwide K13-propeller sequencing to identify and eliminate artemisinin-resistant parasites. C1 [Straimer, Judith; Gnaedig, Nina F.; Dacheux, Melanie; Fidock, David A.] Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA. [Witkowski, Benoit; Duru, Valentine; Khim, Nimol; Menard, Didier] Inst Pasteur Cambodge, Malaria Mol Epidemiol Unit, Phnom Penh, Cambodia. [Amaratunga, Chanaki; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Ramadani, Arba Pramundita; Benoit-Vical, Francoise] CNRS, Chim Coordinat Lab, UPR8241, F-31077 Toulouse, France. [Ramadani, Arba Pramundita; Benoit-Vical, Francoise] Univ Toulouse, Inst Natl Polytech Toulouse, UPS, Toulouse, France. [Zhang, Lei; Lam, Stephen; Gregory, Philip D.; Urnov, Fyodor D.] Sangamo BioSci, Richmond, CA USA. [Mercereau-Puijalon, Odile] Inst Pasteur, Parasite Mol Immunol Unit, Paris, France. [Fidock, David A.] Columbia Univ Coll Phys & Surg, Dept Med, Div Infect Dis, New York, NY 10032 USA. RP Fidock, DA (reprint author), Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, 630 W 168th St, New York, NY 10032 USA. EM df2260@columbia.edu RI Benoit-Vical, Francoise/E-3938-2016 OI Benoit-Vical, Francoise/0000-0002-9468-4823 FU NIH [R01 AI109023]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH; French "Agence Nationale de la Recherche" [ANR-13-BSV3-0018-01]; French "Agence Nationale de la Recherche" (Laboratoire d'Excellence IBEID); Institut Pasteur, Division International (ACIP) [A-10-2010] FX D.A.F. gratefully acknowledges funding from the NIH (R01 AI109023). This study was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH, the French "Agence Nationale de la Recherche" (ANR-13-BSV3-0018-01 and the Laboratoire d'Excellence IBEID), and the Institut Pasteur, Division International (ACIP A-10-2010). Parental and transgenic parasite lines have been deposited and are being made available through BEI Resources (www.mr4.org) with the following accession numbers: MRA-1240, Cam3.IR539T (also known as IPC 5202); MRA-1252, Cam3.Irev; MRA-1241, Cam5I543T (also known as IPC 4912); MRA-1253, Cam5rev; MRA-1236, Cam2C580Y (also known as IPC 3445); MRA-1254, Cam2rev; MRA-1250, CamWT; MRA-1251, CamWTC580Y; MRA-150, Dd2; MRA-1255, Dd2R539T. Parasite lines generated for this study will also be provided upon request from D.A.F. Requests for ZFNs should be directed to F.D.U. (FUrnov@sangamo.com); a materials transfer agreement is required. We extend our gratitude to F. Ariey (Institut Pasteur, Paris) for his important contribution to initiating this study, I. McKeague and O. Lieberman (Columbia University Medical Center) for their statistical and scientific input, and E. Rebar and the Production Group at Sangamo BioSciences for ZFN assembly and validation. L.Z., S.L., P.D.G., and F.D.U. declare that they are full-time employees of Sangamo, which designed, validated, and provided the ZFNs used in this study. B.W., O. M.-P., F. B.-V., and D.M., are co-inventors on the pending patents US61/904651 and US62/062439, and N.K. is a co-inventor on the pending patent US62/062439. Both patents are filed by Institut Pasteur. These patents cover the use of K13 mutations as a molecular marker of P. falciparum ART resistance. Sangamo holds patents on engineered DNA-binding proteins and the use thereof in targeted genome engineering and gene-specific regulation. All other authors declare no competing financial interests. NR 32 TC 106 Z9 110 U1 10 U2 63 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 JAN 23 PY 2015 VL 347 IS 6220 BP 428 EP 431 DI 10.1126/science.1260867 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ4XZ UT WOS:000348225800045 PM 25502314 ER PT J AU Mok, S Ashley, EA Ferreira, PE Zhu, L Lin, ZT Yeo, T Chotivanich, K Imwong, M Pukrittayakamee, S Dhorda, M Nguon, C Lim, P Amaratunga, C Suon, S Hien, TT Htut, Y Faiz, MA Onyamboko, MA Mayxay, M Newton, PN Tripura, R Woodrow, CJ Miotto, O Kwiatkowski, DP Nosten, F Day, NPJ Preiser, PR White, NJ Dondorp, AM Fairhurst, RM Bozdech, Z AF Mok, Sachel Ashley, Elizabeth A. Ferreira, Pedro E. Zhu, Lei Lin, Zhaoting Yeo, Tomas Chotivanich, Kesinee Imwong, Mallika Pukrittayakamee, Sasithon Dhorda, Mehul Nguon, Chea Lim, Pharath Amaratunga, Chanaki Suon, Seila Tran Tinh Hien Htut, Ye Faiz, M. Abul Onyamboko, Marie A. Mayxay, Mayfong Newton, Paul N. Tripura, Rupam Woodrow, Charles J. Miotto, Olivo Kwiatkowski, Dominic P. Nosten, Francois Day, Nicholas P. J. Preiser, Peter R. White, Nicholas J. Dondorp, Arjen M. Fairhurst, Rick M. Bozdech, Zbynek TI Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance SO SCIENCE LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; DIHYDROARTEMISININ-PIPERAQUINE; WESTERN CAMBODIA; CLEARANCE RATE; PROVINCE; PROTEIN; VIVAX AB Artemisinin resistance in Plasmodium falciparum threatens global efforts to control and eliminate malaria. Polymorphisms in the kelch domain-carrying protein K13 are associated with artemisinin resistance, but the underlying molecular mechanisms are unknown. We analyzed the in vivo transcriptomes of 1043 P. falciparum isolates from patients with acute malaria and found that artemisinin resistance is associated with increased expression of unfolded protein response (UPR) pathways involving the major PROSC and TRiC chaperone complexes. Artemisinin-resistant parasites also exhibit decelerated progression through the first part of the asexual intraerythrocytic development cycle. These findings suggest that artemisinin-resistant parasites remain in a state of decelerated development at the young ring stage, whereas their up-regulated UPR pathways mitigate protein damage caused by artemisinin. The expression profiles of UPR-related genes also associate with the geographical origin of parasite isolates, further suggesting their role in emerging artemisinin resistance in the Greater Mekong Subregion. C1 [Mok, Sachel; Ferreira, Pedro E.; Zhu, Lei; Lin, Zhaoting; Yeo, Tomas; Preiser, Peter R.; Bozdech, Zbynek] Nanyang Technol Univ, Sch Biol Sci, Singapore 639798, Singapore. [Ashley, Elizabeth A.; Newton, Paul N.; Tripura, Rupam; Woodrow, Charles J.; Miotto, Olivo; Day, Nicholas P. J.; White, Nicholas J.; Dondorp, Arjen M.] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok 10700, Thailand. [Ashley, Elizabeth A.; Dhorda, Mehul; Newton, Paul N.; Woodrow, Charles J.; Nosten, Francois; Day, Nicholas P. J.; White, Nicholas J.; Dondorp, Arjen M.] Univ Oxford, Nuffield Dept Med, Ctr Trop Med & Global Hlth, Oxford, England. [Chotivanich, Kesinee; Pukrittayakamee, Sasithon] Mahidol Univ, Fac Trop Med, Dept Clin Trop Med, Bangkok 10700, Thailand. [Imwong, Mallika] Mahidol Univ, Fac Trop Med, Dept Mol Trop Med & Genet, Bangkok, Thailand. [Dhorda, Mehul] Mahidol Univ, Asia Reg Ctr, WorldWide Antimalarial Resistance Network WWARN, Bangkok 10700, Thailand. [Dhorda, Mehul] Univ Maryland, Sch Med, WorldWide Antimalarial Resistance Network, Baltimore, MD 21201 USA. [Nguon, Chea; Lim, Pharath; Suon, Seila] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia. [Lim, Pharath; Amaratunga, Chanaki; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Tran Tinh Hien] Hosp Trop Dis, OUCRU, Ho Chi Minh City, Vietnam. [Htut, Ye] Dept Med Res, Lower Myanmar, Yangon, Myanmar. [Faiz, M. Abul] Malaria Res Grp & Dev Care Fdn, Dhaka, Bangladesh. [Onyamboko, Marie A.] Kinshasa Sch Publ Hlth, Kinshasa, Congo. [Mayxay, Mayfong; Newton, Paul N.] Lao Oxford Mahosot Hosp, Wellcome Trust Res Unit, Mahosot Hosp, Viangchan, Laos. [Mayxay, Mayfong] Univ Hlth Sci, Fac Postgrad Studies, Viangchan, Laos. [Miotto, Olivo; Kwiatkowski, Dominic P.] Univ Oxford, Ctr Genom & Global Hlth, MRC, Oxford, England. [Miotto, Olivo; Kwiatkowski, Dominic P.] Wellcome Trust Sanger Inst, Cambridge, England. [Nosten, Francois] Mahidol Univ, Fac Trop Med, Shoklo Malaria Res Unit, Mahidol Oxford Trop Med Res Unit, Mae Sot, Thailand. RP Bozdech, Z (reprint author), Nanyang Technol Univ, Sch Biol Sci, Singapore 639798, Singapore. EM zbozdech@ntu.edu.sg RI Bozdech, Zbynek/A-2205-2011; Ferreira, Pedro Eduardo/Q-6748-2016; OI Ferreira, Pedro Eduardo/0000-0002-2682-7722; Miotto, Olivo/0000-0001-8060-6771; Nosten, Francois/0000-0002-7951-0745; , Peter/0000-0003-4331-7000; Woodrow, Charles/0000-0002-5134-7165 FU Singapore National Medical Council [NMRC/1265/2010, NMRC/1292/2011]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID); UK Department for International Development (DFID); Wellcome Trust of Great Britain; Wellcome Trust; Wellcome Trust Sanger Institute [098051]; WorldWide Antimalarial Resistance Network; Intramural Research Program of NIAID; Bill & Melinda Gates Foundation FX Supported by Singapore National Medical Council grants NMRC/1265/2010 and NMRC/1292/2011 and by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID). We are very grateful to the patients, doctors, nurses, and laboratory technicians who participated in the TRAC clinical studies. TRAC was funded by the UK Department for International Development (DFID) for the benefit of developing countries and coordinated by the Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme funded by the Wellcome Trust of Great Britain. Whole-genome sequencing and genotyping for TRAC were funded by the Wellcome Trust through core funding of the Wellcome Trust Sanger Institute (grant 098051). Additional support was given by the WorldWide Antimalarial Resistance Network, the Intramural Research Program of NIAID, and the Bill & Melinda Gates Foundation. The views expressed and information contained in this publication are not necessarily those of or endorsed by DFID or the other funders, which can accept no responsibility for such views or for any reliance placed on them. We thank W. Guo, K.-Y. Liong, and J. Sim for their assistance. The microarray data have been deposited in NCBI's Gene Expression Omnibus (GEO) and are accessible through GEO Series accession number GSE59099. NR 30 TC 67 Z9 69 U1 6 U2 56 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 JAN 23 PY 2015 VL 347 IS 6220 BP 431 EP 435 DI 10.1126/science.1260403 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ4XZ UT WOS:000348225800046 PM 25502316 ER PT J AU Springborn, M Chowell, G MacLachlan, M Fenichel, EP AF Springborn, Michael Chowell, Gerardo MacLachlan, Matthew Fenichel, Eli P. TI Accounting for behavioral responses during a flu epidemic using home television viewing SO BMC INFECTIOUS DISEASES LA English DT Article DE Epidemic model; Social distancing; A/H1N1; Influenza; SIR ID INFLUENZA-A H1N1; PANDEMIC INFLUENZA; SCHOOL CLOSURE; TRANSMISSION; IMPACT; VIRUS; MEXICO; INFECTION; COMMUNITY; PATTERNS AB Background: Theory suggests that individual behavioral responses impact the spread of flu-like illnesses, but this has been difficult to empirically characterize. Social distancing is an important component of behavioral response, though analyses have been limited by a lack of behavioral data. Our objective is to use media data to characterize social distancing behavior in order to empirically inform explanatory and predictive epidemiological models. Methods: We use data on variation in home television viewing as a proxy for variation in time spent in the home and, by extension, contact. This behavioral proxy is imperfect but appealing since information on a rich and representative sample is collected using consistent techniques across time and most major cities. We study the April-May 2009 outbreak of A/H1N1 in Central Mexico and examine the dynamic behavioral response in aggregate and contrast the observed patterns of various demographic subgroups. We develop and calibrate a dynamic behavioral model of disease transmission informed by the proxy data on daily variation in contact rates and compare it to a standard (non-adaptive) model and a fixed effects model that crudely captures behavior. Results: We find that after a demonstrable initial behavioral response (consistent with social distancing) at the onset of the outbreak, there was attenuation in the response before the conclusion of the public health intervention. We find substantial differences in the behavioral response across age subgroups and socioeconomic levels. We also find that the dynamic behavioral and fixed effects transmission models better account for variation in new confirmed cases, generate more stable estimates of the baseline rate of transmission over time and predict the number of new cases over a short horizon with substantially less error. Conclusions: Results suggest that A/H1N1 had an innate transmission potential greater than previously thought but this was masked by behavioral responses. Observed differences in behavioral response across demographic groups indicate a potential benefit from targeting social distancing outreach efforts. C1 [Springborn, Michael] Univ Calif Davis, Dept Environm Sci & Policy, Davis, CA 95616 USA. [Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30302 USA. [Chowell, Gerardo] Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, NIH, Bethesda, MD 20892 USA. [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Math Computat & Modeling Sci Ctr, Tempe, AZ 85287 USA. [MacLachlan, Matthew] Univ Calif Davis, Dept Agr & Resource Econ, Davis, CA 95616 USA. [Fenichel, Eli P.] Yale Sch Forestry & Environm Studies, New Haven, CT 06511 USA. RP Springborn, M (reprint author), Univ Calif Davis, Dept Environm Sci & Policy, 2104 Wickson Hall,One Shields Ave, Davis, CA 95616 USA. EM mspringborn@ucdavis.edu OI Fenichel, Eli/0000-0002-7649-8250 FU National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health [1R01GM100471-01] FX This publication was made possible by grant number 1R01GM100471-01 from the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS. NR 40 TC 4 Z9 4 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD JAN 23 PY 2015 VL 15 AR 21 DI 10.1186/s12879-014-0691-0 PG 14 WC Infectious Diseases SC Infectious Diseases GA AZ7JN UT WOS:000348395600001 PM 25616673 ER PT J AU Milner, JD Vogel, TP Forbes, L Ma, CA Stray-Pedersen, A Niemela, JE Lyons, JJ Engelhardt, KR Zhang, Y Topcagic, N Roberson, EDO Matthews, H Verbsky, JW Dasu, T Vargas-Hernandez, A Varghese, N McClain, KL Karam, LB Nahmod, K Makedonas, G Mace, EM Sorte, HS Perminow, G Rao, VK O'Connell, MP Price, S Su, HC Butrick, M McElwee, J Hughes, JD Willet, J Swan, D Xu, Y Santibanez-Koref, M Slowik, V Dinwiddie, DL Ciaccio, CE Saunders, CJ Septer, S Kingsmore, SF White, AJ Cant, AJ Hambleton, S Cooper, MA AF Milner, Joshua D. Vogel, Tiphanie P. Forbes, Lisa Ma, Chi A. Stray-Pedersen, Asbjorg Niemela, Julie E. Lyons, Jonathan J. Engelhardt, Karin R. Zhang, Yu Topcagic, Nermina Roberson, Elisha D. O. Matthews, Helen Verbsky, James W. Dasu, Trivikram Vargas-Hernandez, Alexander Varghese, Nidhy McClain, Kenneth L. Karam, Lina B. Nahmod, Karen Makedonas, George Mace, Emily M. Sorte, Hanne S. Perminow, Gori Rao, V. Koneti O'Connell, Michael P. Price, Susan Su, Helen C. Butrick, Morgan McElwee, Joshua Hughes, Jason D. Willet, Joseph Swan, David Xu, Yaobo Santibanez-Koref, Mauro Slowik, Voytek Dinwiddie, Darrell L. Ciaccio, Christina E. Saunders, Carol J. Septer, Seth Kingsmore, Stephen F. White, Andrew J. Cant, Andrew J. Hambleton, Sophie Cooper, Megan A. TI Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations SO BLOOD LA English DT Article ID HYPER-IGE SYNDROME; REGULATORY T-CELLS; IMMUNE DYSREGULATION; SIGNAL TRANSDUCER; DISEASE; POLYENDOCRINOPATHY; IMMUNODEFICIENCY; ENTEROPATHY; ACTIVATOR; JAKS AB Germline loss-of-function mutations in the transcription factor signal transducer and activator of transcription 3 (STAT3) cause immunodeficiency, whereas somatic gain-of-function mutations in STAT3 are associated with large granular lymphocytic leukemic, myelodysplastic syndrome, and aplastic anemia. Recently, germlinemutations in STAT3 have also been associated with autoimmune disease. Here, we report on 13 individuals from 10 families with lymphoproliferation and early-onset solid-organ autoimmunity associated with 9 different germline heterozygous mutations in STAT3. Patients exhibited a variety of clinical features, withmost having lymphadenopathy, autoimmune cytopenias, multiorgan autoimmunity (lung, gastrointestinal, hepatic, and/or endocrine dysfunction), infections, and short stature. Functional analyses demonstrate that these mutations confer a gain-of-function in STAT3 leading to secondary defects in STAT5 and STAT1 phosphorylation and the regulatory T-cell compartment. Treatment targeting a cytokine pathway that signals through STAT3 led to clinical improvement in 1 patient, suggesting a potential therapeutic option for such patients. These results suggest that there is a broad range of autoimmunity caused by germline STAT3 gain-of-function mutations, and that hematologic autoimmunity is a major component of this newly described disorder. Some patients for this study were enrolled in a trial registered at www.clinicaltrials.gov as #NCT00001350. C1 [Milner, Joshua D.; Ma, Chi A.; Lyons, Jonathan J.; O'Connell, Michael P.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Vogel, Tiphanie P.; Topcagic, Nermina; White, Andrew J.; Cooper, Megan A.] Washington Univ, Sch Med, Dept Pediat, Div Rheumatol, St Louis, MO 63110 USA. [Vogel, Tiphanie P.; Roberson, Elisha D. O.] Washington Univ, Sch Med, Dept Internal Med, Div Rheumatol, St Louis, MO 63110 USA. [Forbes, Lisa; Stray-Pedersen, Asbjorg; Vargas-Hernandez, Alexander; Nahmod, Karen; Makedonas, George; Mace, Emily M.] Baylor Coll Med, Sect Immunol Allergy & Rheumatol, Dept Pediat, Houston, TX 77030 USA. [Forbes, Lisa; Stray-Pedersen, Asbjorg; Nahmod, Karen; Makedonas, George; Mace, Emily M.] Texas Childrens Hosp, Baylor Coll Med, Ctr Human Immunobiol, Houston, TX 77030 USA. [Stray-Pedersen, Asbjorg] Baylor Coll Med, Ctr Mendelian Genom, Dept Mol & Human Genet, Houston, TX 77030 USA. [Stray-Pedersen, Asbjorg; Sorte, Hanne S.] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway. [Niemela, Julie E.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Engelhardt, Karin R.; Willet, Joseph; Swan, David; Cant, Andrew J.; Hambleton, Sophie] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Zhang, Yu; Su, Helen C.] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA. [Roberson, Elisha D. O.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Matthews, Helen; Rao, V. Koneti; Price, Susan; Butrick, Morgan] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Verbsky, James W.; Dasu, Trivikram] Med Coll Wisconsin, Div Rheumatol, Dept Pediat, Milwaukee, WI 53226 USA. [Verbsky, James W.; Dasu, Trivikram] Med Coll Wisconsin, Dept Microbiol & Med Genet, Milwaukee, WI 53226 USA. [Dasu, Trivikram] Med Coll Wisconsin, Dept Clin Immunodiagnost, Milwaukee, WI 53226 USA. [Dasu, Trivikram] Med Coll Wisconsin, Res Lab, Milwaukee, WI 53226 USA. [Varghese, Nidhy; McClain, Kenneth L.; Karam, Lina B.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Perminow, Gori] Oslo Univ Hosp, Dept Pediat, Oslo, Norway. [McElwee, Joshua; Hughes, Jason D.] Merck Res Labs, Boston, MA USA. [Xu, Yaobo; Santibanez-Koref, Mauro] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Slowik, Voytek; Septer, Seth] Childrens Mercy Hosp & Clin, Dept Pediat, Sect Pediat Gastroenterol, Kansas City, MO USA. [Dinwiddie, Darrell L.; Saunders, Carol J.; Kingsmore, Stephen F.] Childrens Mercy Hosp & Clin, Ctr Pediat Genom Med, Kansas City, MO USA. [Dinwiddie, Darrell L.] Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Dinwiddie, Darrell L.] Univ New Mexico, Hlth Sci Ctr, Clin Translat Sci Ctr, Albuquerque, NM 87131 USA. [Ciaccio, Christina E.] Childrens Mercy Hosp & Clin, Div Allergy & Immunol, Dept Pediat, Kansas City, MO USA. [Saunders, Carol J.; Kingsmore, Stephen F.] Childrens Mercy Hosp & Clin, Dept Pathol, Kansas City, MO USA. [Saunders, Carol J.; Kingsmore, Stephen F.] Univ Missouri, Sch Med, Kansas City, MO 64108 USA. [Cant, Andrew J.; Hambleton, Sophie] Great North Childrens Hosp, Paediat Immunol & Infect Dis, Newcastle Upon Tyne, Tyne & Wear, England. [Cooper, Megan A.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Milner, JD (reprint author), NIH, Bldg 10 CRC,Room 5-3950, Bethesda, MD 20892 USA. EM jdmilner@niaid.nih.gov; cooper_m@kids.wustl.edu RI Su, Helen/H-9541-2015; Roberson, Elisha/J-1747-2012; OI Su, Helen/0000-0002-5582-9110; Roberson, Elisha/0000-0001-5921-2399; Niemela, Julie/0000-0003-4197-3792; Lyons, Jonathan/0000-0002-2346-8189; Swan, Daniel/0000-0001-8978-8129 FU National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Children's Discovery Institute; St. Louis Children's Hospital; Scleroderma Foundation; Rheumatic Diseases Core Center at Washington University [P30AR048335]; NIH [2T32AR007279]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [P30AR048335]; Sir Jules Thorn Charitable Trust; NIH National Human Genome Research Institute [U54HG006542, U54HG003273]; National Cancer Institute (NCI) Cancer Center [P30 CA91842]; Institute of Clinical and Translational Sciences/Clinical & Translational Science Awards (ICTS/CTSA) from the National Center for Research Resources, a component of the NIH [UL1TR000448]; NIH Roadmap for Medical Research; WT Kemper Foundation; Marion Merrell Dow Foundation; Black Veatch; Pat and Gil Clements Foundation; Claire Giannini Foundation; National Institute of Child Health and Human Development (NICHD) [U19HD077693] FX This work was supported in part by the intramural research program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). Work in M.A.C.'s laboratory was supported by The Children's Discovery Institute and St. Louis Children's Hospital, The Scleroderma Foundation, the Rheumatic Diseases Core Center at Washington University (P30AR048335), and NIH training grant 2T32AR007279 (T.P.V.). Analysis of Washington University exome data was performed by the Human Genetics Facility of the Rheumatic Diseases Core Center (E.D.O.R.), supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) P30AR048335. Work in S.H.'s laboratory was supported by the Sir Jules Thorn Charitable Trust. The Baylor-Hopkins Center for Mendelian Genomics was supported by the NIH National Human Genome Research Institute (U54HG006542 and U54HG003273). Genomic analysis by the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine was partially supported by National Cancer Institute (NCI) Cancer Center support grant P30 CA91842 to the Siteman Cancer Center and Institute of Clinical and Translational Sciences/Clinical & Translational Science Awards (ICTS/CTSA) grant UL1TR000448 from the National Center for Research Resources, a component of the NIH, and the NIH Roadmap for Medical Research. The work at the Children's Mercy Center for Pediatric Genomic Medicine was supported by the WT Kemper Foundation, the Marion Merrell Dow Foundation, Black & Veatch, the Pat and Gil Clements Foundation, the Claire Giannini Foundation, and U19HD077693 from the National Institute of Child Health and Human Development (NICHD). NR 31 TC 66 Z9 68 U1 2 U2 11 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 JAN 22 PY 2015 VL 125 IS 4 BP 591 EP 599 DI 10.1182/blood-2014-09-602763 PG 9 WC Hematology SC Hematology GA CD1DO UT WOS:000350814500006 PM 25359994 ER PT J AU Perez-Andreu, V Roberts, KG Xu, H Smith, C Zhang, H Yang, WJ Harvey, RC Payne-Turner, D Devidas, M Cheng, IM Carroll, WL Heerema, NA Carroll, AJ Raetz, EA Gastier-Foster, JM Marcucci, G Bloomfield, CD Mrozek, K Kohlschmidt, J Stock, W Kornblau, SM Konopleva, M Paietta, E Rowe, JM Luger, SM Tallman, MS Dean, M Burchard, EG Torgerson, DG Yue, F Wang, YL Pui, CH Jeha, S Relling, MV Evans, WE Gerhard, DS Loh, ML Willman, CL Hunger, SP Mullighan, CG Yang, JJ AF Perez-Andreu, Virginia Roberts, Kathryn G. Xu, Heng Smith, Colton Zhang, Hui Yang, Wenjian Harvey, Richard C. Payne-Turner, Debbie Devidas, Meenakshi Cheng, I-Ming Carroll, William L. Heerema, Nyla A. Carroll, Andrew J. Raetz, Elizabeth A. Gastier-Foster, Julie M. Marcucci, Guido Bloomfield, Clara D. Mrozek, Krzysztof Kohlschmidt, Jessica Stock, Wendy Kornblau, Steven M. Konopleva, Marina Paietta, Elisabeth Rowe, Jacob M. Luger, Selina M. Tallman, Martin S. Dean, Michael Burchard, Esteban G. Torgerson, Dara G. Yue, Feng Wang, Yanli Pui, Ching-Hon Jeha, Sima Relling, Mary V. Evans, William E. Gerhard, Daniela S. Loh, Mignon L. Willman, Cheryl L. Hunger, Stephen P. Mullighan, Charles G. Yang, Jun J. TI A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults SO BLOOD LA English DT Article ID CHILDRENS ONCOLOGY GROUP; HYPER-CVAD; RISK; VARIANTS; RELAPSE; CANCER; POPULATIONS; DIAGNOSIS; REGIMEN; KINASE AB Acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA) is characterized by distinct presenting features and inferior prognosis compared with pediatric ALL. We performed a genome-wide association study (GWAS) to comprehensively identify inherited genetic variants associated with susceptibility to AYA ALL. In the discovery GWAS, we compared genotype frequency at 635 297 single nucleotide polymorphisms(SNPs) in 308AYAALL cases and 6,661 non-ALL controls by using a logistic regression model with genetic ancestry as a covariate. SNPs that reached P <= 5 x 10(-8) in GWAS were tested in an independent cohort of 162 AYA ALL cases and 5,755 non-ALL controls. We identified a single genome-wide significant susceptibility locus in GATA3: rs3824662, odds ratio (OR), 1.77 (P = 2.8 x 10(-10)) and rs3781093, OR, 1.73 (P = 3.2 x 10(-9)). These findings were validated in the replication cohort. The risk allele at rs3824662 was most frequent in Philadelphia chromosome (Ph)-like ALL but also conferred susceptibility to non-Ph-like ALL in AYAs. In 1,827 non-selected ALL cases, the risk allele frequency at this SNP was positively correlated with age at diagnosis (P = 6.29 x 10(-11)). Our results from this first GWAS of AYA ALL susceptibility point to unique biology underlying leukemogenesis and potentially distinct disease etiology by age group. C1 [Perez-Andreu, Virginia; Xu, Heng; Smith, Colton; Zhang, Hui; Yang, Wenjian; Relling, Mary V.; Evans, William E.; Yang, Jun J.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Roberts, Kathryn G.; Payne-Turner, Debbie; Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Xu, Heng] Sichuan Univ, West China Med Sch, State Key Lab Biotherapy, Chengdu 610064, Peoples R China. [Xu, Heng] Sichuan Univ, West China Med Sch, Ctr Canc, Chengdu 610064, Peoples R China. [Harvey, Richard C.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Devidas, Meenakshi] Univ Florida, Coll Med, Dept Biostat, Gainesville, FL USA. [Devidas, Meenakshi] Univ Florida, Dept Biostat, Coll Publ Hlth, Gainesville, FL USA. [Devidas, Meenakshi] Univ Florida, Coll Hlth Profess, Dept Biostat, Gainesville, FL USA. [Cheng, I-Ming; Willman, Cheryl L.] Univ New Mexico, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. [Carroll, William L.] NYU, Laura & Isaac Perlmutter Canc Ctr, Langone Med Ctr, New York, NY USA. [Heerema, Nyla A.] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA. [Carroll, Andrew J.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Raetz, Elizabeth A.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Gastier-Foster, Julie M.] Ohio State Univ, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Marcucci, Guido; Bloomfield, Clara D.; Mrozek, Krzysztof; Kohlschmidt, Jessica] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Kohlschmidt, Jessica] Mayo Clin, Alliance Clin Trials Oncol Stat, Rochester, MN USA. [Kohlschmidt, Jessica] Mayo Clin, Ctr Data, Rochester, MN USA. [Stock, Wendy] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Kornblau, Steven M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Sect Mol Hematol & Therapy, Houston, TX 77030 USA. [Konopleva, Marina] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Paietta, Elisabeth] Yeshiva Univ, Albert Einstein Coll Med, Dept Med Oncol, New York, NY 10033 USA. [Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel. [Luger, Selina M.] Univ Penn, Hematol Malignancies Program, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA. [Dean, Michael] NCI, Expt Immunol Lab, Frederick, MD 21701 USA. [Burchard, Esteban G.; Torgerson, Dara G.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Burchard, Esteban G.; Torgerson, Dara G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Yue, Feng; Wang, Yanli] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA USA. [Pui, Ching-Hon; Jeha, Sima] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA. [Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Loh, Mignon L.] Univ Calif San Francisco, Helen Diller Family Canc Ctr, San Francisco, CA 94143 USA. [Hunger, Stephen P.] Univ Colorado, Sch Med, Aurora, CO USA. [Hunger, Stephen P.] Univ Colorado, Sch Med, Childrens Hosp, Aurora, CO USA. RP Yang, JJ (reprint author), St Jude Childrens Res Hosp, Dept Pharmaceut Sci, MS 313,262 Danny Thomas Pl, Memphis, TN 38105 USA. EM charles.mullighan@stjude.org; jun.yang@stjude.org RI Mrozek, Krzysztof/A-3142-2008; OI Harvey, Richard/0000-0002-4904-9767 FU National Institutes of Health, National Cancer Institute [CA145707, CA156449, CA21765, CA36401, CA98543, CA114766, CA98413, CA140729, CA176063, HHSN261200800001E]; National Institute of General Medical Sciences [GM92666]; National Cancer Institute; Stand Up to Cancer Innovative Research Grant; American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital; St. Jude Children's Research Hospital Academic Programs Special Fellowship; Spanish Ministry of Education; American Society of Hematology; Order of St. Francis Foundation; Leukemia and Lymphoma Society; Alex's Lemonade Stand Foundation FX This work was supported by the National Institutes of Health, National Cancer Institute grants CA145707, CA156449, CA21765, CA36401, CA98543, CA114766, CA98413, CA140729, CA176063, and HHSN261200800001E, the National Institute of General Medical Sciences grant GM92666, in part by the intramural Program of the National Cancer Institute, by a Stand Up to Cancer Innovative Research Grant, and by the American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital, by a St. Jude Children's Research Hospital Academic Programs Special Fellowship and a Spanish Ministry of Education Fellowship Grant (V.P.-A.), by the American Society of Hematology Scholar Award and by the Order of St. Francis Foundation (J.J.Y.), and by a Leukemia and Lymphoma Society Fellow Award and Alex's Lemonade Stand Foundation Young Investigator Award (K.G.R.). S.P.H. is the Ergen Family Chair in Pediatric Cancer, C.G.M. is a Pew Scholar in the Biomedical Sciences and a St. Baldrick's Scholar, and H.Z. is a St. Baldrick's International Scholar. NR 50 TC 24 Z9 23 U1 3 U2 11 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 JAN 22 PY 2015 VL 125 IS 4 BP 680 EP 686 DI 10.1182/blood-2014-09-595744 PG 7 WC Hematology SC Hematology GA CD1DO UT WOS:000350814500016 PM 25468567 ER PT J AU Dumitriu, B Feng, XM Townsley, DM Ueda, Y Yoshizato, T Calado, RT Yang, YQ Wakabayashi, Y Kajigaya, S Ogawa, S Zhu, J Young, NS AF Dumitriu, Bogdan Feng, Xingmin Townsley, Danielle M. Ueda, Yasutaka Yoshizato, Tetsuichi Calado, Rodrigo T. Yang, Yanqin Wakabayashi, Yoshiyuki Kajigaya, Sachiko Ogawa, Seishi Zhu, Jun Young, Neal S. TI Telomere attrition and candidate gene mutations preceding monosomy 7 in aplastic anemia SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROMES; ASSOCIATION; INSTABILITY; EVOLUTION; CANCER; CELLS; 7Q AB The pathophysiology of severe aplastic anemia (SAA) is immune-mediated destruction of hematopoietic stem and progenitor cells (HSPCs). Most patients respond to immunosuppressive therapies, but a minority transform to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), frequently associated with monosomy 7 (-7). Thirteen SAA patients were analyzed for acquired mutations in myeloid cells at the time of evolution to -7, and all had a dominant HSPC clone bearing specific acquired mutations. However, mutations in genes associated with MDS/AML were present in only 4 cases. Patients who evolved to MDS and AML showed marked progressive telomere attrition before the emergence of -7. Single telomere length analysis confirmed accumulation of short telomere fragments of individual chromosomes. Our results indicate that accelerated telomere attrition in the setting of a decreased HSPC pool is characteristic of early myeloid oncogenesis, specifically chromosome 7 loss, in MDS/AML after SAA, and provides a possible mechanism for development of aneuploidy. C1 [Dumitriu, Bogdan; Feng, Xingmin; Townsley, Danielle M.; Ueda, Yasutaka; Kajigaya, Sachiko; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Yoshizato, Tetsuichi; Ogawa, Seishi] Kyoto Univ, Dept Pathol & Tumor Biol, Kyoto, Japan. [Calado, Rodrigo T.] Univ Sao Paulo, Sch Med, Dept Internal Med, BR-14049 Ribeirao Preto, SP, Brazil. [Yang, Yanqin; Wakabayashi, Yoshiyuki; Zhu, Jun] NHLBI, DNA Sequencing & Computat Biol Core, NIH, Bethesda, MD 20892 USA. RP Dumitriu, B (reprint author), 10 Ctr Dr MSC 1475,Bldg 10,CRC 3-5216, Bethesda, MD 20892 USA. EM dumitriub@nhlbi.nih.gov RI Calado, Rodrigo/G-2619-2011 FU Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 20 TC 11 Z9 12 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 22 PY 2015 VL 125 IS 4 BP 706 EP 709 DI 10.1182/blood-2014-10-607572 PG 4 WC Hematology SC Hematology GA CD1DO UT WOS:000350814500019 PM 25406353 ER PT J AU Patel, RM Kandefer, S Walsh, MC Bell, EF Carlo, WA Laptook, AR Sanchez, PJ Shankaran, S Van Meurs, KP Ball, MB Hale, EC Newman, NS Das, A Higgins, RD Stoll, BJ AF Patel, Ravi M. Kandefer, Sarah Walsh, Michele C. Bell, Edward F. Carlo, Waldemar A. Laptook, Abbot R. Sanchez, Pablo J. Shankaran, Seetha Van Meurs, Krisa P. Ball, M. Bethany Hale, Ellen C. Newman, Nancy S. Das, Abhik Higgins, Rosemary D. Stoll, Barbara J. CA Eunice Kennedy Shriver Natl Inst TI Causes and Timing of Death in Extremely Premature Infants from 2000 through 2011 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BIRTH-WEIGHT INFANTS; NEONATAL RESEARCH NETWORK; PRETERM INFANTS; GESTATIONAL-AGE; MORTALITY; MORBIDITY; OUTCOMES; TRENDS; BORN AB BACKGROUND Understanding the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families. METHODS We analyzed prospectively collected data on 6075 deaths among 22,248 live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011, with adjustment for baseline differences. RESULTS The number of deaths per 1000 live births was 275 (95% confidence interval [CI], 264 to 285) from 2000 through 2003 and 285 (95% CI, 275 to 295) from 2004 through 2007; the number decreased to 258 (95% CI, 248 to 268) in the 2008-2011 period (P = 0.003 for the comparison across three periods). There were fewer pulmonary-related deaths attributed to the respiratory distress syndrome and bronchopulmonary dysplasia in 2008-2011 than in 2000-2003 and 2004-2007 (68 [95% CI, 63 to 74] vs. 83 [95% CI, 77 to 90] and 84 [95% CI, 78 to 90] per 1000 live births, respectively; P = 0.002). Similarly, in 2008-2011, as compared with 2000-2003, there were decreases in deaths attributed to immaturity (P = 0.05) and deaths complicated by infection (P = 0.04) or central nervous system injury (P < 0.001); however, there were increases in deaths attributed to necrotizing enterocolitis (30 [95% CI, 27 to 34] vs. 23 [95% CI, 20 to 27], P = 0.03). Overall, 40.4% of deaths occurred within 12 hours after birth, and 17.3% occurred after 28 days. CONCLUSIONS We found that from 2000 through 2011, overall mortality declined among extremely premature infants. Deaths related to pulmonary causes, immaturity, infection, and central nervous system injury decreased, while necrotizing enterocolitis-related deaths increased. C1 [Patel, Ravi M.; Hale, Ellen C.; Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. [Patel, Ravi M.; Hale, Ellen C.; Stoll, Barbara J.] Childrens Healthcare Atlanta, Atlanta, GA USA. [Kandefer, Sarah] RTI Int, Social Stat & Environm Sci Unit, Res Triangle Pk, NC USA. [Walsh, Michele C.; Newman, Nancy S.] Case Western Reserve Univ, Dept Pediat, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Sanchez, Pablo J.] Ohio State Univ, Dept Pediat, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA. [Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. [Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Van Meurs, Krisa P.; Ball, M. Bethany] Stanford Univ, Dept Pediat, Div Neonatal & Dev Med, Sch Med, Palo Alto, CA 94304 USA. [Van Meurs, Krisa P.; Ball, M. Bethany] Lucile Packard Childrens Hosp, Palo Alto, CA USA. [Das, Abhik] RTI Int, Social Stat & Environm Sci Unit, Rockville, MD USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Patel, RM (reprint author), Emory Univ, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, 2015 Uppergate Dr NE,3rd Fl, Atlanta, GA 30322 USA. EM rmpatel@emory.edu RI Patel, Ravi/B-7218-2011; OI Patel, Ravi/0000-0002-7444-5550; Lakshminrusimha, Satyan/0000-0001-6098-2155 FU National Institutes of Health (NIH); Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH [HD27904, HD21364, HD68284, HD27853, HD40492, HD27851, HD27856, HD68278, HD36790, HD27880, HD53119, HD34216, HD68270, HD40461, HD53109, HD21397, HD27881, HD53089, HD68244, HD68263, HD40521, HD21415, HD40689, HD21373, HD53124, HD40498, HD21385, HD27871]; National Center for Advancing Translational Sciences, NIH [UL1TR000454, KL2TR000455] FX Supported by grants from the National Institutes of Health (NIH), grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, for the Neonatal Research Network Generic Database Study (U10 awards HD27904, HD21364, HD68284, HD27853, HD40492, HD27851, HD27856, HD68278, HD36790, HD27880, HD53119, HD34216, HD68270, HD40461, HD53109, HD21397, HD27881, HD53089, HD68244, HD68263, HD40521, HD21415, HD40689, HD21373, HD53124, HD40498, HD21385, and HD27871), and grants from the National Center for Advancing Translational Sciences, NIH (UL1TR000454 and KL2TR000455, to Dr. Patel). NR 18 TC 76 Z9 79 U1 0 U2 17 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 JAN 22 PY 2015 VL 372 IS 4 BP 331 EP 340 DI 10.1056/NEJMoa1403489 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AZ4PJ UT WOS:000348204500008 PM 25607427 ER PT J AU Pinsky, PF AF Pinsky, Paul F. TI Cost-Effectiveness of CT Screening in the National Lung Screening Trial SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Bethesda, MD 20892 USA. EM pinskyp@mail.nih.gov NR 2 TC 0 Z9 0 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 JAN 22 PY 2015 VL 372 IS 4 BP 387 EP 387 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AZ4PJ UT WOS:000348204500020 PM 25607438 ER PT J AU Mitra, M Singer, D Mano, Y Hritz, J Nam, G Gorelick, RJ Byeon, IJL Gronenborn, AM Iwatani, Y Levin, JG AF Mitra, Mithun Singer, Dustin Mano, Yu Hritz, Jozef Nam, Gabriel Gorelick, Robert J. Byeon, In-Ja L. Gronenborn, Angela M. Iwatani, Yasumasa Levin, Judith G. TI Sequence and structural determinants of human APOBEC3H deaminase and anti-HIV-1 activities SO RETROVIROLOGY LA English DT Article DE HIV-1; APOBEC3H; Homology model; Deaminase activity; Antiviral activity; Deaminase-independent restriction; Reverse transcription ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 REVERSE TRANSCRIPTION; SINGLE-STRANDED-DNA; FUSION INHIBITOR T-20; CYTIDINE DEAMINASE; ANTIVIRAL ACTIVITY; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; RETROVIRAL RESTRICTION; INTRINSIC IMMUNITY AB Background: Human APOBEC3H (A3H) belongs to the A3 family of host restriction factors, which are cytidine deaminases that catalyze conversion of deoxycytidine to deoxyuridine in single-stranded DNA. A3 proteins contain either one (A3A, A3C, A3H) or two (A3B, A3D, A3F, A3G) Zn-binding domains. A3H has seven haplotypes (I-VII) that exhibit diverse biological phenotypes and geographical distribution in the human population. Its single Zn-coordinating deaminase domain belongs to a phylogenetic cluster (Z3) that is different from the Z1- and Z2-type domains in other human A3 proteins. A3H HapII, unlike A3A or A3C, has potent activity against HIV-1. Here, we sought to identify the determinants of A3H HapII deaminase and antiviral activities, using site-directed sequence- and structure-guided mutagenesis together with cell-based, biochemical, and HIV-1 infectivity assays. Results: We have constructed a homology model of A3H HapII, which is similar to the known structures of other A3 proteins. The model revealed a large cluster of basic residues (not present in A3A or A3C) that are likely to be involved in nucleic acid binding. Indeed, RNase A pretreatment of 293T cell lysates expressing A3H was shown to be required for detection of deaminase activity, indicating that interaction with cellular RNAs inhibits A3H catalytic function. Similar observations have been made with A3G. Analysis of A3H deaminase substrate specificity demonstrated that a 5' T adjacent to the catalytic C is preferred. Changing the putative nucleic acid binding residues identified by the model resulted in reduction or abrogation of enzymatic activity, while substituting Z3-specific residues in A3H to the corresponding residues in other A3 proteins did not affect enzyme function. As shown for A3G and A3F, some A3H mutants were defective in catalysis, but retained antiviral activity against HIV-1vif (-) virions. Furthermore, endogenous reverse transcription assays demonstrated that the E56A catalytic mutant inhibits HIV-1 DNA synthesis, although not as efficiently as wild type. Conclusions: The molecular and biological activities of A3H are more similar to those of the double-domain A3 proteins than to those of A3A or A3C. Importantly, A3H appears to use both deaminase-dependent and -independent mechanisms to target reverse transcription and restrict HIV-1 replication. C1 [Mitra, Mithun; Singer, Dustin; Nam, Gabriel; Levin, Judith G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Viral Gene Regulat, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Mano, Yu; Iwatani, Yasumasa] Natl Hosp Org, Clin Res Ctr, Nagoya Med Ctr, Nagoya, Aichi 4600001, Japan. [Hritz, Jozef; Byeon, In-Ja L.; Gronenborn, Angela M.] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15261 USA. [Hritz, Jozef; Byeon, In-Ja L.; Gronenborn, Angela M.] Univ Pittsburgh, Sch Med, Pittsburgh Ctr HIV Prot Interact, Pittsburgh, PA 15261 USA. [Gorelick, Robert J.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Mitra, Mithun] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. [Hritz, Jozef] Masaryk Univ, Dept Biol Struct, CEITEC, Brno 62500, Czech Republic. RP Levin, JG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Viral Gene Regulat, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM levinju@mail.nih.gov RI Hritz, Jozef/J-6887-2015 OI Hritz, Jozef/0000-0002-4512-9241 FU International Outgoing Fellowship of the European Community program "Support for training and career development of researchers (Marie Curie)" [PIOF-GA-2009-235902]; Intramural Research Program at the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health [P50GM82251]; Ministry of Education, Culture, Sports, Science, and Technology of Japan; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Leidos Biomedical Research, Inc. FX We thank Dr. Viviana Simon and Dr. Marcel Ooms for their generous gift of the WT A3H and empty pTR600 plasmids, Dr. Klaus Strebel for kindly providing the pNL4-3vif(-) plasmid used in the ERT assays, Drs. Simon, Ooms, and Tiyun Wu for valuable discussion, and the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH for antisera and cells, as detailed in the text. J. H. acknowledges financial support by an International Outgoing Fellowship of the European Community program "Support for training and career development of researchers (Marie Curie)", under Contract No. PIOF-GA-2009-235902. This work was supported in part by the Intramural Research Program at the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (MM, DS, GN, and JGL), National Institutes of Health grant P50GM82251 (JH, I-JLB, and AMG), and a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (YM and YI). This project has also been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E with Leidos Biomedical Research, Inc. 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 (RJG). NR 111 TC 6 Z9 6 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JAN 22 PY 2015 VL 12 AR 3 DI 10.1186/s12977-014-0130-8 PG 15 WC Virology SC Virology GA CB0YK UT WOS:000349353400001 PM 25614027 ER PT J AU Park, SW Casalena, DE Wilson, DJ Dai, R Nag, PP Liu, F Boyce, JP Bittker, JA Schreiber, SL Finzel, BC Schnappinger, D Aldrich, CC AF Park, Sae Woong Casalena, Dominick E. Wilson, Daniel J. Dai, Ran Nag, Partha P. Liu, Feng Boyce, Jim P. Bittker, Joshua A. Schreiber, Stuart L. Finzel, Barry C. Schnappinger, Dirk Aldrich, Courtney C. TI Target-Based Identification of Whole-Cell Active Inhibitors of Biotin Biosynthesis in Mycobacterium tuberculosis SO CHEMISTRY & BIOLOGY LA English DT Article ID 7,8-DIAMINOPELARGONIC ACID; ANTIBACTERIAL DISCOVERY; STAPHYLOCOCCUS-AUREUS; TRANSAMINASE BIOA; MECHANISM; LIBRARIES; ASSAY; AMINOTRANSFERASE; COLLECTION; CHALLENGES AB Biotin biosynthesis is essential for survival and persistence of Mycobacterium tuberculosis (Mtb) in vivo. The aminotransferase BioA, which catalyzes the antepenultimate step in the biotin pathway, has been established as a promising target due to its vulnerability to chemical inhibition. We performed high-throughput screening (HTS) employing a fluorescence displacement assay and identified a diverse set of potent inhibitors including many diversity-oriented synthesis (DOS) scaffolds. To efficiently select only hits targeting biotin biosynthesis, we then deployed a whole-cell counterscreen in biotin-free and biotin-containing medium against wild-type Mtb and in parallel with isogenic bioA Mtb strains that possess differential levels of BioA expression. This counterscreen proved crucial to filter out compounds whose whole-cell activity was off target as well as identify hits with weak, but measurable whole-cell activity in BioA-depleted strains. Several of the most promising hits were cocrystallized with BioA to provide a framework for future structure-based drug design efforts. C1 [Park, Sae Woong; Schnappinger, Dirk] Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA. [Casalena, Dominick E.; Nag, Partha P.; Bittker, Joshua A.; Schreiber, Stuart L.] Broad Inst Probe Dev Ctr, Cambridge, MA 02142 USA. [Wilson, Daniel J.; Aldrich, Courtney C.] Univ Minnesota, Ctr Drug Design, Minneapolis, MN 55455 USA. [Dai, Ran; Liu, Feng; Finzel, Barry C.; Aldrich, Courtney C.] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA. [Boyce, Jim P.] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. RP Schnappinger, D (reprint author), Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA. EM dis2003@med.cornell.edu; aldri015@umn.edu OI Finzel, Barry/0000-0001-8761-3384 FU NIH [R03 MH096537, R01AI091790]; NIH-MLPCN program [1 U54 HG005032-1]; University of Minnesota Bighley Graduate Fellowship FX This work was funded in part by grants from the NIH (R03 MH096537 to C.C.A. and R01AI091790 to D.S.) and by the NIH-MLPCN program (1 U54 HG005032-1 awarded to S.L.S.). We also gratefully acknowledge support from the University of Minnesota Bighley Graduate Fellowship (to R.D.) and resources from the University of Minnesota Supercomputing Institute. NR 53 TC 9 Z9 9 U1 5 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 EI 1879-1301 J9 CHEM BIOL JI Chem. Biol. PD JAN 22 PY 2015 VL 22 IS 1 BP 76 EP 86 DI 10.1016/j.chembiol.2014.11.012 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ9CI UT WOS:000348508400010 PM 25556942 ER PT J AU Hung, CC Yen, CC Ciuchta, JL Papoti, D Bock, NA Leopold, DA Silva, AC AF Hung, Chia-Chun Yen, Cecil C. Ciuchta, Jennifer L. Papoti, Daniel Bock, Nicholas A. Leopold, David A. Silva, Afonso C. TI Functional Mapping of Face-Selective Regions in the Extrastriate Visual Cortex of the Marmoset SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ECoG; evolution; face; fMRI; marmoset; visual cortex ID MONKEY INFEROTEMPORAL CORTEX; INFERIOR TEMPORAL CORTEX; COMMON MARMOSET; MODEL SYSTEM; BODY PARTS; MACAQUE; PERCEPTION; FMRI; MOTION; BRAIN AB The cerebral cortex of humans and macaques has specialized regions for processing faces and other visual stimulus categories. It is unknown whether a similar functional organization exists in New World monkeys, such as the common marmoset (Callithrix jacchus), a species of growing interest as a primate model in neuroscience. To address this question, we measured selective neural responses in the brain of four awake marmosets trained to fix their gaze upon images of faces, bodies, objects, and control patterns. In two of the subjects, we measured high gamma-range field potentials from electrocorticography arrays implanted over a large portion of the occipital and inferotemporal cortex. In the other two subjects, we measured BOLD fMRI responses across the entire brain. Both techniques revealed robust, regionally specific patterns of category-selective neural responses. We report that at least six face-selective patches mark the occipitotemporal pathway of the marmoset, with the most anterior patches showing the strongest preference for faces over other stimuli. The similar appearance of these patches to previous findings in macaques and humans, including their apparent arrangement in two parallel pathways, suggests that core elements of the face processing network were present in the common anthropoid primate ancestor living similar to 35 million years ago. The findings also identify the marmoset as a viable animal model system for studying specialized neural mechanisms related to high-level social visual perception in humans. C1 [Hung, Chia-Chun; Yen, Cecil C.; Ciuchta, Jennifer L.; Papoti, Daniel; Silva, Afonso C.] NINDS, Cerebral Microcirculat Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Hung, Chia-Chun; Leopold, David A.] NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Bock, Nicholas A.] McMaster Univ, Hamilton, ON L8S 4K1, Canada. [Leopold, David A.] NINDS, Neurophysiol Imaging Facil, NIMH, NEI,NIH, Bethesda, MD 20182 USA. RP Silva, AC (reprint author), NINDS, Cerebral Microcirculat Sect, Lab Funct & Mol Imaging, NIH, 49 Convent Dr,MSC 1065,Bldg 49,Room 3A72, Bethesda, MD 20892 USA. EM SilvaA@ninds.nih.gov RI Yen, Cecil/C-2212-2009; OI Yen, Cecil/0000-0002-1519-9791; Hung, Chia-chun/0000-0002-5264-9165; Leopold, David/0000-0002-1345-6360 FU Intramural Research Programs of the National Institute of Neurological Disorders and Stroke; National Institute of Mental Health FX This work was supported by the Intramural Research Programs of the National Institute of Neurological Disorders and Stroke and National Institute of Mental Health. We thank Dr. R. Saunders for implanting the ECoG arrays in two animals; J. Day Cooney, L. Zhang, J. Mackel, T. Talbot, and R. Villadiego for technical assistance; and Dr. R. Berman for comments on the manuscript. NR 69 TC 20 Z9 20 U1 1 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 21 PY 2015 VL 35 IS 3 BP 1160 EP 1172 DI 10.1523/JNEUROSCI.2659-14.2015 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CB1TU UT WOS:000349411700027 PM 25609630 ER PT J AU Daye, PM Roberts, DC Zee, DS Optican, LM AF Daye, Pierre M. Roberts, Dale C. Zee, David S. Optican, Lance M. TI Vestibulo-Ocular Reflex Suppression during Head-Fixed Saccades Reveals Gaze Feedback Control SO JOURNAL OF NEUROSCIENCE LA English DT Article DE eye-head saccades; feedback control; VOR ID SUPERIOR COLLICULUS; UNRESTRAINED MONKEY; VIEWING DISTANCE; EYE-MOVEMENTS; SELF-MOTION; SHIFTS; HUMANS; COORDINATION; RESPONSES; PRIMATE AB Previous experiments have shown that the vestibulo-ocular reflex (VOR) is partially suppressed during large head-free gaze (gaze = eye-in-head + head-in-space) shifts when both the eyes and head are moving actively, on a fixed body, or when the eyes are moving actively and the head passively on a fixed body. Wetested, in human subjects, the hypothesis that the VOR is also suppressed during gaze saccades made with en bloc, head and body together, rotations. Subjects made saccades by following a target light. During some trials, the chair rotated so as to move the entire body passively before, during, or after a saccade. The modulation of the VOR was a function of both saccade amplitude and the time of the head perturbation relative to saccade onset. Despite the perturbation, gaze remained accurate. Thus, VOR modulation is similar when gaze changes are programmed for the eyes alone or for the eyes and head moving together. We propose that the brain always programs a change in gaze using feedback based on gaze and head signals, rather than on separate eye and head trajectories. C1 [Daye, Pierre M.] Univ Paris 06, INSERM, CNRS 7225, UMRS 975, Paris, France. [Roberts, Dale C.; Zee, David S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. [Zee, David S.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol, Baltimore, MD 21287 USA. [Zee, David S.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. [Zee, David S.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. [Daye, Pierre M.; Optican, Lance M.] NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA. RP Daye, PM (reprint author), Univ Paris 06, INSERM, CNRS 7225, UMRS 975, Paris, France. EM pierre.daye@gmail.com FU Betty and Paul Cinquegrana; intramural research program of the National Eye Institute of the National Institutes of Health; Fond de La Recherche Medicale; CERVISO program; Lott family foundation FX D.C.R. was supported by Betty and Paul Cinquegrana, P.M.D. and L.M.O. were supported by the intramural research program of the National Eye Institute of the National Institutes of Health, and P.M.D. was supported by le Fond de La Recherche Medicale and the CERVISO program. D.S.Z. was supported by the Lott family foundation. NR 36 TC 4 Z9 4 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 21 PY 2015 VL 35 IS 3 BP 1192 EP 1198 DI 10.1523/JNEUROSCI.3875-14.2015 PG 7 WC Neurosciences SC Neurosciences & Neurology GA CB1TU UT WOS:000349411700030 PM 25609633 ER PT J AU Wang, YQ Chen, HF Gao, Q Yang, YH Gong, QY Gao, FB AF Wang, Yuqing Chen, Huafu Gao, Qing Yang, Yihong Gong, Qiyong Gao, Fabao TI Evaluation of net causal influences in the circuit responding to premotor control during the movement-readiness state using conditional Granger causality SO BRAIN RESEARCH LA English DT Review DE Movement-readiness; Conditional Granger causality analysis; Functional magnetic resonance imaging ID SUPPLEMENTARY MOTOR AREAS; MEDIAL FRONTAL-CORTEX; FALSE DISCOVERY RATE; DEFAULT-MODE; FUNCTIONAL CONNECTIVITY; BASAL GANGLIA; BRAIN NETWORKS; IMAGERY; FMRI; PRECUNEUS AB As an initialization procedure for brain responding to subsequent movement execution (ME), the movement-readiness (MR) state is important for understanding the formation processes from daily movement training to long-term memory of movement pattern. As such, based on functional magnetic resonance imaging (fMRI), the net causal influences among regions contributing to premotor control during the MR state were explored by means of conditional Granger causality (CGC) and graph-theory methods in the present study. Our results found that net causal circuits responding to unimanual MR were identified during right-hand or left-hand MR, involving in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), upper precuneus (UPCU), caudate nucleus (CN), cingulate motor area (CMA), supplementary motor area (SMA) and primary sensorimotor area (S1M1.). Moreover, the contralateral CN, SMA and S1M1 revealed greater net causal influences during unimanual MR, which highlighted the contralateral dominant modulations during unimanual MR. Furthermore, according as the graph-theory analysis, the higher In+Out degrees of upper precuneus (UPCU) during right-hand MR or higher In+Out degrees of cingulate motor area (CMA) and posterior cingulate cortex (PCC) during left-hand MR implied the brain asymmetry of causal connectivity in the circuit responding-to right-hand or left-hand MR. This article is part of a Special Issue entitled SI: Brain and Memory. (C) 2014 Elsevier B.V. All rights reserved. C1 [Wang, Yuqing; Gong, Qiyong; Gao, Fabao] Sichuan Univ, West China Hosp, Dept Radiol, Chengdu 610041, Peoples R China. [Chen, Huafu] Univ Elect Sci & Technol China, Key Lab NeuroInformat Minist Educ, Sch Life Sci & Technol, Chengdu 610054, Peoples R China. [Gao, Qing] Univ Elect Sci & Technol China, Sch Math Sci, Chengdu 610054, Peoples R China. [Gong, Qiyong] Natl Inst Hlth, Natl Inst Drug Abuse, Neuroimaging Res Branch, Baltimore, MD 21224 USA. RP Gao, FB (reprint author), Sichuan Univ, West China Hosp, Dept Radiol, 37 Guoxue Alley, Chengdu 610041, Peoples R China. EM gaofabao_sub@163.com FU National Natural Science Foundation of China [81130027, 81301196]; China National Science & Technology pillar grogram [2012BAI23B08] FX This work is supported by the National Natural Science Foundation of China (81130027, 81301196) and China National Science & Technology pillar grogram during the 12th 5-year-plan period (2012BAI23B08). NR 57 TC 0 Z9 1 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JAN 21 PY 2015 VL 1595 BP 110 EP 119 DI 10.1016/j.brainres.2014.08.004 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CA8UY UT WOS:000349197600011 PM 25148703 ER PT J AU Gopich, IV AF Gopich, Irina V. TI Accuracy of maximum likelihood estimates of a two-state model in single-molecule FRET SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PHOTON ARRIVAL TRAJECTORIES; TRANSITION PATH TIMES; HIDDEN MARKOV-MODELS; FLUORESCENCE SPECTROSCOPY; PROTEIN; DYNAMICS AB Photon sequences from single-molecule Forster resonance energy transfer (FRET) experiments can be analyzed using a maximum likelihood method. Parameters of the underlying kinetic model (FRET efficiencies of the states and transition rates between conformational states) are obtained by maximizing the appropriate likelihood function. In addition, the errors (uncertainties) of the extracted parameters can be obtained from the curvature of the likelihood function at the maximum. We study the standard deviations of the parameters of a two-state model obtained from photon sequences with recorded colors and arrival times. The standard deviations can be obtained analytically in a special case when the FRET efficiencies of the states are 0 and 1 and in the limiting cases of fast and slow conformational dynamics. These results are compared with the results of numerical simulations. The accuracy and, therefore, the ability to predict model parameters depend on how fast the transition rates are compared to the photon count rate. In the limit of slow transitions, the key parameters that determine the accuracy are the number of transitions between the states and the number of independent photon sequences. In the fast transition limit, the accuracy is determined by the small fraction of photons that are correlated with their neighbors. The relative standard deviation of the relaxation rate has a "chevron" shape as a function of the transition rate in the log-log scale. The location of the minimum of this function dramatically depends on how well the FRET efficiencies of the states are separated. C1 Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Gopich, IV (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health FX I thank A. Szabo, H. S. Chung, and S. Presse for helpful discussions and very useful comments. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health. NR 30 TC 1 Z9 1 U1 5 U2 11 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD JAN 21 PY 2015 VL 142 IS 3 AR 034110 DI 10.1063/1.4904381 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AZ6BJ UT WOS:000348302900010 PM 25612692 ER PT J AU Pickrell, AM Youle, RJ AF Pickrell, Alicia M. Youle, Richard J. TI The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson's Disease SO NEURON LA English DT Review ID E3 LIGASE PARKIN; RECESSIVE JUVENILE PARKINSONISM; SUBSTANTIA-NIGRA NEURONS; COMPLEX I DEFICIENCY; ALPHA-SYNUCLEIN; DEPOLARIZED MITOCHONDRIA; DOPAMINERGIC-NEURONS; OXIDATIVE STRESS; DAMAGED MITOCHONDRIA; MEDIATED MITOPHAGY AB Understanding the function of genes mutated in hereditary forms of Parkinson's disease yields insight into disease etiology and reveals new pathways in cell biology. Although mutations or variants in many genes increase the susceptibility to Parkinson's disease, only a handful of monogenic causes of parkinsonism have been identified. Biochemical and genetic studies reveal that the products of two genes that are mutated in autosomal recessive parkinsonism, PINK1 and Parkin, normally work together in the same pathway to govern mitochondrial quality control, bolstering previous evidence that mitochondrial damage is involved in Parkinson's disease. PINK1 accumulates on the outer membrane of damaged mitochondria, activates Parkin's E3 ubiquitin ligase activity, and recruits Parkin to the dysfunctional mitochondrion. Then, Parkin ubiquitinates outer mitochondrial membrane proteins to trigger selective autophagy. This review covers the normal functions that PINK1 and Parkin play within cells, their molecular mechanisms of action, and the pathophysiological consequences of their loss. C1 [Pickrell, Alicia M.; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov FU NIH NINDS; National Institute of General Medical Sciences FX The NIH NINDS intramural program (R.J.Y. and A.M.P.) and the Postdoctoral Research Associate Program at the National Institute of General Medical Sciences (A.M.P.) supported this work. We thank Soojay Banerjee for assistance with artwork. We also thank Katherine Roche for thoughtful reading of the manuscript and members of the Youle lab for comments. NR 196 TC 158 Z9 164 U1 31 U2 143 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 JAN 21 PY 2015 VL 85 IS 2 BP 257 EP 273 DI 10.1016/j.neuron.2014.12.007 PG 17 WC Neurosciences SC Neurosciences & Neurology GA AZ5ZB UT WOS:000348296000006 PM 25611507 ER PT J AU Barrett, HH Myers, KJ Hoeschen, C Kupinski, MA Little, MP AF Barrett, Harrison H. Myers, Kyle J. Hoeschen, Christoph Kupinski, Matthew A. Little, Mark P. TI Task-based measures of image quality and their relation to radiation dose and patient risk SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE radiation dose; image quality; patient risk; ionizing radiation; tomography ID ATOMIC-BOMB SURVIVORS; ABDOMINAL COMPUTED-TOMOGRAPHY; DIGITAL BREAST TOMOSYNTHESIS; CONE-BEAM CT; ITERATIVE RECONSTRUCTION TECHNIQUES; OBSERVER DETECTION PERFORMANCE; POSITRON-EMISSION-TOMOGRAPHY; HOTELLING TRACE CRITERION; MONTE-CARLO CALCULATION; VISUAL SIGNAL-DETECTION AB The theory of task-based assessment of image quality is reviewed in the context of imaging with ionizing radiation, and objective figures of merit (FOMs) for image quality are summarized. The variation of the FOMs with the task, the observer and especially with the mean number of photons recorded in the image is discussed. Then various standard methods for specifying radiation dose are reviewed and related to the mean number of photons in the image and hence to image quality. Current knowledge of the relation between local radiation dose and the risk of various adverse effects is summarized, and some graphical depictions of the tradeoffs between image quality and risk are introduced. Then various dose-reduction strategies are discussed in terms of their effect on task-based measures of image quality. C1 [Barrett, Harrison H.; Kupinski, Matthew A.] Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA. [Barrett, Harrison H.; Kupinski, Matthew A.] Univ Arizona, Dept Med Imaging, Ctr Gamma Ray Imaging, Tucson, AZ 85724 USA. [Myers, Kyle J.] US FDA, Div Imaging Diagnost & Software Reliabil, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Hoeschen, Christoph] Otto Von Guericke Univ, Dept Elect Engn & Informat Technol, D-39106 Magdeburg, Germany. [Hoeschen, Christoph] Helmholtz Zentrum Munchen, Res Unit Med Radiat Phys & Diagnost, D-85764 Oberschleissheim, Germany. [Little, Mark P.] NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Barrett, HH (reprint author), Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA. EM barrett@radiology.arizona.edu OI Little, Mark/0000-0003-0980-7567 FU National Institutes of Health at the University of Arizona [R01 EB000803, P41 EB002035]; Intramural Research Program of the National Institutes of Health FX This research was supported by the National Institutes of Health under grants R01 EB000803 and P41 EB002035 at the University of Arizona. This work was also supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 249 TC 17 Z9 17 U1 1 U2 10 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2015 VL 60 IS 2 BP R1 EP R75 DI 10.1088/0031-9155/60/2/R1 PG 75 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AY6KL UT WOS:000347675100002 PM 25564960 ER PT J AU Zhao, YC Gong, P Chen, YR Nwachukwu, JC Srinivasan, S Ko, CM Bagchi, MK Taylor, RN Korach, KS Nettles, KW Katzenellenbogen, JA Katzenellenbogen, BS AF Zhao, Yuechao Gong, Ping Chen, Yiru Nwachukwu, Jerome C. Srinivasan, Sathish Ko, CheMyong Bagchi, Milan K. Taylor, Robert N. Korach, Kenneth S. Nettles, Kendall W. Katzenellenbogen, John A. Katzenellenbogen, Benita S. TI Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NERVE GROWTH-FACTOR; RECEPTOR-BETA; MOUSE MODEL; AROMATASE INHIBITORS; ER-ALPHA; CELLS; MACROPHAGES; PERITONEAL; EXPRESSION AB Estrogenic and inflammatory components play key roles in a broad range of diseases including endometriosis, a common estrogen-dependent gynecological disorder in which endometrial tissue creates inflammatory lesions at extrauterine sites, causing pelvic pain and reduced fertility. Current medical therapies focus primarily on reducing systemic levels of estrogens, but these are of limited effectiveness and have considerable side effects. We developed estrogen receptor (ER) ligands, chloroindazole (CLI) and oxabicycloheptene sulfonate (OBHS), which showed strong ER-dependent anti-inflammatory activity in a preclinical model of endometriosis that recapitulates the estrogen dependence and inflammatory responses of the disease in immunocompetent mice and in primary human endometriotic stromal cells in culture. Estrogen-dependent phenomena, including cell proliferation, cyst formation, vascularization, and lesion growth, were all arrested by CLI or OBHS, which prevented lesion expansion and also elicited regression of established lesions, suppressed inflammation, angiogenesis, and neurogenesis in the lesions, and interrupted crosstalk between lesion cells and infiltrating macrophages. Studies in ER alpha or ER beta knockout mice indicated that ERa is the major mediator of OBHS effectiveness and ERb is dominant in CLI actions, implying involvement of both ERs in endometriosis. Neither ligand altered estrous cycling or fertility at doses that were effective for suppression of endometriosis. Hence, CLI and OBHS are able to restrain endometriosis by dual suppression of the estrogen-inflammatory axis. Our findings suggest that these compounds have the desired characteristics of preventive and therapeutic agents for clinical endometriosis and possibly other estrogen-driven and inflammation-promoted disorders. C1 [Zhao, Yuechao; Gong, Ping; Chen, Yiru; Bagchi, Milan K.; Katzenellenbogen, Benita S.] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. [Nwachukwu, Jerome C.; Srinivasan, Sathish; Nettles, Kendall W.] Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA. [Ko, CheMyong] Univ Illinois, Dept Comparat Biosci, Urbana, IL 61801 USA. [Taylor, Robert N.] Wake Forest Univ, Bowman Gray Sch Med, Dept Obstet & Gynecol, Winston Salem, NC 27103 USA. [Korach, Kenneth S.] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Katzenellenbogen, John A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA. RP Katzenellenbogen, BS (reprint author), Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. EM katzenel@illinois.edu OI Nwachukwu, Jerome/0000-0003-4313-9187; Korach, Kenneth/0000-0002-7765-418X FU NIH, Kennedy Shriver National Institute of Child Health and Human Development/NIH Centers Program in Reproduction and Infertility Research [U54 HD055787]; NIH [PHS 5R01DK015556, 5R01DK077085]; Frenchman's Creek Women for Cancer Research FX This work was supported by NIH grant U54 HD055787 as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH Centers Program in Reproduction and Infertility Research (B.S.K., M.K.B., and R.N.T.) and by NIH grants PHS 5R01DK015556 (J.A.K.) and 5R01DK077085 (K.W.N.). S.S. was supported by Frenchman's Creek Women for Cancer Research. NR 45 TC 7 Z9 7 U1 2 U2 18 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 JAN 21 PY 2015 VL 7 IS 271 AR 271ra9 DI 10.1126/scitranslmed.3010626 PG 14 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AZ6TS UT WOS:000348353900003 PM 25609169 ER PT J AU Lowery, MA Kelsen, DP Smith, SC Moore, M Kindler, HL Golan, T Segal, A Hollywood, E Maynard, H Capanu, M Moynahan, ME Fusco, A Stadler, ZK Do, KG Chen, AP Yu, KH Tang, LH O'Reilly, EM AF Lowery, Maeve Aine Kelsen, David Paul Smith, Sloane C. Moore, Malcolm Kindler, Hedy Lee Golan, Talia Segal, Amiel Hollywood, Ellen Maynard, Hannah Capanu, Marinela Moynahan, Mary Ellen Fusco, Anne Stadler, Zsofia Kinga Do, Kinh G. Chen, Alice P. Yu, Kenneth H. Tang, Laura H. O'Reilly, Eileen Mary TI Phase II trial of veliparib (V) in patients (pts) with previously treated BRCA or PALB2-mutated (mut) pancreas adenocarcinoma (PC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Princess Margaret Canc Ctr, Dept Med Oncol, Toronto, ON, Canada. Univ Chicago, Chicago, IL 60637 USA. Chaim Sheba Med Ctr, Ramat Gan, Israel. Shaare Zedek Med Ctr, Inst Oncol, Jerusalem, Israel. NCI, NIH, Bethesda, MD 20892 USA. Weill Cornell Med Coll, New York, NY USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA 358 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800356 ER PT J AU Sclafani, F Adams, RA Eng, C Benson, AB Glynne-Jones, R Sebag-Montefiore, D Arnold, D Roy, AC Guren, MG Segelov, E Seymour, MT Bryant, A Peckitt, C Cunningham, D Bridgewater, JA Welch, J O'Dwyer, PJ Dupont, E McConnell, A Rao, S AF Sclafani, Francesco Adams, Richard A. Eng, Cathy Benson, Al Bowen Glynne-Jones, Robert Sebag-Montefiore, David Arnold, Dirk Roy, Amitesh Chandra Guren, Marianne Gronlie Segelov, Eva Seymour, Matthew T. Bryant, Annette Peckitt, Clare Cunningham, David Bridgewater, John A. Welch, Jack O'Dwyer, Peter J. Dupont, Elisabeth McConnell, Andrea Rao, Sheela TI InterAACT: An international multicenter open label randomized phase II advanced anal cancer trial comparing cisplatin (CDDP) plus 5-fluorouracil (5-FU) versus carboplatin (CBDCA) plus weekly paclitaxel (PTX) in patients with inoperable locally recurrent (ILR) or metastatic disease. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Gastrointestinal Cancers Symposium CY JAN 15-17, 2015 CL San Francisco, CA C1 Royal Marsden NHS Fdn Trust, London, England. Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. Velindre Hosp NHS Fdn Trust, Cardiff, S Glam, Wales. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Mt Vernon Canc Ctr, Northwood, Middx, England. St James Univ Hosp, St Jamess Inst Oncol, Leeds, W Yorkshire, England. Univ Canc Ctr Hamburg, Hubertus Wald Tumor Ctr, Hamburg, Germany. Flinders Med Ctr, Bedford Pk, SA, Australia. Oslo Univ Hosp, Dept Oncol, Oslo, Norway. Univ New S Wales, St Vincents Clin Sch, Sydney, NSW, Australia. Canc Res UK Clin Ctr, Leeds, W Yorkshire, England. UCL, UCL Canc Inst, London, England. NCI, NIH, Bethesda, MD 20892 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. NCI Ctr Global Hlth, Brussels, Belgium. Canc Res UK, London, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 SU S MA TPS792 PG 1 WC Oncology SC Oncology GA CL3WY UT WOS:000356883800787 ER PT J AU Abrams, J Kramer, B Doroshow, JH Varmus, H AF Abrams, Jeffrey Kramer, Barry Doroshow, James H. Varmus, Harold TI National Cancer Institute-Supported Clinical Trials Networks SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Abrams, Jeffrey; Kramer, Barry; Doroshow, James H.; Varmus, Harold] NCI, NIH, Bethesda, MD 20892 USA. RP Abrams, J (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 1 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2015 VL 33 IS 3 BP 293 EP 293 DI 10.1200/JCO.2014.59.5421 PG 1 WC Oncology SC Oncology GA CF3BC UT WOS:000352421400022 PM 25452448 ER PT J AU Wolf, NI Toro, C Kister, I Abd Latif, K Leventer, R Pizzino, A Simons, C Abbink, TEM Taft, RJ van der Knaap, MS Vanderver, A AF Wolf, Nicole I. Toro, Camilo Kister, Ilya Abd Latif, Kartikasalwah Leventer, Richard Pizzino, Amy Simons, Cas Abbink, Truus E. M. Taft, Ryan J. van der Knaap, Marjo S. Vanderver, Adeline TI DARS-associated leukoencephalopathy can mimic a steroid-responsive neuroinflammatory disorder SO NEUROLOGY LA English DT Article ID SPINAL-CORD INVOLVEMENT; TRANSFER-RNA SYNTHETASE; BRAIN-STEM; LACTATE ELEVATION; PROTEINS; COMPLEX AB Objective: To describe the expanding clinical spectrum of a recently described hereditary leuko-encephalopathy, hypomyelination with brainstem and spinal cord involvement and leg spasticity, which is caused by mutations in the aspartyl tRNA-synthetase encoding gene DARS, including patients with an adolescent onset. Methods: Three patients with mutations in DARS were identified by combining MRI pattern recognition and genetic analysis. Results: One patient had the typical infantile presentation, but 2 patients with onset in late adolescence had a disease mimicking an acquired inflammatory CNS disorder. Adolescent-onset patients presented with subacute spastic paraplegia and had positive response to steroids. They had only minor focal supratentorial white matter abnormalities, but identical spinal cord changes involving dorsal columns and corticospinal tracts. Clinical presentation included subacute spastic paraplegia with partial improvement on steroids. Conclusions: Focal T2 hyperintense white matter changes on brain MRI in combination with spinal cord signal abnormalities usually suggest acquired inflammatory conditions such as multiple sclerosis, especially in the context of relapsing course and a positive response to steroid treatment. Adolescents with mutations in DARS can present with a comparable clinical picture, broadening the clinical spectrum of hypomyelination with brainstem and spinal cord involvement and leg spasticity. C1 [Wolf, Nicole I.; Abbink, Truus E. M.; van der Knaap, Marjo S.] Vrije Univ Amsterdam, Med Ctr, Dept Child Neurol, Amsterdam, Netherlands. [Wolf, Nicole I.; Abbink, Truus E. M.; van der Knaap, Marjo S.] Neurosci Campus Amsterdam, Amsterdam, Netherlands. [Toro, Camilo] NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Kister, Ilya] NYU, Dept Neurol, Sch Med, Multiple Sclerosis Ctr, New York, NY 10016 USA. [Abd Latif, Kartikasalwah] Hosp Kuala Lumpur, Dept Radiol, Kuala Lumpur, Malaysia. [Leventer, Richard] Univ Melbourne, Dept Neurol, Royal Childrens Hosp, Melbourne, Vic 3010, Australia. [Leventer, Richard] Univ Melbourne, Murdoch Childrens Res Inst, Melbourne, Vic 3010, Australia. [Leventer, Richard] Univ Melbourne, Dept Pediat, Melbourne, Vic 3010, Australia. [Pizzino, Amy; Vanderver, Adeline] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Simons, Cas; Taft, Ryan J.] Univ Queensland, Inst Mol Biosci, St Lucia, Qld, Australia. [Taft, Ryan J.] George Washington Univ, Sch Med, Dept Integrat Syst Biol, Washington, DC USA. [Taft, Ryan J.] George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20052 USA. [Taft, Ryan J.] Illumina Inc, San Diego, CA USA. [van der Knaap, Marjo S.] Vrije Univ Amsterdam, Dept Funct Genom, Ctr Neurogen & Cognit Res, Amsterdam, Netherlands. RP Wolf, NI (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Child Neurol, Amsterdam, Netherlands. EM n.wolf@vumc.nl RI Simons, Cas/A-7905-2011 OI Simons, Cas/0000-0003-3147-8042 FU ZonMw TOP [91211005]; NHGRI intramural program; Common fund for the Undiagnosed Diseases Network; National Human Genome Research Institute FX Supported by ZonMw TOP grant 91211005. The role of C.T. and A.V. was supported by the NHGRI intramural program. The NTH Undiagnosed Diseases Program is funded in part by the Common fund for the Undiagnosed Diseases Network and the Intramural Program of the National Human Genome Research Institute. NR 11 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 20 PY 2015 VL 84 IS 3 BP 226 EP 230 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA CA1XQ UT WOS:000348702600007 PM 25527264 ER PT J AU Gelber, RP Redline, S Ross, GW Petrovitch, H Sonnen, JA Zarow, C Uyehara-Lock, JH Masaki, KH Launer, LJ White, LR AF Gelber, Rebecca P. Redline, Susan Ross, G. Webster Petrovitch, Helen Sonnen, Joshua A. Zarow, Chris Uyehara-Lock, Jane H. Masaki, Kamal H. Launer, Lenore J. White, Lon R. TI Associations of brain lesions at autopsy with polysomnography features before death SO NEUROLOGY LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; JAPANESE-AMERICAN MEN; APOLIPOPROTEIN-E EPSILON-4; COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; DEMENTIA; RISK; MEMORY; ALLELE; HAWAII AB Objective: To determine how sleep-disordered breathing, nocturnal hypoxia, and changes in sleep architecture in the elderly may be related to the development of the neuropathologic correlates of dementia. Methods: The Honolulu-Asia Aging Study is a prospective cohort study of Japanese American men in Honolulu, HI. We examined brain lesions at autopsy (Braak stage, neurofibrillary tangle and neuritic plaque counts, microinfarcts, generalized brain atrophy, lacunar infarcts, Lewy bodies [LBs], neuronal loss and gliosis in the locus ceruleus) in 167 participants who underwent polysomnography in 1999-2000 (mean age, 84 years) and died through 2010 (mean 6.4 years to death). Polysomnography measures included the apnea-hypopnea index, duration of apnea or hypopnea, duration of hypoxemia, minimum oxygen saturation (SpO(2)), duration of slow-wave sleep (SWS, non-REM stage N3), and arousals. Results: Sleep duration with SpO(2) <95% was associated with higher levels of microinfarcts (adjusted odds ratio [OR] 3.88 <95% confidence interval [CI] 1.10-13.76, comparing the highest to lowest quartiles of %sleep with SpO(2) <95%). Greater SWS duration was associated with less generalized atrophy (adjusted OR 0.32, 95% CI 0.10-1.03, comparing highest to lowest quartiles of %sleep in SWS). LBs were less common with greater %sleep with SpO(2) <95%(adjusted OR 0.17, 95% CI 0.04-0.78, comparing highest to lowest quartiles). Higher minimum SpO(2) during REM sleep was associated with less gliosis and neuronal loss in the locus ceruleus. Cognitive scores declined less among men with greater SWS duration. Conclusions: The findings support a role for lower nocturnal oxygenation and SWS in the development of microinfarcts and brain atrophy, but not Alzheimer lesions or LBs. C1 [Gelber, Rebecca P.; Ross, G. Webster; Petrovitch, Helen] Univ Hawaii, John A Burns Sch Med, VA Pacific Isl Hlth Care Syst, Honolulu, HI 96822 USA. [Gelber, Rebecca P.; Ross, G. Webster; Petrovitch, Helen; Uyehara-Lock, Jane H.; White, Lon R.] Univ Hawaii, John A Burns Sch Med, Pacific Hlth Res & Educ Inst, Honolulu, HI 96822 USA. [Ross, G. Webster; Petrovitch, Helen] Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. [Ross, G. Webster; Petrovitch, Helen; Masaki, Kamal H.; White, Lon R.] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA. [Uyehara-Lock, Jane H.] Univ Hawaii, John A Burns Sch Med, Dept Pathol, Honolulu, HI 96822 USA. [Masaki, Kamal H.] Kuakini Med Ctr, Honolulu, HI USA. [Sonnen, Joshua A.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Zarow, Chris] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. [Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Redline, Susan] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Redline, Susan] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Redline, Susan] Harvard Univ, Sch Med, Boston, MA USA. [Launer, Lenore J.; White, Lon R.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Gelber, RP (reprint author), Univ Hawaii, John A Burns Sch Med, VA Pacific Isl Hlth Care Syst, Honolulu, HI 96822 USA. EM rebecca.gelber@va.gov RI Sonnen, 37382016/H-3738-2016 OI Sonnen, 37382016/0000-0001-9267-8705 FU National Institute on Aging (NIA) [R03 AG046614, U01 AG046871, R01 AG017155, U01 AG019349]; NIA; Alzheimer's Association [ZEN-12-239028]; Hawaii Community Foundation; Office of Research and Development, Department of Veterans Affairs Pacific Islands Health Care System FX Supported by the National Institute on Aging (NIA) (R03 AG046614, U01 AG046871, R01 AG017155, U01 AG019349); the Intramural Research Program, NIA; the Alzheimer's Association (ZEN-12-239028); the Hawaii Community Foundation; and the Office of Research and Development, Department of Veterans Affairs Pacific Islands Health Care System. The information contained in this article does not necessarily reflect the position or the policy of the United States Government, and no official endorsement should be inferred. NR 39 TC 7 Z9 8 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JAN 20 PY 2015 VL 84 IS 3 BP 296 EP 303 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CA1XQ UT WOS:000348702600016 PM 25503626 ER PT J AU Yin, J Yuan, Q AF Yin, Jun Yuan, Quan TI Structural homeostasis in the nervous system: a balancing act for wiring plasticity and stability SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE structural plasticity; homeostasis; neural development; neuronal morphology; activity-dependent plasticity ID AXON INITIAL SEGMENT; DROSOPHILA NEUROMUSCULAR-JUNCTION; MOUSE VISUAL-CORTEX; SYNAPTIC PLASTICITY; NEURONAL PLASTICITY; DENDRITIC SPINES; EXCITATORY SYNAPSES; INHIBITORY SYNAPSES; QUANTAL AMPLITUDE; ADULT NEOCORTEX AB Experience-dependent modifications of neural circuits provide the cellular basis for functional adaptation and learning, while presenting significant challenges to the stability of neural networks. The nervous system copes with these perturbations through a variety of compensatory mechanisms with distinct spatial and temporal profiles. Mounting evidence suggests that structural plasticity, through modifications of the number and structure of synapses, or changes in local and long-range connectivity, might contribute to the stabilization of network activity and serve as an important component of the homeostatic regulation of the nervous system. Conceptually similar to the homeostatic regulation of synaptic strength and efficacy, homeostatic structural plasticity has a profound and lasting impact on the intrinsic excitability of the neuron and circuit properties, yet remains largely unexplored. In this review, we examine recent reports describing structural modifications associated with functional compensation in both developing and adult nervous systems, and discuss the potential role for structural homeostasis in maintaining network stability and its implications in physiological and pathological conditions of the nervous systems. C1 [Yin, Jun; Yuan, Quan] NINDS, NIH, Bethesda, MD 20892 USA. RP Yuan, Q (reprint author), NINDS, NIH, 35 Convent Dr,1B-1002, Bethesda, MD 20892 USA. EM quan.yuan@nih.gov FU intramural research program of the National Institute of Neurological Disorders and Stroke FX We thank Uzma Javed, Bo Qin and Devee Schoenberg for the help with the preparation of the manuscript. This work is supported by the intramural research program of the National Institute of Neurological Disorders and Stroke. NR 69 TC 4 Z9 4 U1 5 U2 18 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD JAN 20 PY 2015 VL 8 AR 439 DI 10.3389/fncel.2014.00439 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CA7BZ UT WOS:000349073400001 ER PT J AU Lu, JH Chu, J Zou, ZC Hamacher, NB Rixon, MW Sun, PD AF Lu, Jinghua Chu, Jonathan Zou, Zhongcheng Hamacher, Nels B. Rixon, Mark W. Sun, Peter D. TI Structure of Fc gamma RI in complex with Fc reveals the importance of glycan recognition for high-affinity IgG binding SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CD64; FcgRI; IgG recognition; crystal structure; glycan recognition ID CRYSTAL-STRUCTURE; RECEPTOR; GLYCOSYLATION; FRAGMENT; HYPERSENSITIVITY; ANTIBODIES; IMPACT; FUCOSE AB Fc gamma receptor I (Fc gamma RI) contributes to protective immunity against bacterial infections, but exacerbates certain autoimmune diseases. The sole high-affinity IgG receptor, Fc gamma RI plays a significant role in immunotherapy. To elucidate the molecular mechanism of its high-affinity IgG binding, we determined the crystal structure of the extracellular domains of human Fc gamma RI in complex with the Fc domain of human IgG1. Fc gamma RI binds to the Fc in a similar mode as the low-affinity Fc gamma RII and Fc gamma RIII receptors. In addition to many conserved contacts, Fc gamma RI forms additional hydrogen bonds and salt bridges with the lower hinge region of Fc. Unique to the high-affinity receptor-Fc complex, however, is the conformation of the receptor D2 domain FG loop, which enables a charged KHR motif to interact with proximal carbohydrate units of the Fc glycans. Both the length and the charge of the Fc gamma RI FG loop are well conserved among mammalian species. Ala and Glu mutations of the FG loop KHR residues showed significant contributions of His-174 and Arg-175 to antibody binding, and the loss of the FG loop-glycan interaction resulted in an similar to 20-to 30-fold decrease in Fc gamma RI affinity to all three subclasses of IgGs. Furthermore, deglycosylation of IgG1 resulted in a 40-fold loss in Fc gamma RI binding, demonstrating involvement of the receptor FG loop in glycan recognition. These results highlight a unique glycan recognition in Fc gamma RI function and open potential therapeutic avenues based on antibody glycan engineering or small molecular glycan mimics to target Fc gamma RI for certain autoimmune diseases. C1 [Lu, Jinghua; Chu, Jonathan; Zou, Zhongcheng; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Hamacher, Nels B.] Bristol Myers Squibb Co, Dept Bioproc Dev, Seattle, WA 98102 USA. [Rixon, Mark W.] Bristol Myers Squibb Co, Dept Immunol, Seattle, WA 98102 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM psun@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the intramural research funding from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 34 TC 30 Z9 32 U1 1 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 JAN 20 PY 2015 VL 112 IS 3 BP 833 EP 838 DI 10.1073/pnas.1418812112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ2BY UT WOS:000348040700055 PM 25561553 ER PT J AU Shcheynikov, N Son, A Hong, JH Yamazaki, O Ohana, E Kurtz, I Shin, DM Muallem, S AF Shcheynikov, Nikolay Son, Aran Hong, Jeong Hee Yamazaki, Osamu Ohana, Ehud Kurtz, Ira Shin, Dong Min Muallem, Shmuel TI Intracellular Cl- as a signaling ion that potently regulates Na+/HCO3- transporters SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE intracellular Cl-; signaling ion; transporters ID SODIUM-BICARBONATE COTRANSPORTER; RECEPTOR-BINDING PROTEIN; FUNCTIONAL-CHARACTERIZATION; CHLORIDE CONCENTRATION; ACINAR-CELLS; IP3 RECEPTOR; IRBIT; SECRETION; FAMILY; NA+ AB Cl- is a major anion in mammalian cells involved in transport processes that determines the intracellular activity of many ions and plasma membrane potential. Surprisingly, a role of intracellular Cl- (Cl-in(-)) as a signaling ion has not been previously evaluated. Here we report that Cl-in(-) functions as a regulator of cellular Na+ and HCO3- concentrations and transepithelial transport through modulating the activity of several electrogenic Na+-HCO3- transporters. We describe the molecular mechanism(s) of this regulation by physiological Cl-in(-) concentrations highlighting the role of GXXXP motifs in Cl-sensing. Regulation of the ubiquitous Na+-HCO3- co-transport (NBC)e1-B is mediated by two GXXXP-containing sites; regulation of NBCe2-C is dependent on a single GXXXP motif; and regulation of NBCe1-A depends on a cryptic GXXXP motif. In the basal state NBCe1-B is inhibited by high Cl-in(-) interacting at a low affinity GXXXP-containing site. IP3 receptor binding protein released with IP3 (IRBIT) activation of NBCe1-B unmasks a second high affinity Cl-in(-) interacting GXXXP-dependent site. By contrast, NBCe2-C, which does not interact with IRBIT, has a single high affinity N-terminal GXXP-containing Cl-in(-) interacting site. NBCe1-A is unaffected by Cl-in(-) between 5 and 140 mM. However, deletion of NBCe1-A residues 29-41 unmasks a cryptic GXXXP-containing site homologous with the NBCe1-B low affinity site that is involved in inhibition of NBCe1-A by Cl-in(-). These findings reveal a cellular Cl-in(-) sensing mechanism that plays an important role in the regulation of Na+ and HCO3- transport, with critical implications for the role of Cl-in(-) cellular ion homeostasis and epithelial fluid and electrolyte secretion. C1 [Shcheynikov, Nikolay; Son, Aran; Hong, Jeong Hee; Yamazaki, Osamu; Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Phys & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Hong, Jeong Hee] Gachon Univ, Grad Sch Med, Dept Physiol, Inchon 406799, South Korea. [Ohana, Ehud] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Biochem, IL-8410501 Bear Sheva, Israel. [Kurtz, Ira] Univ Calif Los Angeles, Dept Med, Div Nephrol, Los Angeles, CA 90095 USA. [Kurtz, Ira] Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90095 USA. [Shin, Dong Min] Yonsei Univ, Coll Dent, Dept Oral Biol, BK 21 PLUS Project, Seoul 120752, South Korea. RP Shcheynikov, N (reprint author), Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Phys & Therapeut Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research [Z1A-DE000735]; Nakatomi; Sumitomo Life Welfare and Culture; Mochida Memorial Foundation; NIH [R01-DK077162]; Allan Smidt Charitable Fund; Factor Family Foundation; Arvey Foundation; National Research Foundation of Korea - Korea government [Ministry of Science, ICT and Future Planning (MSIP)] [2012R1A2A1A01003487] FX This work was funded in part by Intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research Grant Z1A-DE000735 (to S.M.), by fellowships from the Nakatomi, Sumitomo Life Welfare and Culture and the Mochida Memorial Foundations (O.Y.), by the National Research Foundation of Korea grant funded by the Korea government [Ministry of Science, ICT and Future Planning (MSIP)] (2012R1A2A1A01003487) (to D.M.S.), and by NIH Grant R01-DK077162, the Allan Smidt Charitable Fund, the Factor Family Foundation, and the Arvey Foundation (I.K.). NR 50 TC 12 Z9 12 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 20 PY 2015 VL 112 IS 3 BP E329 EP E337 DI 10.1073/pnas.1415673112 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ2BY UT WOS:000348040700014 PM 25561556 ER PT J AU Delling, FN Rong, J Larson, MG Lehman, B Osypiuk, E Stantchev, P Slaugenhaupt, SA Benjamin, EJ Levine, RA Vasan, RS AF Delling, Francesca N. Rong, Jian Larson, Martin G. Lehman, Birgitta Osypiuk, Ewa Stantchev, Plamen Slaugenhaupt, Susan A. Benjamin, Emelia J. Levine, Robert A. Vasan, Ramachandran S. TI Familial Clustering of Mitral Valve Prolapse in the Community SO CIRCULATION LA English DT Article DE echocardiography; epidemiology; genetics; mitral valve prolapse ID LATE SYSTOLIC MURMUR; MIDSYSTOLIC CLICK; NATURAL-HISTORY; REGURGITATION; HEART; DIAGNOSIS; LEAFLET; LOCUS; DETERMINANTS; INHERITANCE AB Background-Knowledge of mitral valve prolapse (MVP) inheritance is based on pedigree observation and M-mode echocardiography. The extent of familial clustering of MVP among unselected individuals in the community using current, more specific echocardiographic criteria is unknown. In addition, the importance of nondiagnostic MVP morphologies (NDMs; first described in large pedigrees) has not been investigated in the general population. We hypothesized that parental MVP and NDMs increase the risk of offspring MVP. Methods and Results-Study participants were 3679 Generation 3 individuals with available parental data in the Offspring or the New Offspring Spouse cohorts. MVP and NDMs were distinguished by leaflet displacement >2 versus <= 2 mm beyond the mitral annulus, respectively. We compared MVP prevalence in Generation 3 participants with at least 1 parent with MVP (n=186) with that in individuals without parental MVP (n=3493). Among 3679 participants (53% women; mean age, 40 +/- 9 years), 49 (1%) had MVP. Parental MVP was associated with a higher prevalence of MVP in Generation 3 participants (10 of 186, 5.4%) compared with no parental MVP (39 of 3493, 1.1%; adjusted odds ratio, 4.51; 95% confidence interval, 2.13-9.54; P<0.0001). When parental NDMs were examined alone, the prevalence of Generation 3 MVP remained higher (12 of 484, 2.5%) compared with those without parental MVP or NDMs (27 of 3009, 0.9%; adjusted odds ratio, 2.52; 95% confidence interval, 1.25-5.10; P=0.01). Conclusions-Parental MVP and NDMs are associated with increased prevalence of offspring MVP, highlighting the genetic substrate of MVP and the potential clinical significance of NDMs in the community. C1 [Delling, Francesca N.; Rong, Jian; Larson, Martin G.; Lehman, Birgitta; Osypiuk, Ewa; Stantchev, Plamen; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Framingham, MA USA. [Delling, Francesca N.; Rong, Jian; Larson, Martin G.; Lehman, Birgitta; Osypiuk, Ewa; Stantchev, Plamen; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Delling, Francesca N.] Harvard Univ, Sch Med, Dept Med, Cardiovasc Div,Beth Israel Deaconess Med Ctr, Boston, MA USA. [Rong, Jian] Boston Univ, Sch Med, Dept Med, Neurol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Sect Math & Stat, Boston, MA 02215 USA. [Slaugenhaupt, Susan A.] Univ Hartford, Ctr Human Genet Res, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Levine, Robert A.] Univ Hartford, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Dept Med,Med Sch, Boston, MA USA. RP Delling, FN (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Div, 330 Brookline Ave,E-SH-458, Boston, MA 02215 USA. EM fdelling@bidmc.harvard.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Founders Affiliate American Heart Association Clinical Research Program; National Heart, Lung, and Blood Institute FHS [N01-HC-25195]; [R01HL080124]; [RO1HL0107385]; [K23HL116652] FX This work was supported by the Founders Affiliate American Heart Association Clinical Research Program (Dr Delling), National Heart, Lung, and Blood Institute FHS contract No. N01-HC-25195, and research grants R01HL080124, RO1HL0107385 (Dr Vasan), and K23HL116652 (Dr Delling). NR 39 TC 7 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 20 PY 2015 VL 131 IS 3 BP 263 EP + DI 10.1161/CIRCULATIONAHA.114.012594 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AZ3KT UT WOS:000348126800011 PM 25361552 ER PT J AU Laky, K Evans, S Perez-Diez, A Fowlkes, BJ AF Laky, Karen Evans, Sharron Perez-Diez, Ainhoa Fowlkes, B. J. TI Notch Signaling Regulates Antigen Sensitivity of Naive CD4(+) T Cells by Tuning Co-stimulation SO IMMUNITY LA English DT Article ID TRANSFERRIN RECEPTOR; TCR ENGAGEMENT; LYMPHOCYTES-T; ACTIVATION; EXPRESSION; DIFFERENTIATION; INTERLEUKIN-2; RESPONSES; PROLIFERATION; INHIBITION AB Adaptive immune responses begin when naive CD4(+) T cells engage peptide+major histocompatibility complex class II and co-stimulatory molecules on antigen-presenting cells (APCs). Notch signaling can influence effector functions in differentiated CD4(+) T helper and T regulatory cells. Whether and how ligand-induced Notch signaling influences the initial priming of CD4(+) T cells has not been addressed. We have found that Delta Like Ligand 4 (DLL4)-induced Notch signaling potentiates phosphatidylinositol 3-OH kinase (PI3K)-dependent signaling downstream of the T cell receptor+CD28, allowing naive CD4(+) T cells to respond to lower doses of antigen. In vitro, DLL4-deficient APCs were less efficient stimulators of CD4(+) T cell activation, metabolism, proliferation, and cytokine secretion. With deletion of DLL4 from CD11c(+) APCs in vivo, these deficits translated to an impaired ability to mount an effective CD4(+)-dependent anti-tumor response. These data implicate Notch signaling as an important regulator of adaptive immune responses. C1 [Laky, Karen; Evans, Sharron; Fowlkes, B. J.] NIAID, T Cell Dev Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Perez-Diez, Ainhoa] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Fowlkes, BJ (reprint author), NIAID, T Cell Dev Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM bfowlkes@nih.gov FU Intramural Research Program of the NIAID, NIH FX We thank N. Singh, R. Varma, E. Shevach, F. Ramsdell, L. Lefrancois, and P. Schwartzberg for their valuable suggestions regarding experimental design, interpretation of the data, and/or writing of the manuscript; R. Germain, T. Honjo, and S. Habu for critical reagents; T. Moyer and C. Eigsti of the NIAID Flow Cytometry Core Facility for sorting; and S. Friend and R. DeMarco of Amnis/EMD Millipore and D. Stephany of the NIAID Flow Cytometry Core Facility for assistance with the Imagestream analyses. This research was supported by the Intramural Research Program of the NIAID, NIH. NR 58 TC 16 Z9 16 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD JAN 20 PY 2015 VL 42 IS 1 BP 80 EP 94 DI 10.1016/j.immuni.2014.12.027 PG 15 WC Immunology SC Immunology GA AZ4NC UT WOS:000348197500013 PM 25607460 ER PT J AU Helmstetter, C Flossdorf, M Peine, M Kupz, A Zhu, JF Hegazy, AN Duque-Correa, MA Zhang, Q Vainshtein, Y Radbruch, A Kaufmann, SH Paul, WE Hofer, T Lohning, M AF Helmstetter, Caroline Flossdorf, Michael Peine, Michael Kupz, Andreas Zhu, Jinfang Hegazy, Ahmed N. Duque-Correa, Maria A. Zhang, Qin Vainshtein, Yevhen Radbruch, Andreas Kaufmann, Stefan H. Paul, William E. Hoefer, Thomas Loehning, Max TI Individual T Helper Cells Have a Quantitative Cytokine Memory SO IMMUNITY LA English DT Article ID NF-KAPPA-B; GENE-EXPRESSION; TRANSCRIPTION FACTOR; TH1 DEVELOPMENT; PROTEIN-LEVELS; RAPID ON/OFF; IFN-GAMMA; BET; RESPONSES; HETEROGENEITY AB The probabilistic expression of cytokine genes in differentiated T helper (Th) cell populations remains ill defined. By single-cell analyses and mathematical modeling, we show that one stimulation featured stable cytokine nonproducers as well as stable producers with wide cell-to-cell variability in the magnitude of expression. Focusing on interferon-gamma (IFN-gamma) expression by Th1 cells, mathematical modeling predicted that this behavior reflected different cell-intrinsic capacities and not mere gene-expression noise. In vivo, Th1 cells sort purified by secreted IFN-gamma amounts preserved a quantitative memory for both probability and magnitude of IFN-gamma re-expression for at least 1 month. Mechanistically, this memory resulted from quantitatively distinct transcription of individual alleles and was controlled by stable expression differences of the Th1 cell lineage-specifying transcription factor T-bet. Functionally, Th1 cells with graded IFN-gamma production competence differentially activated Salmonella-infected macrophages for bacterial killing. Thus, individual Th cells commit to produce distinct amounts of a given cytokine, thereby generating functional intrapopulation heterogeneity. C1 [Helmstetter, Caroline; Peine, Michael; Hegazy, Ahmed N.; Loehning, Max] Charite, Dept Rheumatol & Clin Immunol, D-10117 Berlin, Germany. [Helmstetter, Caroline; Peine, Michael; Hegazy, Ahmed N.; Radbruch, Andreas; Loehning, Max] Leibniz Inst, German Rheumatism Res Ctr DRFZ, D-10117 Berlin, Germany. [Flossdorf, Michael; Zhang, Qin; Vainshtein, Yevhen; Hoefer, Thomas] German Canc Res Ctr, Div Theoret Syst Biol, D-69120 Heidelberg, Germany. [Flossdorf, Michael; Zhang, Qin; Vainshtein, Yevhen; Hoefer, Thomas] Heidelberg Univ, Bioquant Ctr, D-69120 Heidelberg, Germany. [Kupz, Andreas; Duque-Correa, Maria A.; Kaufmann, Stefan H.] Max Planck Inst Infect Biol, Dept Immunol, D-10117 Berlin, Germany. [Kupz, Andreas] James Cook Univ, Queensland Trop Hlth Alliance Res Lab, Smithfield, Qld 4878, Australia. [Zhu, Jinfang; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Hegazy, Ahmed N.] Charite, Dept Gastroenterol Hepatol & Endocrinol, D-10117 Berlin, Germany. RP Hofer, T (reprint author), German Canc Res Ctr, Div Theoret Syst Biol, D-69120 Heidelberg, Germany. EM t.hoefer@dkfz-heidelberg.de; loehning@drfz.de RI Hofer, Thomas/G-5665-2013; Zhu, Jinfang/B-7574-2012; OI Hofer, Thomas/0000-0003-3560-8780; Vainshtein, Yevhen/0000-0001-7944-8892 FU German Federal Ministry of Education and Research (FORSYS and e: Bio/T-Sys); German Research Foundation [SFB618, TPC3, SFB650, TP28, LO1542/3-1, HO02050/4-1]; Volkswagen Foundation (Lichtenberg program); National Health and Medical Research Council of Australia through a CJ Martin Biomedical Early Career Fellowship [APP1052764]; EMBO long-term fellowship [ALTF 116-2012]; Marie Curie fellowship [FP7-PEOPLE-2012-IEF, 330621]; Division of Intramural Research, NIAID, NIH, USA; US National Science Foundation [NSF PHY11-25915] FX We thank V. Holecska, S. Ebel, I. Panse, and U. Zedler for expert technical assistance and the FCCF at DRFZ for cell sorting. This work was supported by the German Federal Ministry of Education and Research (FORSYS and e: Bio/T-Sys), the German Research Foundation (SFB618, TPC3; SFB650, TP28; LO1542/3-1, and HO02050/4-1), and the Volkswagen Foundation (Lichtenberg program to M. L.). C. H., M. P., and M. A. D.-C. were fellows of the International Max Planck Research School for Infectious Diseases and Immunology. A. K. was supported by the National Health and Medical Research Council of Australia through a CJ Martin Biomedical Early Career Fellowship (APP1052764). A.N.H. is supported by an EMBO long-term fellowship (ALTF 116-2012) and a Marie Curie fellowship (FP7-PEOPLE-2012-IEF, Proposal 330621). J.Z. and W. E. P. are supported by the Division of Intramural Research, NIAID, NIH, USA. T. H. and M. F. are supported in part by the US National Science Foundation (NSF PHY11-25915). T. H. is a member of CellNetworks. NR 46 TC 11 Z9 11 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD JAN 20 PY 2015 VL 42 IS 1 BP 108 EP 122 DI 10.1016/j.immuni.2014.12.018 PG 15 WC Immunology SC Immunology GA AZ4NC UT WOS:000348197500015 PM 25607461 ER PT J AU Gerner, MY Torabi-Parizi, P Germain, RN AF Gerner, Michael Y. Torabi-Parizi, Parizad Germain, Ronald N. TI Strategically Localized Dendritic Cells Promote Rapid T Cell Responses to Lymph-Borne Particulate Antigens SO IMMUNITY LA English DT Article ID SUBCAPSULAR SINUS MACROPHAGES; LEISHMANIA-MAJOR INFECTION; NODE B-CELLS; IN-VIVO; IMMUNITY; CD4; EXPRESSION; DYNAMICS; DISTINCT; SUBSETS AB Upon infection, adaptive immune responses play catch-up with rapidly replicating pathogens. While mechanisms for efficient humoral responses to lymph-borne antigens have been characterized, the current paradigm for T cell responses to infections and particulate vaccines involves delayed migration of peripheral antigen-bearing dendritic cells (DCs) to lymph nodes (LNs), where they elicit effector T cell responses. Utilizing whole LN 3D imaging, histo-cytometry, and intravital 2-photon microscopy, we have identified a specialized population of DCs, enriched in the LN-resident CD11b(+) subset, which resides within the lymphatic sinus endothelium and scans lymph with motile dendrites. These DCs capture draining particles and present associated antigens to T lymphocytes, inducing T cell responses much sooner than and independently of migratory DCs. Thus, strategic DC subset positioning in LNs limits a potentially costly delay in generation of T cell responses to lymph-borne antigens, contributing to effective host defense. These findings are also highly relevant to vaccine design. C1 [Gerner, Michael Y.; Torabi-Parizi, Parizad; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Torabi-Parizi, Parizad] NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Gerner, MY (reprint author), NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. EM gernermy@niaid.nih.gov; rgermain@nih.gov FU NIAID, NIH FX We would like to thank Dr. Michel Nussenzweig for providing the Zbtb46-DTR mouse line. We would also like to thank Dr. Yasmine Belkaid, Dr. Timothy Hand, and Dr. Denise Morais Da Fonseca for experimental contributions. In addition, we thank members of the LBS, LSB, as well as Dr. Kerry Casey, for many helpful comments during the course of these studies and for critical input during preparation of this manuscript. This research was supported by the Intramural Research Program, NIAID, NIH. NR 44 TC 46 Z9 46 U1 5 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD JAN 20 PY 2015 VL 42 IS 1 BP 172 EP 185 DI 10.1016/j.immuni.2014.12.024 PG 14 WC Immunology SC Immunology GA AZ4NC UT WOS:000348197500020 PM 25607462 ER PT J AU Burke, JF Merkow, MB Jacobs, J Kahana, MJ Zaghloul, KA AF Burke, John F. Merkow, Maxwell B. Jacobs, Joshua Kahana, Michael J. Zaghloul, Kareem A. TI Brain computer interface to enhance episodic memory in human participants SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE BCI; episodic memory; ECoG; theta ID PREDICTS LATER RECOLLECTION; FREE-RECALL; THETA OSCILLATIONS; PREFRONTAL CORTEX; SERIAL POSITION; NETWORK REORGANIZATION; DECLARATIVE MEMORY; PRESTIMULUS THETA; TEMPORAL-LOBE; HIPPOCAMPAL AB Recent research has revealed that neural oscillations in the theta (4-8 Hz) and alpha (9-14 Hz) bands are predictive of future success in memory encoding. Because these signals occur before the presentation of an upcoming stimulus, they are considered stimulus-independent in that they correlate with enhanced memory encoding independent of the item being encoded. Thus, such stimulus-independent activity has important implications for the neural mechanisms underlying episodic memory as well as the development of cognitive neural prosthetics. Here, we developed a brain computer interface (BCI) to test the ability of such pre-stimulus activity to modulate subsequent memory encoding. We recorded intracranial electroencephalography (iEEG) in neurosurgical patients as they performed a free recall memory task, and detected iEEG theta and alpha oscillations that correlated with optimal memory encoding. We then used these detected oscillatory changes to trigger the presentation of items in the free recall task. We found that item presentation contingent upon the presence of pre-stimulus theta and alpha oscillations modulated memory performance in more sessions than expected by chance. Our results suggest that an electrophysiological signal may be causally linked to a specific behavioral condition, and contingent stimulus presentation has the potential to modulate human memory encoding. C1 [Burke, John F.] Univ Penn, Dept Psychol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Merkow, Maxwell B.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. [Jacobs, Joshua] Columbia Univ, Dept Biomed Engn, New York, NY USA. [Kahana, Michael J.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Zaghloul, Kareem A.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Kahana, MJ (reprint author), Univ Penn, Dept Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA. EM kahana@psych.upenn.edu; kareem.zaghloul@nih.gov FU National Institutes of Health [R21N5067316]; Dana Foundation FX This work was supported by National Institutes of Health grant R21N5067316 and the Dana Foundation. NR 59 TC 4 Z9 4 U1 1 U2 13 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD JAN 20 PY 2015 VL 8 AR 1055 DI 10.3389/fnhum.2014.01055 PG 10 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AZ1US UT WOS:000348023800001 ER PT J AU Pasapera, AM Plotnikov, SV Fischer, RS Case, LB Egelhoff, TT Waterman, CM AF Pasapera, Ana M. Plotnikov, Sergey V. Fischer, Robert S. Case, Lindsay B. Egelhoff, Thomas T. Waterman, Clare M. TI Rac1-Dependent Phosphorylation and Focal Adhesion Recruitment of Myosin IIA Regulates Migration and Mechanosensing SO CURRENT BIOLOGY LA English DT Article ID PROTEIN-KINASE-C; RBL-2H3 MAST-CELLS; HEAVY-CHAIN; LEADING-EDGE; P21-ACTIVATED KINASE; B PHOSPHORYLATION; STRESS FIBERS; RHO GTPASES; ACTIN; RAC AB Background: Cell migration requires coordinated formation of focal adhesions (FAs) and assembly and contraction of the actin cytoskeleton. Nonmuscle myosin II (MII) is a critical mediator of contractility and FA dynamics in cell migration. Signaling downstream of the small GTPase Rac1 also regulates FA and actin dynamics, but its role in regulation of MII during migration is less clear. Results: We found that Rac1 promotes association of MIIA with FA. Live-cell imaging showed that, whereas most MIIA at the leading edge assembled into dorsal contractile arcs, a substantial subset assembled in or was captured within maturing FA, and this behavior was promoted by active Rac1. Protein kinase C (PKC) activation was necessary and sufficient for integrin-and Rac1-dependent phosphorylation of MIIA heavy chain (HC) on serine1916 (S1916) and recruitment to FA. S1916 phosphorylation of MIIA HC and localization in FA was enhanced during cell spreading and ECM stiffness mechanosensing, suggesting upregulation of this pathway during physiological Rac1 activation. Phosphomimic and non-phosphorylatable MIIA HC mutants demonstrated that S1916 phosphorylation was necessary and sufficient for the capture and assembly of MIIA minifilaments in FA. S1916 phosphorylation was also sufficient to promote the rapid assembly of FAs to enhance cell migration and for the modulation of traction force, spreading, and migration by ECM stiffness. Conclusions: Our study reveals for the first time that Rac1 and integrin activation regulates MIIA HC phosphorylation through a PKC-dependent mechanism that promotes MIIA association with FAs and acts as a critical modulator of cell migration and mechanosensing. C1 [Pasapera, Ana M.; Plotnikov, Sergey V.; Fischer, Robert S.; Case, Lindsay B.; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Plotnikov, Sergey V.] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON M5S 3G5, Canada. [Egelhoff, Thomas T.] Cleveland Clin Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44195 USA. RP Waterman, CM (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM watermancm@nhlbi.nih.gov OI Waterman, Clare/0000-0001-6142-6775 FU NHLBI Division of Intramural Research; NIH [GM50009] FX We thank Bill Shin for maintaining C.M.W.'s lab microscopes, Schwanna Thacker for administrative assistance, and Jordan Beach and the Sellers and Adelstein labs at NHLBI for helpful discussions. A.M.P., L.B.C., S.V.P., R.S.F., and C.M.W. were supported by the NHLBI Division of Intramural Research. T.T.E. was supported by NIH grant GM50009. NR 54 TC 17 Z9 17 U1 4 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD JAN 19 PY 2015 VL 25 IS 2 BP 175 EP 186 DI 10.1016/j.cub.2014.11.043 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AZ3LN UT WOS:000348129100018 PM 25544611 ER PT J AU Roche, J Louis, JM Bax, A AF Roche, Julien Louis, John M. Bax, Ad TI Conformation of Inhibitor-Free HIV-1 Protease Derived from NMR Spectroscopy in a Weakly Oriented Solution SO CHEMBIOCHEM LA English DT Article DE active sites; flap dynamics; HIV protease; liquid crystal NMR spectroscopy; residual dipolar coupling ID RESIDUAL DIPOLAR COUPLINGS; LIQUID-CRYSTALLINE PHASE; CLINICAL INHIBITORS; DYNAMICS; BINDING; FLEXIBILITY; VALIDATION; POTENT; SHIFTS; FLAPS AB Flexibility of the glycine-rich flaps is known to be essential for catalytic activity of the HIV-1 protease, but their exact conformations at the different stages of the enzymatic pathway remain subject to much debate. Although hundreds of crystal structures of protease-inhibitor complexes have been solved, only about a dozen inhibitor-free protease structures have been reported. These latter structures reveal a large diversity of flap conformations, ranging from closed to semi-open to wide open. To evaluate the average structure in solution, we measured residual dipolar couplings (RDCs) and compared these to values calculated for crystal structures representative of the closed, semi-open, and wide-open states. The RDC data clearly indicate that the inhibitor-free protease, on average, adopts a closed conformation in solution that is very similar to the inhibitor-bound state. By contrast, a highly drug-resistant protease mutant, PR20, adopts the wide-open flap conformation. C1 [Roche, Julien; Louis, John M.; Bax, Ad] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Roche, J (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM julien.roche@nih.gov; johnl@niddk.nih.gov; bax@nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases Advanced Mass Spectrometry Core; National Institutes of Health (NIH) Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases; Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH FX We thank Annie Aniana, James L. Baber, and Jinfa Ying for technical assistance and Dennis A. Torchia for helpful discussions. We acknowledge support from the National Institute of Diabetes and Digestive and Kidney Diseases Advanced Mass Spectrometry Core. This work was funded by the National Institutes of Health (NIH) Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases and by the Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH. NR 30 TC 10 Z9 10 U1 0 U2 16 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1439-4227 EI 1439-7633 J9 CHEMBIOCHEM JI ChemBioChem PD JAN 19 PY 2015 VL 16 IS 2 BP 214 EP 218 DI 10.1002/cbic.201402585 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AY8CA UT WOS:000347780800004 PM 25470009 ER PT J AU Shao, YH Gan, ZT Epifanovsky, E Gilbert, ATB Wormit, M Kussmann, J Lange, AW Behn, A Deng, J Feng, XT Ghosh, D Goldey, M Horn, PR Jacobson, LD Kaliman, I Khaliullin, RZ Kus, T Landau, A Liu, J Proynov, EI Rhee, YM Richard, RM Rohrdanz, MA Steele, RP Sundstrom, EJ Woodcock, HL Zimmerman, PM Zuev, D Albrecht, B Alguire, E Austin, B Beran, GJO Bernard, YA Berquist, E Brandhorst, K Bravaya, KB Brown, ST Casanova, D Chang, CM Chen, YQ Chien, SH Closser, KD Crittenden, DL Diedenhofen, M DiStasio, RA Do, H Dutoi, AD Edgar, RG Fatehi, S Fusti-Molnar, L Ghysels, A Golubeva-Zadorozhnaya, A Gomes, J Hanson-Heine, MWD Harbach, PHP Hauser, AW Hohenstein, EG Holden, ZC Jagau, TC Ji, HJ Kaduk, B Khistyaev, K Kim, J Kim, J King, RA Klunzinger, P Kosenkov, D Kowalczyk, T Krauter, CM Lao, KU Laurent, AD Lawler, KV Levchenko, SV Lin, CY Liu, F Livshits, E Lochan, RC Luenser, A Manohar, P Manzer, SF Mao, SP Mardirossian, N Marenich, AV Maurer, SA Mayhall, NJ Neuscamman, E Oana, CM Olivares-Amaya, R O'Neill, DP Parkhill, JA Perrine, TM Peverati, R Prociuk, A Rehn, DR Rosta, E Russ, NJ Sharada, SM Sharma, S Small, DW Sodt, A Stein, T Stuck, D Su, YC Thom, AJW Tsuchimochi, T Vanovschi, V Vogt, L Vydrov, O Wang, T Watson, MA Wenzel, J White, A Williams, CF Yang, J Yeganeh, S Yost, SR You, ZQ Zhang, IY Zhang, X Zhao, Y Brooks, BR Chan, GKL Chipman, DM Cramer, CJ Goddard, WA Gordon, MS Hehre, WJ Klamt, A Schaefer, HF Schmidt, MW Sherrill, CD Truhlar, DG Warshel, A Xu, X Aspuru-Guzik, A Baer, R Bell, AT Besley, NA Chai, JD Dreuw, A Dunietz, BD Furlani, TR Gwaltney, SR Hsu, CP Jung, YS Kong, J Lambrecht, DS Liang, WZ Ochsenfeld, C Rassolov, VA Slipchenko, LV Subotnik, JE Van Voorhis, T Herbert, JM Krylov, AI Gill, PMW Head-Gordon, M AF Shao, Yihan Gan, Zhengting Epifanovsky, Evgeny Gilbert, Andrew T. B. Wormit, Michael Kussmann, Joerg Lange, Adrian W. Behn, Andrew Deng, Jia Feng, Xintian Ghosh, Debashree Goldey, Matthew Horn, Paul R. Jacobson, Leif D. Kaliman, Ilya Khaliullin, Rustam Z. Kus, Tomasz Landau, Arie Liu, Jie Proynov, Emil I. Rhee, Young Min Richard, Ryan M. Rohrdanz, Mary A. Steele, Ryan P. Sundstrom, Eric J. Woodcock, H. Lee, III Zimmerman, Paul M. Zuev, Dmitry Albrecht, Ben Alguire, Ethan Austin, Brian Beran, Gregory J. O. Bernard, Yves A. Berquist, Eric Brandhorst, Kai Bravaya, Ksenia B. Brown, Shawn T. Casanova, David Chang, Chun-Min Chen, Yunqing Chien, Siu Hung Closser, Kristina D. Crittenden, Deborah L. Diedenhofen, Michael DiStasio, Robert A., Jr. Do, Hainam Dutoi, Anthony D. Edgar, Richard G. Fatehi, Shervin Fusti-Molnar, Laszlo Ghysels, An Golubeva-Zadorozhnaya, Anna Gomes, Joseph Hanson-Heine, Magnus W. D. Harbach, Philipp H. P. Hauser, Andreas W. Hohenstein, Edward G. Holden, Zachary C. Jagau, Thomas-C. Ji, Hyunjun Kaduk, Benjamin Khistyaev, Kirill Kim, Jaehoon Kim, Jihan King, Rollin A. Klunzinger, Phil Kosenkov, Dmytro Kowalczyk, Tim Krauter, Caroline M. Lao, Ka Un Laurent, Adele D. Lawler, Keith V. Levchenko, Sergey V. Lin, Ching Yeh Liu, Fenglai Livshits, Ester Lochan, Rohini C. Luenser, Arne Manohar, Prashant Manzer, Samuel F. Mao, Shan-Ping Mardirossian, Narbe Marenich, Aleksandr V. Maurer, Simon A. Mayhall, Nicholas J. Neuscamman, Eric Oana, C. Melania Olivares-Amaya, Roberto O'Neill, Darragh P. Parkhill, John A. Perrine, Trilisa M. Peverati, Roberto Prociuk, Alexander Rehn, Dirk R. Rosta, Edina Russ, Nicholas J. Sharada, Shaama M. Sharma, Sandeep Small, David W. Sodt, Alexander Stein, Tamar Stueck, David Su, Yu-Chuan Thom, Alex J. W. Tsuchimochi, Takashi Vanovschi, Vitalii Vogt, Leslie Vydrov, Oleg Wang, Tao Watson, Mark A. Wenzel, Jan White, Alec Williams, Christopher F. Yang, Jun Yeganeh, Sina Yost, Shane R. You, Zhi-Qiang Zhang, Igor Ying Zhang, Xing Zhao, Yan Brooks, Bernard R. Chan, Garnet K. L. Chipman, Daniel M. Cramer, Christopher J. Goddard, William A., III Gordon, Mark S. Hehre, Warren J. Klamt, Andreas Schaefer, Henry F., III Schmidt, Michael W. Sherrill, C. David Truhlar, Donald G. Warshel, Arieh Xu, Xin Aspuru-Guzik, Alan Baer, Roi Bell, Alexis T. Besley, Nicholas A. Chai, Jeng-Da Dreuw, Andreas Dunietz, Barry D. Furlani, Thomas R. Gwaltney, Steven R. Hsu, Chao-Ping Jung, Yousung Kong, Jing Lambrecht, Daniel S. Liang, WanZhen Ochsenfeld, Christian Rassolov, Vitaly A. Slipchenko, Lyudmila V. Subotnik, Joseph E. Van Voorhis, Troy Herbert, John M. Krylov, Anna I. Gill, Peter M. W. Head-Gordon, Martin TI Advances in molecular quantum chemistry contained in the Q-Chem 4 program package SO MOLECULAR PHYSICS LA English DT Article DE quantum chemistry; electron correlation; electronic structure theory; Q-Chem; computational modelling; software; density functional theory ID DENSITY-FUNCTIONAL THEORY; MATRIX RENORMALIZATION-GROUP; SPIN-COUPLING-CONSTANTS; ELECTRONIC-STRUCTURE CALCULATIONS; PLESSET PERTURBATION-THEORY; EXCITATION-ENERGY TRANSFER; FRAGMENT POTENTIAL METHOD; NUCLEAR-MAGNETIC-RESONANCE; CONTINUUM SOLVATION MODELS; BASIS-SET LIMIT AB A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Moller-Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr-2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube. C1 [Shao, Yihan; Gan, Zhengting; Epifanovsky, Evgeny; Proynov, Emil I.; Brown, Shawn T.; Chang, Chun-Min; Chien, Siu Hung; Closser, Kristina D.; Fusti-Molnar, Laszlo; Marenich, Aleksandr V.; Russ, Nicholas J.; Kong, Jing] Q Chem Inc, Pleasanton, CA USA. [Epifanovsky, Evgeny; Feng, Xintian; Ghosh, Debashree; Kus, Tomasz; Landau, Arie; Zuev, Dmitry; Bernard, Yves A.; Bravaya, Ksenia B.; Golubeva-Zadorozhnaya, Anna; Jagau, Thomas-C.; Khistyaev, Kirill; Laurent, Adele D.; Levchenko, Sergey V.; Manohar, Prashant; Oana, C. Melania; Rosta, Edina; Vanovschi, Vitalii; Wang, Tao; Warshel, Arieh; Krylov, Anna I.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. [Epifanovsky, Evgeny; Behn, Andrew; Goldey, Matthew; Sundstrom, Eric J.; Austin, Brian; Brandhorst, Kai; Casanova, David; Golubeva-Zadorozhnaya, Anna; Gomes, Joseph; Hauser, Andreas W.; Kim, Jihan; Laurent, Adele D.; Lawler, Keith V.; Mardirossian, Narbe; Marenich, Aleksandr V.; Mayhall, Nicholas J.; Neuscamman, Eric; Parkhill, John A.; Small, David W.; Sodt, Alexander; Stueck, David; Thom, Alex J. W.; White, Alec; Sherrill, C. David; Bell, Alexis T.; Krylov, Anna I.; Head-Gordon, Martin] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. [Gilbert, Andrew T. B.; Deng, Jia; Crittenden, Deborah L.; Lin, Ching Yeh; O'Neill, Darragh P.; Gill, Peter M. W.] Australian Natl Univ, Res Sch Chem, Canberra, ACT, Australia. [Wormit, Michael; Harbach, Philipp H. P.; Krauter, Caroline M.; Rehn, Dirk R.; Wenzel, Jan; Dreuw, Andreas] Heidelberg Univ, Interdisciplinary Ctr Sci Comp, Heidelberg, Germany. [Kussmann, Joerg; Luenser, Arne; Maurer, Simon A.; Ochsenfeld, Christian] Univ Munich LMU, Dept Chem, Munich, Germany. [Lange, Adrian W.; Jacobson, Leif D.; Liu, Jie; Richard, Ryan M.; Rohrdanz, Mary A.; Holden, Zachary C.; Lao, Ka Un; Williams, Christopher F.; You, Zhi-Qiang; Zhang, Xing; Herbert, John M.] Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA. [Kaliman, Ilya; Kosenkov, Dmytro; Slipchenko, Lyudmila V.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Liu, Jie; Liang, WanZhen] Xiamen Univ, Dept Chem, Xiamen 361005, Peoples R China. [Steele, Ryan P.; Fatehi, Shervin] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA. [Zimmerman, Paul M.; Chen, Yunqing; Perrine, Trilisa M.; Prociuk, Alexander] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. [Albrecht, Ben; Berquist, Eric; Lambrecht, Daniel S.] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. [Beran, Gregory J. O.] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA. [Casanova, David] IKERBASQUE Basque Fdn Sci, Donostia San Sebastian, Spain. [Casanova, David] DIPC, Donostia San Sebastian, Spain. [Casanova, David] Euskal Herriko Unibertsitatea UPV EHU, Kimika Fak, Donostia San Sebastian, Spain. [Diedenhofen, Michael; Klamt, Andreas] OCOSMOl GmbH & Co KG, Leverkusen, Germany. [Do, Hainam; Hanson-Heine, Magnus W. D.; Besley, Nicholas A.] Univ Nottingham, Sch Chem, Nottingham NG7 2RD, England. [Dutoi, Anthony D.] Univ Pacific, Dept Chem, Stockton, CA 95211 USA. [Edgar, Richard G.; Olivares-Amaya, Roberto; Vogt, Leslie; Watson, Mark A.; Aspuru-Guzik, Alan] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Alguire, Ethan; Fatehi, Shervin; Subotnik, Joseph E.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Ghysels, An; Sodt, Alexander; Brooks, Bernard R.] NIH, Computat Biophys Sect, Heart Lung & Blood Inst, Bethesda, MD 20892 USA. [Hohenstein, Edward G.; Sherrill, C. David] Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA. [Ji, Hyunjun; Kim, Jaehoon; Jung, Yousung] Korea Adv Inst Sci & Technol, Grad Sch EEWS, Taejon 305701, South Korea. [Kaduk, Benjamin; Kowalczyk, Tim; Tsuchimochi, Takashi; Vydrov, Oleg; Yeganeh, Sina; Yost, Shane R.; Van Voorhis, Troy] MIT, Dept Chem, Cambridge, MA 02139 USA. [King, Rollin A.] Bethel Univ, Dept Chem, St Paul, MN USA. [Klunzinger, Phil; Hehre, Warren J.] Wavefunction Inc, Irvine, CA USA. [Livshits, Ester; Stein, Tamar; Baer, Roi] Hebrew Univ Jerusalem, Chaim Weizmann Inst Chem, Jerusalem, Israel. [Livshits, Ester; Stein, Tamar; Baer, Roi] Hebrew Univ Jerusalem, Fritz Haber Res Ctr Mol Dynam, IL-91904 Jerusalem, Israel. [Mao, Shan-Ping; Su, Yu-Chuan; Chai, Jeng-Da] Natl Taiwan Univ, Dept Phys, Taipei 10764, Taiwan. [Marenich, Aleksandr V.; Peverati, Roberto; Zhao, Yan; Cramer, Christopher J.; Truhlar, Donald G.] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. [Olivares-Amaya, Roberto; Sharma, Sandeep; Watson, Mark A.; Yang, Jun; Chan, Garnet K. L.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA. [Woodcock, H. Lee, III] Univ S Florida, Dept Chem, Tampa, FL 33620 USA. [You, Zhi-Qiang; Hsu, Chao-Ping] Acad Sinica, Inst Chem, Taipei, Taiwan. [Zhang, Igor Ying; Xu, Xin] Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China. [Chipman, Daniel M.] Univ Notre Dame, Radiat Lab, Notre Dame, IN 46556 USA. [Goddard, William A., III] CALTECH, Mat & Proc Simulat Ctr, Pasadena, CA 91125 USA. [Gordon, Mark S.; Schmidt, Michael W.] Iowa State Univ, Dept Chem, Ames, IA USA. [Schaefer, Henry F., III] Univ Georgia, Dept Chem, Athens, GA 30602 USA. [Dunietz, Barry D.] Kent State Univ, Dept Chem & Biochem, Kent, OH 44242 USA. [Liu, Fenglai; Furlani, Thomas R.] SUNY Buffalo, Ctr Computat Res, Buffalo, NY 14260 USA. [Gwaltney, Steven R.] Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA. [Gwaltney, Steven R.] Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. RP Head-Gordon, M (reprint author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. EM mhg@cchem.berkeley.edu RI Ghysels, An/M-9095-2015; Zhao, Yan/A-2375-2008; Cramer, Christopher/B-6179-2011; Chai, Jeng-Da/C-3897-2009; Liang, Wanzhen /F-6879-2010; Hsu, Chao-Ping/E-1303-2011; Besley, Nicholas/I-7769-2013; Herbert, John/A-9573-2008; Chipman, Daniel/C-7704-2015; Ochsenfeld, Christian/E-8021-2015; Kussmann, Jorg/G-3016-2015; Truhlar, Donald/G-7076-2015; Jung, Yousung/D-1676-2010; Casanova, David/F-9752-2011; Gill, Peter/A-1201-2010; Kim, Jihan/H-8002-2013; Wenzel, Jan/C-3117-2016; DONOSTIA INTERNATIONAL PHYSICS CTR., DIPC/C-3171-2014; Laurent, Adele/G-5190-2011; Feng, Xintian/D-1292-2017; OI Rosta, Edina/0000-0002-9823-4766; Rassolov, Vitaly/0000-0002-7244-8870; Hauser, Andreas/0000-0001-6918-3106; Sherrill, David/0000-0002-5570-7666; Berquist, Eric/0000-0001-8186-9522; Bell, Alexis/0000-0002-5738-4645; Ghosh, Debashree/0000-0003-0726-7878; Cramer, Christopher/0000-0001-5048-1859; Chai, Jeng-Da/0000-0002-3994-2279; Hsu, Chao-Ping/0000-0002-7187-427X; Besley, Nicholas/0000-0003-1011-6675; Herbert, John/0000-0002-1663-2278; Chipman, Daniel/0000-0002-9992-6684; Ochsenfeld, Christian/0000-0002-4189-6558; Kussmann, Jorg/0000-0002-4724-8551; Truhlar, Donald/0000-0002-7742-7294; Jung, Yousung/0000-0003-2615-8394; Casanova, David/0000-0002-8893-7089; Gill, Peter/0000-0003-1042-6331; Laurent, Adele/0000-0001-9553-9014; Peverati, Roberto/0000-0001-7774-9923; Klamt, Andreas/0000-0002-5320-6219 FU National Institutes of Health [2R44GM073408, 2R44GM069255, 1R43GM086987, 2R44GM076847, 2R44GM081928, 2R44GM084555, 1R43GM096678]; Department of Energy [DE-SC0011297]; National Science Foundation FX Electronic structure software development at Q-CHEM has been supported during the period reviewed in this paper by SBIR grants from the National Institutes of Health [grant number 2R44GM073408], [grant number 2R44GM069255], [grant number 1R43GM086987], [grant number 2R44GM076847], [grant number 2R44GM081928], [grant number 2R44GM084555], [grant number 1R43GM096678], and from the Department of Energy [grant number DE-SC0011297]. In addition, the academic research groups that have contributed to Q-CHEM have been supported within the US by grants from the Department of Energy, the National Science Foundation, and other Federal agencies, and by corresponding national agencies in other countries. NR 412 TC 346 Z9 346 U1 51 U2 292 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0026-8976 EI 1362-3028 J9 MOL PHYS JI Mol. Phys. PD JAN 17 PY 2015 VL 113 IS 2 BP 184 EP 215 DI 10.1080/00268976.2014.952696 PG 32 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AW6DC UT WOS:000346358600007 ER PT J AU Pollack, AZ Mumford, SL Mendola, P Perkins, NJ Rotman, Y Wactawski-Wende, J Schisterman, EF AF Pollack, Anna Z. Mumford, Sunni L. Mendola, Pauline Perkins, Neil J. Rotman, Yaron Wactawski-Wende, Jean Schisterman, Enrique F. TI Kidney Biomarkers Associated with Blood Lead, Mercury, and Cadmium in Premenopausal Women: A Prospective Cohort Study SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID LOW-LEVEL CADMIUM; NUTRITION EXAMINATION SURVEY; RENAL TUBULAR FUNCTION; OXIDATIVE STRESS; NATIONAL-HEALTH; UNITED-STATES; OCCUPATIONAL-EXPOSURE; INORGANIC MERCURY; FISH CONSUMPTION; FACTORY-WORKERS AB Certain metals are harmful to the kidney and liver at high levels, but associations with functional biomarkers at low exposure levels among premenopausal women apparently has not been evaluated. Healthy, regularly menstruating women (n = 259) were followed for up to 2 menstrual cycles with up to 16 visits. Renal and liver biomarkers were measured in serum at each clinic visit. Cadmium (Cd), lead (Pb), and mercury (Hg) were measured in whole blood at baseline. Linear mixed models were adjusted for age, body mass index (BMI), race, average calories, alcohol intake, smoking, and cycle day. Median levels of Cd, Pb, and Hg were 0.31 mu g/L, 0.88 mu g/dl, and 1.1 mu g/L, respectively. One-third of women had diminished glomerular filtration rate (eGFR) (<90 ml/min/1.73 m(2)). Each twofold increase in Cd was associated with a negative 4.9% change in blood urea nitrogen (BUN) and bilirubin. Each twofold rise in Pb was associated with decreased eGFR and increased creatinine. A twofold elevation in Hg was associated with higher protein and reduced alkaline phosphatase. In healthy, predominantly nonsmoking women, low levels of Cd, Pb, and Hg were associated with changes in select biomarkers of kidney and liver function. C1 [Pollack, Anna Z.; Mumford, Sunni L.; Mendola, Pauline; Perkins, Neil J.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. [Pollack, Anna Z.] George Mason Univ, Dept Global & Community Hlth, Fairfax, VA 22030 USA. [Rotman, Yaron] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Buffalo, NY 14260 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,Suite 7B03, Bethesda, MD 20892 USA. EM schistee@mail.nih.gov OI Perkins, Neil/0000-0002-6802-4733; Pollack, Anna/0000-0002-4313-3298; Mendola, Pauline/0000-0001-5330-2844; Schisterman, Enrique/0000-0003-3757-641X FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HHSN275200403394C]; Long-Range Research Initiative grant of the American Chemistry Council FX The authors thank the BioCycle Study staff and participants for their extraordinary commitment to the study and Dr. Leila Jackson for leading the ancillary study of metals. This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract HHSN275200403394C). Anna Z. Pollack was partially supported by the Long-Range Research Initiative grant of the American Chemistry Council to Dr. Schisterman, PI. NR 46 TC 11 Z9 11 U1 0 U2 15 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1528-7394 EI 1087-2620 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD JAN 17 PY 2015 VL 78 IS 2 BP 119 EP 131 DI 10.1080/15287394.2014.944680 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AU1ES UT WOS:000345364500005 PM 25424620 ER EF