FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Reidy, M Masison, D AF Reidy, Michael Masison, Daniel TI Deciphering the molecular chaperone network using yeast prions SO PRION LA English DT Meeting Abstract C1 [Reidy, Michael; Masison, Daniel] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.76 BP S51 EP S51 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900094 ER PT J AU Saijo, E Hughson, A Raymond, G Horiuchi, M Caughey, B AF Saijo, Eri Hughson, Andrew Raymond, Gregory Horiuchi, Motohiro Caughey, Byron TI Scrapie-specific C-terminal antibody reveals conformational differences between prion strains SO PRION LA English DT Meeting Abstract C1 [Saijo, Eri; Hughson, Andrew; Raymond, Gregory; Caughey, Byron] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Horiuchi, Motohiro] Hokkaido Univ, Grad Sch Vet Med, Lab Vet Hyg, Sapporo, Hokkaido, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA O.12 BP S7 EP S7 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900013 ER PT J AU Vallabh, S Minikel, E Caughey, B AF Vallabh, Sonia Minikel, Eric Caughey, Byron TI Behavior of antiprion small molecules in RT-QuIC SO PRION LA English DT Meeting Abstract C1 [Vallabh, Sonia; Minikel, Eric] Prion Alliance, Cambridge, MA USA. [Vallabh, Sonia; Minikel, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Caughey, Byron] NIAID, Lab Persistant Viral Dis, Rocky Mt Labs, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.64 BP S44 EP S45 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900082 ER PT J AU Yuan, J Cooperman, L Orru, C Han, DY Fujioka, H Shick, E Zhan, YA Rodgers, M Wyza, R Appleby, B Quinones-Mateu, M Zhang, SL Mu, TW Caughey, B Qi, X Tesar, P Zou, WQ AF Yuan, Jue Cooperman, Leslie Orru, Christina Han, Dongyun Fujioka, Hisashi Shick, Elizabeth Zhan, Yi-An Rodgers, Mark Wyza, Robert Appleby, Brian Quinones-Mateu, Miguel Zhang, Shulin Mu, Tingwei Caughey, Byron Qi, Xin Tesar, Paul Zou, Wen-Quan TI Using patient-specific fibroblasts and iPSC-derived neurons to uncover cellular phenotypes associated with prion diseases SO PRION LA English DT Meeting Abstract C1 [Yuan, Jue; Cooperman, Leslie; Han, Dongyun; Fujioka, Hisashi; Shick, Elizabeth; Zhan, Yi-An; Rodgers, Mark; Wyza, Robert; Appleby, Brian; Quinones-Mateu, Miguel; Zhang, Shulin; Mu, Tingwei; Qi, Xin; Tesar, Paul; Zou, Wen-Quan] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Orru, Christina; Caughey, Byron] NIAID, NIH, Rocky Mt Labs, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.114 BP S70 EP S71 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900132 ER PT J AU Gupta, J Dominic, EA Fink, JC Ojo, AO Barrows, IR Reilly, MP Townsend, RR Joffe, MM Rosas, SE Wolman, M Patel, SS Keane, MG Feldman, HI Kusek, JW Raj, DS AF Gupta, Jayanta Dominic, Elizabeth A. Fink, Jeffrey C. Ojo, Akinlolu O. Barrows, Ian R. Reilly, Muredach P. Townsend, Raymond R. Joffe, Marshall M. Rosas, Sylvia E. Wolman, Melanie Patel, Samir S. Keane, Martin G. Feldman, Harold I. Kusek, John W. Raj, Dominic S. CA CRIC Study Investigators TI Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study SO PLOS ONE LA English DT Article ID C-REACTIVE PROTEIN; LEFT-VENTRICULAR HYPERTROPHY; NECROSIS-FACTOR-ALPHA; RENAL-INSUFFICIENCY COHORT; CARDIOVASCULAR MORTALITY; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; PROGNOSTIC VALUE; HEART-FAILURE; INTERLEUKIN-6 AB Background Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function. Methods Plasma levels of interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory. Results LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin-creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p< 0.001), IL-1RA (1.23 [1.13, 1.34], p< 0.0001), IL-6 (1.25 [1.14, 1.36], p< 0.001) and TNF-alpha (1.14 [1.04, 1.25], p = 0.004) were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 [1.18, 1.48], p< 0.001) and IL-6 (1.34 [1.21, 1.49], p< 0.001). Only hs-CRP was associated with diastolic dysfunction (1.14 [1.04, 1.26], p = 0.005). Conclusion In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction. C1 [Gupta, Jayanta] Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, El Paso, TX USA. [Dominic, Elizabeth A.; Barrows, Ian R.] George Washington Univ, Sch Med, Washington, DC USA. [Fink, Jeffrey C.] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. [Ojo, Akinlolu O.] Univ Michigan, Div Nephrol, Ann Arbor, MI 48109 USA. [Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Townsend, Raymond R.; Feldman, Harold I.] Univ Penn, Renal & Electrolyte Div, Philadelphia, PA 19104 USA. [Joffe, Marshall M.; Wolman, Melanie; Feldman, Harold I.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Rosas, Sylvia E.] Harvard Univ, Sch Med, Joslyn Diabet Ctr, Boston, MA USA. [Patel, Samir S.; Raj, Dominic S.] George Washington Univ, Div Renal Dis & Hypertens, Washington, DC 20052 USA. [Keane, Martin G.] Temple Univ, Dept Med, Philadelphia, PA 19122 USA. [Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA. RP Raj, DS (reprint author), George Washington Univ, Div Renal Dis & Hypertens, Washington, DC 20052 USA. EM draj@mfa.gwu.edu OI Fink, Jeffrey/0000-0002-5622-5052 FU National Institutes of Health [1R01DK073665-01A1, 1U01DK099924-01, 1U01DK099914-01]; National Institute of Diabetes and Digestive and Kidney Diseases [U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902]; University of Pennsylvania CTRC CTSA [UL1 RR-024134]; Johns Hopkins University [UL1 RR-025005]; University of Maryland [GCRC M01 RR-16500]; Clinical and Translational Science Collaborative of Cleveland; National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research [UL1TR000439]; Michigan Institute for Clinical and Health Research (MICHR) [UL1RR024986]; University of Illinois at Chicago CTSA [UL1RR029879]; Tulane University Translational Research in Hypertension and Renal Biology [P30GM103337]; Kaiser Permanente Northern California NIH/NCRR UCSF-CTSI [UL1 RR-024131] FX Dr. Raj is supported by the National Institutes of Health Grants 1R01DK073665-01A1, 1U01DK099924-01 and 1U01DK099914-01. Funding for the CRIC Study was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by: the University of Pennsylvania CTRC CTSA UL1 RR-024134, Johns Hopkins University UL1 RR-025005, University of Maryland GCRC M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research (MICHR) UL1RR024986, University of Illinois at Chicago CTSA UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30GM103337, Kaiser Permanente Northern California NIH/NCRR UCSF-CTSI UL1 RR-024131. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 6 Z9 7 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 24 PY 2015 VL 10 IS 4 AR e0124772 DI 10.1371/journal.pone.0124772 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG6AH UT WOS:000353376800104 PM 25909952 ER PT J AU Kovacs, M Kiss, A Gonczi, M Miskolczi, G Seprenyi, G Kaszaki, J Kohr, MJ Murphy, E Vegh, A AF Kovacs, Maria Kiss, Attila Gonczi, Mrton Miskolczi, Gottfried Seprenyi, Gyorgy Kaszaki, Jozsef Kohr, Mark J. Murphy, Elizabeth Vegh, Agnes TI Effect of Sodium Nitrite on Ischaemia and Reperfusion-Induced Arrhythmias in Anaesthetized Dogs: Is Protein S-Nitrosylation Involved? SO PLOS ONE LA English DT Article ID MYOCARDIAL-ISCHEMIA; INORGANIC NITRATE; CARDIOVASCULAR HEALTH; RYANODINE RECEPTOR; GAP-JUNCTIONS; EMERGING ROLE; L-ARGININE; IN-VIVO; OXIDE; PROTECTION AB Background and Purpose To provide evidence for the protective role of inorganic nitrite against acute ischaemia and reperfusion-induced ventricular arrhythmias in a large animal model. Experimental Approach Dogs, anaesthetized with chloralose and urethane, were administered intravenously with sodium nitrite (0.2 mu molkg(-1)min(-1)) in two protocols. In protocol 1 nitrite was infused 10 min prior to and during a 25 min occlusion of the left anterior descending (LAD) coronary artery (NaNO2-PO; n = 14), whereas in protocol 2 the infusion was started 10 min prior to reperfusion of the occluded vessel (NaNO2-PR; n = 12). Control dogs (n = 15) were infused with saline and subjected to the same period of ischaemia and reperfusion. Severities of ischaemia and ventricular arrhythmias, as well as changes in plasma nitrate/nitrite (NOx) levels in the coronary sinus blood, were assessed throughout the experiment. Myocardial superoxide and nitrotyrosine (NT) levels were determined during reperfusion. Changes in protein S-nitrosylation (SNO) and S-glutathionylation were also examined. Key Results Compared with controls, sodium nitrite administered either pre-occlusion or pre-reperfusion markedly suppressed the number and severity of ventricular arrhythmias during occlusion and increased survival (0% vs. 50 and 92%) upon reperfusion. There were also significant decreases in superoxide and NT levels in the nitrite treated dogs. Compared with controls, increased SNO was found only in NaNO2-PR dogs, whereas S-glutathionylation occurred primarily in NaNO2-PO dogs. Conclusions Intravenous infusion of nitrite profoundly reduced the severity of ventricular arrhythmias resulting from acute ischaemia and reperfusion in anaesthetized dogs. This effect, among several others, may result from an NO-mediated reduction in oxidative stress, perhaps through protein SNO and/or S-glutathionylation. C1 [Kovacs, Maria; Kiss, Attila; Gonczi, Mrton; Miskolczi, Gottfried; Vegh, Agnes] Univ Szeged, Dept Pharmacol & Pharmacotherapy, Fac Med, Szeged, Hungary. [Seprenyi, Gyorgy] Univ Szeged, Dept Med Biol, Fac Med, Szeged, Hungary. [Kaszaki, Jozsef] Univ Szeged, Inst Surg Res, Albert Szent Gyorgyi Med Ctr, Szeged, Hungary. [Kohr, Mark J.; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Vegh, A (reprint author), Univ Szeged, Dept Pharmacol & Pharmacotherapy, Fac Med, Szeged, Hungary. EM vegh.agnes@med.u-szeged.hu FU Hungarian Scientific Research Foundation (OTKA) [K75281, K105252]; MTA Postdoctoral Research Programme; National Institutes of Health Intramural Research Program FX This work was supported by the Hungarian Scientific Research Foundation (OTKA; Project number K75281 and K105252) and the MTA Postdoctoral Research Programme. This work was also supported, in part, by the National Institutes of Health Intramural Research Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 2 Z9 2 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 24 PY 2015 VL 10 IS 4 AR e0122243 DI 10.1371/journal.pone.0122243 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG6AH UT WOS:000353376800019 PM 25909651 ER PT J AU Pincus, NB Reckhow, JD Saleem, D Jammeh, ML Datta, SK Myles, IA AF Pincus, Nathan B. Reckhow, Jensen D. Saleem, Danial Jammeh, Momodou L. Datta, Sandip K. Myles, Ian A. TI Strain Specific Phage Treatment for Staphylococcus aureus Infection Is Influenced by Host Immunity and Site of Infection SO PLOS ONE LA English DT Article ID ESCHERICHIA-COLI O157-H7; LONG-TERM IMPACTS; BACTERIOPHAGE THERAPY; METHICILLIN-RESISTANT; HUMAN MICROBIOME; COCKTAIL; DISEASE; MICE; KERATINOCYTES; ANTIBIOTICS AB The response to multi-drug resistant bacterial infections must be a global priority. While mounting resistance threatens to create what the World Health Organization has termed a "post-antibiotic era", the recent discovery that antibiotic use may adversely impact the microbiome adds further urgency to the need for new developmental approaches for anti-pathogen treatments. Methicillin-resistant Staphylococcus aureus (MRSA), in particular, has declared itself a serious threat within the United States and abroad. A potential solution to the problem of antibiotic resistance may not entail looking to the future for completely novel treatments, but instead looking into our history of bacteriophage therapy. This study aimed to test the efficacy, safety, and commercial viability of the use of phages to treat Staphylococcus aureus infections using the commercially available phage SATA-8505. We found that SATA-8505 effectively controls Staphylococcus aureus growth and reduces bacterial viability both in vitro and in a skin infection mouse model. However, this killing effect was not observed when phage was cultured in the presence of human whole blood. SATA-8505 did not induce inflammatory responses in peripheral blood mononuclear cultures. However, phage did induce IFN gamma production in primary human keratinocyte cultures and induced inflammatory responses in our mouse models, particularly in a mouse model of chronic granulomatous disease. Our findings support the potential efficacy of phage therapy, although regulatory and market factors may limit its wider investigation and use. C1 [Pincus, Nathan B.; Reckhow, Jensen D.; Saleem, Danial; Jammeh, Momodou L.; Datta, Sandip K.; Myles, Ian A.] NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Myles, IA (reprint author), NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mylesi@niaid.nih.gov OI Datta, Sandip/0000-0003-0243-7815 FU Intramural Research Program of The National Institutes of Health; National Institute of Allergy and Infectious Disease FX This work was supported by the Intramural Research Program of The National Institutes of Health and The National Institute of Allergy and Infectious Disease. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 7 Z9 7 U1 9 U2 34 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 24 PY 2015 VL 10 IS 4 AR e0124280 DI 10.1371/journal.pone.0124280 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG6AH UT WOS:000353376800074 PM 25909449 ER PT J AU Tripathi, S Wang, GS White, M Qi, L Taubenberger, J Hartshorn, KL AF Tripathi, Shweta Wang, Guangshun White, Mitchell Qi, Li Taubenberger, Jeffery Hartshorn, Kevan L. TI Antiviral Activity of the Human Cathelicidin, LL-37, and Derived Peptides on Seasonal and Pandemic Influenza A Viruses SO PLOS ONE LA English DT Article ID SURFACTANT PROTEIN-D; ANTIMICROBIAL PEPTIDES; HOST-DEFENSE; INFECTION; MICE; HEMAGGLUTININ; MECHANISM; COLLECTIN; BINDING; REGION AB Human LL-37, a cationic antimicrobial peptide, was recently shown to have antiviral activity against influenza A virus (IAV) strains in vitro and in vivo. In this study we compared the anti-influenza activity of LL-37 with that of several fragments derived from LL-37. We first tested the peptides against a seasonal H3N2 strain and the mouse adapted H1N1 strain, PR-8. The N-terminal fragment, LL-23, had slight neutralizing activity against these strains. In LL-23V9 serine 9 is substituted by valine creating a continuous hydrophobic surface. LL-23V9 has been shown to have increased anti-bacterial activity compared to LL-23 and we now show slightly increased antiviral activity compared to LL-23 as well. The short central fragments, FK-13 and KR-12, which have anti-bacterial activity did not inhibit IAV. In contrast, a longer 20 amino acid central fragment of LL-37 (GI-20) had neutralizing activity similar to LL-37. None of the peptides inhibited viral hemagglutination or neuraminidase activity. We next tested activity of the peptides against a strain of pandemic H1N1 of 2009 (A/California/04/09/H1N1 or "Cal09"). Unexpectedly, LL-37 had markedly reduced activity against Cal09 using several cell types and assays of antiviral activity. A mutant viral strain containing just the hemagglutinin (HA) of 2009 pandemic H1N1 was inhibited by LL-37, suggested that genes other than the HA are involved in the resistance of pH1N1. In contrast, GI-20 did inhibit Cal09. In conclusion, the central helix of LL-37 incorporated in GI-20 appears to be required for optimal antiviral activity. The finding that GI-20 inhibits Cal09 suggests that it may be possible to engineer derivatives of LL-37 with improved antiviral properties. C1 [Tripathi, Shweta; White, Mitchell; Hartshorn, Kevan L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Wang, Guangshun] Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. [Qi, Li; Taubenberger, Jeffery] NIAID, Bethesda, MD 20892 USA. RP Hartshorn, KL (reprint author), Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. EM khartsho@bu.edu FU NIH [AI-83222, HL069031]; NIH intramural funds (JKT); Nebraska Research Initiative FX This work was supported by NIH Grant AI-83222 (KLH) and Grant HL069031 (KLH), NIH intramural funds (JKT) and the Nebraska Research Initiative (GW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 6 Z9 7 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 24 PY 2015 VL 10 IS 4 AR e0124706 DI 10.1371/journal.pone.0124706 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG6AH UT WOS:000353376800102 PM 25909853 ER PT J AU Sadd, BM Barribeau, SM Bloch, G de Graaf, DC Dearden, P Elsik, CG Gadau, J Grimmelikhuijzen, CJP Hasselmann, M Lozier, JD Robertson, HM Smagghe, G Stolle, E Van Vaerenbergh, M Waterhouse, RM Bornberg-Bauer, E Klasberg, S Bennett, AK Caamara, F Guigo, R Hoff, K Mariotti, M Munoz-Torres, M Murphy, T Santesmasses, D Amdam, GV Beckers, M Beye, M Biewer, M Bitondi, MMG Blaxter, ML Bourke, AFG Brown, MJF Buechel, SD Cameron, R Cappelle, K Carolan, JC Christiaens, O Ciborowski, KL Clarke, DF Colgan, TJ Collins, DH Cridge, AG Dalmay, T Dreier, S du Plessis, L Duncan, E Erler, S Evans, J Falcon, T Flores, K Freitas, FCP Fuchikawa, T Gempe, T Hartfelder, K Hauser, F Helbing, S Humann, FC Irvine, F Jermiin, LS Johnson, CE Johnson, RM Jones, AK Kadowaki, T Kidner, JH Koch, V Kohler, A Kraus, FB Lattorff, HMG Leask, M Lockett, GA Mallon, EB Antonio, DSM Marxer, M Meeus, I Moritz, RFA Nair, A Napflin, K Nissen, I Niu, J Nunes, FMF Oakeshott, JG Osborne, A Otte, M Pinheiro, DG Rossie, N Rueppell, O Santos, CG Schmid-Hempel, R Schmitt, BD Schulte, C Simoes, ZLP Soares, MPM Swevers, L Winnebeck, EC Wolschin, F Yu, N Zdobnov, EM Aqrawi, PK Blankenburg, KP Coyle, M Francisco, L Hernandez, AG Holder, M Hudson, ME Jackson, L Jayaseelan, J Joshi, V Kovar, C Lee, SL Mata, R Mathew, T Newsham, IF Ngo, R Okwuonu, G Pham, C Pu, LL Saada, N Santibanez, J Simmons, D Thornton, R Venkat, A Walden, KKO Wu, YQ Debyser, G Devreese, B Asher, C Blommaert, J Chipman, AD Chittka, L Fouks, B Liu, J O'Neill, MP Sumner, S Puiu, D Qu, J Salzberg, SL Scherer, SE Muzny, DM Richards, S Robinson, GE Gibbs, RA Schmid-Hempel, P Worley, KC AF Sadd, Ben M. Barribeau, Seth M. Bloch, Guy de Graaf, Dirk C. Dearden, Peter Elsik, Christine G. Gadau, Juergen Grimmelikhuijzen, Cornelis J. P. Hasselmann, Martin Lozier, Jeffrey D. Robertson, Hugh M. Smagghe, Guy Stolle, Eckart Van Vaerenbergh, Matthias Waterhouse, Robert M. Bornberg-Bauer, Erich Klasberg, Steffen Bennett, Anna K. Camara, Francisco Guigo, Roderic Hoff, Katharina Mariotti, Marco Munoz-Torres, Monica Murphy, Terence Santesmasses, Didac Amdam, Gro V. Beckers, Matthew Beye, Martin Biewer, Matthias Bitondi, Marcia M. G. Blaxter, Mark L. Bourke, Andrew F. G. Brown, Mark J. F. Buechel, Severine D. Cameron, Rossanah Cappelle, Kaat Carolan, James C. Christiaens, Olivier Ciborowski, Kate L. Clarke, David F. Colgan, Thomas J. Collins, David H. Cridge, Andrew G. Dalmay, Tamas Dreier, Stephanie du Plessis, Louis Duncan, Elizabeth Erler, Silvio Evans, Jay Falcon, Tiago Flores, Kevin Freitas, Flavia C. P. Fuchikawa, Taro Gempe, Tanja Hartfelder, Klaus Hauser, Frank Helbing, Sophie Humann, Fernanda C. Irvine, Frano Jermiin, Lars S. Johnson, Claire E. Johnson, Reed M. Jones, Andrew K. Kadowaki, Tatsuhiko Kidner, Jonathan H. Koch, Vasco Koehler, Arian Kraus, F. Bernhard Lattorff, H. Michael G. Leask, Megan Lockett, Gabrielle A. Mallon, Eamonn B. Antonio, David S. Marco Marxer, Monika Meeus, Ivan Moritz, Robin F. A. Nair, Ajay Napflin, Kathrin Nissen, Inga Niu, Jinzhi Nunes, Francis M. F. Oakeshott, John G. Osborne, Amy Otte, Marianne Pinheiro, Daniel G. Rossie, Nina Rueppell, Olav Santos, Carolina G. Schmid-Hempel, Regula Schmitt, Bjoern D. Schulte, Christina Simoes, Zila L. P. Soares, Michelle P. M. Swevers, Luc Winnebeck, Eva C. Wolschin, Florian Yu, Na Zdobnov, Evgeny M. Aqrawi, Peshtewani K. Blankenburg, Kerstin P. Coyle, Marcus Francisco, Liezl Hernandez, Alvaro G. Holder, Michael Hudson, Matthew E. Jackson, LaRonda Jayaseelan, Joy Joshi, Vandita Kovar, Christie Lee, Sandra L. Mata, Robert Mathew, Tittu Newsham, Irene F. Ngo, Robin Okwuonu, Geoffrey Pham, Christopher Pu, Ling-Ling Saada, Nehad Santibanez, Jireh Simmons, DeNard Thornton, Rebecca Venkat, Aarti Walden, Kimberly K. O. Wu, Yuan-Qing Debyser, Griet Devreese, Bart Asher, Claire Blommaert, Julie Chipman, Ariel D. Chittka, Lars Fouks, Bertrand Liu, Jisheng O'Neill, Meaghan P. Sumner, Seirian Puiu, Daniela Qu, Jiaxin Salzberg, Steven L. Scherer, Steven E. Muzny, Donna M. Richards, Stephen Robinson, Gene E. Gibbs, Richard A. Schmid-Hempel, Paul Worley, Kim C. TI The genomes of two key bumblebee species with primitive eusocial organization SO GENOME BIOLOGY LA English DT Article ID BEE APIS-MELLIFERA; SEX-DETERMINATION PATHWAY; MULTIPLE SEQUENCE ALIGNMENT; BOMBUS-TERRESTRIS LINNAEUS; MALE COURTSHIP BEHAVIOR; HONEY-BEE; DROSOPHILA-MELANOGASTER; PHYLOGENETIC ANALYSES; DNA METHYLATION; HIGH-THROUGHPUT AB Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation. C1 [Sadd, Ben M.] Illinois State Univ, Sch Biol Sci, Normal, IL 61790 USA. [Sadd, Ben M.; Barribeau, Seth M.; Buechel, Severine D.; Marxer, Monika; Napflin, Kathrin; Schmid-Hempel, Regula; Schmid-Hempel, Paul] ETH, Inst Integrat Biol, Expt Ecol, CH-8092 Zurich, Switzerland. [Barribeau, Seth M.] E Carolina Univ, Dept Biol, Greenville, NC 27858 USA. [Bloch, Guy; Fuchikawa, Taro; Chipman, Ariel D.] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Ecol Evolut & Behav, Jerusalem, Israel. [de Graaf, Dirk C.; Van Vaerenbergh, Matthias] Univ Ghent, Fac Sci, Lab Zoophysiol, B-9000 Ghent, Belgium. [Dearden, Peter; Cameron, Rossanah; Cridge, Andrew G.; Duncan, Elizabeth; Irvine, Frano; Leask, Megan; Nair, Ajay; Osborne, Amy; Blommaert, Julie] Univ Otago, Dept Biochem, Labo Evolut & Dev Genet, Dunedin 9054, New Zealand. [Dearden, Peter; Cameron, Rossanah; Cridge, Andrew G.; Duncan, Elizabeth; Irvine, Frano; Leask, Megan; Nair, Ajay; Osborne, Amy; Blommaert, Julie; O'Neill, Meaghan P.] Univ Otago, Dept Biochem, Natl Res Ctr Growth & Dev, Dunedin 9054, New Zealand. [Elsik, Christine G.] Univ Missouri, Div Plant Sci, Div Anim Sci, Columbia, MO 65211 USA. [Elsik, Christine G.] Univ Missouri, MU Informat Inst, Columbia, MO 65211 USA. [Elsik, Christine G.; Bennett, Anna K.; Munoz-Torres, Monica; Venkat, Aarti] Georgetown Univ, Dept Biol, Washington, DC 20057 USA. [Gadau, Juergen; Amdam, Gro V.; Wolschin, Florian] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. [Grimmelikhuijzen, Cornelis J. P.; Hauser, Frank] Univ Copenhagen, Dept Biol, Ctr Funct & Comparat Insect Gen, Copenhagen, Denmark. [Hasselmann, Martin; Biewer, Matthias] Univ Hohenheim, Inst Anim Sci, D-70599 Stuttgart, Germany. [Lozier, Jeffrey D.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA. [Robertson, Hugh M.; Cappelle, Kaat; Johnson, Claire E.; Walden, Kimberly K. O.] Univ Illinois, Dept Entomol, Urbana, IL 61801 USA. [Smagghe, Guy; Christiaens, Olivier; Meeus, Ivan; Niu, Jinzhi; Yu, Na; Liu, Jisheng] Univ Ghent, Fac Biosci Engn, Dept Crop Protect, Lab Agrozool, B-9000 Ghent, Belgium. [Stolle, Eckart; Erler, Silvio; Helbing, Sophie; Kidner, Jonathan H.; Kraus, F. Bernhard; Lattorff, H. Michael G.; Moritz, Robin F. A.; Otte, Marianne; Fouks, Bertrand] Univ Halle Wittenberg, Inst Biol, Wittenberg, Germany. [Waterhouse, Robert M.; Zdobnov, Evgeny M.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Waterhouse, Robert M.; Zdobnov, Evgeny M.] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland. [Waterhouse, Robert M.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Waterhouse, Robert M.] MIT & Harvard, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Bornberg-Bauer, Erich; Klasberg, Steffen] Univ Munster, Inst Evolut & Biodivers, D-48149 Munster, Germany. [Camara, Francisco; Guigo, Roderic; Mariotti, Marco; Santesmasses, Didac] Ctr Genom Regulat CRG, Barcelona 08003, Spain. [Camara, Francisco; Guigo, Roderic; Mariotti, Marco; Santesmasses, Didac] UPF, Barcelona, Spain. [Hoff, Katharina] Ernst Moritz Arndt Univ Greifswald, Inst Math & Comp Sci, D-17487 Greifswald, Germany. [Munoz-Torres, Monica] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA. [Murphy, Terence] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Amdam, Gro V.; Wolschin, Florian] Norwegian Univ Food Sci, Dept Chem Biotechnol & Food Sci, N-1432 As, Norway. [Beckers, Matthew] Univ E Anglia, Sch Comp Sci, Norwich NR4 7TJ, Norfolk, England. [Beye, Martin; Gempe, Tanja; Koch, Vasco; Koehler, Arian; Nissen, Inga; Rossie, Nina; Schmitt, Bjoern D.; Schulte, Christina] Univ Dusseldorf, Inst Evolut Genet, D-40225 Dusseldorf, Germany. [Biewer, Matthias] Univ Cologne, Inst Genet, Cologne, Germany. [Bitondi, Marcia M. G.; Simoes, Zila L. P.] Univ Sao Paulo, Dept Biol, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14040901 Ribeirao Preto, Brazil. [Blaxter, Mark L.] Univ Edinburgh, Ashworth Labs, Inst Evolutionary Biol & Edinburgh Gen, Edinburgh EH9 3FL, Midlothian, Scotland. [Bourke, Andrew F. G.; Collins, David H.; Dalmay, Tamas] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England. [Brown, Mark J. F.] Royal Holloway Univ London, Sch Biol Sci, London, England. [Carolan, James C.] Maynooth Univ, Dept Biol, Co, Kildare, Ireland. [Ciborowski, Kate L.; Sumner, Seirian] Univ Bristol, Sch Biol Sci, Bristol BS8 1TQ, Avon, England. [Clarke, David F.; Jermiin, Lars S.; Oakeshott, John G.] CSIRO, Land & Water Flagship, Canberra, ACT, Australia. [Colgan, Thomas J.] Trin Coll Dublin, Sch Nat Sci, Dept Zool, Dublin, Ireland. [Dreier, Stephanie; Asher, Claire] Zool Soc London, Inst Zool, London NW1 4RY, England. [du Plessis, Louis] ETH, Inst Integrat Biol, Theoret Biol, CH-8092 Zurich, Switzerland. [du Plessis, Louis] Swiss Inst Bioinformat, Lausanne, Switzerland. [du Plessis, Louis] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Computat Evolut, Basel, Switzerland. [Evans, Jay] USDA ARS, Bee Res Lab, Washington, DC 20250 USA. [Falcon, Tiago; Freitas, Flavia C. P.; Hartfelder, Klaus; Antonio, David S. Marco; Soares, Michelle P. M.] Univ Sao Paulo, Dept Genet, Fac Med Ribeirao Preto, BR-14040900 Ribeirao Preto, Brazil. [Flores, Kevin] N Carolina State Univ, Ctr Res Sci Computat, Raleigh, NC 27695 USA. [Fuchikawa, Taro] Kyoto Univ, Grad Sch Agr, Lab Insect Ecol, Kyoto, Japan. [Santos, Carolina G.] Univ Sao Paulo, Dept Biol Celular & Mol & Bioagentes Patogen, Fac Med Ribeirao Preto, BR-14040900 Ribeirao Preto, Brazil. [Humann, Fernanda C.] Inst Fed Educ Ciencia & Tecnol Sao Paulo, BR-15991502 Matao, Brazil. [Johnson, Reed M.] Ohio State Univ, Dept Entomol, Wooster, OH 44791 USA. [Jones, Andrew K.] Oxford Brookes Univ, Fac Hlth & Life Sci, Dept Biol & Med Sci, Oxford OX3 0BP, England. [Kadowaki, Tatsuhiko] Xian Jiaotong Liverpool Univ, Dept Biol Sci, Suzhou, Peoples R China. [Kraus, F. Bernhard] Univ Hosp Halle Saale, Dept Lab Med, Halle, Germany. [Lattorff, H. Michael G.] German Ctr Integrat Biodivers Res iDiv, Leipzig, Germany. [Lockett, Gabrielle A.] Univ Southampton, Southampton, Hants, England. [Mallon, Eamonn B.] Univ Leicester, Dept Biol, Leicester, Leics, England. [Nunes, Francis M. F.] Univ Fed Sao Carlos, Ctr Ciencias Biol & Saude, Dept Genet & Evolucao, BR-13565905 Sao Carlos, SP, Brazil. [Pinheiro, Daniel G.] Univ Estadual Paulista, Fac Ciencias Agr & Vet, Dept Tecnol, BR-14884900 Jaboticabal, Brazil. [Rueppell, Olav; Fouks, Bertrand] Univ N Carolina, Dept Biol, Greensboro, NC 27403 USA. [Swevers, Luc] Natl Ctr Sci Res Demokritos, Inst Biosci & Applicat, Athens, Greece. [Winnebeck, Eva C.] Univ Munich, Munich, Germany. [Aqrawi, Peshtewani K.; Blankenburg, Kerstin P.; Coyle, Marcus; Francisco, Liezl; Holder, Michael; Jackson, LaRonda; Jayaseelan, Joy; Joshi, Vandita; Kovar, Christie; Lee, Sandra L.; Mata, Robert; Mathew, Tittu; Ngo, Robin; Okwuonu, Geoffrey; Pham, Christopher; Pu, Ling-Ling; Saada, Nehad; Santibanez, Jireh; Simmons, DeNard; Thornton, Rebecca; Wu, Yuan-Qing; Qu, Jiaxin; Muzny, Donna M.; Richards, Stephen; Gibbs, Richard A.; Worley, Kim C.] Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Hernandez, Alvaro G.] Univ Illinois, Roy J Carver Biotechnol, Urbana, IL 61801 USA. [Hudson, Matthew E.] Univ Illinois, Dept Crop Sci, Urbana, IL 61801 USA. [Hudson, Matthew E.] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA. [Newsham, Irene F.] MD Anderson Canc Ctr, Sch Hlth Profess, Mol Genet Technol Program, Unit 2, Houston, TX 77025 USA. [Venkat, Aarti] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Debyser, Griet; Devreese, Bart] Univ Ghent, Dept Biochem & Microbiol, Lab Prot Biochem & Biomol Engn, B-9000 Ghent, Belgium. [Chittka, Lars] Queen Mary Univ London, Sch Biol & Chem Sci, Dept Biol & Expt Psychol, London E1 4NS, England. [Liu, Jisheng; Scherer, Steven E.] Guangzhou Univ, Sch Life Sci, Guangzhou, Guangdong, Peoples R China. [Puiu, Daniela; Salzberg, Steven L.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Ctr Computat Biol, Baltimore, MD 21205 USA. [Robinson, Gene E.] Univ Illinois, Neurosci Program, Dept Entomol, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA. RP Sadd, BM (reprint author), Illinois State Univ, Sch Biol Sci, Normal, IL 61790 USA. EM bmsadd@ilstu.edu RI Evans, Jay/C-8408-2012; Dearden, Peter/B-7607-2008; Waterhouse, Robert/A-1858-2010; Bornberg-Bauer, Erich/A-1563-2013; Freitas, Flavia /M-4720-2014; Lopes, Tiago/G-3409-2016; Blaxter, Mark/B-4113-2010; Nunes, Francis/F-5871-2010; Zdobnov, Evgeny/K-1133-2012; Bitondi, Marcia/E-8014-2012; Elsik, Christine/C-4120-2017; Moritz, Robin/K-6053-2012; Erler, Silvio/B-4162-2012; Lattorff, H. Michael/F-6287-2010; Hauser, Frank/M-2952-2014; Marco Antonio, David/G-2642-2012; JAYASEELAN, JOY CHRISTINA/F-9824-2015; Oakeshott, John/B-5365-2009; Camara Ferreira, Francisco/G-9841-2015; Kraus, Frank Bernhard/B-8172-2011; Guigo, Roderic/D-1303-2010; Hudson, Matthew/A-4438-2008; Hartfelder, Klaus/A-4293-2009; Jermiin, Lars/C-2458-2009; Johnson, Reed/H-3742-2011 OI Winnebeck, Eva/0000-0002-0717-9432; Duncan, Elizabeth/0000-0002-1841-504X; Childers, Anna/0000-0002-0747-8539; Sadd, Ben/0000-0003-3136-5144; Rueppell, Olav/0000-0001-5370-4229; Stolle, Eckart/0000-0001-7638-4061; Cridge, Andrew/0000-0002-1399-5188; Lockett, Gabrielle A./0000-0003-3759-2145; Napflin, Kathrin/0000-0002-1088-5282; Bloch, Guy/0000-0003-1624-4926; Evans, Jay/0000-0002-0036-4651; Dearden, Peter/0000-0001-7790-9675; Waterhouse, Robert/0000-0003-4199-9052; Bornberg-Bauer, Erich/0000-0002-1826-3576; Freitas, Flavia /0000-0002-3162-4890; Lopes, Tiago/0000-0002-8936-0381; Blaxter, Mark/0000-0003-2861-949X; Nunes, Francis/0000-0002-7769-3058; Bitondi, Marcia/0000-0002-5619-6378; Elsik, Christine/0000-0002-4248-7713; Moritz, Robin/0000-0003-0791-887X; Erler, Silvio/0000-0002-9425-8103; Lattorff, H. Michael/0000-0002-8603-6332; Hauser, Frank/0000-0001-5563-2345; JAYASEELAN, JOY CHRISTINA/0000-0002-7759-0139; Camara Ferreira, Francisco/0000-0002-1971-5466; Kraus, Frank Bernhard/0000-0003-4354-9952; Guigo, Roderic/0000-0002-5738-4477; Hudson, Matthew/0000-0002-4737-0936; Hartfelder, Klaus/0000-0001-7981-8427; Jermiin, Lars/0000-0002-9619-3809; Johnson, Reed/0000-0002-2431-0180 FU National Institutes of Health (NIH) [DP1 OD006416, U54 HG003273]; Agriculture and Food Research Initiative Competitive grant from the USDA National Institute of Food and Agriculture [2010-65106-21301]; Research Council of Norway (NFR); PEW Charitable Trust; University of East Anglia, UK; Israel Science Foundation (ISF); Biotechnology and Biological Sciences Research Council, UK; University of East Anglia; University of Alabama College of Arts and Sciences; Sao Paulo Research Foundation grant (FAPESP) [11/03171-5]; Marie Curie International Outgoing Fellowship [PIOF-GA-2011-303312]; Swiss National Science Foundation [31003A-125350, 31003A-143936]; New Faculty Initiative Grant (NFIG) from Illinois State University College of Arts and Sciences; DFG; Instituto Nacional de Bioinformatica (INB) from ISCIII in Spain FX The sequencing, annotation, and assembly of the B. impatiens genome was supported by National Institutes of Health (NIH) Pioneer Award DP1 OD006416 (GER). The B. terrestris genome sequencing, assembly and project coordination was supported by NIH grant U54 HG003273 (RAG). Contributions from members of the CGE lab were supported by Agriculture and Food Research Initiative Competitive grant no. 2010-65106-21301 from the USDA National Institute of Food and Agriculture. GVA was supported by the Research Council of Norway (NFR) and the PEW Charitable Trust. MB was supported by a student fellowship from the University of East Anglia, UK. GB was supported by the Israel Science Foundation (ISF). DHC was supported by a studentship funded by the Biotechnology and Biological Sciences Research Council, UK, and the University of East Anglia. JDL was supported by the University of Alabama College of Arts and Sciences. ZPLS was supported by a Sao Paulo Research Foundation grant (FAPESP number 11/03171-5). RMW was supported by Marie Curie International Outgoing Fellowship PIOF-GA-2011-303312 and by Swiss National Science Foundation awards 31003A-125350 and 31003A-143936 to EMZ. BMS was supported by a New Faculty Initiative Grant (NFIG) from Illinois State University College of Arts and Sciences. MHasselmann received financial support from the DFG. The work of FC, RG, and MM was supported by the Instituto Nacional de Bioinformatica (INB) from ISCIII in Spain. We thank Justin Reese and Christopher Childers for setting up genome annotation tools at Hymenoptera Genome Database. NR 213 TC 53 Z9 55 U1 31 U2 164 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PD APR 24 PY 2015 VL 16 AR 76 DI 10.1186/s13059-015-0623-3 PG 31 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CG9YT UT WOS:000353676700001 PM 25908251 ER PT J AU Li, GH Anderson, C Jaeger, L Do, T Major, EO Nath, A AF Li, Guan-Han Anderson, Caroline Jaeger, Laura Do, Thao Major, Eugene O. Nath, Avindra TI Cell-to-cell contact facilitates HIV transmission from lymphocytes to astrocytes via CXCR4 SO AIDS LA English DT Article DE astrocyte; brain; cell-to-cell transmission; CXCR4; HIV infection; lymphocyte; virological synapse ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; HUMAN FETAL ASTROCYTES; NECROSIS-FACTOR-ALPHA; HUMAN GLIAL-CELLS; CHEMOKINE RECEPTORS; TYPE-1 INFECTION; VIROLOGICAL SYNAPSES; HUMAN BRAIN; PRODUCTIVE INFECTION AB Objectives:HIV reservoir in the brain represents a major barrier for curing HIV infection. As the most abundant, long-lived cell type, astrocytes play a critical role in maintaining the reservoir; however, the mechanism of infection remains unknown. Here, we determine how viral transmission occurs from HIV-infected lymphocytes to astrocytes by cell-to-cell contact.Design and methods:Human astrocytes were exposed to HIV-infected lymphocytes and monitored by live-imaging, confocal microscopy, transmission and three-dimensional electron microscopy. A panel of receptor antagonists was used to determine the mechanism of viral entry.Results:We found that cell-to-cell contact resulted in efficient transmission of X4 or X4R5-using viruses from T lymphocytes to astrocytes. In co-cultures of astrocytes with HIV-infected lymphocytes, the interaction occurred through a dynamic process of attachment and detachment of the two cell types. Infected lymphocytes invaginated into astrocytes or the contacts occurred via filopodial extensions from either cell type, leading to the formation of virological synapses. In the synapses, budding of immature or incomplete HIV particles from lymphocytes occurred directly onto the membranes of astrocytes. This cell-to-cell transmission could be almost completely blocked by anti-CXCR4 antibody and its antagonist, but only partially inhibited by anti-CD4, ICAM1 antibodies.Conclusion:Cell-to-cell transmission was mediated by a unique mechanism by which immature viral particles initiated a fusion process in a CXCR4-dependent, CD4-independent manner. These observations have important implications for developing approaches to prevent formation of HIV reservoirs in the brain. C1 [Li, Guan-Han; Anderson, Caroline; Jaeger, Laura; Nath, Avindra] NINDS, Sect Infect Nervous Syst, Bethesda, MD 20892 USA. [Do, Thao] NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Nath, A (reprint author), Bldg 10,7C-103,10 Ctr Dr, Bethesda, MD 20892 USA. EM natha@ninds.nih.gov FU NIMH; NINDS FX The study was supported by NIMH P30 Pilot Award (G.L.) and the NINDS intramural funds. We thank David Levy at the New York University and Amanda Brown at the Johns Hopkins University (JHU) for providing HIV-1 reporter viruses NLENG1 and SF162R3, respectively; Michael Delannoy at the JHU Microscope Facility, Andrew Roholt at Renovo Neural Inc. and Sriram Subramaniam and Lesley Earl at the NCI forcorrelative EM and 3D-EM; Joseph Steiner and Suneil Hosmane at the JHU for time-lapse imaging; Alan Hoofring at NIH for editing pictures, movies, and cartoons; and Tianxia Wu for statistical analysis. NR 78 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD APR 24 PY 2015 VL 29 IS 7 BP 755 EP 766 DI 10.1097/QAD.0000000000000605 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA CG7FV UT WOS:000353469000001 PM 25985398 ER PT J AU Pena-Munzenmayer, G Catalan, MA Kondo, Y Jaramillo, Y Liu, F Shull, GE Melvin, JE AF Pena-Muenzenmayer, Gaspar Catalan, Marcelo A. Kondo, Yusuke Jaramillo, Yasna Liu, Frances Shull, Gary E. Melvin, James E. TI Ae4 (Slc4a9) Anion Exchanger Drives Cl- Uptake-dependent Fluid Secretion by Mouse Submandibular Gland Acinar Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MANDIBULAR SALIVARY-GLAND; CL-/HCO3-EXCHANGER; UP-REGULATION; NKCC1-DEFICIENT MICE; TARGETED DISRUPTION; INTERCALATED CELLS; INTRACELLULAR PH; MURINE DUODENUM; ION-TRANSPORT; COTRANSPORTER AB Transcellular Cl- movement across acinar cells is the rate-limiting step for salivary gland fluid secretion. Basolateral Nkcc1 Na+-K+-2Cl(-) cotransporters play a critical role in fluid secretion by promoting the intracellular accumulation of Cl- above its equilibrium potential. However, salivation is only partially abolished in the absence of Nkcc1 cotransporter activity, suggesting that another Cl- uptake pathway concentrates Cl- ions in acinar cells. To identify alternative molecular mechanisms, we studied mice lacking Ae2 and Ae4 Cl-/HCO3- exchangers. We found that salivation stimulated by muscarinic and beta-adrenergic receptor agonists was normal in the submandibular glands of Ae2(-/-) mice. In contrast, saliva secretion was reduced by 35% in Ae4(-/-) mice. The decrease in salivation was not related to loss of Na+-K+-2Cl(-) cotransporter or Na+/H+ exchanger activity in Ae4(-/-) mice but correlated with reduced Cl- uptake during beta-adrenergic receptor activation of cAMP signaling. Direct measurements of Cl-/HCO3- exchanger activity revealed that HCO3--dependent Cl- uptake was reduced in the acinar cells of Ae2(-/-) and Ae4(-/-) mice. Moreover, Cl-/HCO3- exchanger activity was nearly abolished in double Ae4/Ae2 knock-out mice, suggesting that most of the Cl-/HCO3- exchanger activity in submandibular acinar cells depends on Ae2 and Ae4 expression. In conclusion, both Ae2 and Ae4 anion exchangers are functionally expressed in submandibular acinar cells; however, only Ae4 expression appears to be important for cAMP-dependent regulation of fluid secretion. C1 [Pena-Muenzenmayer, Gaspar; Catalan, Marcelo A.; Kondo, Yusuke; Jaramillo, Yasna; Liu, Frances; Melvin, James E.] NIDCR, Secretory Mech & Dysfunct Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Shull, Gary E.] Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Coll Med, Cincinnati, OH 45267 USA. [Kondo, Yusuke] Kyushu Dent Univ, Dept Oral Reconstruct & Rehabil, Kitakyushu, Fukuoka, Japan. RP Melvin, JE (reprint author), NIDCR, Secretory Mech & Dysfunct Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA. EM james.melvin@nih.gov RI Regan, Clinton/E-6250-2012 FU National Institutes of Health (NIH), NIDCR, Division of Intramural Research; NIH [DK050594] FX This work was supported, in whole or in part, by the National Institutes of Health (NIH), NIDCR, Division of Intramural Research (to the Secretory Mechanisms and Dysfunction Section) and NIH Grant DK050594 (to G. E. S.). NR 58 TC 4 Z9 4 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 APR 24 PY 2015 VL 290 IS 17 BP 10677 EP 10688 DI 10.1074/jbc.M114.612895 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CG6IX UT WOS:000353404500011 PM 25745107 ER PT J AU Marzi, A Halfmann, P Hill-Batorski, L Feldmann, F Shupert, WL Neumann, G Feldmann, H Kawaoka, Y AF Marzi, Andrea Halfmann, Peter Hill-Batorski, Lindsay Feldmann, Friederike Shupert, W. Lesley Neumann, Gabriele Feldmann, Heinz Kawaoka, Yoshihiro TI An Ebola whole-virus vaccine is protective in nonhuman primates SO SCIENCE LA English DT Article ID I CLINICAL-TRIAL; CELLULAR-IMMUNITY; MARBURG VIRUSES; INFECTION; CHALLENGE; IMMUNOGENICITY; INFLUENZA; RESPONSES; MACAQUES AB Zaire ebolavirus is the causative agent of the current outbreak of hemorrhagic fever disease in West Africa. Previously, we showed that a whole Ebola virus (EBOV) vaccine based on a replication-defective EBOV (EBOV Delta VP30) protects immunized mice and guinea pigs against lethal challenge with rodent-adapted EBOV. Here, we demonstrate that EBOV Delta VP30 protects nonhuman primates against lethal infection with EBOV. Although EBOV Delta VP30 is replication-incompetent, we additionally inactivated the vaccine with hydrogen peroxide; the chemically inactivated vaccine remained antigenic and protective in nonhuman primates. EBOV Delta VP30 thus represents a safe, efficacious, whole-EBOV vaccine candidate that differs from other EBOV vaccine platforms in that it presents all viral proteins and the viral RNA to the host immune system, which might contribute to protective immune responses. C1 [Marzi, Andrea; Shupert, W. Lesley; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA. [Halfmann, Peter; Hill-Batorski, Lindsay; Neumann, Gabriele; Kawaoka, Yoshihiro] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Influenza Res Inst, Madison, WI 53706 USA. [Feldmann, Friederike] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH, Hamilton, MT USA. [Kawaoka, Yoshihiro] Univ Tokyo, Int Res Ctr Infect Dis, Inst Med Sci, Dept Microbiol & Immunol,Div Virol, Tokyo, Japan. [Kawaoka, Yoshihiro] Japan Sci & Technol Agcy, ERATO Infect Induced Host Responses Project, Saitama, Japan. RP Kawaoka, Y (reprint author), Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Influenza Res Inst, Madison, WI 53706 USA. EM kawaokay@svm.vetmed.wisc.edu FU Region V "Great Lakes" Regional Center of Excellence (GLRCE) [U54 AI 57153]; Health and Labour Sciences Research Grants, Japan; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH FX We thank E. Ollmann-Saphire (Scripps Research Institute, La Jolla, CA) for purified EBOV NP. We also thank S. Watson for editing the manuscript, T. Armbrust for excellent technical assistance, and staff of the Rocky Mountain Veterinary Branch for assistance with animal work. Y.K. and G.N. are inventors on a patent (held by the University of Wisconsin Alumni Research Foundation) for EBOV reverse genetics; therefore, a Material Transfer Agreement (MTA) is required to obtain this system. Funding for this research was provided by the Region V "Great Lakes" Regional Center of Excellence (GLRCE; U54 AI 57153) and by Health and Labour Sciences Research Grants, Japan. The study was partially funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. Raw data can be found at https://docs.google.com/spreadsheets/d/1dBgzt5_z4rp-qOuxXcI_FbUz8wNqMvHy 6kVP_tpW0MY/edit?usp=sharing. NR 27 TC 17 Z9 20 U1 3 U2 30 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD APR 24 PY 2015 VL 348 IS 6233 BP 439 EP 442 DI 10.1126/science.aaa4919 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG5NF UT WOS:000353338000035 PM 25814063 ER PT J AU Wu, XL Zhang, ZH Schramm, CA Joyce, MG Do Kwon, Y Zhou, TQ Sheng, ZZ Zhang, BS O'Dell, S Mckee, K Georgiev, IS Chuang, GY Longo, NS Lynch, RM Saunders, KO Soto, C Srivatsan, S Yang, YP Bailer, RT Louder, MK Mullikin, JC Connors, M Kwong, PD Mascola, JR Shapiro, L AF Wu, Xueling Zhang, Zhenhai Schramm, Chaim A. Joyce, M. Gordon Do Kwon, Young Zhou, Tongqing Sheng, Zizhang Zhang, Baoshan O'Dell, Sijy Mckee, Krisha Georgiev, Ivelin S. Chuang, Gwo-Yu Longo, Nancy S. Lynch, Rebecca M. Saunders, Kevin O. Soto, Cinque Srivatsan, Sanjay Yang, Yongping Bailer, Robert T. Louder, Mark K. Mullikin, James C. Connors, Mark Kwong, Peter D. Mascola, John R. Shapiro, Lawrence CA Program, NCS TI Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection SO CELL LA English DT Article ID BROADLY NEUTRALIZING ANTIBODIES; B-CELL RECEPTORS; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; POTENT NEUTRALIZATION; CD4-BINDING SITE; RATIONAL DESIGN; ENVELOPE TRIMER; BINDING-SITE; GENE USAGE AB HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals, although highly effective antibodies are generally observed only after years of chronic infection. Here, we characterize the rate of maturation and extent of diversity for the lineage that produced the broadly neutralizing antibody VRC01 through longitudinal sampling of peripheral B cell transcripts over 15 years and co-crystal structures of lineage members. Next-generation sequencing identified VRC01-lineage transcripts, which encompassed diverse antibodies organized into distinct phylogenetic clades. Prevalent clades maintained characteristic features of antigen recognition, though each evolved binding loops and disulfides that formed distinct recognition surfaces. Over the course of the study period, VRC01-lineage clades showed continuous evolution, with rates of similar to 2 substitutions per 100 nucleotides per year, comparable to that of HIV-1 evolution. This high rate of antibody evolution provides a mechanism by which antibody lineages can achieve extraordinary diversity and, over years of chronic infection, develop effective HIV-1 neutralization. C1 [Wu, Xueling; Zhang, Zhenhai; Joyce, M. Gordon; Do Kwon, Young; Zhou, Tongqing; Zhang, Baoshan; O'Dell, Sijy; Mckee, Krisha; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Longo, Nancy S.; Lynch, Rebecca M.; Saunders, Kevin O.; Soto, Cinque; Srivatsan, Sanjay; Yang, Yongping; Bailer, Robert T.; Louder, Mark K.; Kwong, Peter D.; Mascola, John R.; Shapiro, Lawrence] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Wu, Xueling] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. [Zhang, Zhenhai; Schramm, Chaim A.; Sheng, Zizhang; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Zhang, Zhenhai; Schramm, Chaim A.; Sheng, Zizhang; Shapiro, Lawrence] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA. [Zhang, Zhenhai] Southern Med Univ, Nanfang Hosp, State Key Lab Organ Failure Res, Guangzhou 510515, Guangdong, Peoples R China. [Zhang, Zhenhai] Southern Med Univ, Nanfang Hosp, Natl Clin Res Ctr Kidney Dis, Guangzhou 510515, Guangdong, Peoples R China. [Mullikin, James C.; Program, NCS] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Connors, Mark] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pdkwong@nih.gov; jmascola@nih.gov; lss8@columbia.edu RI Zhou, Tongqing/A-6880-2010; Kwon, Young Do/A-6957-2010 OI Zhou, Tongqing/0000-0002-3935-4637; FU Intramural Research Program of the VRC; NHGRI; NIH [P01-AI104722]; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38] FX We thank E. Turk and C.-L. Lin for technical assistance with large neutralization panels. We thank members of the Structural Biology Section, Structural Bioinformatics Core Section, and Humoral Immunology Core Section, Vaccine Research Center (VRC), NIAID, NIH, for comments and suggestions on the manuscript. We thank J. Baalwa, D. Ellenberger, F. Gao, B. Hahn, K. Hong, J. Kim, F. McCutchan, D. Montefiori, L. Morris, J. Overbaugh, E. Sanders-Buell, G. Shaw, R. Swanstrom, M. Thomson, S. Tovanabutra, C. Williamson, and L. Zhang for contributing the HIV-1 Envelope plasmids used in our neutralization panel. The sequences of NIH45-177 and NIH45-243 were kindly provided by J. Scheid and M. Nussenzweig. We thank F. Alt for helpful discussions on antibody lineage development and rates. Support for this work was provided by the Intramural Research Program of the VRC and the NHGRI and by NIH grant P01-AI104722. Use of sector 22 at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract number W-31-109-Eng-38. NR 49 TC 47 Z9 47 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD APR 23 PY 2015 VL 161 IS 3 BP 470 EP 485 DI 10.1016/j.cell.2015.03.004 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CG8JN UT WOS:000353553600009 PM 25865483 ER PT J AU Mishra, A Kumar, R Tyagi, A Kohaar, I Hedau, S Bharti, AC Sarker, S Dey, D Saluja, D Das, B AF Mishra, Alok Kumar, Rakesh Tyagi, Abhishek Kohaar, Indu Hedau, Suresh Bharti, Alok C. Sarker, Subhodeep Dey, Dipankar Saluja, Daman Das, Bhudev TI Curcumin modulates cellular AP-1, NF-kB, and HPV16 E6 proteins in oral cancer SO ECANCERMEDICALSCIENCE LA English DT Article DE activator protein-1 (AP-1); curcumin; human papilloma virus (HPA); nuclear factor kappaB (NF-kB); transcription ID HUMAN-PAPILLOMAVIRUS TYPE-16; FACTOR-KAPPA-B; GENE-EXPRESSION; TRANSCRIPTIONAL CONTROL; OROPHARYNGEAL CANCER; BINDING-ACTIVITY; FAMILY PROTEINS; TUMOR PROMOTION; CELLS; ACTIVATION AB In this study, we investigated the effects of the natural antioxidant curcumin on the HPV16-positive oral carcinoma cell line 93VU147T and demonstrated that curcumin is not only a potent inhibitor for the activity of host nuclear transcription factors AP-1 and NF-kB but it also selectively suppresses transcription of the HPV16/E6 oncogene during the carcinogenic process in oral cancer cells. This study suggests a therapeutic potential of curcumin for high-risk human papilloma virus (HPV)-infected oral cancers. C1 [Mishra, Alok; Kumar, Rakesh; Tyagi, Abhishek; Kohaar, Indu; Hedau, Suresh; Bharti, Alok C.; Sarker, Subhodeep; Dey, Dipankar; Das, Bhudev] Inst Cytol & Prevent Oncol ICMR, Noida 201301, India. [Mishra, Alok; Kumar, Rakesh; Tyagi, Abhishek; Saluja, Daman; Das, Bhudev] Univ Delhi, ACBR, Delhi 110007, India. [Mishra, Alok; Kohaar, Indu] NCI, NIH, Bethesda, MD 20892 USA. [Kumar, Rakesh] Mayo Clin, Rochester, MN 55905 USA. [Das, Bhudev] Amity Univ, Noida 201303, India. RP Mishra, A (reprint author), Inst Cytol & Prevent Oncol ICMR, 1-7,Sect 39, Noida 201301, India. EM alok.mishra@emory.edu OI Sarker, Subhodeep/0000-0002-2222-2072 NR 36 TC 6 Z9 7 U1 1 U2 6 PU CANCER INTELLIGENCE LTD PI BRISTOL PA 11 ALMA VALE RD,, BRISTOL, BS8 2HL, ENGLAND SN 1754-6605 J9 ECANCERMEDICALSCIENC JI eCancerMedicalScience PD APR 23 PY 2015 VL 9 AR 525 DI 10.3332/ecancer.2015.525 PG 12 WC Oncology SC Oncology GA CQ4YV UT WOS:000360611400001 PM 25932049 ER PT J AU Hoots, WK Kiley, JP Mockrin, SC Lauer, M Mensah, GA Patel, Y Cook, NL Patterson, AP Gibbons, GH AF Hoots, William Keith Kiley, James P. Mockrin, Stephen C. Lauer, Michael Mensah, George A. Patel, Yasin Cook, Nakela L. Patterson, Amy P. Gibbons, Gary H. TI NHLBI Strategic Visioning: setting an agenda together for the NHLBI of 2025 SO BLOOD LA English DT Letter ID DISEASE C1 [Hoots, William Keith; Kiley, James P.] NHLBI, NIH, Div Blood Dis & Resources, Bethesda, MD 20892 USA. [Mockrin, Stephen C.] NHLBI, NIH, Div Extramural Res Activ, Bethesda, MD 20892 USA. [Lauer, Michael] NHLBI, NIH, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Mensah, George A.] NHLBI, NIH, Ctr Translat Res & Implementat Sci, Bethesda, MD 20892 USA. [Patel, Yasin; Cook, Nakela L.; Patterson, Amy P.; Gibbons, Gary H.] NHLBI, NIH, Immediate Off, Bethesda, MD 20892 USA. RP Hoots, WK (reprint author), NHLBI, NIH, Div Blood Dis & Resources, 6701 Rockledge Dr,Room 9136, Bethesda, MD 20892 USA. EM hootswk@nhlbi.nih.gov NR 15 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD APR 23 PY 2015 VL 125 IS 17 BP 2733 EP 2735 DI 10.1182/blood-2015-02-626689 PG 3 WC Hematology SC Hematology GA CJ7DF UT WOS:000355653600025 PM 25907905 ER PT J AU Ong, CC Gierke, S Pitt, C Sagolla, M Cheng, CK Zhou, W Jubb, AM Strickland, L Schmidt, M Duron, SG Campbell, DA Zheng, W Dehdashti, S Shen, M Yang, NR Behnke, ML Huang, WW Mckew, JC Chernoff, J Forrest, WF Haverty, PM Chin, SF Rakha, EA Green, AR Ellis, IO Caldas, C O'Brien, T Friedman, LS Koeppen, H Rudolph, J Hoeflich, KP AF Ong, Christy C. Gierke, Sarah Pitt, Cameron Sagolla, Meredith Cheng, Christine K. Zhou, Wei Jubb, Adrian M. Strickland, Laura Schmidt, Maike Duron, Sergio G. Campbell, David A. Zheng, Wei Dehdashti, Seameen Shen, Min Yang, Nora Behnke, Mark L. Huang, Wenwei Mckew, John C. Chernoff, Jonathan Forrest, William F. Haverty, Peter M. Chin, Suet-Feung Rakha, Emad A. Green, Andrew R. Ellis, Ian O. Caldas, Carlos O'Brien, Thomas Friedman, Lori S. Koeppen, Hartmut Rudolph, Joachim Hoeflich, Klaus P. TI Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents SO BREAST CANCER RESEARCH LA English DT Article ID TUMOR-FORMATION; PAK1; CELLS; RAS; PHOSPHORYLATION; TRANSFORMATION; LOCALIZATION; FAMILY; TARGET AB Introduction: Breast cancer, the most common cause of cancer-related deaths worldwide among women, is a molecularly and clinically heterogeneous disease. Extensive genetic and epigenetic profiling of breast tumors has recently revealed novel putative driver genes, including p21-activated kinase (PAK) 1. PAK1 is a serine/threonine kinase downstream of small GTP-binding proteins, Rac1 and Cdc42, and is an integral component of growth factor signaling networks and cellular functions fundamental to tumorigenesis. Methods: PAK1 dysregulation (copy number gain, mRNA and protein expression) was evaluated in two cohorts of breast cancer tissues (n = 980 and 1,108). A novel small molecule inhibitor, FRAX1036, and RNA interference were used to examine PAK1 loss of function and combination with docetaxel in vitro. Mechanism of action for the therapeutic combination, both cellular and molecular, was assessed via time-lapse microscopy and immunoblotting. Results: We demonstrate that focal genomic amplification and overexpression of PAK1 are associated with poor clinical outcome in the luminal subtype of breast cancer (P = 1.29 x 10(-4) and P = 0.015, respectively). Given the role for PAK1 in regulating cytoskeletal organization, we hypothesized that combination of PAK1 inhibition with taxane treatment could be combined to further interfere with microtubule dynamics and cell survival. Consistent with this, administration of docetaxel with either a novel small molecule inhibitor of group I PAKs, FRAX1036, or PAK1 small interfering RNA oligonucleotides dramatically altered signaling to cytoskeletal-associated proteins, such as stathmin, and induced microtubule disorganization and cellular apoptosis. Live-cell imaging revealed that the duration of mitotic arrest mediated by docetaxel was significantly reduced in the presence of FRAX1036, and this was associated with increased kinetics of apoptosis. Conclusions: Taken together, these findings further support PAK1 as a potential target in breast cancer and suggest combination with taxanes as a viable strategy to increase anti-tumor efficacy. C1 [Ong, Christy C.; Pitt, Cameron; Cheng, Christine K.; Zhou, Wei; O'Brien, Thomas; Friedman, Lori S.; Hoeflich, Klaus P.] Genentech Inc, Dept Translat Oncol, San Francisco, CA 94080 USA. [Gierke, Sarah; Sagolla, Meredith; Jubb, Adrian M.; Koeppen, Hartmut] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA. [Strickland, Laura; Schmidt, Maike] Genentech Inc, Dept Diagnost, San Francisco, CA 94080 USA. [Duron, Sergio G.; Campbell, David A.] Afraxis, La Jolla, CA USA. [Dehdashti, Seameen; Shen, Min; Yang, Nora; Behnke, Mark L.; Huang, Wenwei; Mckew, John C.] Natl Ctr Adv Translat Sci, Bethesda, MD USA. [Chernoff, Jonathan] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Forrest, William F.] Genentech Inc, Dept Biostat, San Francisco, CA 94080 USA. [Haverty, Peter M.] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA. [Chin, Suet-Feung; Caldas, Carlos] Univ Cambridge, Canc Res UK, Cambridge, England. [Rakha, Emad A.; Green, Andrew R.; Ellis, Ian O.] Univ Nottingham, Sch Med, Div Canc & Stem Cells, Histopathol, Nottingham, England. [Rakha, Emad A.; Green, Andrew R.; Ellis, Ian O.] Univ Nottingham Hosp, Nottingham NG7 2UH, England. [Rudolph, Joachim] Genentech Inc, Discovery Chem, San Francisco, CA 94080 USA. RP Rudolph, J (reprint author), Genentech Inc, Discovery Chem, San Francisco, CA 94080 USA. EM rudolph.joachim@gene.com; klaushoeflich@hotmail.com RI Zheng, Wei/J-8889-2014; OI Zheng, Wei/0000-0003-1034-0757; chin, suet-feung/0000-0001-5697-1082; O'Brien, Thomas/0000-0002-9161-8070 FU Genentech FX CCO, SG, CKC, MSa, WZho, AMJ, LS, MSc, WFF, PMH, TOB, LSF, HK and JR own stock in Hoffmann-La Roche. KPH is a shareholder of Blueprint Medicines. DAC and SGD own shares in Afraxis. CC receives research funding from Genentech and is a member of the Scientific Advisory Board at AstraZeneca. CP, WZhe, SD, MS, NY, MLB, WH, JCM, JC, SFC, EAR, ARG and IOE declare that they have no competing interests. NR 31 TC 13 Z9 13 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PD APR 23 PY 2015 VL 17 AR 59 DI 10.1186/s13058-015-0564-5 PG 12 WC Oncology SC Oncology GA CI9LR UT WOS:000355092100001 PM 25902869 ER PT J AU Sargolzaei, S Sargolzaei, A Cabrerizo, M Chen, G Goryawala, M Noei, S Zhou, Q Duara, R Barker, W Adjouadi, M AF Sargolzaei, Saman Sargolzaei, Arman Cabrerizo, Mercedes Chen, Gang Goryawala, Mohammed Noei, Shirin Zhou, Qi Duara, Ranjan Barker, Warren Adjouadi, Malek TI A practical guideline for intracranial volume estimation in patients with Alzheimer's disease SO BMC BIOINFORMATICS LA English DT Article ID MILD COGNITIVE IMPAIRMENT; HEALTHY-ADULTS; ATROPHY; MRI; RELIABILITY; SCHIZOPHRENIA; SEGMENTATION; MORPHOMETRY; BIOMARKERS; MATTER AB Background: Intracranial volume (ICV) is an important normalization measure used in morphometric analyses to correct for head size in studies of Alzheimer Disease (AD). Inaccurate ICV estimation could introduce bias in the outcome. The current study provides a decision aid in defining protocols for ICV estimation in patients with Alzheimer disease in terms of sampling frequencies that can be optimally used on the volumetric MRI data, and the type of software most suitable for use in estimating the ICV measure. Methods: Two groups of 22 subjects are considered, including adult controls (AC) and patients with Alzheimer Disease (AD). Reference measurements were calculated for each subject by manually tracing intracranial cavity by the means of visual inspection. The reliability of reference measurements were assured through intra-and inter-variation analyses. Three publicly well-known software packages (Freesurfer, FSL, and SPM) were examined in their ability to automatically estimate ICV across the groups. Results: Analysis of the results supported the significant effect of estimation method, gender, cognitive condition of the subject and the interaction among method and cognitive condition factors in the measured ICV. Results on sub-sampling studies with a 95% confidence showed that in order to keep the accuracy of the interleaved slice sampling protocol above 99%, the sampling period cannot exceed 20 millimeters for AC and 15 millimeters for AD. Freesurfer showed promising estimates for both adult groups. However SPM showed more consistency in its ICV estimation over the different phases of the study. Conclusions: This study emphasized the importance in selecting the appropriate protocol, the choice of the sampling period in the manual estimation of ICV and selection of suitable software for the automated estimation of ICV. The current study serves as an initial framework for establishing an appropriate protocol in both manual and automatic ICV estimations with different subject populations. C1 [Sargolzaei, Saman; Sargolzaei, Arman; Cabrerizo, Mercedes; Zhou, Qi; Adjouadi, Malek] Florida Int Univ, Dept Elect & Comp Engn, Miami, FL 33174 USA. [Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, HHS, Bethesda, MD USA. [Goryawala, Mohammed] Univ Miami, Miller Sch Med, Dept Biol, Miami, FL 33136 USA. [Noei, Shirin] Florida Int Univ, Dept Civil & Environm Engn, Miami, FL 33199 USA. [Duara, Ranjan; Barker, Warren] Mt Sinai Med Ctr, Wien Ctr Alzheimers Dis & Memory Disorders, Miami Beach, FL 33140 USA. RP Sargolzaei, S (reprint author), Florida Int Univ, Dept Elect & Comp Engn, Miami, FL 33174 USA. EM ssarg004@fiu.edu FU National Science Foundation [CNS-0959985, CNS-1042341, HRD-0833093, IIP-1230661]; Ware Foundation FX This work is supported by the National Science Foundation under grants CNS-0959985, CNS-1042341, HRD-0833093, and IIP-1230661. The support of the Ware Foundation is greatly appreciated. NR 54 TC 7 Z9 7 U1 1 U2 3 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 APR 23 PY 2015 VL 16 SU 7 AR S8 DI 10.1186/1471-2105-16-S7-S8 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA CH4BR UT WOS:000353976600008 PM 25953026 ER PT J AU Cai, LM Lyu, XM Luo, WR Cui, XF Ye, YF Yuan, CC Peng, QX Wu, DH Liu, TF Wang, E Marincola, FM Yao, KT Fang, WY Cai, HB Li, X AF Cai, L-M Lyu, X-M Luo, W-R Cui, X-F Ye, Y-F Yuan, C-C Peng, Q-X Wu, D-H Liu, T-F Wang, E. Marincola, F-M Yao, K-T Fang, W-Y Cai, H-B Li, X. TI EBV-miR-BART7-3p promotes the EMT and metastasis of nasopharyngeal carcinoma cells by suppressing the tumor suppressor PTEN SO ONCOGENE LA English DT Article ID EPSTEIN-BARR-VIRUS; EPITHELIAL-MESENCHYMAL TRANSITION; CANCER STEM-CELLS; ENCODED MICRORNAS; TARGETING PTEN; LUNG-CANCER; E-CADHERIN; EXPRESSION; PROTEIN; INVASION AB The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3 beta signaling and eventually leading to the high expression and nuclear accumulation of Snail and beta-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and beta-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target. C1 [Cai, L-M; Lyu, X-M; Luo, W-R; Ye, Y-F; Yuan, C-C; Yao, K-T; Fang, W-Y; Li, X.] Southern Med Univ, Canc Res Inst, Guangzhou 510515, Guangdong, Peoples R China. [Lyu, X-M] Southern Med Univ, Dept Lab Med, Affiliated Hosp 3, Guangzhou 510515, Guangdong, Peoples R China. [Cui, X-F] 463 Hosp Chinese PLA, Dept ENT, Shenyang, Peoples R China. [Peng, Q-X; Cai, H-B] Southern Med Univ, Sch Chinese Tradit Med, Guangzhou 510515, Guangdong, Peoples R China. [Wu, D-H] Southern Med Univ, Nanfang Hosp, Dept Radiat Oncol, Guangzhou 510515, Guangdong, Peoples R China. [Liu, T-F] Southern Med Univ, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China. [Wang, E.; Marincola, F-M] NIH, Infect Dis & Immunogenet Sect, DTM, Ctr Clin, Bethesda, MD 20892 USA. RP Li, X (reprint author), Southern Med Univ, Canc Res Inst, Guangzhou 510515, Guangdong, Peoples R China. EM fangweiyi1975@yahoo.com.cn; chbing2008@126.com; xinli268@gmail.com FU National Natural Science Foundation of China [81372895, 81172586]; Research Fund for the Doctoral Program of Higher Education of China [20134433110013]; Natural Science Foundation of Guangdong Province [S2011010004157]; Guangzhou Science and Technology research project [2014J4100149] FX This study was financially supported by grants from National Natural Science Foundation of China (No. 81372895, 81172586), Research Fund for the Doctoral Program of Higher Education of China (No. 20134433110013), Natural Science Foundation of Guangdong Province (No. S2011010004157) and Guangzhou Science and Technology research project (No. 2014J4100149). NR 63 TC 27 Z9 28 U1 3 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD APR 23 PY 2015 VL 34 IS 17 BP 2156 EP 2166 DI 10.1038/onc.2014.341 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CG7HG UT WOS:000353473000002 PM 25347742 ER PT J AU Heslop, E Csimma, C Straub, V McCall, J Nagaraju, K Wagner, KR Caizergues, D Korinthenberg, R Flanigan, KM Kaufmann, P McNeil, E Mendell, J Hesterlee, S Wells, DJ AF Heslop, Emma Csimma, Cristina Straub, Volker McCall, John Nagaraju, Kanneboyina Wagner, Kathryn R. Caizergues, Didier Korinthenberg, Rudolf Flanigan, Kevin M. Kaufmann, Petra McNeil, Elizabeth Mendell, Jerry Hesterlee, Sharon Wells, Dominic J. CA Kate Bushby Behalf TACT TI The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Article DE Neuromuscular disease; Rare disease; Review; De-risking; Drug development ID REGISTRIES; DESIGN; CARE AB Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD. We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme. To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics. Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to market. C1 [Heslop, Emma; Straub, Volker; Kate Bushby Behalf TACT] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Csimma, Cristina] Cydan Dev Inc, Cambridge, MA USA. [McCall, John] PharMac LLL, Boca Grande, FL USA. [Nagaraju, Kanneboyina] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Wagner, Kathryn R.] Johns Hopkins Univ, Baltimore, MD USA. [Caizergues, Didier] Genethon, Evry, France. [Korinthenberg, Rudolf] Univ Freiburg, D-79106 Freiburg, Germany. [Flanigan, Kevin M.; Mendell, Jerry] Nationwide Childrens Hosp, Columbus, OH USA. [Kaufmann, Petra; McNeil, Elizabeth] Natl Inst Hlth, Washington, DC USA. [Hesterlee, Sharon] Parent Project Muscular Dystrophy, Hackensack, NJ USA. [Wells, Dominic J.] Univ London Royal Vet Coll, London, England. RP Heslop, E (reprint author), Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. OI Flanigan, Kevin/0000-0001-6440-3376; Ryan, Monique/0000-0001-6397-1910; Wells, Dominic/0000-0002-1425-6344; Korinthenberg, Rudolf/0000-0002-4638-3460 FU TREAT-NMD from the European Commission through FP6 [036825]; Second Public Health Programme [2012 3307]; Medical Research Council [MR/K501074/1]; US department of defence [W81XWH-11-1-0782 K]; Parent Project Muscular Dystrophy and Cure Duchenne; Parent Project Muscular Dystrophy (PPMD); Cure Duchenne; Association Francaise contre les Myopathies (AFM); Jesses Journey; Muscular Dystrophy Campaign (MDC); Muscular Dystrophy Association (MDA); Action Duchenne; Cure CMD; Foundation to Eradicate Duchenne (FED) FX We acknowledge funding support for TREAT-NMD from the European Commission through FP6 (contract number 036825) and the Second Public Health Programme (contract number 2012 3307), as well as support from the Medical Research Council (grant number MR/K501074/1), US department of defence (Award W81XWH-11-1-0782 K Nagaraju, CNMC, USA), Parent Project Muscular Dystrophy and Cure Duchenne.; Support from patient organisations - Parent Project Muscular Dystrophy (PPMD), Cure Duchenne, Association Francaise contre les Myopathies (AFM), Jesses Journey, Muscular Dystrophy Campaign (MDC), Muscular Dystrophy Association (MDA), Action Duchenne, Cure CMD, and Foundation to Eradicate Duchenne (FED). NR 17 TC 3 Z9 3 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1172 J9 ORPHANET J RARE DIS JI Orphanet J. Rare Dis. PD APR 23 PY 2015 VL 10 AR 49 DI 10.1186/s13023-015-0258-1 PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA CH0BT UT WOS:000353684600001 PM 25902795 ER PT J AU Vahedi, G Kanno, Y Furumoto, Y Jiang, K Parker, SCJ Erdos, MR Davis, SR Roychoudhuri, R Restifo, NP Gadina, M Tang, ZH Ruan, YJ Collins, FS Sartorelli, V O'Shea, JJ AF Vahedi, Golnaz Kanno, Yuka Furumoto, Yasuko Jiang, Kan Parker, Stephen C. J. Erdos, Michael R. Davis, Sean R. Roychoudhuri, Rahul Restifo, Nicholas P. Gadina, Massimo Tang, Zhonghui Ruan, Yijun Collins, Francis S. Sartorelli, Vittorio O'Shea, John J. TI Super-enhancers delineate disease-associated regulatory nodes in T cells SO NATURE LA English DT Article ID GENETIC ARCHITECTURE; SUSCEPTIBILITY LOCI; IDENTITY GENES; RISK LOCI; IDENTIFICATION; TRANSCRIPTION; METAANALYSIS; EXPRESSION; DIFFERENTIATION; DOMAINS AB Enhancers regulate spatiotemporal gene expression and impart cellspecific transcriptional outputs that drive cell identity'. Super-enhancers (SEs), also known as stretch-enhancers, are a subset of enhancers especially important for genes associated with cell identity and genetic risk of disease(2-6). CD4(+) T cells are critical for host defence and autoimmunity. Here we analysed maps of mouse T-cell SEs as a non-biased means of identifying key regulatory nodes involved in cell specification. We found that cytokines and cytokine receptors were the dominant class of genes exhibiting SE architecture in T cells. Nonetheless, the locus encoding Bach2, a key negative regulator of effector differentiation, emerged as the most prominent T-cell SE, revealing a network in which SE-associated genes critical for T-cell biology are repressed by BACH2. Disease-associated single-nucleotide polymorphisms for immune-mediated disorders, including rheumatoid arthritis, were highly enriched for T-cell SEs versus typical enhancers or SEs in other cell lineages'. Intriguingly, treatment of T cells with the Janus kinase (JAK) inhibitor tofacitinib disproportionately altered the expression of rheumatoid arthritis risk genes with SE structures. Together, these results indicate that genes with SE architecture in T cells encompass a variety of cytokines and cytokine receptors but are controlled by a 'guardian' transcription factor, itself endowed with an SE. Thus, enumeration of SEs allows the unbiased determination of key regulatory nodes in T cells, which are preferentially modulated by pharmacological intervention. C1 [Vahedi, Golnaz; Kanno, Yuka; Jiang, Kan; O'Shea, John J.] NIAMSD, Lymphocyte Cell Biol Sect, NIH, Bethesda, MD 20892 USA. [Furumoto, Yasuko; Gadina, Massimo] NIAMS, Translat Immunol Sect, NIH, Bethesda, MD 20892 USA. [Parker, Stephen C. J.; Erdos, Michael R.; Collins, Francis S.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA. [Davis, Sean R.; Roychoudhuri, Rahul; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Tang, Zhonghui; Ruan, Yijun] Univ Connecticut, Jackson Lab Genom Med, Farmington, CT 06030 USA. [Tang, Zhonghui; Ruan, Yijun] Univ Connecticut, Dept Genet & Dev Biol, Farmington, CT 06030 USA. [Sartorelli, Vittorio] NIAMS, La Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. RP Vahedi, G (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, NIH, Bethesda, MD 20892 USA. EM vahedig@mail.nih.gov; osheaj@arb.niams.nih.gov RI Roychoudhuri, Rahul/A-7442-2010; OI Roychoudhuri, Rahul/0000-0002-5392-1853; Kanno, Yuka/0000-0001-5668-9319; Restifo, Nicholas P./0000-0003-4229-4580; Davis, Sean/0000-0002-8991-6458 FU Sir Henry Dale Fellowship - Wellcome Trust [105663/Z/14/Z]; Sir Henry Dale Fellowship - Royal Society [105663/Z/14/Z]; Intramural Research Program of NIAMS; NCI [R01 CA186714] FX The authors thank B. Afzali, A. Nussenzweig, A. Poholek, S. Canna, A. Richard and E. Mathe for critically reading this manuscript. We are grateful to R. Faryabi, H.-Y. Shih, W. Resch, M. Ombrello, Z. Deng and E. Remmers for their contributions to experimental and analytical components of this study. We also thank H. Sun, G. Gutierrez-Cruz, J. Simone, J. Lay and K. Tinsley for their excellent technical support. This study used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health. R.R. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 105663/Z/14/Z). This work was supported by the Intramural Research Program of NIAMS and by NCI grant R01 CA186714. NR 32 TC 61 Z9 62 U1 3 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 23 PY 2015 VL 520 IS 7548 BP 558 EP + DI 10.1038/nature14154 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG5LX UT WOS:000353334500047 PM 25686607 ER PT J AU Nelson, CP Hamby, SE Saleheen, D Hopewell, JC Zeng, L Assimes, TL Kanoni, S Willenborg, C Burgess, S Amouyel, P Anand, S Blankenberg, S Boehm, BO Clarke, RJ Collins, R Dedoussis, G Farrall, M Franks, PW Groop, L Hall, AS Hamsten, A Hengstenberg, C Hovingh, GK Ingelsson, E Kathiresan, S Kee, F Konig, IR Kooner, J Lehtimaki, T Marz, W McPherson, R Metspalu, A Nieminen, MS O'Donnell, CJ Palmer, CNA Peters, A Perola, M Reilly, MP Ripatti, S Roberts, R Salomaa, V Shah, SH Schreiber, S Siegbahn, A Thorsteinsdottir, U Veronesi, G Wareham, N Willer, CJ Zalloua, PA Erdmann, J Deloukas, P Watkins, H Schunkert, H Danesh, J Thompson, JR Samani, NJ AF Nelson, C. P. Hamby, S. E. Saleheen, D. Hopewell, J. C. Zeng, L. Assimes, T. L. Kanoni, S. Willenborg, C. Burgess, S. Amouyel, P. Anand, S. Blankenberg, S. Boehm, B. O. Clarke, R. J. Collins, R. Dedoussis, G. Farrall, M. Franks, P. W. Groop, L. Hall, A. S. Hamsten, A. Hengstenberg, C. Hovingh, G. Kees Ingelsson, E. Kathiresan, S. Kee, F. Koenig, I. R. Kooner, J. Lehtimaeki, T. Maerz, W. McPherson, R. Metspalu, A. Nieminen, M. S. O'Donnell, C. J. Palmer, C. N. A. Peters, A. Perola, M. Reilly, M. P. Ripatti, S. Roberts, R. Salomaa, V. Shah, S. H. Schreiber, S. Siegbahn, A. Thorsteinsdottir, U. Veronesi, G. Wareham, N. Willer, C. J. Zalloua, P. A. Erdmann, J. Deloukas, P. Watkins, H. Schunkert, H. Danesh, J. Thompson, J. R. Samani, N. J. CA CARDIoGRAM C4D Consortium TI Genetically Determined Height and Coronary Artery Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BODY-MASS INDEX; BLOOD-PRESSURE; ASSOCIATION; RISK; LOCI; ATHEROSCLEROSIS; METAANALYSIS; VARIANTS; PLAQUES; LIPIDS AB BACKGROUND The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quar-tile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. CONCLUSIONS There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. C1 [Nelson, C. P.; Hamby, S. E.; Samani, N. J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England. [Thompson, J. R.] Univ Leicester, Dept Hlth Sci, Leicester LE3 9QP, Leics, England. [Nelson, C. P.; Hamby, S. E.; Samani, N. J.] Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England. [Saleheen, D.; Burgess, S.; Danesh, J.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Ripatti, S.; Deloukas, P.] Wellcome Trust Sanger Inst, Cambridge, England. [Wareham, N.] Addenbrookes Hosp, Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England. [Hopewell, J. C.; Clarke, R. J.; Collins, R.] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Hopewell, J. C.; Clarke, R. J.; Collins, R.] Univ Oxford, Epidemiol Studies Unit, Oxford, England. [Farrall, M.; Watkins, H.] Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England. [Farrall, M.; Watkins, H.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Kanoni, S.; Deloukas, P.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England. [Boehm, B. O.] Univ London Imperial Coll Sci Technol & Med, London, England. [Kooner, J.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Hall, A. S.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Kee, F.] Queens Univ Belfast, Clin Res Collaborat Ctr Excellence Publ Hlth Nort, Belfast, Antrim, North Ireland. [Palmer, C. N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland. [Saleheen, D.] Ctr Noncommunicable Dis, Karachi, Pakistan. [Saleheen, D.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Reilly, M. P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Zeng, L.; Clarke, R. J.; Collins, R.; Hengstenberg, C.; Schunkert, H.] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. [Zeng, L.; Clarke, R. J.; Collins, R.; Hengstenberg, C.; Schunkert, H.] Partner Site Munich Heart Alliance, Deutsch Zentrum Herz Kreislauf Forsch, Munich, Germany. [Peters, A.] German Ctr Cardiovasc Res Partner Site Munich, Munich, Germany. [Willenborg, C.; Erdmann, J.] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23538 Lubeck, Germany. [Willenborg, C.; Erdmann, J.] Partner Site Hamburg Lubeck Kiel, German Ctr Cardiovasc Res, Lubeck, Germany. [Koenig, I. R.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Blankenberg, S.] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany. [Boehm, B. O.] Univ Ulm, Med Ctr, Dept Internal Med 1, D-89069 Ulm, Germany. [Maerz, W.] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria. [Maerz, W.] Heidelberg Univ, Mannheim Med Fac, Med Clin 5, Synlab Acad,Synlab Serv, Mannheim, Germany. [Peters, A.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Schreiber, S.] Univ Kiel, Inst Klin Mol Biol, Kiel, Germany. [Assimes, T. L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Amouyel, P.] Univ Lille Nord France, INSERM, U744, Inst Pasteur Lille, Lille, France. [Anand, S.] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada. [McPherson, R.; Roberts, R.] Univ Ottawa Heart Inst, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada. [McPherson, R.; Roberts, R.] Univ Ottawa Heart Inst, Atherogen Lab, Ottawa, ON, Canada. [Boehm, B. O.] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, Singapore. [Dedoussis, G.] Harokopio Univ, Dept Dietet Nutr, Athens, Greece. [Franks, P. W.] Lund Univ, Ctr Diabet, Skane Univ Hosp, Genet & Mol Epidemiol Unit,Dept Clin Sci, Malmo, Sweden. [Groop, L.] Lund Univ, Univ Hosp Malmo, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Franks, P. W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Hamsten, A.] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden. [Ingelsson, E.] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden. [Siegbahn, A.] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Franks, P. W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Kathiresan, S.] Massachusetts Gen Hosp, Div Cardiol, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, S.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, S.] Harvard Univ, Sch Med, Boston, MA USA. [Kathiresan, S.] Broad Inst Harvard & MIT, Cambridge, MA USA. [O'Donnell, C. J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Hovingh, G. Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Lehtimaeki, T.] Univ Tampere, Fimlab Labs, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaeki, T.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Nieminen, M. S.] Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Helsinki, Finland. [Perola, M.; Salomaa, V.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Ripatti, S.] Univ Helsinki, Hjelt Inst, Helsinki, Finland. [Ripatti, S.] Univ Helsinki, Inst Mol Med, Helsinki, Finland. [Metspalu, A.; Perola, M.] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Shah, S. H.] Duke Univ, Dept Med, Div Cardiol, Duke Mol Physiol Inst, Durham, NC USA. [Thorsteinsdottir, U.] deCODE Genet, Reykjavik, Iceland. [Veronesi, G.] Univ Insubria, Dept Clin & Expt Med, Res Ctr Epidemiol & Prevent Med, Varese, Italy. [Willer, C. J.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Willer, C. J.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Willer, C. J.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Zalloua, P. A.] Lebanese Amer Univ, Beirut, Lebanon. [Deloukas, P.] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. RP Samani, NJ (reprint author), Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, BHF Cardiovasc Res Ctr, Groby Rd, Leicester LE3 9QP, Leics, England. EM njs@le.ac.uk RI Erdmann, Jeanette/P-7513-2014; Boehm, Bernhard/F-8750-2015; Veronesi, Giovanni/E-3859-2010; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Kessler, Thorsten/O-7426-2015; Peters, Annette/A-6117-2011; Lyytikainen, Leo-Pekka/C-8544-2016; Tregouet, David-Alexandre/E-3961-2016; Deloukas, Panos/B-2922-2013; Study, GoDARTS/K-9448-2016; Konig, Inke/A-4544-2009; Palmer, Colin/C-7053-2008 OI Assimes, Themistocles/0000-0003-2349-0009; Burgess, Stephen/0000-0001-5365-8760; Kleber, Marcus/0000-0003-0663-7275; Peters, Annette/0000-0001-6645-0985; Esko, Tonu/0000-0003-1982-6569; Shungin, Dmitry/0000-0001-7900-5856; Ouwehand, Willem/0000-0002-7744-1790; Kristiansson, Kati/0000-0003-4688-107X; Erdmann, Jeanette/0000-0002-4486-6231; Gigante, Bruna/0000-0003-4508-7990; zalloua, pierre/0000-0002-8494-5081; Kuulasmaa, Kari/0000-0003-2165-1411; Watkins, Hugh/0000-0002-5287-9016; Veronesi, Giovanni/0000-0002-4119-6615; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Deloukas, Panos/0000-0001-9251-070X; Palmer, Colin/0000-0002-6415-6560 FU British Heart Foundation FX Funded by the British Heart Foundation and others. NR 27 TC 48 Z9 48 U1 5 U2 21 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 23 PY 2015 VL 372 IS 17 BP 1608 EP 1618 DI 10.1056/NEJMoa1404881 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CG4XX UT WOS:000353294000006 PM 25853659 ER PT J AU Pirie, A Guo, Q Kraft, P Canisius, S Eccles, DM Rahman, N Nevanlinna, H Chen, C Khan, S Tyrer, J Bolla, MK Wang, Q Dennis, J Michailidou, K Lush, M Dunning, AM Shah, M Czene, K Darabi, H Eriksson, M Lambrechts, D Weltens, C Leunen, K van Ongeval, C Nordestgaard, BG Nielsen, SF Flyger, H Rudolph, A Seibold, P Flesch-Janys, D Blomqvist, C Aittomaaki, K Fagerholm, R Muranen, TA Olsen, JE Hallberg, E Vachon, C Knight, JA Glendon, G Mulligan, AM Broeks, A Cornelissen, S Haiman, CA Henderson, BE Schumacher, F Le Marchand, L Hopper, JL Tsimiklis, H Apicella, C Southey, MC Cross, SS Reed, MWR Giles, GG Milne, RL McLean, C Winqvist, R Pylkas, K Jukkola-Vuorinen, A Grip, M Hooning, MJ Hollestelle, A Martens, JWM van den Ouweland, AMW Marme, F Schneeweiss, A Yang, RX Burwinkel, B Figueroa, J Chanock, SJ Lissowska, J Sawyer, EJ Tomlinson, I Kerin, MJ Miller, N Brenner, H Butterbach, K Holleczek, B Kataja, V Kosma, VM Hartikainen, JM Li, JM Brand, JS Humphreys, K Devilee, P Tollenaar, RAEM Seynaeve, C Radice, P Peterlongo, P Manoukian, S Ficarazzi, F Beckmann, MW Hein, A Ekici, AB Balleine, R Phillips, KA Benitez, J Zamora, MP Perez, JIA Menendez, P Jakubowska, A Lubinski, J Gronwald, J Durda, K Hamann, U Kabisch, M Ulmer, HU Rudiger, T Margolin, S Kristensen, V Nord, S Evans, DG Abraham, J Earl, H Poole, CJ Hiller, L Dunn, JA Bowden, S Yang, R Campa, D Diver, WR Gapstur, SM Gaudet, MM Hankinson, S Hoover, RN Husing, A Kaaks, R Machiela, MJ Willett, W Barrdahl, M Canzian, F Chin, SF Caldas, C Hunter, DJ Lindstrom, S Garcia-Closas, M Couch, FJ Chenevix-Trench, G Mannermaa, A Andrulis, IL Hall, P Chang-Claude, J Easton, DF Bojesen, SE Cox, A Fasching, PA Pharoah, PDP Schmidt, MK AF Pirie, Ailith Guo, Qi Kraft, Peter Canisius, Sander Eccles, Diana M. Rahman, Nazneen Nevanlinna, Heli Chen, Constance Khan, Sofia Tyrer, Jonathan Bolla, Manjeet K. Wang, Qin Dennis, Joe Michailidou, Kyriaki Lush, Michael Dunning, Alison M. Shah, Mitul Czene, Kamila Darabi, Hatef Eriksson, Mikael Lambrechts, Dieter Weltens, Caroline Leunen, Karin van Ongeval, Chantal Nordestgaard, Borge G. Nielsen, Sune F. Flyger, Henrik Rudolph, Anja Seibold, Petra Flesch-Janys, Dieter Blomqvist, Carl Aittomaki, Kristiina Fagerholm, Rainer Muranen, Taru A. Olsen, Janet E. Hallberg, Emily Vachon, Celine Knight, Julia A. Glendon, Gord Mulligan, Anna Marie Broeks, Annegien Cornelissen, Sten Haiman, Christopher A. Henderson, Brian E. Schumacher, Frederick Le Marchand, Loic Hopper, John L. Tsimiklis, Helen Apicella, Carmel Southey, Melissa C. Cross, Simon S. Reed, Malcolm W. R. Giles, Graham G. Milne, Roger L. McLean, Catriona Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Grip, Mervi Hooning, Maartje J. Hollestelle, Antoinette Martens, John W. M. van den Ouweland, Ans M. W. Marme, Federick Schneeweiss, Andreas Yang, Rongxi Burwinkel, Barbara Figueroa, Jonine Chanock, Stephen J. Lissowska, Jolanta Sawyer, Elinor J. Tomlinson, Ian Kerin, Michael J. Miller, Nicola Brenner, Hermann Butterbach, Katja Holleczek, Bernd Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M. Li, Jingmei Brand, Judith S. Humphreys, Keith Devilee, Peter Tollenaar, Robert A. E. M. Seynaeve, Caroline Radice, Paolo Peterlongo, Paolo Manoukian, Siranoush Ficarazzi, Filomena Beckmann, Matthias W. Hein, Alexander Ekici, Arif B. Balleine, Rosemary Phillips, Kelly-Anne Benitez, Javier Zamora, M. Pilar Perez, Jose Ignacio Arias Menendez, Primitiva Jakubowska, Anna Lubinski, Jan Gronwald, Jacek Durda, Katarzyna Hamann, Ute Kabisch, Maria Ulmer, Hans Ulrich Ruediger, Thomas Margolin, Sara Kristensen, Vessela Nord, Siljie Evans, D. Gareth Abraham, Jean Earl, Helena Poole, Christopher J. Hiller, Louise Dunn, Janet A. Bowden, Sarah Yang, Rose Campa, Daniele Diver, W. Ryan Gapstur, Susan M. Gaudet, Mia M. Hankinson, Susan Hoover, Robert N. Husing, Anika Kaaks, Rudolf Machiela, Mitchell J. Willett, Walter Barrdahl, Myrto Canzian, Federico Chin, Suet-Feung Caldas, Carlos Hunter, David J. Lindstrom, Sara Garcia-Closas, Montserrat Couch, Fergus J. Chenevix-Trench, Georgia Mannermaa, Arto Andrulis, Irene L. Hall, Per Chang-Claude, Jenny Easton, Douglas F. Bojesen, Stig E. Cox, Angela Fasching, Peter A. Pharoah, Paul D. P. Schmidt, Marjanka K. CA KConFab Investigators NBCS Investigators TI Common germline polymorphisms associated with breast cancer-specific survival SO BREAST CANCER RESEARCH LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; THAN-T POLYMORPHISM; GENETIC POLYMORPHISMS; ADJUVANT THERAPY; RISK; PROGNOSIS; OUTCOMES; VARIANTS; GENOTYPE AB Introduction: Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. Methods: A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. Results: Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease. Conclusions: Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels. C1 [Pirie, Ailith; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, 2 Worts Causeway, Cambridge CB1 8RN, England. [Guo, Qi; Tyrer, Jonathan; Dunning, Alison M.; Shah, Mitul; Abraham, Jean; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England. [Kraft, Peter; Chen, Constance] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA. [Kraft, Peter; Hankinson, Susan; Hunter, David J.; Lindstrom, Sara] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Canisius, Sander; Broeks, Annegien; Cornelissen, Sten; Schmidt, Marjanka K.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. [Eccles, Diana M.] Univ Southampton, Fac Med, Southampton SO17 1BJ, Hants, England. [Rahman, Nazneen; Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England. [Nevanlinna, Heli; Khan, Sofia; Fagerholm, Rainer; Muranen, Taru A.] Univ Helsinki, Dept Obstet & Gynecol, FIN-00029 Hus Helsinki, Finland. [Nevanlinna, Heli; Khan, Sofia; Fagerholm, Rainer; Muranen, Taru A.] Univ Helsinki, Cent Hosp, FIN-00029 Hus Helsinki, Finland. [Darabi, Hatef; Eriksson, Mikael; Li, Jingmei; Brand, Judith S.; Humphreys, Keith; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden. [Lambrechts, Dieter] VIB, Vesalius Res Ctr VRC, B-3000 Leuven, Belgium. [Lambrechts, Dieter] Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Leuven, Belgium. [Weltens, Caroline; Leunen, Karin; van Ongeval, Chantal] Univ Hosp Gasthuisberg, Dept Oncol, B-3000 Leuven, Belgium. [Nordestgaard, Borge G.; Nielsen, Sune F.; Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, DK-2730 Copenhagen, Denmark. [Nordestgaard, Borge G.; Nielsen, Sune F.; Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Copenhagen, Denmark. [Nordestgaard, Borge G.; Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, DK-2220 Copenhagen, Denmark. [Flyger, Henrik] Herlev Hosp, Copenhagen Univ Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark. [Rudolph, Anja; Seibold, Petra; Campa, Daniele; Husing, Anika; Kaaks, Rudolf; Barrdahl, Myrto; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, D-20246 Hamburg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, D-20246 Hamburg, Germany. [Blomqvist, Carl; Fagerholm, Rainer] Univ Helsinki, Cent Hosp, Dept Oncol, Lohja Helsinki 08200, Finland. [Aittomaki, Kristiina; Fagerholm, Rainer] Univ Helsinki, Cent Hosp, Dept Clin Genet, Lohja Helsinki 08200, Finland. [Olsen, Janet E.; Vachon, Celine] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Hallberg, Emily; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5T 3M7, Canada. [Glendon, Gord; Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada. [Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. [Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON M5G 2C4, Canada. [Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Frederick] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Le Marchand, Loic] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Hopper, John L.; Apicella, Carmel; Giles, Graham G.; Milne, Roger L.; Phillips, Kelly-Anne] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Tsimiklis, Helen; Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield S10 2HQ, S Yorkshire, England. [Reed, Malcolm W. R.; Cox, Angela] Univ Sheffield, Dept Oncol, CRUK YCR Sheffield Canc Res Ctr, Sheffield S10 2RX, S Yorkshire, England. [Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [McLean, Catriona] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, Oulu Univ Hosp, Dept Clin Genet, Lab Canc Genet & Tumor Biol, FI-90220 Oulu, Finland. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, Oulu Univ Hosp, Bioctr Oulu, FI-90220 Oulu, Finland. [Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, FI-90220 Oulu, Finland. [Grip, Mervi] Univ Oulu, Oulu Univ Hosp, Dept Surg, FI-90220 Oulu, Finland. [Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W. M.; van den Ouweland, Ans M. W.; Seynaeve, Caroline] Erasmus McCancer Inst, Family Canc Clin, Dept Med Oncol, NL-3015 CE Rotterdam, Netherlands. [Marme, Federick; Schneeweiss, Andreas; Yang, Rongxi; Burwinkel, Barbara] Heidelberg Univ, Dept Obstet & Gynecol, D-69115 Heidelberg, Germany. [Marme, Federick; Schneeweiss, Andreas] Heidelberg Univ, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany. [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, D-69120 Heidelberg, Germany. [Figueroa, Jonine; Chanock, Stephen J.; Hoover, Robert N.; Machiela, Mitchell J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Chanock, Stephen J.] Core Genotyping Facil, Frederick Natl Lab Canc Res, Gaithersburg, MD 20877 USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, PL-02781 Warsaw, Poland. [Sawyer, Elinor J.] Kings Coll London, Guys & St Thomas NHS Fdn Trust, NIHR Comprehens Biomed Res Ctr, Div Canc Studies, London SE1 1UL, England. [Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX3 7BN, England. [Kerin, Michael J.; Miller, Nicola] Univ Hosp Galway, Inst Clin Sci, Galway, Ireland. [Brenner, Hermann; Butterbach, Katja] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany. [Brenner, Hermann] German Canc Consortium DKTK, D-69120 Heidelberg, Germany. [Holleczek, Bernd] Saarland Canc Registry, D-66119 Saarbrucken, Germany. [Kataja, Vesa] Kuopio Univ Hosp, Inst Clin Med, Sch Med, Kuopio 70210, Finland. [Kataja, Vesa] Kuopio Univ Hosp, Ctr Canc, Kuopio 70210, Finland. [Kosma, Veli-Matti; Hartikainen, Jaana M.; Mannermaa, Arto] Univ Eastern Finland, Sch Med, Inst Clin Med Pathol & Forens Med, Kuopio 70210, Finland. [Kosma, Veli-Matti; Hartikainen, Jaana M.; Mannermaa, Arto] Univ Eastern Finland, Canc Ctr Eastern Finland, Kuopio 70210, Finland. [Kosma, Veli-Matti; Hartikainen, Jaana M.; Mannermaa, Arto] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, SF-70210 Kuopio, Finland. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 AA Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, NL-2333 AA Leiden, Netherlands. [Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, NL-2333 AA Leiden, Netherlands. [Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20139 Milan, Italy. [Peterlongo, Paolo; Ficarazzi, Filomena] Fdn Ist FIRC Oncol Mol, IFOM, I-20139 Milan, Italy. [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, I-20139 Milan, Italy. [Ficarazzi, Filomena] Cogentech Canc Genet Test Lab, I-20139 Milan, Italy. [Beckmann, Matthias W.; Hein, Alexander] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen Emn, D-91054 Erlangen, Germany. [Ekici, Arif B.; Fasching, Peter A.] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen Emn, D-91054 Erlangen, Germany. [Balleine, Rosemary] Univ Sydney, Westmead Millennium Inst Med Res, Western Sydney & Nepean Blue Mountains Local Hlth, Sydney, NSW 2145, Australia. [Phillips, Kelly-Anne; KConFab Investigators] Peter Maccallum Canc Ctr, Melbourne, Vic 3002, Australia. [Phillips, Kelly-Anne] Univ Melbourne, Sir Peter Maccallum Dept Oncol, Melbourne, Vic 3002, Australia. [Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genet Grp, Madrid 28029, Spain. [Benitez, Javier] Ctr Invest Red Enfermedades Raras CIBERER, Valencia 46010, Spain. [Zamora, M. Pilar] Hosp Univ La Paz, Serv Oncol Med, Madrid 28046, Spain. [Perez, Jose Ignacio Arias] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo 33012, Spain. [Menendez, Primitiva] Hosp Monte Naranco, Serv Anat Patol, Oviedo 33012, Spain. [Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Hamann, Ute; Kabisch, Maria] German Canc Res Ctr, Mol Genet Breast Canc, D-69120 Heidelberg, Germany. [Ulmer, Hans Ulrich] Frauenklin Stadtklin Baden Baden, D-76532 Baden Baden, Germany. [Ruediger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, D-76133 Karlsruhe, Germany. [Margolin, Sara] Karolinska Inst, Department Oncol Pathol, S-17165 Stockholm, Sweden. [Kristensen, Vessela; Nord, Siljie; NBCS Investigators] Univ Oslo UiO, Fac Med, Fac Div Ahus, N-0313 Oslo, Norway. [Kristensen, Vessela; Nord, Siljie] Radiumhosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, N-0379 Oslo, Norway. [Evans, D. Gareth] Univ Manchester, Cent Manchester Fdn Trust, St Marys Hosp, Genom Med,Manchester Acad Hlth Sci Ctr, Manchester M13 9WL, Lancs, England. [Abraham, Jean; Earl, Helena; Caldas, Carlos] Cambridge Expt Canc Med Ctr, Cambridge CB2 0RE, England. [Abraham, Jean; Earl, Helena; Caldas, Carlos] Univ Cambridge NHS Fdn Hosp, Cambridge Breast Unit, Cambridge CB2 0QQ, England. [Abraham, Jean; Earl, Helena; Caldas, Carlos] Univ Cambridge NHS Fdn Hosp, NIHR Cambridge Biomed Res, Cambridge CB2 0QQ, England. [Poole, Christopher J.; Hiller, Louise; Dunn, Janet A.] Univ Warwick, Warwick Clin Trials Unit, Coventry CV4 7AL, W Midlands, England. [Bowden, Sarah] Univ Birmingham, Inst Canc Studies, Canc Res UK Clin Trials Unit, Birmingham B15 2TT, W Midlands, England. [Yang, Rose] NCI, Early Detect Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Campa, Daniele] Univ Pisa, Dept Biol, I-56126 Pisa, Italy. [Diver, W. Ryan; Gapstur, Susan M.; Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA. [Hankinson, Susan] Univ Massachusetts, Amherst Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01002 USA. [Hankinson, Susan] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Willett, Walter] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany. [Chin, Suet-Feung; Caldas, Carlos] Univ Cambridge, Canc Res UK Cambridge Inst, Breast Canc Funct Genom Lab, Li Ka Shing Ctr, Cambridge CB2 0RE, England. [Hunter, David J.; Lindstrom, Sara] Harvard Univ, Program Mol & Genet Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. [Garcia-Closas, Montserrat] Breakthrough Breast Canc Res Ctr, Div Breast Canc Res, Inst Canc Res, London SW7 3RP, England. [Chenevix-Trench, Georgia] Qimr Berghofer Med Res Inst, Dept Genet, Brisbane, Qld 4006, Australia. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. RP Pirie, A (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, 2 Worts Causeway, Cambridge CB1 8RN, England. EM ap736@medschl.cam.ac.uk; mk.schmidt@nki.nl RI Nord, Silje/R-5212-2016; Gronwald, Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; Rahman, Nazneen/D-2802-2013; Hein, Alexander/F-6999-2010; Hartikainen, Jaana/E-6256-2015; Li, Jingmei/I-2904-2012; Andrulis, Irene/E-7267-2013; Campa, Daniele/K-1617-2016; Knight, Julia/A-6843-2012 OI Evans, Gareth/0000-0002-8482-5784; benitez, javier/0000-0002-0923-7202; Cross, Simon/0000-0003-2044-1754; Phillips, Kelly-Anne/0000-0002-0475-1771; Earl, Helena/0000-0003-1549-8094; Dunning, Alison Margaret/0000-0001-6651-7166; Khan, Sofia/0000-0003-4185-8882; Muranen, Taru/0000-0002-5895-1808; Cox, Angela/0000-0002-5138-1099; Machiela, Mitchell/0000-0001-6538-9705; Giles, Graham/0000-0003-4946-9099; Ewing, Ailith/0000-0002-2272-1277; Nord, Silje/0000-0002-3271-5356; Gronwald, Jacek/0000-0002-3643-2871; Brenner, Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562; Rahman, Nazneen/0000-0003-4376-0440; chin, suet-feung/0000-0001-5697-1082; Hein, Alexander/0000-0003-2601-3398; Li, Jingmei/0000-0001-8587-7511; Campa, Daniele/0000-0003-3220-9944; FU COGS project through a European Commission's Seventh Framework Programme grant [223175 - HEALTH-F2-2009-223175]; Breast Cancer Association Consortium (BCAC) - Cancer Research-UK [C1287/A10118, C1287/A12014]; European Union COST programme [BM0606] FX The COGS project was funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). The Breast Cancer Association Consortium (BCAC) is funded by Cancer Research-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). ELAN Program of the University Hospital Erlangen (BBCC). NR 66 TC 3 Z9 3 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PD APR 22 PY 2015 VL 17 AR 58 DI 10.1186/s13058-015-0570-7 PG 11 WC Oncology SC Oncology GA DD3WI UT WOS:000369853600001 PM 25897948 ER PT J AU Weth, D Benetti, C Rauch, C Gstraunthaler, G Schmidt, H Geisslinger, G Sabbadini, R Proia, RL Kress, M AF Weth, Daniela Benetti, Camilla Rauch, Caroline Gstraunthaler, Gerhard Schmidt, Helmut Geisslinger, Gerd Sabbadini, Roger Proia, Richard L. Kress, Michaela TI Activated platelets release sphingosine 1-phosphate and induce hypersensitivity to noxious heat stimuli in vivo SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE platelet; post-operative pain; sphingosine 1-phosphate; heat nociception; S1P receptors ID PROTEIN-COUPLED RECEPTOR; DORSAL-ROOT GANGLIA; SENSORY NEURONS; NOCICEPTIVE RESPONSE; ENDOTHELIAL-CELLS; P2X RECEPTORS; RAT SKIN; SPHINGOSINE-1-PHOSPHATE; PAIN; HYPERALGESIA AB At the site of injury activated platelets release various mediators, one of which is sphingosine 1-phosphate (S1P). It was the aim of this study to explore whether activated human platelets had a pronociceptive effect in an in vivo mouse model and whether this effect was based on the release of S1P and subsequent activation of neuronal S1P receptors 1 or 3. Human platelets were prepared in different concentrations (10(5)/mu l, 10(6)/mu l, 10(7)/mu l) and assessed in mice with different genetic backgrounds (WT, S1P(1)(fl/fl), SNS-S1P(1)(-/-), S1P(3)(-/-)). Intracutaneous injections of activated human platelets induced a significant, dose-dependent hypersensitivity to noxious thermal stimulation. The degree of heat hypersensitivity correlated with the platelet concentration as well as the platelet S1P content and the amount of S1P released upon platelet activation as measured with LC MS/MS. Despite the significant correlations between S1P and platelet count, no difference in paw withdrawal latency (PWL) was observed in mice with a global null mutation of the S1P(3) receptor or a conditional deletion of the S1P(1) receptor in nociceptive primary afferents. Furthermore, neutralization of S1P with a selective anti-S1P antibody did not abolish platelet induced heat hypersensitivity. Our results suggest that activated platelets release S1P and induce heat hypersensitivity in vivo. However, the platelet induced heat hypersensitivity was caused by mediators other than S1P. C1 [Weth, Daniela; Benetti, Camilla; Rauch, Caroline; Gstraunthaler, Gerhard; Kress, Michaela] Med Univ Innsbruck, Dept Physiol & Med Phys, Div Physiol, A-6020 Innsbruck, Austria. [Schmidt, Helmut; Geisslinger, Gerd] Pharmazentrum Frankfurt ZAFES, Inst Clin Pharmacol, Frankfurt, Germany. [Sabbadini, Roger] Lpath Inc, San Diego, CA USA. [Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. RP Kress, M (reprint author), Med Univ Innsbruck, Dept Physiol & Med Phys, Div Physiol, Fritz Pregl Str 3, A-6020 Innsbruck, Austria. EM michaela.kress@i-med.ac.at FU Austrian Research Funding Agency FWF [P20562, P25345, SPIN-01206-B6, SFB 1039/Z01]; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the Austrian Research Funding Agency FWF (project grants P20562, P25345, and SPIN-01206-B6) to MK, SFB 1039/Z01 to GGe and by the Intramural Research Programs of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases to RP. The authors thank Kathrin Braun, Theresa Martha and Markus Doblander for expert technical assistance. NR 58 TC 1 Z9 1 U1 0 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD APR 22 PY 2015 VL 9 AR 140 DI 10.3389/fnins.2015.00140 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CG9OZ UT WOS:000353647300001 PM 25954148 ER PT J AU Dan, XL Wong, JH Fang, EF Chan, FCW Ng, TB AF Dan, Xiuli Wong, Jack Ho Fang, Evandro Fei Chan, Francis Chun Wai Tzi Bun Ng TI Purification and Characterization of a Novel Hemagglutinin with Inhibitory Activity toward Osteocarcinoma Cells from Northeast China Black Beans SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE anticancer drug; apoptosis; cytokine; hemagglutinin; lectin; protein purification ID PHOSPHATIDYLSERINE EXTERNALIZATION; CONCANAVALIN-A; LECTIN; OSTEOSARCOMA; PROTEINS; SOYBEANS; CULTIVAR; CANCER; SEEDS AB In the present study, we isolated a novel hemagglutinin from an edible legume and explored its growth-inhibitory effect on osteocarcinoma and liver cancer cells. The protein was purified by liquid chromatography techniques which entailed affinity chromatography on Affi-gel blue gel, ion-exchange chromatography on Mono Q and gel filtration on Superdex 75 with an FPLC system. The hemagglutinating activity of this hemagglutinin was demonstrated to be ion dependent and stable over a wide range of temperature and pH values. Antiproliferative activity was observed in the tumor cell lines MG-63 and HepG2 but not in the normal cell line WRL 68. Osteocarcinoma cells treated with the hemagglutinin underwent obvious cell shrinkage, chromatin condensation, mitochondrial membrane depolarization, and apoptosis. The mRNA expression level of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) were found to be up-regulated to different extents after treatment of this hemagglutinin. C1 [Dan, Xiuli; Wong, Jack Ho; Tzi Bun Ng] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. [Fang, Evandro Fei] NIA, NIH, Baltimore, MD 21224 USA. [Chan, Francis Chun Wai] Chinese Univ Hong Kong, Fac Med, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China. RP Ng, TB (reprint author), Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. EM b021770@mailserv.cuhk.edu.hk FU NIH, National Institute of Aging FX E.F.F. was supported by the Intramural Research Program of the NIH, National Institute of Aging. NR 32 TC 5 Z9 7 U1 4 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR 22 PY 2015 VL 63 IS 15 BP 3903 EP 3914 DI 10.1021/acs.jafc.5b00106 PG 12 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA CG9AC UT WOS:000353605800010 PM 25816710 ER PT J AU Lee, E Seo, M Dal Monte, O Averbeck, BB AF Lee, Eunjeong Seo, Moonsang Dal Monte, Olga Averbeck, Bruno B. TI Injection of a Dopamine Type 2 Receptor Antagonist into the Dorsal Striatum Disrupts Choices Driven by Previous Outcomes, But Not Perceptual Inference SO JOURNAL OF NEUROSCIENCE LA English DT Article DE action value; dorsal striatum; neuromodulation; Parkinson's disease; reinforcement learning; sequential decision making ID DECISION-MAKING; D2 RECEPTORS; CHOLINERGIC INTERNEURONS; PREDICTION ERRORS; PREFRONTAL CORTEX; CUE INTEGRATION; PARIETAL CORTEX; BASAL GANGLIA; REWARD; REINFORCEMENT AB Decisions are often driven by a combination of immediate perception and previous experience. In this study, we investigated how these two sources of information are integrated and the neural systems that mediate this process. Specifically, we injected a dopamine type 1 antagonist (D1A; SCH23390) or a dopamine type 2 antagonist (D2A; eticlopride) into the dorsal striatum while macaques performed a task in which their choices were driven by perceptual inference and/or reinforcement of past choices. We found that the D2A affected choices based on previous outcomes. However, there were no effects of the D2A on choices driven by perceptual inference. We found that the D1A did not affect perceptual inference or reinforcement learning. Finally, a Bayesian model applied to the results suggested that the D2A may be increasing noise in the striatal representation of value, perhaps by disrupting the striatal population that normally represents value. C1 [Lee, Eunjeong; Seo, Moonsang; Dal Monte, Olga; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA. EM bruno.averbeck@nih.gov OI dal monte, olga/0000-0002-7823-4769 FU Brain Research Trust; Wellcome Trust; Intramural Research Program of the National Institute of Mental Health FX This work was supported by the Brain Research Trust, the Wellcome Trust, and the Intramural Research Program of the National Institute of Mental Health. NR 43 TC 4 Z9 4 U1 2 U2 13 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 22 PY 2015 VL 35 IS 16 BP 6298 EP 6306 DI 10.1523/JNEUROSCI.4561-14.2015 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CG6HL UT WOS:000353399800005 PM 25904783 ER PT J AU Hernandez, A Burton, AC O'Donnell, P Schoenbaum, G Roesch, MR AF Hernandez, Alex Burton, Amanda C. O'Donnell, Patricio Schoenbaum, Geoffrey Roesch, Matthew R. TI Altered Basolateral Amygdala Encoding in an Animal Model of Schizophrenia SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amygdala; behavior; electrophysiology; rat; salience; schizophrenia ID PREFRONTAL CORTICAL INTERNEURONS; LATENT INHIBITION; BEHAVIORAL FLEXIBILITY; ORIENTING RESPONSE; NUCLEUS-ACCUMBENS; CINGULATE CORTEX; LINKING BIOLOGY; GENE-EXPRESSION; WORKING-MEMORY; REWARD AB It has been proposed that schizophrenia results, in part, from the inappropriate or spurious attribution of salience to cues in the environment. We have recently reported neural correlates of salience in the basolateral amygdala (ABL) of rats during learning in an odor-guided discrimination task. Here we tested whether this dopamine-dependent salience signal is altered in rats with neonatal ventral hippocampal lesions (NVHLs), a rodent model of schizophrenia. We found that ABL signals related to violations in reward prediction were only mildly affected by NVHL; however, neurons in rats with NVHLs showed significantly stronger selectivity during odor sampling, particularly for the more salient large-reward cue. The elevated cue-evoked activity in NVHL rats was correlated with heightened orienting behavior and also with changes in firing to the shifts in reward, suggesting that it reflected abnormal signaling of the large reward-predicting cue's salience. These results are broadly consistent with the proposal that schizophrenics suffer from enhanced signaling of salience. C1 [O'Donnell, Patricio; Roesch, Matthew R.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Burton, Amanda C.; Roesch, Matthew R.] Univ Maryland, Program Neurosci & Cognit Sci, College Pk, MD 20742 USA. [Schoenbaum, Geoffrey] NIDA IRP, Baltimore, MD 21224 USA. [Schoenbaum, Geoffrey] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21287 USA. [Hernandez, Alex; Schoenbaum, Geoffrey] Univ Maryland, Dept Anat & Neurobiol, Sch Med, Baltimore, MD 21201 USA. RP Roesch, MR (reprint author), Univ Maryland, 1147 Biol Psychol Bldg, College Pk, MD 20742 USA. EM mroesch@umd.edu FU National Institute on Drug Abuse; [R01DA031695] FX This work was supported by funding from the National Institute on Drug Abuse (G.S.) and R01DA031695 (M.R.R.). NR 57 TC 1 Z9 1 U1 2 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 22 PY 2015 VL 35 IS 16 BP 6394 EP 6400 DI 10.1523/JNEUROSCI.5096-14.2015 PG 7 WC Neurosciences SC Neurosciences & Neurology GA CG6HL UT WOS:000353399800013 PM 25904791 ER PT J AU Fields, RD Woo, DH Basser, PJ AF Fields, R. Douglas Woo, Dong Ho Basser, Peter J. TI Glial Regulation of the Neuronal Connectome through Local and Long-Distant Communication SO NEURON LA English DT Review ID MOUSE SOMATOSENSORY CORTEX; CENTRAL-NERVOUS-SYSTEM; ADHESION MOLECULE L1; ACTION-POTENTIALS; IN-VIVO; CONDUCTION-VELOCITY; D-SERINE; SYNAPTIC PLASTICITY; PYRAMIDAL NEURONS; TERM POTENTIATION AB If "the connectome'' represents a complete map of anatomical and functional connectivity in the brain, it should also include glia. Glia define and regulate both the brain's anatomical and functional connectivity over a broad range of length scales, spanning the whole brain to subcellular domains of synaptic interactions. This Perspective article examines glial interactions with the neuronal connectome (including long-range networks, local circuits, and individual synaptic connections) and highlights opportunities for future research. Our understanding of the structure and function of the neuronal connectome would be incomplete without an understanding of how all types of glia contribute to neuronal connectivity and function, from single synapses to circuits. C1 [Fields, R. Douglas; Woo, Dong Ho] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Nervous Syst Dev & Plast Sect, Bethesda, MD 20892 USA. [Basser, Peter J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Nervous Syst Dev & Plast Sect, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH FX This work was supported by the Intramural Research Program, The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH. NR 140 TC 24 Z9 25 U1 4 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD APR 22 PY 2015 VL 86 IS 2 BP 374 EP 386 DI 10.1016/j.neuron.2015.01.014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CG6KS UT WOS:000353410000008 PM 25905811 ER PT J AU Best, SM AF Best, Sonja M. TI Is the third interferon a charm? SO Science Translational Medicine LA English DT Editorial Material ID MURINE NOROVIRUS INFECTION C1 NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Best, SM (reprint author), NIAID, Virol Lab, Rocky Mt Labs, NIH, 903 S Fourth St, Hamilton, MT 59840 USA. EM sbest@niaid.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 22 PY 2015 VL 7 IS 284 AR 284fs16 DI 10.1126/scitranslmed.aaa2817 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CG6AN UT WOS:000353377400002 PM 25904738 ER PT J AU Johnson, KR Hindmarch, CCT Salinas, YD Shi, YJ Greenwood, M Hoe, SZ Murphy, D Gainer, H AF Johnson, Kory R. Hindmarch, C. C. T. Salinas, Yasmmyn D. Shi, YiJun Greenwood, Michael Hoe, See Ziau Murphy, David Gainer, Harold TI A RNA-Seq Analysis of the Rat Supraoptic Nucleus Transcriptome: Effects of Salt Loading on Gene Expression SO PLOS ONE LA English DT Article ID HYPOTHALAMO-NEUROHYPOPHYSEAL SYSTEM; VASOPRESSIN HETERONUCLEAR RNA; DOMINANT-NEGATIVE INHIBITOR; IMMEDIATE-EARLY GENES; CELL-SIZE CHANGES; HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM; MAGNOCELLULAR NEURONS; MESSENGER-RNA; IN-VIVO; C-FOS AB Magnocellular neurons (MCNs) in the hypothalamo-neurohypophysial system (HNS) are highly specialized to release large amounts of arginine vasopressin (Avp) or oxytocin (Oxt) into the blood stream and play critical roles in the regulation of body fluid homeostasis. The MCNs are osmosensory neurons and are excited by exposure to hypertonic solutions and inhibited by hypotonic solutions. The MCNs respond to systemic hypertonic and hypotonic stimulation with large changes in the expression of their Avp and Oxt genes, and microarray studies have shown that these osmotic perturbations also cause large changes in global gene expression in the HNS. In this paper, we examine gene expression in the rat supraoptic nucleus (SON) under normosmotic and chronic salt-loading SL) conditions by the first time using "new-generation", RNA sequencing (RNA-Seq) methods. We reliably detect 9,709 genes as present in the SON by RNA-Seq, and 552 of these genes were changed in expression as a result of chronic SL. These genes reflect diverse functions, and 42 of these are involved in either transcriptional or translational processes. In addition, we compare the SON transcriptomes resolved by RNA-Seq methods with the SON transcriptomes determined by Affymetrix microarray methods in rats under the same osmotic conditions, and find that there are 6,466 genes present in the SON that are represented in both data sets, although 1,040 of the expressed genes were found only in the microarray data, and 2,762 of the expressed genes are selectively found in the RNA-Seq data and not the microarray data. These data provide the research community a comprehensive view of the transcriptome in the SON under normosmotic conditions and the changes in specific gene expression evoked by salt loading. C1 [Johnson, Kory R.] NINDS, Bioinformat Sect, Informat Technol & Bioinformat Program, NIH, Bethesda, MD 20892 USA. [Salinas, Yasmmyn D.; Shi, YiJun; Gainer, Harold] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Hindmarch, C. C. T.; Greenwood, Michael; Murphy, David] Univ Bristol, Sch Clin Sci, Bristol BS1 3NY, England. [Hindmarch, C. C. T.; Hoe, See Ziau; Murphy, David] Univ Malaya, Fac Med, Dept Physiol, Kuala Lumpur 50603, Malaysia. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM gainerh@ninds.nih.gov RI HOE, SEE ZIAU/B-8637-2010 FU NIH, NINDS; BHF [RG/11/28714]; BBSRC [BB/J005452/1]; High Impact Research Chancellory Grant from the University of Malaya [UM.C/625/1/HIR/MOHE/MED/22 H-20001-E000086] FX This research was supported by the Intramural Research Program of the NIH, NINDS (KJ, HG), and by funding from the BHF (RG/11/28714, MG, DM), the BBSRC (BB/J005452/1, CH, DM) and a High Impact Research Chancellory Grant (UM.C/625/1/HIR/MOHE/MED/22 H-20001-E000086) from the University of Malaya (SZH, CH, DM). NR 70 TC 2 Z9 2 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 21 PY 2015 VL 10 IS 4 AR e0124523 DI 10.1371/journal.pone.0124523 PG 28 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG3XJ UT WOS:000353212600071 PM 25897513 ER PT J AU Kvistborg, P Gouttefangeas, C Aghaeepour, N Cazaly, A Chattopadhyay, PK Chan, C Eckl, J Finak, G Hadrup, SR Maecker, HT Maurer, D Mosmann, T Qiu, P Scheuermann, RH Welters, MJP Ferrari, G Brinkman, RR Britten, CM AF Kvistborg, Pia Gouttefangeas, Cecile Aghaeepour, Nima Cazaly, Angelica Chattopadhyay, Pratip K. Chan, Cliburn Eckl, Judith Finak, Greg Hadrup, Sine Reker Maecker, Holden T. Maurer, Dominik Mosmann, Tim Qiu, Peng Scheuermann, Richard H. Welters, Marij J. P. Ferrari, Guido Brinkman, Ryan R. Britten, Cedrik M. TI Thinking Outside the Gate: Single-Cell Assessments in Multiple Dimensions SO IMMUNITY LA English DT Letter ID FLOW-CYTOMETRY DATA C1 [Kvistborg, Pia] Netherlands Canc Inst, NL-1006 BE Amsterdam, Netherlands. [Gouttefangeas, Cecile] Univ Tubingen, Dept Immunol, Inst Cell Biol, D-72076 Tubingen, Germany. [Aghaeepour, Nima] Univ Southampton, Southampton SO17 1BJ, Hants, England. [Cazaly, Angelica] NIH, ImmunoTechnol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Chattopadhyay, Pratip K.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. [Chan, Cliburn] Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany. [Eckl, Judith] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Dept Biostat Bioinformat & Epidemiol, Seattle, WA 98155 USA. [Finak, Greg] Herlev Hosp, Ctr Canc Immune Therapy, DK-2730 Herlev, Denmark. [Hadrup, Sine Reker] Stanford Univ, Stanford Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA. [Maecker, Holden T.] Immat Biotechnol GmbH, D-72076 Tubingen, Germany. [Maurer, Dominik] Univ Rochester, David D Smith Ctr Vaccine Biol & Immunol, Med Ctr, Rochester, NY 14642 USA. [Mosmann, Tim] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30322 USA. [Qiu, Peng] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Scheuermann, Richard H.] J Craig Venter Inst, La Jolla, CA 92037 USA. [Scheuermann, Richard H.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Welters, Marij J. P.] Leiden Univ, Dept Clin Oncol, Med Ctr, NL-2300 RA Leiden, Netherlands. [Ferrari, Guido] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Britten, Cedrik M.] BioNTech RNA Pharmaceut GmbH, D-55131 Mainz, Germany. RP Brinkman, RR (reprint author), British Columbia Canc Agcy, Terry Fox Lab, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM rbrinkman@bccrc.ca; cebritten@web.de RI Hadrup, Sine Reker/P-3388-2014; Brinkman, Ryan/B-1108-2008; OI Hadrup, Sine Reker/0000-0002-5937-4344; Brinkman, Ryan/0000-0002-9765-2990; Finak, Greg/0000-0003-4341-9090; Chattopadhyay, Pratip/0000-0002-5457-9666 FU NCI NIH HHS [R01 CA163481]; NIAID NIH HHS [R24 AI054953]; NIBIB NIH HHS [R01 EB008400] NR 8 TC 13 Z9 13 U1 1 U2 8 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 APR 21 PY 2015 VL 42 IS 4 BP 591 EP 592 DI 10.1016/j.immuni.2015.04.006 PG 2 WC Immunology SC Immunology GA CG5QF UT WOS:000353347500001 PM 25902473 ER PT J AU Zhong, C Zhu, JF AF Zhong, Chao Zhu, Jinfang TI Tet2: Breaking Down Barriers to T Cell Cytokine Expression SO IMMUNITY LA English DT Editorial Material ID EPIGENETIC CONTROL; DIFFERENTIATION; PLASTICITY C1 [Zhong, Chao; Zhu, Jinfang] NIAID, Mol & Cellular Immunoregulat Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Zhu, JF (reprint author), NIAID, Mol & Cellular Immunoregulat Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM jfzhu@niaid.nih.gov RI Zhu, Jinfang/B-7574-2012 FU Intramural NIH HHS [ZIA AI001169-03] NR 9 TC 0 Z9 0 U1 1 U2 7 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 APR 21 PY 2015 VL 42 IS 4 BP 593 EP 595 DI 10.1016/j.immuni.2015.04.003 PG 3 WC Immunology SC Immunology GA CG5QF UT WOS:000353347500002 PM 25902474 ER PT J AU Dzutsev, A Trinchieri, G AF Dzutsev, Amiran Trinchieri, Giorgio TI Proteus mirabilis: The Enemy Within SO IMMUNITY LA English DT Editorial Material ID INFLAMMASOME; INTERLEUKIN-18 C1 [Dzutsev, Amiran; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Dzutsev, Amiran] Leidos Biomed Res Inc, Frederick, MD 21702 USA. RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM trinchig@mail.nih.gov NR 9 TC 0 Z9 0 U1 2 U2 5 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 APR 21 PY 2015 VL 42 IS 4 BP 602 EP 604 DI 10.1016/j.immuni.2015.04.004 PG 4 WC Immunology SC Immunology GA CG5QF UT WOS:000353347500006 PM 25902478 ER PT J AU Kobayashi, T Glatz, M Horiuchi, K Kawasaki, H Akiyama, H Kaplan, DH Kong, HH Amagai, M Nagao, K AF Kobayashi, Tetsuro Glatz, Martin Horiuchi, Keisuke Kawasaki, Hiroshi Akiyama, Haruhiko Kaplan, Daniel H. Kong, Heidi H. Amagai, Masayuki Nagao, Keisuke TI Dysbiosis and Staphyloccus aureus Colonization Drives Inflammation in Atopic Dermatitis SO IMMUNITY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; HUMAN SKIN MICROBIOME; LANGERHANS CELLS; DENDRITIC CELLS; BARRIER; EGFR; ACTIVATION; MANAGEMENT; MUTATIONS; FILAGGRIN AB Staphyloccus aureus skin colonization is universal in atopic dermatitis and common in cancer patients treated with epidermal growth factor receptor inhibitors. However, the causal relationship of dysbiosis and eczema has yet to be clarified. Herein, we demonstrate that Adam17(fl/fl) Sox9-Cre mice, generated to model ADAM17-deficiency in human, developed eczematous dermatitis with naturally occurring dysbiosis, similar to that observed in atopic dermatitis. Corynebacterium mastitidis, S. aureus, and Corynebacterium bovis sequentially emerged during the onset of eczematous dermatitis, and antibiotics specific for these bacterial species almost completely reversed dysbiosis and eliminated skin inflammation. Whereas S. aureus prominently drove eczema formation, C. bovis induced robust T helper 2 cell responses. Langerhans cells were required for eliciting immune responses against S. aureus inoculation. These results characterize differential contributions of dysbiotic flora during eczema formation, and highlight the microbiota-host immunity axis as a possible target for future therapeutics in eczematous dermatitis. C1 [Kobayashi, Tetsuro; Kawasaki, Hiroshi; Amagai, Masayuki; Nagao, Keisuke] Keio Univ, Sch Med, Dept Dermatol, Tokyo 1608582, Japan. [Kobayashi, Tetsuro; Glatz, Martin; Kong, Heidi H.; Nagao, Keisuke] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Horiuchi, Keisuke] Keio Univ, Sch Med, Dept Orthoped Surg, Tokyo 1608582, Japan. [Akiyama, Haruhiko] Gifu Univ, Dept Orthoped, Gifu 5011194, Japan. [Kaplan, Daniel H.] Univ Minnesota, Ctr Immunol, Dept Dermatol, Minneapolis, MN 55414 USA. RP Nagao, K (reprint author), Keio Univ, Sch Med, Dept Dermatol, Tokyo 1608582, Japan. EM keisuke.nagao@nih.gov RI Nagao, Keisuke/J-5116-2013; Kaplan, Daniel/N-2779-2013; Amagai, Masayuki/K-5325-2013; Horiuchi, Keisuke/L-2277-2013; OI Nagao, Keisuke/0000-0002-7005-3138; Kaplan, Daniel/0000-0002-7851-7320; Amagai, Masayuki/0000-0003-3314-7052; Horiuchi, Keisuke/0000-0001-7063-9609; Kong, Heidi/0000-0003-4424-064X FU Ministry of Health, Labor and Welfare of Japan FX This work was supported by Research for Prevention and Treatment of Immune/Allergic Diseases from the Ministry of Health, Labor and Welfare of Japan, Grant-in-Aid for JSPS Fellows and the US National Institutes of Health (NIH) NCI Intramural Research Programs. We thank Julie A. Segre and Mark C. Udey for helpful discussions and Cynthia Ng, Morgan Park, and Sean Conlan for underlying efforts. NR 51 TC 43 Z9 44 U1 3 U2 12 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 APR 21 PY 2015 VL 42 IS 4 BP 756 EP 766 DI 10.1016/j.immuni.2015.03.014 PG 11 WC Immunology SC Immunology GA CG5QF UT WOS:000353347500020 PM 25902485 ER PT J AU Malech, HL Ochs, HD AF Malech, Harry L. Ochs, Hans D. TI An Emerging Era of Clinical Benefit From Gene Therapy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID SEVERE COMBINED IMMUNODEFICIENCY; GAMMARETROVIRAL VECTOR; LENTIVIRAL VECTOR; T-CELLS; ACTIVATION; EFFICACY; SCID-X1; DISEASE; SAFETY; SITES C1 [Malech, Harry L.] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA. [Ochs, Hans D.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Ochs, Hans D.] Seattle Childrens Res Inst, Seattle, WA USA. RP Malech, HL (reprint author), NIAID, Lab Host Def, NIH, 10 Ctr Dr,M5C1456,Bldg 10,Room 5-3750, Bethesda, MD 20892 USA. EM hmalech@nih.gov NR 20 TC 1 Z9 1 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 21 PY 2015 VL 313 IS 15 BP 1522 EP 1523 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CG3SA UT WOS:000353198700016 PM 25898049 ER PT J AU Tomlinson, T De Vries, R Kim, SYH AF Tomlinson, Tom De Vries, Raymond Kim, Scott Y. H. TI Ethical Standards for Research Biobank Donation Reply 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] Univ Michigan, Sch Med, Ctr Bioeth & Social Sci Med, Ann Arbor, MI USA. [Kim, Scott Y. H.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Tomlinson, T (reprint author), Michigan State Univ, 965 Fee Rd, E Lansing, MI 48824 USA. EM tom.tomlinson@ht.msu.edu OI De Vries, Raymond/0000-0003-3087-3040 NR 0 TC 1 Z9 1 U1 0 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 APR 21 PY 2015 VL 313 IS 15 BP 1574 EP 1574 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CG3SA UT WOS:000353198700028 PM 25898062 ER PT J AU Fordyce, CB Roe, MT Ahmad, T Libby, P Borer, JS Hiatt, WR Bristow, MR Packer, M Wasserman, SM Braunstein, N Pitt, B DeMets, DL Cooper-Arnold, K Armstrong, PW Berkowitz, SD Scott, R Prats, J Galis, ZS Stockbridge, N Peterson, ED Califf, RM AF Fordyce, Christopher B. Roe, Matthew T. Ahmad, Tariq Libby, Peter Borer, Jeffrey S. Hiatt, William R. Bristow, Michael R. Packer, Milton Wasserman, Scott M. Braunstein, Ned Pitt, Bertram DeMets, David L. Cooper-Arnold, Katharine Armstrong, Paul W. Berkowitz, Scott D. Scott, Rob Prats, Jayne Galis, Zorina S. Stockbridge, Norman Peterson, Eric D. Califf, Robert M. TI Cardiovascular Drug Development SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE biomarkers; cardiovascular; agents; clinical trials; drug costs; pharmacological; policy ID PROGRESSION-FREE SURVIVAL; DECOMPENSATED HEART-FAILURE; ACUTE CORONARY SYNDROMES; CLINICAL-RESEARCH; END-POINTS; SURROGATE MARKERS; RANDOMIZED-TRIALS; ARTERY-DISEASE; STATIN THERAPY; UNITED-STATES AB Despite the global burden of cardiovascular disease, investment in cardiovascular drug development has stagnated over the past 2 decades, with relative underinvestment compared with other therapeutic areas. The reasons for this trend are multifactorial, but of primary concern is the high cost of conducting cardiovascular outcome trials in the current regulatory environment that demands a direct assessment of risks and benefits, using clinically-evident cardiovascular end-points. To work toward consensus on improving the environment for cardiovascular drug development, stakeholders from academia, industry, regulatory bodies, and government agencies convened for a think tank meeting in July 2014 in Washington, DC. This paper summarizes the proceedings of the meeting and aims to delineate the current adverse trends in cardiovascular drug development, understand the key issues that underlie these trends within the context of a recognized need for a rigorous regulatory review process, and provide potential solutions to the problems identified. (C) 2015 by the American College of Cardiology Foundation. C1 [Fordyce, Christopher B.; Roe, Matthew T.; Ahmad, Tariq; Peterson, Eric D.; Califf, Robert M.] Duke Clin Res Inst, Durham, NC 27705 USA. [Libby, Peter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Borer, Jeffrey S.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Hiatt, William R.; Bristow, Michael R.] Univ Colorado, Sch Med, Aurora, CO USA. [Packer, Milton; Scott, Rob] Univ Texas SW Med Ctr Dallas, Dept Clin Neurosci, Dallas, TX 75390 USA. [Wasserman, Scott M.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Braunstein, Ned] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Pitt, Bertram] Univ Michigan, Sch Med, Ann Arbor, MI USA. [DeMets, David L.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Cooper-Arnold, Katharine; Galis, Zorina S.] NHLBI, NIH, Bethesda, MD 20892 USA. [Armstrong, Paul W.] Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Whippany, NJ USA. [Prats, Jayne] Medicines Co, Parsippany, NJ USA. [Stockbridge, Norman] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Fordyce, CB (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM christopher.fordyce@duke.edu FU Boehringer Ingelheim; Merck Sharp Dohme; Duke Clinical Research Institute (DCRI); GlaxoSmithKiline; Amylin Pharmaceutical, Inc.; DCRI; Merck Co., Inc.; F. Hoffmann-La Roche Ltd.; American College of Cardiology; American Heart Association; Eli Lilly Co.; Janssen Pharmaceutical Products; Merck Co.; Sanofi-Aventis; Amylin; Bristol-Myers Squibb; Janssen Research and Development LLC; Merck; Novartis; Amgen; Bayer Healthcare; BMEB Services LLC; Medscape LLC/heart; Regado NJ; Roche FX Dr. Armstrong received research grants from Boehringer Ingelheim, Merck Sharp & Dohme in conjunction with Duke Clinical Research Institute (DCRI), GlaxoSmithKiline, Amylin Pharmaceutical, Inc. in conjunction with DCRI, Merck & Co., Inc., Sanofi-aventis Research and Development, and Regado Bioscience; and received consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck & Co., Inc., F. Hoffmann-La Roche Ltd., Axio/Orexigen, Merck, Eli Lilly, and Bayer. Dr. Berkowitz is an employee of Bayer HealthCare. Dr. Scott is an employee of and shareholder of Amgen, Inc. Dr. Prats is an employee of The Medicines Company. Dr. Stockbridge is an employee of the Food and Drug Administration. Dr. Peterson has received research grants from the American College of Cardiology, American Heart Association, Eli Lilly & Co., Janssen Pharmaceutical Products, and the Society of Thoracic Surgeons; and has received consulting fees from AstraZeneca, Bayer AG, Boehringer Ingelheim, Genentech, Janssen Pharmaceutical Products, Merck & Co., and Sanofi-Aventis. Dr. Califf has received research grants from Amylin, Bristol-Myers Squibb, Eli Lilly & Co., Janssen Research and Development LLC, Merck, and Novartis; and received consulting fees from Amgen, Bayer Healthcare, BMEB Services LLC, Medscape LLC/heart. org, Merck, Novartis, Regado NJ, and Roche; and has equity in N30 Pharma and Portola. The views expressed are those of the authors and do not necessarily reflect official National Heart, Lung, and Blood Institute positions. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 100 TC 22 Z9 22 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 21 PY 2015 VL 65 IS 15 BP 1567 EP 1582 DI 10.1016/j.jacc.2015.03.016 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG0KW UT WOS:000352956500011 PM 25881939 ER PT J AU Bielekova, B McDermott, MP AF Bielekova, Bibiana McDermott, Michael P. TI Will CSF biomarkers guide future therapeutic decisions in multiple sclerosis? SO NEUROLOGY LA English DT Editorial Material ID NEUROFILAMENT LIGHT; DISEASE; DAMAGE; MS AB Contrast-enhancing lesions (CELs) on MRI of the brain and spinal cord revolutionized care of patients with relapsing-remitting multiple sclerosis (RRMS) by facilitating screening of new therapeutics in economical, but still well-powered, phase II trials, and by providing an assessment of efficacy of approved agents in individual patients. However, CELs capture only a specific aspect of multiple sclerosis (MS) pathology: opening of the blood-brain barrier, which is associated with perivascular inflammation, acute demyelination, and axonal loss in RRMS. As disease progresses, CELs and relapses become less common, and pathology studies indicate that immune cell infiltration shifts from predominantly perivascular locations to diffuse permeation of CNS parenchyma and to consolidation in meninges. Whenever disease-modifying treatments (DMTs) were tested in different stages of the MS disease process (i.e., clinically isolated syndrome, RRMS, and progressive MS), their efficacy decreased with disease duration, suggesting that either this more diffuse inflammation is inaccessible to current DMTs, or that other neurodegenerative mechanisms drive progression of disability. Consequently, even those drugs that exert a dramatic inhibitory effect on CELs do not completely abrogate all signs of MS disease activity: a large proportion of patients in 2-year clinical trials either still form new lesions or progress on disability or brain atrophy measures.(1) Because axonal loss is considered the most definite substrate of sustained disability in MS, reliable biomarkers of axonal damage are needed to replace CELs as a measurable target of therapeutic development for this residual disease activity, especially in progressive MS. C1 [Bielekova, Bibiana] NINDS, Neuroimmunol Dis, NIH, Bethesda, MD 20892 USA. [McDermott, Michael P.] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14627 USA. RP Bielekova, B (reprint author), NINDS, Neuroimmunol Dis, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM bibi.bielekova@nih.gov FU Intramural NIH HHS NR 11 TC 5 Z9 5 U1 1 U2 4 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 APR 21 PY 2015 VL 84 IS 16 BP 1620 EP 1621 DI 10.1212/WNL.0000000000001506 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CG4GJ UT WOS:000353243200006 PM 25809305 ER PT J AU Battesti, A Majdalani, N Gottesman, S AF Battesti, Aurelia Majdalani, Nadim Gottesman, Susan TI Stress sigma factor RpoS degradation and translation are sensitive to the state of central metabolism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RssB; ClpXP; acetyl CoA; RpoS; pyruvate dehydrogenase ID ESCHERICHIA-COLI; SMALL RNA; ADAPTER PROTEIN; ANTI-ADAPTERS; GENE; RSSB; BIOSYNTHESIS; EXPRESSION; REGULATOR; STABILITY AB RpoS, the stationary phase/stress sigma factor of Escherichia coli, regulates a large cohort of genes important for the cell to deal with suboptimal conditions. Its level increases quickly in the cell in response to many stresses and returns to low levels when growth resumes. Increased RpoS results from increased translation and decreased RpoS degradation. Translation is positively regulated by small RNAs (sRNAs). Protein stability is positively regulated by anti-adaptors, which prevent the RssB adaptor-mediated degradation of RpoS by the ClpXP protease. Inactivation of aceE, a subunit of pyruvate dehydrogenase (PDH), was found to increase levels of RpoS by affecting both translation and protein degradation. The stabilization of RpoS in aceE mutants is dependent on increased transcription and translation of IraP and IraD, two known anti-adaptors. The aceE mutation also leads to a significant increase in rpoS translation. The sRNAs known to positively regulate RpoS are not responsible for the increased translation; sequences around the start codon are sufficient for the induction of translation. PDH synthesizes acetyl-CoA; acetate supplementation allows the cell to synthesize acetyl-CoA by an alternative, less favored pathway, in part dependent upon RpoS. Acetate addition suppressed the effects of the aceE mutant on induction of the anti-adaptors, RpoS stabilization, and rpoS translation. Thus, the bacterial cell responds to lowered levels of acetyl-CoA by inducing RpoS, allowing reprogramming of E. coli metabolism. C1 [Battesti, Aurelia; Majdalani, Nadim; Gottesman, Susan] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bethesda, MD 20892 USA. EM gottesms@helix.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; Fondation pour la Recherche Medicale FX We thank M. Cashel, P. Moreau, P. Mandin, and members of our laboratory for comments on the manuscript; E. Bouveret for discussion of the work; M. Cashel and R. Harinarayanan for sharing unpublished results; and F. Barras for providing facilities and support during a portion of this work. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. A.B. was supported in part by the Fondation pour la Recherche Medicale. NR 37 TC 11 Z9 11 U1 0 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 21 PY 2015 VL 112 IS 16 BP 5159 EP 5164 DI 10.1073/pnas.1504639112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG4FJ UT WOS:000353239100080 PM 25847996 ER PT J AU Penno, C Sharma, V Coakley, A Motherway, MO van Sinderen, D Lubkowska, L Kireeva, ML Kashlev, M Baranov, PV Atkins, JF AF Penno, Christophe Sharma, Virag Coakley, Arthur Motherway, Mary O'Connell van Sinderen, Douwe Lubkowska, Lucyna Kireeva, Maria L. Kashlev, Mikhail Baranov, Pavel V. Atkins, John F. TI Productive mRNA stem loop-mediated transcriptional slippage: Crucial features in common with intrinsic terminators SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE transcriptional realignment; stem loop stimulator; heteropolymeric slippage-prone motifs; frameshifting ID III SECRETION APPARATUS; ESCHERICHIA-COLI; SHIGELLA-FLEXNERI; ACTIVE-SITE; DNA HYBRID; POLYMERASE; ELONGATION; BACTERIAL; SEQUENCE; MECHANISM AB Escherichia coli and yeast DNA-dependent RNA polymerases are shown to mediate efficient nascent transcript stem loop formation-dependent RNA-DNA hybrid realignment. The realignment was discovered on the heteropolymeric sequence T5C5 and yields transcripts lacking a C residue within a corresponding U5C4. The sequence studied is derived from a Roseiflexus insertion sequence (IS) element where the resulting transcriptional slippage is required for transposase synthesis. The stability of the RNA structure, the proximity of the stem loop to the slippage site, the length and composition of the slippage site motif, and the identity of its 3' adjacent nucleotides (nt) are crucial for transcripts lacking a single C. In many respects, the RNA structure requirements for this slippage resemble those for hairpin-dependent transcription termination. In a purified in vitro system, the slippage efficiency ranges from 5% to 75% depending on the concentration ratios of the nucleotides specified by the slippage sequence and the 3' nt context. The only previous proposal of stem loop mediated slippage, which was in Ebola virus expression, was based on incorrect data interpretation. We propose a mechanical slippage model involving the RNAP translocation state as the main motor in slippage directionality and efficiency. It is distinct from previously described models, including the one proposed for paramyxovirus, where following random movement efficiency is mainly dependent on the stability of the new realigned hybrid. In broadening the scope for utilization of transcription slippage for gene expression, the stimulatory structure provides parallels with programmed ribosomal frameshifting at the translation level. C1 [Penno, Christophe; Sharma, Virag; Coakley, Arthur; Motherway, Mary O'Connell; van Sinderen, Douwe; Baranov, Pavel V.; Atkins, John F.] Natl Univ Ireland Univ Coll Cork, Sch Biochem, Cork, Ireland. [Penno, Christophe; Sharma, Virag; Coakley, Arthur; Motherway, Mary O'Connell; van Sinderen, Douwe; Baranov, Pavel V.; Atkins, John F.] Natl Univ Ireland Univ Coll Cork, Sch Microbiol, Cork, Ireland. [Penno, Christophe; Sharma, Virag; Coakley, Arthur; Motherway, Mary O'Connell; van Sinderen, Douwe; Baranov, Pavel V.; Atkins, John F.] Natl Univ Ireland Univ Coll Cork, Alimentary Pharmabiot Ctr, Cork, Ireland. [Lubkowska, Lucyna; Kireeva, Maria L.; Kashlev, Mikhail] NCI, Ctr Canc Res, Frederick, MD 21702 USA. [Atkins, John F.] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. RP Atkins, JF (reprint author), Natl Univ Ireland Univ Coll Cork, Sch Biochem, Cork, Ireland. EM j.atkins@ucc.ie RI Baranov, Pavel/A-2782-2011; OI Baranov, Pavel/0000-0001-9017-0270; van Sinderen, Douwe/0000-0003-1823-7957; Atkins, John/0000-0001-7933-0165 FU Irish Research Council; Science Foundation Ireland [13/IA/1853, 07/CE/B1365, 12/RC/2273]; Wellcome Trust [094423]; Irish Health Research Board [PDTM/2011/09]; National Institutes of Health; University College Cork FX We thank D. J. Jin, D. Friedman, and M. Cashel for bacterial strains; G. Loughran, L. Renault, and S. Rinke for support; H. Feldmann and M. Mehedi for sending the coding sequence information of Ebola virus cassettes used in their work; and O. Fayet for stimulating us to investigate IS elements and a rewarding collaboration. This work was supported by an Irish Research Council fellowship (to C.P.), Science Foundation Ireland Grants 13/IA/1853, 07/CE/B1365, and 12/RC/2273 (to J.F.A. and D.v.S.), Wellcome Trust Grant 094423 (to P.V.B.), an Irish Health Research Board postdoctoral fellowship Grant PDTM/2011/09 (to M.O.M.), a National Institutes of Health intramural award (to M.K.), and a University College Cork seed grant (to J.F.A.). NR 54 TC 6 Z9 6 U1 1 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 21 PY 2015 VL 112 IS 16 BP E1984 EP E1993 DI 10.1073/pnas.1418384112 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG4FJ UT WOS:000353239100006 PM 25848054 ER PT J AU Harmon, KJ Miao, HX Gomella, AA Bennett, EE Foster, BA Bhandarkar, P Wen, H AF Harmon, Katherine J. Miao, Houxun Gomella, Andrew A. Bennett, Eric E. Foster, Barbara A. Bhandarkar, Priya Wen, Han TI Motionless electromagnetic phase stepping versus mechanical phase stepping in x-ray phase-contrast imaging with a compact source SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE x-ray phase contrast imaging; x-ray radiography; x-ray phase stepping; x-ray Talbot-Lau interferometer; motionless; x-ray scattering; x-ray dark field imaging ID FRINGE-PATTERN ANALYSIS; FOURIER-TRANSFORM; GRATING INTERFEROMETER; TOMOGRAPHY AB X-ray phase contrast imaging based on grating interferometers detects the refractive index distribution of an object without relying on radiation attenuation, thereby having the potential for reduced radiation absorption. These techniques belong to the broader category of optical wavefront measurement, which requires stepping the phase of the interference pattern to obtain a pixel-wise map of the phase distortion of the wavefront. While phase stepping traditionally involves mechanical scanning of a grating or mirror, we developed electromagnetic phase stepping (EPS) for imaging with compact sources to obviate the need for mechanical movement. In EPS a solenoid coil is placed outside the x-ray tube to shift its focal spot with a magnetic field, causing a relative movement between the projection of the sample and the interference pattern in the image. Here we present two embodiments of this method. We verified experimentally that electromagnetic and mechanical phase stepping give the same results and attain the same signal-to-noise ratios under the same radiation dose. We found that the relative changes of interference fringe visibility were within 3.0% when the x-ray focal spot was shifted by up to 1.0 mm in either direction. We conclude that when using x-ray tube sources, EPS is an effective means of phase stepping without the need for mechanical movement. C1 [Harmon, Katherine J.; Miao, Houxun; Gomella, Andrew A.; Bennett, Eric E.; Wen, Han] NHLBI, Biochem & Biophys Ctr, Imaging Phys Lab, NIH, Bethesda, MD 20892 USA. [Foster, Barbara A.; Bhandarkar, Priya] Walter Reed Natl Mil Med Ctr, Breast Imaging Ctr, Bethesda, MD 20889 USA. RP Harmon, KJ (reprint author), NHLBI, Biochem & Biophys Ctr, Imaging Phys Lab, NIH, Bethesda, MD 20892 USA. EM wenh@nhlbi.nih.gov RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 NR 37 TC 1 Z9 1 U1 3 U2 18 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 APR 21 PY 2015 VL 60 IS 8 BP 3031 EP 3043 DI 10.1088/0031-9155/60/8/3031 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CF4NF UT WOS:000352525200006 PM 25803511 ER PT J AU Zhang, LS Zhang, YQ Mehta, A Boufraqech, M Davis, S Wang, J Tian, Z Yu, ZY Boxer, MB Kiefer, JA Copland, JA Smallridge, RC Li, ZY Shen, M Kebebew, E AF Zhang, Lisa Zhang, Yaqin Mehta, Amit Boufraqech, Myriem Davis, Sean Wang, Jing Tian, Ze Yu, Zhiya Boxer, Matthew B. Kiefer, Jeffrey A. Copland, John A. Smallridge, Robert C. Li, Zhuyin Shen, Min Kebebew, Electron TI Dual inhibition of HDAC and EGFR signaling with CUDC-101 induces potent suppression of tumor growth and metastasis in anaplastic thyroid cancer SO ONCOTARGET LA English DT Article DE CUDC-101; Anaplastic Thyroid Cancer; Quantitative High-Throughput Screening; EGFR; HDAC ID HISTONE DEACETYLASE; FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; MULTITARGETED INHIBITOR; ANTICANCER ACTIVITY; THERAPEUTIC TARGET; MOUSE MODEL; PHASE-II; CARCINOMA; EXPRESSION AB Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies that currently has no effective therapy. We performed quantitative high-throughput screening (qHTS) in three ATC cell lines using 3,282 clinically approved drugs and drug candidates, and identified 100 active agents. Enrichment analysis of active compounds showed that inhibitors of EGFR and histone deacetylase (HDAC) were most active. Of these, the first-in-class dual inhibitor of EGFR, HER2 and HDACs, CUDC-101, had the highest efficacy and lower IC50 than established drugs. We validated that CUDC-101 inhibited cellular proliferation and resulted in cell death by inducing cell cycle arrest and caspase-dependent apoptosis. CUDC-101 also inhibited cellular migration in vitro. Mechanistically, CUDC-101 inhibited MAPK signaling and histone deacetylation in ATC cell lines with multiple driver mutations present in human ATC. The anticancer effect of CUDC-101 was associated with increased expression of p21 and E-cadherin, and reduced expression of survivin, XIAP, alpha-catenin, N-cadherin, and Vimentin. In an in vivo mouse model of metastatic ATC, CUDC-101 inhibited tumor growth and metastases, and significantly prolonged survival. Response to CUDC-101 treatment in vivo was associated with increased histone 3 acetylation and reduced survivin expression. Our findings provide a preclinical basis to evaluate CUDC-101 therapy in ATC. C1 [Zhang, Lisa; Mehta, Amit; Boufraqech, Myriem; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA. [Zhang, Yaqin; Boxer, Matthew B.; Li, Zhuyin; Shen, Min] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD USA. [Mehta, Amit] Geisel Sch Med Dartmouth, Hanover, NH USA. [Davis, Sean] NCI, Canc Genet Branch, Ctr Canc Res, Bethesda, MD USA. [Wang, Jing; Tian, Ze] Curis Inc, Translat Sci, Lexington, MA USA. [Yu, Zhiya] NCI, Surg Branch, NIH, Bethesda, MD USA. [Kiefer, Jeffrey A.] Translat Genom Res Inst, Div Informat Sci, Phoenix, AZ USA. [Copland, John A.; Smallridge, Robert C.] Mayo Clin, Dept Canc Biol, Jacksonville, FL 32224 USA. [Smallridge, Robert C.] Mayo Clin, Dept Internal Med, Endocrinol Div, Jacksonville, FL 32224 USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA. EM kebebewe@mail.nih.gov RI Boufraqech, Myriem/E-4823-2016 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX We are grateful to Ms. Kelli Gaskins (NCI/NIH) for technical help and Mr. Jules Choumbeun for caring animals. This research was supported by the intramural research program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 50 TC 10 Z9 10 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR 20 PY 2015 VL 6 IS 11 BP 9073 EP 9085 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CN9NB UT WOS:000358774600046 PM 25940539 ER PT J AU Le, DT Wang-Gillam, A Picozzi, V Greten, TF Crocenzi, T Springett, G Morse, M Zeh, H Cohen, D Fine, RL Onners, B Uram, JN Laheru, DA Lutz, ER Solt, S Murphy, AL Skoble, J Lemmens, E Grous, J Dubensky, T Brockstedt, DG Jaffee, EM AF Le, Dung T. Wang-Gillam, Andrea Picozzi, Vincent Greten, Tim F. Crocenzi, Todd Springett, Gregory Morse, Michael Zeh, Herbert Cohen, Deirdre Fine, Robert L. Onners, Beth Uram, Jennifer N. Laheru, Daniel A. Lutz, Eric R. Solt, Sara Murphy, Aimee Luck Skoble, Justin Lemmens, Ed Grous, John Dubensky, Thomas, Jr. Brockstedt, Dirk G. Jaffee, Elizabeth M. TI Safety and Survival With GVAX Pancreas Prime and Listeria Monocytogenes-Expressing Mesothelin (CRS-207) Boost Vaccines for Metastatic Pancreatic Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RESISTANT PROSTATE-CANCER; IMMUNE ACTIVATION; IMMUNOTHERAPY; EFFICACY; CELLS; TRIAL AB Purpose GVAX pancreas, granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells, induces T-cell immunity to cancer antigens, including mesothelin. GVAX is administered with low-dose cyclophosphamide (Cy) to inhibit regulatory T cells. CRS-207, live-attenuated Listeria monocytogenes-expressing mesothelin, induces innate and adaptive immunity. On the basis of preclinical synergy, we tested prime/boost vaccination with GVAX and CRS-207 in pancreatic adenocarcinoma. Patients and Methods Previously treated patients with metastatic pancreatic adenocarcinoma were randomly assigned at a ratio of 2:1 to two doses of Cy/GVAX followed by four doses of CRS-207 (arm A) or six doses of Cy/GVAX (arm B) every 3 weeks. Stable patients were offered additional courses. The primary end point was overall survival (OS) between arms. Secondary end points were safety and clinical response. Results A total of 90 patients were treated (arm A, n = 61; arm B, n = 29); 97% had received prior chemotherapy; 51% had received two regimens for metastatic disease. Mean number of doses ( standard deviation) administered in arms A and B were 5.5 +/- 4.5 and 3.7 +/- 2.2, respectively. The most frequent grade 3 to 4 related toxicities were transient fevers, lymphopenia, elevated liver enzymes, and fatigue. OS was 6.1 months in arm A versus 3.9 months in arm B (hazard ratio [HR], 0.59; P = .02). In a prespecified per-protocol analysis of patients who received at least three doses (two doses of Cy/GVAX plus one of CRS-207 or three of Cy/GVAX), OS was 9.7 versus 4.6 months (arm A v B; HR, 0.53; P = .02). Enhanced mesothelin-specific CD8 T-cell responses were associated with longer OS, regardless of treatment arm. Conclusion Heterologous prime/boost with Cy/GVAX and CRS-207 extended survival for patients with pancreatic cancer, with minimal toxicity. (C) 2015 by American Society of Clinical Oncology C1 [Le, Dung T.; Onners, Beth; Uram, Jennifer N.; Laheru, Daniel A.; Lutz, Eric R.; Solt, Sara; Jaffee, Elizabeth M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Greten, Tim F.] NCI, Bethesda, MD 20892 USA. [Wang-Gillam, Andrea] Washington Univ, Siteman Canc Ctr, St Louis, MO USA. [Picozzi, Vincent] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Crocenzi, Todd] Providence Portland Med Ctr, Portland, OR USA. [Springett, Gregory] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Morse, Michael] Duke Univ, Med Ctr, Durham, NC USA. [Zeh, Herbert] Univ Pittsburgh, Pittsburgh, PA USA. [Cohen, Deirdre] NYU, Langone Med Ctr, New York, NY 10003 USA. [Fine, Robert L.] Columbia Univ, Med Ctr, New York, NY USA. [Murphy, Aimee Luck; Skoble, Justin; Lemmens, Ed; Grous, John; Dubensky, Thomas, Jr.; Brockstedt, Dirk G.] Aduro BioTech, Berkeley, CA USA. RP Le, DT (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St,Room 407, Baltimore, MD 21287 USA. EM dle2@jhmi.edu OI Cohen, Deirdre/0000-0002-6178-9266 FU Aduro BioTech; National Institutes of Health [5K23 CA163672-02]; Washington University Institute of Clinical and Translational Sciences Grants from the National Center for Advancing Translational Sciences [UL1 TR000448, KL2 TR000450] FX Supported by Aduro BioTech, National Institutes of Health Grant No. 5K23 CA163672-02, and Washington University Institute of Clinical and Translational Sciences Grants No. UL1 TR000448 and KL2 TR000450 from the National Center for Advancing Translational Sciences. NR 15 TC 102 Z9 105 U1 8 U2 32 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2015 VL 33 IS 12 BP 1325 EP + DI 10.1200/JCO.2014.57.4244 PG 12 WC Oncology SC Oncology GA CK2RH UT WOS:000356058800005 PM 25584002 ER PT J AU Pogue-Geile, KL Song, N Jeong, JH Gavin, PG Kim, SR Blackmon, NL Finnigan, M Rastogi, P Fehrenbacher, L Mamounas, EP Swain, SM Wickerham, DL Geyer, CE Costantino, JP Wolmark, N Paik, S AF Pogue-Geile, Katherine L. Song, Nan Jeong, Jong-Hyeon Gavin, Patrick G. Kim, Seong-Rim Blackmon, Nicole L. Finnigan, Melanie Rastogi, Priya Fehrenbacher, Louis Mamounas, Eleftherios P. Swain, Sandra M. Wickerham, D. Lawrence Geyer, Charles E., Jr. Costantino, Joseph P. Wolmark, Norman Paik, Soonmyung TI Intrinsic Subtypes, PIK3CA Mutation, and the Degree of Benefit From Adjuvant Trastuzumab in the NSABP B-31 Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HER2-POSITIVE BREAST-CANCER; TENSIN HOMOLOG; PI3K PATHWAY; PTEN LOSS; CELLS; PHOSPHATASE; ACTIVATION; EFFICACY; RISK AB Purpose Considerable molecular heterogeneity exists among human epidermal growth factor receptor 2 (HER2) -positive breast cancer regarding gene expression and mutation profiling. Evidence from preclinical, clinical neoadjuvant, and metastatic clinical trials suggested that PIK3CA mutational status and PAM50 intrinsic subtype of a tumor were markers of response to anti-HER2 therapies. We evaluated the predictive value of these two biomarkers in the adjuvant setting using archived tumor blocks from National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31. Patients and Methods Expression data for 49 genes using the nCounter platform were used to generate PAM50 intrinsic subtypes for 1,578 archived tumor blocks from patients in the B-31 trial. Six PIK3CA hotspot mutations were examined by mass spectrometry of the primer extension products in a randomly selected subset (n = 671). We examined the heterogeneity of trastuzumab treatment effect across different subsets defined by each marker using Cox regression and disease-free survival as the end point. Results Seven hundred forty-one (47.0%) of 1,578 tumors were classified as HER2-enriched (HER2E) subtype, and 166 (24.7%) of 671 tumors had PIK3CA mutations. Hazard ratios (HRs) for trastuzumab in HER2E and other subtypes were 0.44 (95% CI, 0.34 to 0.58; P < .001) and 0.47 (95% CI, 0.35 to 0.62; P < .001), respectively (interaction P = .67). HRs for trastuzumab in PIK3CA wild-type and mutated tumors were 0.51 (95% CI, 0.37 to 0.71; P < .001) and 0.44 (95% CI, 0.24 to 0.82; P = .009), respectively (interaction P = .64). Conclusion Unlike results seen in the metastatic and neoadjuvant clinical trials, PIK3CA and PAM50 intrinsic subtypes were not predictive biomarkers for adjuvant trastuzumab in NSABP B-31. These data suggest that results from the metastatic and neoadjuvant setting may not be always applicable to the adjuvant setting. (C) 2015 by American Society of Clinical Oncology C1 [Pogue-Geile, Katherine L.; Song, Nan; Gavin, Patrick G.; Kim, Seong-Rim; Blackmon, Nicole L.; Finnigan, Melanie; Rastogi, Priya; Fehrenbacher, Louis; Mamounas, Eleftherios P.; Swain, Sandra M.; Wickerham, D. Lawrence; Geyer, Charles E., Jr.; Wolmark, Norman; Paik, Soonmyung] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. [Jeong, Jong-Hyeon; Costantino, Joseph P.] NRG Oncol Stat & Data Management Ctr, Pittsburgh, PA USA. [Jeong, Jong-Hyeon; Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Rastogi, Priya] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Wickerham, D. Lawrence; Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. [Fehrenbacher, Louis] Kaiser Permanente No Calif, Vallejo, CA USA. [Mamounas, Eleftherios P.] Orlando Hlth, UF Hlth Canc Ctr, Orlando, FL USA. [Swain, Sandra M.] Medstar Washington Hosp Ctr, Washington Canc Inst, Washington, DC USA. [Geyer, Charles E., Jr.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA. [Geyer, Charles E., Jr.] Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA. [Paik, Soonmyung] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul, South Korea. RP Paik, S (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, 1307 Fed St,Ste 303, Pittsburgh, PA 15212 USA. EM soon.paik@nsabp.org OI Jeong, Jong/0000-0003-0596-2201; Swain, Sandra/0000-0002-1320-3830 FU National Cancer Institute, Department of Health and Human Services, Public Health Service [U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974]; Pennsylvania State Department of Health; Genentech FX Supported by Grants No. U10-CA-12027, U10-CA-69651, U10-CA-37377, and U10-CA-69974 from the National Cancer Institute, Department of Health and Human Services, Public Health Service; by a grant from the Pennsylvania State Department of Health; and by Genentech. NR 26 TC 37 Z9 40 U1 2 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2015 VL 33 IS 12 BP 1340 EP + DI 10.1200/JCO.2014.56.2439 PG 9 WC Oncology SC Oncology GA CK2RH UT WOS:000356058800007 PM 25559813 ER PT J AU Joffe, S Miller, FG AF Joffe, Steven Miller, Franklin G. TI User Beware: We Need More Science and Less Art When Measuring Financial Toxicity in Oncology Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Joffe, Steven] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Miller, Franklin G.] NIH, Bethesda, MD 20892 USA. RP Joffe, S (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2015 VL 33 IS 12 DI 10.1200/JCO.2014.60.1096 PG 2 WC Oncology SC Oncology GA CK2RH UT WOS:000356058800022 ER PT J AU Horstick, EJ Jordan, DC Bergeron, SA Tabor, KM Serpe, M Feldman, B Burgess, HA AF Horstick, Eric J. Jordan, Diana C. Bergeron, Sadie A. Tabor, Kathryn M. Serpe, Mihaela Feldman, Benjamin Burgess, Harold A. TI Increased functional protein expression using nucleotide sequence features enriched in highly expressed genes in zebrafish SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TOL2 TRANSPOSABLE ELEMENT; GREEN FLUORESCENT PROTEIN; ESCHERICHIA-COLI; TRANSGENE EXPRESSION; IN-VIVO; TRANSLATION TERMINATION; MESSENGER-RNAS; STOP CODON; X-PROTEIN; INTRON AB Many genetic manipulations are limited by difficulty in obtaining adequate levels of protein expression. Bioinformatic and experimental studies have identified nucleotide sequence features that may increase expression, however it is difficult to assess the relative influence of these features. Zebrafish embryos are rapidly injected with calibrated doses of mRNA, enabling the effects of multiple sequence changes to be compared in vivo. Using RNAseq and microarray data, we identified a set of genes that are highly expressed in zebrafish embryos and systematically analyzed for enrichment of sequence features correlated with levels of protein expression. We then tested enriched features by embryo microinjection and functional tests of multiple protein reporters. Codon selection, releasing factor recognition sequence and specific introns and 3' untranslated regions each increased protein expression between 1.5- and 3-fold. These results suggested principles for increasing protein yield in zebrafish through biomolecular engineering. We implemented these principles for rational gene design in software for codon selection (CodonZ) and plasmid vectors incorporating the most active non-coding elements. Rational gene design thus significantly boosts expression in zebrafish, and a similar approach will likely elevate expression in other animal models. C1 [Horstick, Eric J.; Jordan, Diana C.; Bergeron, Sadie A.; Tabor, Kathryn M.; Burgess, Harold A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA. [Serpe, Mihaela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Cellular Regulat & Metab, Bethesda, MD 20892 USA. [Feldman, Benjamin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Zebrafish Core, Bethesda, MD 20892 USA. RP Burgess, HA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA. EM haroldburgess@mail.nih.gov OI Burgess, Harold/0000-0003-1966-7801; Bergeron, Sadie/0000-0002-1238-8730; Jordan, Diana C/0000-0001-9469-9358 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; Division of Intramural Research of the National Institute of Child Health and Human Development FX Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Funding for open access charge: Division of Intramural Research of the National Institute of Child Health and Human Development. NR 91 TC 4 Z9 5 U1 2 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 20 PY 2015 VL 43 IS 7 AR e48 DI 10.1093/nar/gkv035 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI4MD UT WOS:000354722500006 PM 25628360 ER PT J AU Litwin, TR Sola, M Holt, IJ Neuman, KC AF Litwin, Tamara R. Sola, Maria Holt, Ian J. Neuman, Keir C. TI A robust assay to measure DNA topology-dependent protein binding affinity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MITOCHONDRIAL TRANSCRIPTION FACTOR; NITROCELLULOSE FILTER BINDING; COLI TOPOISOMERASE-IV; ESCHERICHIA-COLI; SUPERCOILED DNA; THERMODYNAMIC PROPERTIES; IIA TOPOISOMERASES; STRUCTURAL BASIS; SPECIFICITY; MECHANISM AB DNA structure and topology pervasively influence aspects of DNA metabolism including replication, transcription and segregation. However, the effects of DNA topology on DNA-protein interactions have not been systematically explored due to limitations of standard affinity assays. We developed a method to measure protein binding affinity dependence on the topology (topological linking number) of supercoiled DNA. A defined range of DNA topoisomers at equilibrium with a DNA binding protein is separated into free and protein-bound DNA populations using standard nitrocellulose filter binding techniques. Electrophoretic separation and quantification of bound and free topoisomers combined with a simple normalization procedure provide the relative affinity of the protein for the DNA as a function of linking number. Employing this assay we measured topology-dependent DNA binding of a helicase, a type IB topoisomerase, a type IIA topoisomerase, a non-specific mitochondrial DNA binding protein and a type II restriction endonuclease. Most of the proteins preferentially bind negatively supercoiled DNA but the details of the topology-dependent affinity differ among proteins in ways that expose differences in their interactions with DNA. The topology-dependent binding assay provides a robust and easily implemented method to probe topological influences on DNA-protein interactions for a wide range of DNA binding proteins. C1 [Litwin, Tamara R.; Neuman, Keir C.] NHLBI, NIH, Bethesda, MD 20814 USA. [Litwin, Tamara R.] MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England. [Sola, Maria] CSIC, Mol Biol Inst Barcelona, Dept Struct Biol, E-08028 Barcelona, Spain. [Holt, Ian J.] Natl Inst Med Res, MRC, The Ridgeway, London NW7 1AA, England. RP Neuman, KC (reprint author), NHLBI, NIH, Bethesda, MD 20814 USA. EM neumankc@mail.nih.gov RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 FU Intramural Research Program of the National Heart, Lung, and Blood Institute of the National Institutes of Health; Medical Research Council of the United Kingdom; University of Cambridge FX Intramural Research Program of the National Heart, Lung, and Blood Institute of the National Institutes of Health; Medical Research Council of the United Kingdom. Cambridge International Scholarship Scheme from the University of Cambridge [to T.R.L.]. Funding for open access charge: Intramural Research Program of the National Heart, Lung, and Blood Institute of the National Institutes of Health. NR 44 TC 1 Z9 1 U1 2 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 20 PY 2015 VL 43 IS 7 AR e43 DI 10.1093/nar/gku1381 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI4MD UT WOS:000354722500001 PM 25552413 ER PT J AU Mons, U Muezzinler, A Gellert, C Schottker, B Abnet, CC Bobak, M de Groot, L Freedman, ND Jansen, E Kee, F Kromhout, D Kuulasmaa, K Laatikainen, T O'Doherty, MG Bueno-de-Mesquita, B Orfanos, P Peters, A van der Schouw, YT Wilsgaard, T Wolk, A Trichopoulou, A Boffetta, P Brenner, H AF Mons, Ute Mueezzinler, Aysel Gellert, Carolin Schoettker, Ben Abnet, Christian C. Bobak, Martin de Groot, Lisette Freedman, Neal D. Jansen, Eugene Kee, Frank Kromhout, Daan Kuulasmaa, Kari Laatikainen, Tiina O'Doherty, Mark G. Bueno-de-Mesquita, Bas Orfanos, Philippos Peters, Annette van der Schouw, Yvonne T. Wilsgaard, Tom Wolk, Alicja Trichopoulou, Antonia Boffetta, Paolo Brenner, Hermann CA CHANCES Consortium TI Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID RATE ADVANCEMENT PERIODS; MYOCARDIAL-INFARCTION; CIGARETTE-SMOKING; UNITED-STATES; RISK-FACTORS; HEALTH; DISEASE; POPULATION; STROKE; WOMEN AB OBJECTIVE To investigate the impact of smoking and smoking cessation on cardiovascular mortality, acute coronary events, and stroke events in people aged 60 and older, and to calculate and report risk advancement periods for cardiovascular mortality in addition to traditional epidemiological relative risk measures. DESIGN Individual participant meta-analysis using data from 25 cohorts participating in the CHANCES consortium. Data were harmonised, analysed separately employing Cox proportional hazard regression models, and combined by meta-analysis. RESULTS Overall, 503 905 participants aged 60 and older were included in this study, of whom 37 952 died from cardiovascular disease. Random effects meta-analysis of the association of smoking status with cardiovascular mortality yielded a summary hazard ratio of 2.07 (95% CI 1.82 to 2.36) for current smokers and 1.37 (1.25 to 1.49) for former smokers compared with never smokers. Corresponding summary estimates for risk advancement periods were 5.50 years (4.25 to 6.75) for current smokers and 2.16 years (1.38 to 2.39) for former smokers. The excess risk in smokers increased with cigarette consumption in a dose-response manner, and decreased continuously with time since smoking cessation in former smokers. Relative risk estimates for acute coronary events and for stroke events were somewhat lower than for cardiovascular mortality, but patterns were similar. CONCLUSIONS Our study corroborates and expands evidence from previous studies in showing that smoking is a strong independent risk factor of cardiovascular events and mortality even at older age, advancing cardiovascular mortality by more than five years, and demonstrating that smoking cessation in these age groups is still beneficial in reducing the excess risk. C1 [Mons, Ute; Mueezzinler, Aysel; Gellert, Carolin; Schoettker, Ben; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany. [Mueezzinler, Aysel] Heidelberg Univ, NAR, Heidelberg, Germany. [Abnet, Christian C.; Freedman, Neal D.] NCI, Bethesda, MD 20892 USA. [Bobak, Martin] UCL, Dept Epidemiol & Publ Hlth, London, England. [de Groot, Lisette; Kromhout, Daan] Wageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, Netherlands. [Jansen, Eugene] Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, Bilthoven, Netherlands. [Kee, Frank; O'Doherty, Mark G.] Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth, Belfast, Antrim, North Ireland. [Kuulasmaa, Kari; Laatikainen, Tiina] Natl Inst Hlth & Welf THL, Helsinki, Finland. [Laatikainen, Tiina] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland. [Laatikainen, Tiina] Hosp Dist North Karelia, Joensuu, Finland. [Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands. [Bueno-de-Mesquita, Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Bueno-de-Mesquita, Bas] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Bueno-de-Mesquita, Bas] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia. [Orfanos, Philippos; Trichopoulou, Antonia; Boffetta, Paolo] Hellen Hlth Fdn, Athens, Greece. [Orfanos, Philippos; Trichopoulou, Antonia] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece. [Peters, Annette] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Peters, Annette] German Ctr Cardiovasc Dis Res DZHK eV, Munich, Germany. [van der Schouw, Yvonne T.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands. [Wilsgaard, Tom] UiT Arctic Univ Norway, Dept Community Med, Tromso, Norway. [Wolk, Alicja] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA. [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. RP Mons, U (reprint author), German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Neuenheimer Feld 581, D-69120 Heidelberg, Germany. EM u.mons@dkfz.de RI Freedman, Neal/B-9741-2015; Abnet, Christian/C-4111-2015; Peters, Annette/A-6117-2011; Brenner, Hermann/B-4627-2017; OI Freedman, Neal/0000-0003-0074-1098; Abnet, Christian/0000-0002-3008-7843; Brenner, Hermann/0000-0002-6129-1572; Pikhart, Hynek/0000-0001-5277-4049; Feskens, Edith/0000-0001-5819-2488; Kuulasmaa, Kari/0000-0003-2165-1411; Kontto, Jukka/0000-0003-3899-9852; Peters, Annette/0000-0001-6645-0985 FU European Commission [HEALTH-F3-2010-242244, QLK6-CT-2001-00360, RII-CT-2006-062193, CIT5-CT-2005-028857, CIT4-CT-2006-028812, 211909, 227822, 261982]; National Institute of Aging in the United States; ELSA; Hellenic Health Foundation; European Commission (DG SANCO); Dutch Ministry of Public Health, Welfare and Sports (VWS); National Institute for Public Health and the Environment; Dutch Cancer Society, the Netherlands Organisation for Health Research and Development (ZONMW); World Cancer Research Fund (WCRF); Health Research Fund (FIS) of the Spanish Ministry of Health RTICC 'Red Tematica de Investigacion Cooperativa en Cancer [Rd06/0020/0091, Rd12/0036/0018]; Regional Governments of Andalucia, Asturias, Basque Country, Murcia [6236]; Navarra, Instituto de Salud Carlos III, Redes de Investigacion Cooperativa [RD06/0020]; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane; Baden-Wurttemberg state Ministry of Science, Research and Arts (Stuttgart, Germany); Federal Ministry of Education and Research (Berlin, Germany); Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany); Wellcome Trust [064947, 081081]; US National Institute on Aging [R01 AG23522-01, U01 AG09740-13S2, P01 AG005842, P01 AG08291, P30 AG12815, R21 AG025169, Y1-AG-4553-01, IAG BSR06-11, OGHA 04-064]; Mac Arthur Foundation; European Union [HEALTH-F4-2007-201413, 278913]; Intramural Research Program of the National Cancer Institute (NCI), NIH; German Ministry of Education and Research; Swedish Research Council; Karolinska Institutet; UiT The Arctic University of Norway; National Screening Service; Research Council of Norway; Netherlands Prevention Foundation; Klaus Tschira Foundation FX Data used throughout the present study are derived from the CHANCES project. The project is coordinated by the Hellenic Health Foundation, Greece. The project received funding by the FP7 framework programme of DG-RESEARCH in the European Commission (grant agreement no. HEALTH-F3-2010-242244). ELSA: The data of the ELSA cohort were made available through the UK Data Archive (UKDA). ELSA was developed by a team of researchers based at the NatCen Social Research, University College London and the Institute for Fiscal Studies. The data were collected by NatCen Social Research. The funding is provided by the National Institute of Aging in the United States, and a consortium of UK government departments coordinated by the Office for National Statistics. The developers and funders of ELSA and the archive do not bear any responsibility for the analyses or interpretations presented here. EPIC Greece: funded by the Hellenic Health Foundation. EPIC Netherlands: funded by European Commission (DG SANCO); Dutch Ministry of Public Health, Welfare and Sports (VWS); The National Institute for Public Health and the Environment; the Dutch Cancer Society, the Netherlands Organisation for Health Research and Development (ZONMW); World Cancer Research Fund (WCRF). EPIC Spain: supported by Health Research Fund (FIS) of the Spanish Ministry of Health RTICC 'Red Tematica de Investigacion Cooperativa en Cancer (grant numbers: Rd06/0020/0091 and Rd12/0036/0018), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (project 6236), and Navarra, Instituto de Salud Carlos III, Redes de Investigacion Cooperativa (RD06/0020). EPIC Sweden: funded by the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skane. ESTHER: funded by the Baden-Wurttemberg state Ministry of Science, Research and Arts (Stuttgart, Germany), the Federal Ministry of Education and Research (Berlin, Germany), and the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany). HAPIEE: funded by the Wellcome Trust (064947 and 081081), the US National Institute on Aging (R01 AG23522-01) and a grant from Mac Arthur Foundation. MORGAM: MORGAM Project has received additional funding from European Union FP 7 projects ENGAGE (HEALTH-F4-2007-201413) and BiomarCaRE (278913). This has supported central coordination, workshops and part of the activities of the MORGAM Data Centre, at THL in Helsinki, Finland. MORGAM Participating Centres are funded by regional and national governments, research councils, charities, and other local sources. NIH-AARP: support for the National Institutes of Health (NIH)-AARP Diet and Health Study was provided by the Intramural Research Program of the National Cancer Institute (NCI), NIH. NHANES: The study is conducted by the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention. The findings and conclusions in this paper are those of the authors and not necessarily those of the agency. SENECA: SENECA is a Concerted Action within the EURONUT programme of the European Union. SHARE: SHARE data collection has been primarily funded by the European Commission through the 5th Framework Programme (project QLK6-CT-2001-00360 in the thematic programme Quality of Life), through the 6th Framework Programme (projects SHARE-I3, RII-CT-2006-062193, COMPARE, CIT5-CT-2005-028857, and SHARELIFE, CIT4-CT-2006-028812) and through the 7th Framework Programme (SHARE-PREP, No 211909, SHARE-LEAP, No 227822 and SHARE M4, No 261982).; Additional funding from the US National Institute on Aging (U01 AG09740-13S2, P01 AG005842, P01 AG08291, P30 AG12815, R21 AG025169, Y1-AG-4553-01, IAG BSR06-11, and OGHA 04-064) and the German Ministry of Education and Research as well as from various national sources is gratefully acknowledged (see www.share-project.org for a full list of funding institutions). SMC: funded by the Swedish Research Council and Strategic Funds from Karolinska Institutet. Tromso: funded by: UiT The Arctic University of Norway, the National Screening Service, and the Research Council of Norway. Zutphen Elderly Study: funded by the Netherlands Prevention Foundation. The work of Aysel Muezzinler was supported by a scholarship from the Klaus Tschira Foundation. NR 35 TC 29 Z9 32 U1 2 U2 12 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 APR 20 PY 2015 VL 350 AR h1551 DI 10.1136/bmj.h1551 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CG8PY UT WOS:000353572900001 PM 25896935 ER PT J AU Pu, J Schindler, C Jia, R Jarnik, M Backlund, P Bonifacino, JS AF Pu, Jing Schindler, Christina Jia, Rui Jarnik, Michal Backlund, Peter Bonifacino, Juan S. TI BORC, a Multisubunit Complex that Regulates Lysosome Positioning SO DEVELOPMENTAL CELL LA English DT Article ID ARF-LIKE GTPASE; CAENORHABDITIS-ELEGANS; SPATIAL-DISTRIBUTION; NONNEURONAL CELLS; RAB7 EFFECTOR; BIOGENESIS; ORGANELLES; PROTEIN; BLOC-1; TRAFFICKING AB The positioning of lysosomes within the cytoplasm is emerging as a critical determinant of many lysosomal functions. Here we report the identification of a multi-subunit complex named BORC that regulates lysosome positioning. BORC comprises eight subunits, some of which are shared with the BLOC-1 complex involved in the biogenesis of lysosome-related organelles, and the others of which are products of previously uncharacterized open reading frames. BORC associates peripherally with the lysosomal membrane, where it functions to recruit the small GTPase Arl8. This initiates a chain of interactions that promotes the kinesin-dependent movement of lysosomes toward the plus ends of microtubules in the peripheral cytoplasm. Interference with BORC or other components of this pathway results in collapse of the lysosomal population into the pericentriolar region. In turn, this causes reduced cell spreading and migration, highlighting the importance of BORC-dependent centrifugal transport for non-degradative functions of lysosomes. C1 [Pu, Jing; Schindler, Christina; Jia, Rui; Jarnik, Michal; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Backlund, Peter] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biomed Mass Spectrometry Facil, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM bonifacinoj@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 FU Intramural Program of NICHD, NIH [ZIA HD001607] FX We thank X. Zhu and N. Tsai for expert technical assistance; E. Dell'Angelica, J. Brumell, and S. Meresse for the kind gifts of reagents; X. Ren, S.Y. Park, and M. Machner for help with some experimental procedures; and D. Gershlick and R. Mattera for critical comments on the manuscript. This work was funded by the Intramural Program of NICHD, NIH (ZIA HD001607). NR 42 TC 34 Z9 35 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD APR 20 PY 2015 VL 33 IS 2 BP 176 EP 188 DI 10.1016/j.devcel.2015.02.011 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CG5RS UT WOS:000353352300008 PM 25898167 ER PT J AU Lo, IC Gupta, V Midde, KK Taupin, V Lopez-Sanchez, I Kufareva, I Abagyan, R Randazzo, PA Farquhar, MG Ghosh, P AF Lo, I-Chung Gupta, Vijay Midde, Krishna K. Taupin, Vanessa Lopez-Sanchez, Inmaculada Kufareva, Irina Abagyan, Ruben Randazzo, Paul A. Farquhar, Marilyn G. Ghosh, Pradipta TI Activation of G alpha i at the Golgi by GIV/Girdin Imposes Finiteness in Arf1 Signaling SO DEVELOPMENTAL CELL LA English DT Article ID HETEROTRIMERIC G-PROTEINS; COPI-COATED VESICLES; TRIMERIC G-PROTEIN; ENDOPLASMIC-RETICULUM; LIVING CELLS; BETA-COP; TRANSPORT; MEMBRANES; BINDING; RECEPTOR AB A long-held tenet of heterotrimeric G protein signal transduction is that it is triggered by G protein-coupled receptors (GPCRs) at the PM. Here, we demonstrate that Gi is activated in the Golgi by GIV/Girdin, a non-receptor guanine-nucleotide exchange factor (GEF). GIV-dependent activation of Gi at the Golgi maintains the finiteness of the cyclical activation of ADP-ribosylation factor 1 (Arf1), a fundamental step in vesicle traffic in all eukaryotes. Several interactions with other major components of Golgi trafficking-e.g., active Arf1, its regulator, ArfGAP2/3, and the adaptor protein beta-COP-enable GIV to coordinately regulate Arf1 signaling. When the GIV-G alpha i pathway is selectively inhibited, levels of GTP-bound Arf1 are elevated and protein transport along the secretory pathway is delayed. These findings define a paradigm in non-canonical G protein signaling at the Golgi, which places GIV-GEF at the crossroads between signals gated by the trimeric G proteins and the Arf family of monomeric GTPases. C1 [Lo, I-Chung; Gupta, Vijay; Taupin, Vanessa; Farquhar, Marilyn G.] Univ Calif San Diego, Dept Cellular Med, La Jolla, CA 92093 USA. [Lo, I-Chung; Gupta, Vijay; Taupin, Vanessa; Farquhar, Marilyn G.] Univ Calif San Diego, Dept Mol Med, La Jolla, CA 92093 USA. [Midde, Krishna K.; Lopez-Sanchez, Inmaculada; Ghosh, Pradipta] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Kufareva, Irina; Abagyan, Ruben] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Randazzo, Paul A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA. RP Farquhar, MG (reprint author), Univ Calif San Diego, Dept Cellular Med, La Jolla, CA 92093 USA. EM mfarquhar@ucsd.edu; prghosh@ucsd.edu RI gupta, vijay/O-5007-2016 FU NIH [CA100768, CA160911, R01 GM071872, U01 GM094612, U54 GM094618]; Intramural Program of the NIH [BC 007365]; National Science Council of Taiwan [NSC 100-2917-1-564-032]; American Heart Association (AHA) [14POST20050025] FX We thank Gordon Gill, Peter Novick (UCSD), and Deepali Bhandari (CSULB) for helpful comments and Ruibai Luo (NIH/NCI) for technical support. This work was supported by NIH grants CA100768 to M.G.F. and CA160911 to P.G. P.A.R. was supported by the Intramural Program of the NIH (Project #BC 007365) and I.K. and R.A. by NIH (R01 GM071872, U01 GM094612, and U54 GM094618). I.-C.L. was supported in part by a Fellowship (NSC 100-2917-1-564-032) from the National Science Council of Taiwan and I.L.-S. by the American Heart Association (AHA #14POST20050025). R.A. is a cofounder and shareholder at Molsoft LLC. NR 49 TC 8 Z9 8 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD APR 20 PY 2015 VL 33 IS 2 BP 189 EP 203 DI 10.1016/j.devcel.2015.02.009 PG 15 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CG5RS UT WOS:000353352300009 PM 25865347 ER PT J AU Brinkworth, AJ Hammer, CH Olano, LR Kobayashi, SD Chen, L Kreiswirth, BN Deleo, FR AF Brinkworth, Amanda J. Hammer, Carl H. Olano, L. Renee Kobayashi, Scott D. Chen, Liang Kreiswirth, Barry N. DeLeo, Frank R. TI Identification of Outer Membrane and Exoproteins of Carbapenem-Resistant Multilocus Sequence Type 258 Klebsiella pneumoniae SO PLOS ONE LA English DT Article ID LACTAMASE-PRODUCING ENTEROBACTERIACEAE; IRON-ACQUISITION-SYSTEMS; BETA-LACTAMASE; ESCHERICHIA-COLI; UNITED-STATES; PROTEIN; INFECTIONS; IMPACT; COMBINATION; EPIDEMIOLOGY AB Carbapenem-resistant Klebsiella pneumoniae strains have emerged as a cause of life-threatening infections in susceptible individuals (e.g., transplant recipients and critically ill patients). Strains classified as multilocus sequence type (ST) 258 are among the most prominent causes of carbapenem-resistant K. pneumoniae infections worldwide, but the basis for the success of this lineage remains incompletely determined. To gain a more comprehensive view of the molecules potentially involved in the success of ST258, we used a proteomics approach to identify surface-associated and culture supernatant proteins produced by ST258. Protein samples were prepared from varied culture conditions in vitro, and were analyzed by a combination of two-dimensional electrophoresis and liquid chromatography followed by tandem mass spectrometry (LC-MS/MS). We identified a total of 193 proteins in outer membrane preparations from bacteria cultured in Luria-Bertani broth (LB) or RPMI 1640 tissue culture media (RPMI). Compared with LB, several iron-acquisition proteins, including IutA, HmuR, HmuS, CirA, FepA, FitA, FoxA, FhuD, and YfeX, were more highly expressed in RPMI. Of the 177 proteins identified in spent media, only the fimbrial subunit, MrkA, was predicted to be extracellular, a finding that suggests few proteins (or a limited quantity) are freely secreted by ST258. Notably, we discovered 203 proteins not reported in previous K. pneumoniaeproteome studies. In silico modeling of proteins with unknown function revealed several proteins with beta-barrel transmembrane structures typical of porins, as well as possible host-interacting proteins. Taken together, these findings contribute several new targets for the mechanistic study of drug-resistance and pathogenesis by ST258 K. pneumoniaeisolates. C1 [Brinkworth, Amanda J.; Kobayashi, Scott D.; DeLeo, Frank R.] NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogens, NIH, Hamilton, MT 59840 USA. [Hammer, Carl H.; Olano, L. Renee] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. [Chen, Liang; Kreiswirth, Barry N.] Rutgers State Univ, New Jersey Med Sch, Publ Hlth Res Inst TB Ctr, Newark, NJ 07102 USA. RP Deleo, FR (reprint author), NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogens, NIH, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This research was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 47 TC 2 Z9 2 U1 3 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 20 PY 2015 VL 10 IS 4 AR e0123219 DI 10.1371/journal.pone.0123219 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG3XA UT WOS:000353211700029 PM 25893665 ER PT J AU Hiyoshi, Y Schetter, AJ Okayama, H Inamura, K Anami, K Nguyen, GH Horikawa, I Hawkes, JE Bowman, ED Leung, SY Harris, CC AF Hiyoshi, Yukiharu Schetter, Aaron J. Okayama, Hirokazu Inamura, Kentaro Anami, Katsuhiro Nguyen, Giang H. Horikawa, Izumi Hawkes, Jason E. Bowman, Elise D. Leung, Suet Yi Harris, Curtis C. TI Increased MicroRNA-34b and-34c Predominantly Expressed in Stromal Tissues Is Associated with Poor Prognosis in Human Colon Cancer SO PLOS ONE LA English DT Article ID COLORECTAL-CANCER; MIR-34A; APOPTOSIS; CELLS; IDENTIFICATION; METHYLATION; SURVIVAL; TARGETS; MIRNAS; LOOP AB The microRNA-34 family (miR-34a, -34b and -34c) have been reported to be tumor suppressor microRNAs (miRNAs) that are regulated by the TP53 and DNA hypermethylation. However, the expression, regulation, and prognostic value of the miR-34 family have not been systematically studied in colon cancer. To elucidate the roles of miR-34 family in colon carcinogenesis, miR-34a/b/c were measured in tumors and adjacent noncancerous tissues from 159 American and 113 Chinese colon cancer patients using quantitative RT-PCR, and we examined associations between miR-34a/b/c expression with TNM staging, cancer-specific mortality, TP53 mutation status and Affymetrix microarray data. All miR-34 family members were significantly increased in colon tumors, counter to the proposed tumor suppressor role for these miRNAs. Increased miR-34b/c were observed in more advanced tumors in two independent cohorts and increased expression of miR-34b/c was associated with poor cancer-specific mortality. While the expression of miR-34 family was not associated with TP53 mutation status, TP53 transcriptional activity was associated with miR-34a/b/c expression that is consistent with the proposed regulation of miR-34a/b/c by TP53. To examine where the miR-34 family is expressed, the expression of miR-34 family was compared between epitheliums and stromal tissues using laser microdissection technique. The expression of miR-34b/c was increased significantly in stromal tissues, especially in cancer stroma, compared with epithelial tissue. In conclusion, increased miR-34b/c predominantly expressed in stromal tissues is associated with poor prognosis in colon cancer. MiR-34 may contribute to cancer-stromal interaction associated with colon cancer progression. C1 [Hiyoshi, Yukiharu; Schetter, Aaron J.; Okayama, Hirokazu; Inamura, Kentaro; Anami, Katsuhiro; Nguyen, Giang H.; Horikawa, Izumi; Hawkes, Jason E.; Bowman, Elise D.; Leung, Suet Yi; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov RI Leung, Suet Yi/C-4340-2009; OI Hawkes, Jason E./0000-0001-5870-181X NR 38 TC 6 Z9 6 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 20 PY 2015 VL 10 IS 4 AR UNSP e0124899 DI 10.1371/journal.pone.0124899 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG3XA UT WOS:000353211700128 PM 25894979 ER PT J AU Ish-Am, O Kristensen, DM Ruppin, E AF Ish-Am, Oren Kristensen, David M. Ruppin, Eytan TI Evolutionary Conservation of Bacterial Essential Metabolic Genes across All Bacterial Culture Media SO PLOS ONE LA English DT Article ID PROTEIN DISPENSABILITY; NONESSENTIAL GENES; GLOBAL-NETWORK; OPTIMIZATION; PROKARYOTES; DATABASE; GENOMES; MODELS AB One of the basic postulates of molecular evolution is that functionally important genes should evolve slower than genes of lesser significance. Essential genes, whose knockout leads to a lethal phenotype are considered of high functional importance, yet whether they are truly more conserved than nonessential genes has been the topic of much debate, fuelled by a host of contradictory findings. Here we conduct the first large-scale study utilizing genome-scale metabolic modeling and spanning many bacterial species, which aims to answer this question. Using the novel Media Variation Analysis, we examine the range of conservation of essential vs. nonessential metabolic genes in a given species across all possible media. We are thus able to obtain for the first time, exact upper and lower bounds on the levels of differential conservation of essential genes for each of the species studied. The results show that bacteria do exhibit an overall tendency for differential conservation of their essential genes vs. their non-essential ones, yet this tendency is highly variable across species. We show that the model bacterium E. coli K12 may or may not exhibit differential conservation of essential genes depending on its growth medium, shedding light on previous experimental studies showing opposite trends. C1 [Ish-Am, Oren; Ruppin, Eytan] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Kristensen, David M.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Ruppin, Eytan] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Ruppin, Eytan] Univ Maryland, Dept Comp Sci, College Pk, MD USA. [Ruppin, Eytan] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD USA. RP Ruppin, E (reprint author), Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM ishamor@gmail.com; eyruppin@gmail.com FU MICROME project; INFECT FP7 EU project; I-CORE Program of the Planning and Budgeting Committee; Israel Science Foundation [41/11] FX This work was supported by grants from the MICROME and the INFECT FP7 EU projects, the I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (grant No 41/11), supporting ER's research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 4 Z9 4 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 20 PY 2015 VL 10 IS 4 AR e0123785 DI 10.1371/journal.pone.0123785 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG3XA UT WOS:000353211700057 PM 25894004 ER PT J AU Ravenell, J Leighton-Herrmann, E Abel-Bey, A DeSorbo, A Teresi, J Valdez, L Gordillo, M Gerin, W Hecht, M Ramirez, M Noble, J Cohn, E Jean-Louis, G Spruill, T Waddy, S Ogedegbe, G Williams, O AF Ravenell, Joseph Leighton-Herrmann, Ellyn Abel-Bey, Amparo DeSorbo, Alexandra Teresi, Jeanne Valdez, Lenfis Gordillo, Madeleine Gerin, William Hecht, Michael Ramirez, Mildred Noble, James Cohn, Elizabeth Jean-Louis, Giardin Spruill, Tanya Waddy, Salina Ogedegbe, Gbenga Williams, Olajide TI Tailored approaches to stroke health education (TASHE): study protocol for a randomized controlled trial SO TRIALS LA English DT Article DE Stroke; Community-based research; Narrative persuasion; Health disparities; Randomized trial; Stroke health education; Stroke action test ID TISSUE-PLASMINOGEN ACTIVATOR; AFRICAN-AMERICAN WOMEN; PHYSICAL-ACTIVITY INTERVENTION; ACUTE ISCHEMIC-STROKE; HIGH-RISK COMMUNITY; HIP-HOP STROKE; ENTERTAINMENT-EDUCATION; ETHNIC DISPARITIES; PUBLIC RECOGNITION; BEHAVIOR-CHANGE AB Background: Stroke is a leading cause of adult disability and mortality. Intravenous thrombolysis can minimize disability when patients present to the emergency department for treatment within the 3 - 41/2 h of symptom onset. Blacks and Hispanics are more likely to die and suffer disability from stroke than whites, due in part to delayed hospital arrival and ineligibility for intravenous thrombolysis for acute stroke. Low stroke literacy (poor knowledge of stroke symptoms and when to call 911) among Blacks and Hispanics compared to whites may contribute to disparities in acute stroke treatment and outcomes. Improving stroke literacy may be a critical step along the pathway to reducing stroke disparities. The aim of the current study is to test a novel intervention to increase stroke literacy in minority populations in New York City. Design and Methods: In a two-arm cluster randomized trial, we will evaluate the effectiveness of two culturally tailored stroke education films - one in English and one in Spanish - on changing behavioral intent to call 911 for suspected stroke, compared to usual care. These films will target knowledge of stroke symptoms, the range of severity of symptoms and the therapeutic benefit of calling 911, as well as address barriers to timely presentation to the hospital. Given the success of previous church-based programs targeting behavior change in minority populations, this trial will be conducted with 250 congregants across 14 churches (125 intervention; 125 control). Our proposed outcomes are (1) recognition of stroke symptoms and (2) behavioral intent to call 911 for suspected stroke, measured using the Stroke Action Test at the 6-month and 1-year follow-up. Discussion: This is the first randomized trial of a church-placed narrative intervention to improve stroke outcomes in urban Black and Hispanic populations. A film intervention has the potential to make a significant public health impact, as film is a highly scalable and disseminable medium. Since there is at least one church in almost every neighborhood in the USA, churches have the ability and reach to play an important role in the dissemination and translation of stroke prevention programs in minority communities. C1 [Ravenell, Joseph; Jean-Louis, Giardin; Spruill, Tanya; Ogedegbe, Gbenga] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Leighton-Herrmann, Ellyn; Abel-Bey, Amparo; DeSorbo, Alexandra; Valdez, Lenfis; Gordillo, Madeleine; Noble, James; Williams, Olajide] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. [Teresi, Jeanne; Ramirez, Mildred] Hebrew Home Riverdale, Div Res, Bronx, NY 10471 USA. [Gerin, William; Hecht, Michael] Penn State Univ, University Pk, PA 16802 USA. [Cohn, Elizabeth] Adelphi Univ, Ctr Hlth Innovat, Garden City, NY 11530 USA. [Waddy, Salina] NINDS, NIH, North Bethesda, MD 20852 USA. RP Leighton-Herrmann, E (reprint author), Columbia Univ, Med Ctr, Dept Neurol, 710 W 168th St, New York, NY 10032 USA. EM el2766@columbia.edu RI Vila, Vanessa/B-4982-2014; OI Spruill, Tanya/0000-0003-2998-3007 FU National Institute of Neurological Disorders and Stroke [U54 NS081765] FX This study is supported by the National Institute of Neurological Disorders and Stroke (U54 NS081765). We have permission to use the educational film materials presented in this protocol. They were specifically developed for use in this study. NR 62 TC 1 Z9 1 U1 2 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD APR 19 PY 2015 VL 16 AR 176 DI 10.1186/s13063-015-0703-4 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CH0AH UT WOS:000353680700001 PM 25927452 ER PT J AU Ren, G Cui, KR Zhang, ZY Zhao, KJ AF Ren, Gang Cui, Kairong Zhang, Zhiying Zhao, Keji TI Division of labor between IRF1 and IRF2 in regulating different stages of transcriptional activation in cellular antiviral activities SO CELL AND BIOSCIENCE LA English DT Article DE IRF1; IRF2; BRG1; ChIP; Transcription; Antiviral activities ID TOLL-LIKE RECEPTOR-3; BAF COMPLEX; GENES; CELLS; INDUCTION; IFN; FAMILY; COACTIVATOR; EXPRESSION; PROMOTER AB Background: Cellular antiviral activities are critically controlled by transcriptional activation of interferon-inducible genes, involving interferon regulatory factors (IRFs). Previous data suggested that IRF1 is an activator and IRF2 is a repressor, which functionally antagonize each other in transcriptional regulation. However, it is not clear how these two factors function to regulate cellular antiviral activities. Results: We show that IRF2 is critically required for the induction of the TLR3 and other interferon-inducible genes in a chromatin environment. While both IRF1 and IRF2 directly interact with the BAF chromatin remodeling complex, IRF2 is associated with the TLR3 promoter in the unstimulated state and IRF1 binding to the promoter is strongly induced by stimulation with interferon, suggesting that these two factors may function at different stages of gene induction in the recruitment of the BAF complex. IRF2 acts to maintain the basal level expression, an open chromatin structure, and active histone modification marks (H3K9, K14 acetylation and H3K4 tri-methylation) of the TLR3 promoter in the unstimulated state, while IRF1 serves to rapidly activate the promoter upon stimulation. Conclusions: IRF1 and IRF2 of the IRF family of transcription factors play distinct roles in cellular response to viral infection. IRF2 binds to TLR3 and other IFN-inducible gene promoters and maintains an active chromatin structure in the unstimulated state, which is required for their induction, while IRF1 binding to these promoters activates their transcription upon viral infection. Thus, the division of labor between the IRF transcription factor family members plays a pivotal role in coordinating the transcriptional activation in the cellular antiviral response. C1 [Ren, Gang; Zhang, Zhiying] Northwest A&F Univ, Coll Anim Sci & Technol, Yangling 712100, Shaanxi, Peoples R China. [Ren, Gang; Cui, Kairong; Zhao, Keji] NHLBI, Syst Biol Ctr, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Zhang, ZY (reprint author), Northwest A&F Univ, Coll Anim Sci & Technol, Yangling 712100, Shaanxi, Peoples R China. EM zhangzhy@nwsuaf.edu.cn; zhaok@nhlbi.nih.gov OI Zhang, Zhiying/0000-0001-6012-0889 FU Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health; China State Scholarship Fund FX This work was supported by Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health. G.R. was supported by a Ph.D. Student Fellowship from the China State Scholarship Fund (2012-2014). NR 28 TC 5 Z9 6 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2045-3701 J9 CELL BIOSCI JI Cell Biosci. PD APR 18 PY 2015 VL 5 AR 17 DI 10.1186/s13578-015-0007-0 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CH5FR UT WOS:000354061200001 PM 25960866 ER PT J AU Kibuuka, H Berkowitz, NM Millard, M Enama, ME Tindikahwa, A Sekiziyivu, AB Costner, P Sitar, S Glover, D Hu, ZH Joshi, G Stanley, D Kunchai, M Eller, LA Bailer, RT Koup, RA Nabel, GJ Mascola, JR Sullivan, NJ Graham, BS Roederer, M Michael, NL Robb, ML Ledgerwood, JE AF Kibuuka, Hannah Berkowitz, Nina M. Millard, Monica Enama, Mary E. Tindikahwa, Allan Sekiziyivu, Arthur B. Costner, Pamela Sitar, Sandra Glover, Deline Hu, Zonghui Joshi, Gyan Stanley, Daphne Kunchai, Meghan Eller, Leigh Anne Bailer, Robert T. Koup, Richard A. Nabel, Gary J. Mascola, John R. Sullivan, Nancy J. Graham, Barney S. Roederer, Mario Michael, Nelson L. Robb, Merlin L. Ledgerwood, Julie E. CA RV 247 Study Team TI Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial SO LANCET LA English DT Article ID NONHUMAN-PRIMATES; NEUTROPENIA; VACCINATION; INFECTION; FEVER AB Background Ebola virus and Marburg virus cause serious disease outbreaks with high case fatality rates. We aimed to assess the safety and immunogenicity of two investigational DNA vaccines, one (EBO vaccine) encoding Ebola virus Zaire and Sudan glycoproteins and one (MAR) encoding Marburg virus glycoprotein. Methods RV 247 was a phase 1b, double-blinded, randomised, placebo-controlled clinical trial in Kampala, Uganda to examine the safety and immunogenicity of the EBO and MAR vaccines given individually and concomitantly. Healthy adult volunteers aged 18-50 years were randomly assigned (5: 1) to receive three injections of vaccine or placebo at weeks 0, 4, and 8, with vaccine allocations divided equally between three active vaccine groups: EBO vaccine only, MAR vaccine only, and both vaccines. The primary study objective was to investigate the safety and tolerability of the vaccines, as assessed by local and systemic reactogenicity and adverse events. We also assessed immunogenicity on the basis of antibody responses (ELISA) and T-cell responses (ELISpot and intracellular cytokine staining assays) 4 weeks after the third injection. Participants and investigators were masked to group assignment. Analysis was based on the intention-to-treat principle. This trial is registered at ClinicalTrials.gov, number NCT00997607. Findings 108 participants were enrolled into the study between Nov 2, 2009, and April 15, 2010. All 108 participants received at least one study injection (including 100 who completed the injection schedule) and were included in safety and tolerability analyses; 107 for whom data were available were included in the immunogenicity analyses. Study injections were well tolerated, with no significant differences in local or systemic reactions between groups. The vaccines elicited antibody and T-cell responses specific to the glycoproteins received and we detected no differences between the separate and concomitant use of the two vaccines. 17 of 30 (57%, 95% CI 37-75) participants in the EBO vaccine group had an antibody response to the Ebola Zaire glycoprotein, as did 14 of 30 (47%, 28-66) in the group that received both vaccines. 15 of 30 (50%, 31-69) participants in the EBO vaccine group had an antibody response to the Ebola Sudan glycoprotein, as did 15 of 30 (50%, 31-69) in the group that received both vaccines. Nine of 29 (31%, 15-51) participants in the MAR vaccine groups had an antibody response to the Marburg glycoprotein, as did seven of 30 (23%, 10-42) in the group that received both vaccines. 19 of 30 (63%, 44-80) participants in the EBO vaccine group had a T-cell response to the Ebola Zaire glycoprotein, as did 10 of 30 (33%, 17-53) in the group that received both vaccines. 13 of 30 (43%, 25-63) participants in the EBO vaccine group had a T-cell response to the Ebola Sudan glycoprotein, as did 10 of 30 (33%, 17-53) in the group that received both vaccines. 15 of 29 (52%, 33-71) participants in the MAR vaccine group had a T-cell response to the Marburg glycoprotein, as did 13 of 30 (43%, 25-63) in the group that received both vaccines. Interpretation This study is the first Ebola or Marburg vaccine trial done in Africa, and the results show that, given separately or together, both vaccines were well tolerated and elicited antigen-specific humoral and cellular immune responses. These findings have contributed to the accelerated development of more potent Ebola virus vaccines that encode the same wild-type glycoprotein antigens as the EBO vaccine, which are being assessed during the 2014 Ebola virus disease outbreak in west Africa. C1 [Kibuuka, Hannah; Millard, Monica; Tindikahwa, Allan; Sekiziyivu, Arthur B.] Makerere Univ, Walter Reed Project, Kampala, Uganda. [Berkowitz, Nina M.; Enama, Mary E.; Costner, Pamela; Sitar, Sandra; Stanley, Daphne; Bailer, Robert T.; Koup, Richard A.; Nabel, Gary J.; Mascola, John R.; Sullivan, Nancy J.; Graham, Barney S.; Roederer, Mario; Ledgerwood, Julie E.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hu, Zonghui] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Glover, Deline; Eller, Leigh Anne; Michael, Nelson L.; Robb, Merlin L.] US Mil HIV Res Program, Bethesda, MD USA. [Joshi, Gyan] Frederick Natl Lab Canc Res, Clin Monitoring Res Program, Leidos Biomed Res, Frederick, MD USA. [Kunchai, Meghan] EMMES Corp, Rockville, MD USA. [Nabel, Gary J.] Sanofi, Cambridge, MA USA. [Michael, Nelson L.] Walter Reed Army Inst Res, Silver Spring, MD USA. RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Ledgerwood@mail.nih.gov FU US Department of Defense Infectious Disease Clinical Research Program; US National Institutes of Health Intramural Research Program FX US Department of Defense Infectious Disease Clinical Research Program and US National Institutes of Health Intramural Research Program. NR 33 TC 22 Z9 24 U1 3 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 18 PY 2015 VL 385 IS 9977 BP 1545 EP 1554 DI 10.1016/S0140-6736(14)62385-0 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CG3ZT UT WOS:000353220000036 PM 25540891 ER PT J AU Mitra, A Luo, J He, YH Gu, YL Zhang, HM Zhao, KJ Cui, KR Song, JZ AF Mitra, Apratim Luo, Juan He, Yanghua Gu, Yulan Zhang, Huanmin Zhao, Keji Cui, Kairong Song, Jiuzhou TI Histone modifications induced by MDV infection at early cytolytic and latency phases SO BMC GENOMICS LA English DT Article ID MAREKS-DISEASE VIRUS; TUMOR-SUPPRESSOR GENE; UBIQUITIN-MEDIATED PROTEOLYSIS; CELL-PROLIFERATION; COLORECTAL-CANCER; SIGNALING PATHWAYS; NERVOUS-SYSTEM; HOST RESPONSES; EXPRESSION; KINASE AB Background: Marek's disease (MD) is a highly contagious, lymphomatous disease of chickens induced by a herpesvirus, Marek's disease virus (MDV) that is the cause of major annual losses to the poultry industry. MD pathogenesis involves multiple stages including an early cytolytic phase and latency, and transitions between these stages are governed by several host and environmental factors. The success of vaccination strategies has led to the increased virulence of MDV and selective breeding of naturally resistant chickens is seen as a viable alternative. While multiple gene expression studies have been performed in resistant and susceptible populations, little is known about the epigenetic effects of infection. Results: In this study, we investigated temporal chromatin signatures induced by MDV by analyzing early cytolytic and latent phases of infection in the bursa of Fabricius of MD-resistant and -susceptible birds. Major global variations in chromatin marks were observed at different stages of MD in the two lines. Differential H3K27me3 marks were associated with immune-related pathways, such as MAP kinase signaling, focal adhesion and neuroactive ligand receptor interaction, and suggested varying degrees of silencing in response to infection. Immune-related microRNAs, e.g. gga-miR-155 and gga-miR-10b, bore chromatin signatures, which suggested their contribution to MD-susceptibility. Finally, several members of the focal adhesion pathway, e.g. THBS4 and ITGA1, showed marked concordance between gene expression and chromatin marks indicating putative epigenetic regulation in response to MDV infection. Conclusion: Our comprehensive analysis of chromatin signatures, therefore, revealed further clues about the epigenetic effects of MDV infection although further studies are necessary to elucidate the functional implications of the observed variations in histone modifications. C1 [Mitra, Apratim; Luo, Juan; He, Yanghua; Song, Jiuzhou] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Zhang, Huanmin] USDA ARS, Avian Dis & Oncol Lab, E Lansing, MI 48823 USA. [Zhao, Keji; Cui, Kairong] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Gu, Yulan] China Agr Univ, Coll Anim Sci, Dept Anim Breeding & Genet, Beijing 100193, Peoples R China. RP Song, JZ (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. EM songj88@umd.edu FU National Research Initiative Competitive Grant [USDA-NRI/NIFA 2008-35204-04660]; USDA National Institute of Food and Agriculture [USDA-NRI/NIFA 2010-65205-20588] FX The authors would like to thank Fei Zhan for assistance in RNA-Seq analysis and Jose Carrillo and Ding Yi for helpful discussions. This project was supported by National Research Initiative Competitive Grant no. USDA-NRI/NIFA 2008-35204-04660 and USDA-NRI/NIFA 2010-65205-20588 from the USDA National Institute of Food and Agriculture. NR 51 TC 0 Z9 0 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD APR 18 PY 2015 VL 16 AR 311 DI 10.1186/s12864-015-1492-6 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CG2LS UT WOS:000353106800001 PM 25896894 ER PT J AU Kawel-Boehm, N Maceira, A Valsangiacomo-Buechel, ER Vogel-Claussen, J Turkbey, EB Williams, R Plein, S Tee, M Eng, J Bluemke, DA AF Kawel-Boehm, Nadine Maceira, Alicia Valsangiacomo-Buechel, Emanuela R. Vogel-Claussen, Jens Turkbey, Evrim B. Williams, Rupert Plein, Sven Tee, Michael Eng, John Bluemke, David A. TI Normal values for cardiovascular magnetic resonance in adults and children SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Review DE Normal values; Reference values; Cardiovascular magnetic resonance ID STATE FREE-PRECESSION; EXTRACELLULAR VOLUME FRACTION; DIFFUSE MYOCARDIAL FIBROSIS; LEFT ATRIAL DIMENSIONS; LEFT-VENTRICULAR MASS; PHASE-CONTRAST MRI; AORTIC-VALVE STENOSIS; PULSE-WAVE VELOCITY; AGE-RELATED-CHANGES; DIASTOLIC FUNCTION AB Morphological and functional parameters such as chamber size and function, aortic diameters and distensibility, flow and T1 and T2* relaxation time can be assessed and quantified by cardiovascular magnetic resonance (CMR). Knowledge of normal values for quantitative CMR is crucial to interpretation of results and to distinguish normal from disease. In this review, we present normal reference values for morphological and functional CMR parameters of the cardiovascular system based on the peer-reviewed literature and current CMR techniques and sequences. C1 [Kawel-Boehm, Nadine] Kantonsspital Graubuenden, Dept Radiol, CH-7000 Chur, Switzerland. [Maceira, Alicia] Eresa Med Ctr, Cardiac Imaging Unit, Valencia 46015, Spain. [Valsangiacomo-Buechel, Emanuela R.] Univ Childrens Hosp Zurich, Div Paediat Cardiol, CH-8032 Zurich, Switzerland. [Vogel-Claussen, Jens] Hannover Med Sch, Dept Diagnost & Intervent Radiol, D-30625 Hannover, Germany. [Turkbey, Evrim B.] NIH, Radiol & Imaging Sci Clin Image Proc Serv, Ctr Clin, Bethesda, MD 20892 USA. [Williams, Rupert] Kings Coll London, St Thomas Hosp, Rayne Inst, London SE1 7EH, England. [Plein, Sven] Univ Leeds, Multidisciplinary Cardiovasc Res Ctr, Leeds LS2 9JT, W Yorkshire, England. [Plein, Sven] Univ Leeds, Leeds Inst Cardiovasc & Metab Med, LIGHT Labs, Leeds LS2 9JT, W Yorkshire, England. [Tee, Michael; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Eng, John] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. RP Bluemke, DA (reprint author), Natl Inst Biomed Imaging & Bioengn, Radiol & Imaging Sci, 10 Ctr Dr, Bethesda, MD 20892 USA. EM bluemked@nih.gov OI Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health Intramural research program FX This work was funded in part by the National Institutes of Health Intramural research program. NR 104 TC 45 Z9 45 U1 2 U2 12 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 APR 18 PY 2015 VL 17 AR 29 DI 10.1186/s12968-015-0111-7 PG 33 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CG2MT UT WOS:000353109500001 PM 25928314 ER PT J AU Sanchez-Vega, F Gotea, V Margolin, G Elnitski, L AF Sanchez-Vega, Francisco Gotea, Valer Margolin, Gennady Elnitski, Laura TI Pan-cancer stratification of solid human epithelial tumors and cancer cell lines reveals commonalities and tissue-specific features of the CpG island methylator phenotype SO EPIGENETICS & CHROMATIN LA English DT Article DE Cancer; DNA methylation; CpG island methylator phenotype; CIMP; TCGA; ENCODE; Pan-cancer ID COMPREHENSIVE MOLECULAR CHARACTERIZATION; DNA METHYLATION; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; GENE-EXPRESSION; BREAST-CANCER; HUMAN-DISEASE; CARCINOMA; PATTERNS; MUTATIONS AB Background: The term CpG island methylator phenotype (CIMP) has been used to describe widespread DNA hypermethylation at CpG-rich genomic regions affecting clinically distinct subsets of cancer patients. Even though there have been numerous studies of CIMP in individual cancer types, a uniform analysis across tissues is still lacking. Results: We analyze genome-wide patterns of CpG island hypermethylation in 5,253 solid epithelial tumors from 15 cancer types from TCGA and 23 cancer cell lines from ENCODE. We identify differentially methylated loci that define CIMP+ and CIMP- samples, and we use unsupervised clustering to provide a robust molecular stratification of tumor methylomes for 12 cancer types and all cancer cell lines. With a minimal set of 89 discriminative loci, we demonstrate accurate pan-cancer separation of the 12 CIMP+/- subpopulations, based on their average levels of methylation. Tumor samples in different CIMP subclasses show distinctive correlations with gene expression profiles and recurrence of somatic mutations, copy number variations, and epigenetic silencing. Enrichment analyses indicate shared canonical pathways and upstream regulators for CIMP-targeted regions across cancer types. Furthermore, genomic alterations showing consistent associations with CIMP+/- status include genes involved in DNA repair, chromatin remodeling genes, and several histone methyltransferases. Associations of CIMP status with specific clinical features, including overall survival in several cancer types, highlight the importance of the CIMP+/- designation for individual tumor evaluation and personalized medicine. Conclusions: We present a comprehensive computational study of CIMP that reveals pan-cancer commonalities and tissue-specific differences underlying concurrent hypermethylation of CpG islands across tumors. Our stratification of solid tumors and cancer cell lines based on CIMP status is data-driven and agnostic to tumor type by design, which protects against known biases that have hindered classic methods previously used to define CIMP. The results that we provide can be used to refine existing molecular subtypes of cancer into more homogeneously behaving subgroups, potentially leading to more uniform responses in clinical trials. C1 [Sanchez-Vega, Francisco; Gotea, Valer; Margolin, Gennady; Elnitski, Laura] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA. RP Elnitski, L (reprint author), NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA. EM elnitski@mail.nih.gov OI Gotea, Valer/0000-0001-7857-3309 FU Intramural Program of the National Human Genome Research Institute, National Institutes of Health FX This work was supported by the Intramural Program of the National Human Genome Research Institute, National Institutes of Health. NR 60 TC 5 Z9 5 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8935 J9 EPIGENET CHROMATIN JI Epigenetics Chromatin PD APR 17 PY 2015 VL 8 AR 14 DI 10.1186/s13072-015-0007-7 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA CH5NE UT WOS:000354081800001 PM 25960768 ER PT J AU Ghosh, A Jana, M Modi, K Gonzalez, FJ Sims, KB Berry-Kravis, E Pahan, K AF Ghosh, Arunava Jana, Malabendu Modi, Khushbu Gonzalez, Frank J. Sims, Katherine B. Berry-Kravis, Elizabeth Pahan, Kalipada TI Activation of Peroxisome Proliferator-activated Receptor alpha Induces Lysosomal Biogenesis in Brain Cells IMPLICATIONS FOR LYSOSOMAL STORAGE DISORDERS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Astrocyte; Lysosomal Storage Disease; Neurodegeneration; Peroxisome proliferator-activated Receptor (PPAR); Retinoic Acid ID RETINOID-X-RECEPTOR; LIPID-LOWERING DRUG; DENSITY-LIPOPROTEIN-CHOLESTEROL; CELLULAR CLEARANCE; GENE-EXPRESSION; ADOPTIVE TRANSFER; MESSENGER-RNAS; UP-REGULATION; GEMFIBROZIL; TFEB AB Lysosomes are ubiquitous membrane-enclosed organelles filled with an acidic interior and are central to the autophagic, endocytic, or phagocytic pathway. In contrast to its classical function as the waste management machinery, lysosomes are now considered to be an integral part of various cellular signaling processes. The diverse functionality of this single organelle requires a very complex and coordinated regulation of its activity with transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, at its core. However, mechanisms by which TFEB is regulated are poorly understood. This study demonstrates that gemfibrozil, an agonist of peroxisome proliferator-activated receptor (PPAR) , alone and in conjunction with all-trans-retinoic acid is capable of enhancing TFEB in brain cells. We also observed that PPAR, but not PPAR and PPAR, is involved in gemfibrozil-mediated up-regulation of TFEB. Reporter assay and chromatin immunoprecipitation studies confirmed the recruitment of retinoid X receptor , PPAR, and PGC1 on the PPAR-binding site on the Tfeb promoter as well. Subsequently, the drug-mediated induction of TFEB caused an increase in lysosomal protein and the lysosomal abundance in cell. Collectively, this study reinforces the link between lysosomal biogenesis and lipid metabolism with TFEB at the crossroads. Furthermore, gemfibrozil may be of therapeutic value in the treatment of lysosomal storage disorders in which autophagy-lysosome pathway plays an important role. C1 [Ghosh, Arunava; Jana, Malabendu; Modi, Khushbu; Pahan, Kalipada] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Berry-Kravis, Elizabeth] Rush Univ, Med Ctr, Dept Pediat Neurol Sci & Biochem, Chicago, IL 60612 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sims, Katherine B.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Pahan, Kalipada] Jesse Brown Vet Affairs Med Ctr, Div Res & Dev, Chicago, IL 60612 USA. RP Pahan, K (reprint author), Rush Univ, Med Ctr, Dept Neurol Sci, 1735 West Harrison St,Ste Cohn 320, Chicago, IL 60612 USA. EM Kalipada_Pahan@rush.edu RI di Ronza, Alberto/H-7674-2016 OI di Ronza, Alberto/0000-0002-9813-5143 FU National Institutes of Health [AT6681, NS083054]; Veteran Affairs [I01BX003033-01]; Noah's Hope, Hope for Bridgett, Cures Within Reach, and Two Hearts Rock FX This work was supported, in whole or in part, by National Institutes of Health Grants AT6681 and NS083054. This work was also supported by Merit Award I01BX003033-01 from Veteran Affairs and funds from Noah's Hope, Hope for Bridgett, Cures Within Reach, and Two Hearts Rock. NR 69 TC 10 Z9 10 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 17 PY 2015 VL 290 IS 16 BP 10309 EP 10324 DI 10.1074/jbc.M114.610659 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CG4FU UT WOS:000353241100034 PM 25750174 ER PT J AU Singh, D Gawel, D Itsko, M Hochkoeppler, A Krahn, JM London, RE Schaaper, RM AF Singh, Deepa Gawel, Damian Itsko, Mark Hochkoeppler, Alejandro Krahn, Juno M. London, Robert E. Schaaper, Roel M. TI Structure of Escherichia coli dGTP Triphosphohydrolase A HEXAMERIC ENZYME WITH DNA EFFECTOR MOLECULES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Allosteric Regulation; Cooperativity; Crystal Structure; DNA-binding Protein; Escherichia coli (E; coli); dGTPase; Mutator Phenotype ID DEOXYGUANOSINE TRIPHOSPHATE TRIPHOSPHOHYDROLASE; RESTRICTION FACTOR SAMHD1; GENE 1.2 PROTEIN; DNTP TRIPHOSPHOHYDROLASE; ALLOSTERIC ACTIVATION; ENTEROCOCCUS-FAECALIS; BACTERIOPHAGE-T7; INHIBITION; INSIGHT; DENSITY AB Background: The Escherichia coli Dgt enzyme hydrolyzes the important DNA building block dGTP, but the cellular role of this activity is still unclear. Results: The enzyme is shown to be a hexameric structure containing regulatory DNA molecules. Conclusion: DNA mediates the regulation of dGTPase activity in the cell. Significance: This is the first demonstration of regulation of dNTPase by DNA. The Escherichia coli dgt gene encodes a dGTP triphosphohydrolase whose detailed role still remains to be determined. Deletion of dgt creates a mutator phenotype, indicating that the dGTPase has a fidelity role, possibly by affecting the cellular dNTP pool. In the present study, we have investigated the structure of the Dgt protein at 3.1- resolution. One of the obtained structures revealed a protein hexamer that contained two molecules of single-stranded DNA. The presence of DNA caused significant conformational changes in the enzyme, including in the catalytic site of the enzyme. Dgt preparations lacking DNA were able to bind single-stranded DNA with high affinity (K-d approximate to 50 nm). DNA binding positively affected the activity of the enzyme: dGTPase activity displayed sigmoidal (cooperative) behavior without DNA but hyperbolic (Michaelis-Menten) kinetics in its presence, consistent with a specific lowering of the apparent K-m for dGTP. A mutant Dgt enzyme was also created containing residue changes in the DNA binding cleft. This mutant enzyme, whereas still active, was incapable of DNA binding and could no longer be stimulated by addition of DNA. We also created an E. coli strain containing the mutant dgt gene on the chromosome replacing the wild-type gene. The mutant also displayed a mutator phenotype. Our results provide insight into the allosteric regulation of the enzyme and support a physiologically important role of DNA binding. C1 [Singh, Deepa; Itsko, Mark; Krahn, Juno M.; London, Robert E.; Schaaper, Roel M.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Gawel, Damian] Ctr Postgrad Med Educ, Dept Biochem & Mol Biol, PL-01813 Warsaw, Poland. [Hochkoeppler, Alejandro] Univ Bologna, Dept Ind Chem, I-40136 Bologna, Italy. RP Schaaper, RM (reprint author), POB 12233, Res Triangle Pk, NC 27709 USA. EM schaaper@niehs.nih.gov FU United States Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX We thank Drs. K. Bebenek and L. Pedersen, NIEHS, for helpful comments on the manuscript. Crystallographic data were collected at the Southeast Regional Collaborative Access Team 22-ID beam line at the Advanced Photon Source, Argonne National Laboratory. Use of the Advanced Photon Source was supported by the United States Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract W-31-109-Eng-38. NR 40 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 17 PY 2015 VL 290 IS 16 BP 10418 EP 10429 DI 10.1074/jbc.M115.636936 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CG4FU UT WOS:000353241100042 PM 25694425 ER PT J AU Brookes, MJ Hall, EL Robson, SE Price, D Palaniyappan, L Liddle, EB Liddle, PF Robinson, SE Morris, PG AF Brookes, Matthew J. Hall, Emma L. Robson, Sian E. Price, Darren Palaniyappan, Lena Liddle, Elizabeth B. Liddle, Peter F. Robinson, Stephen E. Morris, Peter G. TI Complexity Measures in Magnetoencephalography: Measuring "Disorder" in Schizophrenia SO PLOS ONE LA English DT Article ID DIMENSIONAL COMPLEXITY; BRAIN ACTIVITY; EEG; MEG; BEAMFORMER; NONLINEARITY AB This paper details a methodology which, when applied to magnetoencephalography (MEG) data, is capable of measuring the spatio-temporal dynamics of 'disorder' in the human brain. Our method, which is based upon signal entropy, shows that spatially separate brain regions (or networks) generate temporally independent entropy time-courses. These time-courses are modulated by cognitive tasks, with an increase in local neural processing characterised by localised and transient increases in entropy in the neural signal. We explore the relationship between entropy and the more established time-frequency decomposition methods, which elucidate the temporal evolution of neural oscillations. We observe a direct but complex relationship between entropy and oscillatory amplitude, which suggests that these metrics are complementary. Finally, we provide a demonstration of the clinical utility of our method, using it to shed light on aberrant neurophysiological processing in schizophrenia. We demonstrate significantly increased task induced entropy change in patients (compared to controls) in multiple brain regions, including a cingulo-insula network, bilateral insula cortices and a right fronto-parietal network. These findings demonstrate potential clinical utility for our method and support a recent hypothesis that schizophrenia can be characterised by abnormalities in the salience network (a well characterised distributed network comprising bilateral insula and cingulate cortices). C1 [Brookes, Matthew J.; Hall, Emma L.; Robson, Sian E.; Price, Darren; Morris, Peter G.] Univ Nottingham, Sch Phys & Astron, Sir Peter Mansfield Magnet Resonance Ctr, Nottingham NG7 2RD, England. [Palaniyappan, Lena; Liddle, Elizabeth B.; Liddle, Peter F.] Univ Nottingham, Inst Mental Hlth, Nottingham NG7 2RD, England. [Robinson, Stephen E.] NIH, Bethesda, MD 20892 USA. RP Brookes, MJ (reprint author), Univ Nottingham, Sch Phys & Astron, Sir Peter Mansfield Magnet Resonance Ctr, Univ Pk, Nottingham NG7 2RD, England. EM matthew.brookes@nottingham.ac.uk RI Palaniyappan, Lena/L-8911-2016; Liddle, Elizabeth/A-2034-2015; OI Palaniyappan, Lena/0000-0003-1640-7182; Liddle, Elizabeth/0000-0002-9299-094X; Price, Darren/0000-0002-4786-3976; Brookes, Matthew/0000-0002-8687-8185 FU Dr Hadwen Trust; Medical Research Council New Investigator Grant [MR/M006301/1]; Intramural Research Program of the National Institutes of Mental Health; Wellcome Clinical Research Fellowship [WT096002/z/11] FX This study was funded by the Dr Hadwen Trust. The Dr Hadwen Trust for Humane Research (DHT) is the UK leading medical research charity that funds and promotes exclusively human-relevant research that encourages the progress of medicine with the replacement of the use of animals in research. MJB is funded by a Medical Research Council New Investigator Grant (MR/M006301/1). SE Robinson is supported by the Intramural Research Program of the National Institutes of Mental Health. LP was funded by a Wellcome Clinical Research Fellowship (WT096002/z/11). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 7 Z9 7 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 17 PY 2015 VL 10 IS 4 AR e0120991 DI 10.1371/journal.pone.0120991 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1EX UT WOS:000353017000014 PM 25886553 ER PT J AU Crank, MC Gordon, IJ Yamshchikov, GV Sitar, S Hu, ZH Enama, ME Holman, LA Bailer, RT Pearce, MB Koup, RA Mascola, JR Nebel, GJ Tumpey, TM Schwartz, RM Graham, BS Ledgerwood, JE AF Crank, Michelle C. Gordon, Ingelise J. Yamshchikov, Galina V. Sitar, Sandra Hu, Zonghui Enama, Mary E. Holman, LaSonji A. Bailer, Robert T. Pearce, Melissa B. Koup, Richard A. Mascola, John R. Nebel, Gary J. Tumpey, Terrence M. Schwartz, Richard M. Graham, Barney S. Ledgerwood, Julie E. CA VRC 308 Study Team TI Phase 1 Study of Pandemic H1 DNA Vaccine in Healthy Adults SO PLOS ONE LA English DT Article ID I CLINICAL-TRIAL; SEASONAL INFLUENZA VACCINE; NEUTRALIZING ANTIBODY; PROTECTIVE IMMUNITY; CANDIDATE VACCINE; HEPATITIS-B; VIRUS; IMMUNOGENICITY; RESPONSES; HUMANS AB Background A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV). Methods 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry. Results Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine. Conclusions H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics. C1 [Crank, Michelle C.; Gordon, Ingelise J.; Yamshchikov, Galina V.; Sitar, Sandra; Enama, Mary E.; Holman, LaSonji A.; Bailer, Robert T.; Koup, Richard A.; Mascola, John R.; Nebel, Gary J.; Schwartz, Richard M.; Graham, Barney S.; Ledgerwood, Julie E.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hu, Zonghui] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Pearce, Melissa B.; Tumpey, Terrence M.] US Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Ledgerwood@mail.nih.gov FU National Institutes of Health Intramural Research Program FX This research was supported by the National Institutes of Health Intramural Research Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 3 Z9 3 U1 1 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 APR 17 PY 2015 VL 10 IS 4 AR e0123969 DI 10.1371/journal.pone.0123969 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1EX UT WOS:000353017000096 PM 25884189 ER PT J AU Parham, GP Mwanahamuntu, MH Kapambwe, S Muwonge, R Bateman, AC Blevins, M Chibwesha, CJ Pfaendler, KS Mudenda, V Shibemba, AL Chisele, S Mkumba, G Vwalika, B Hicks, ML Vermund, SH Chi, BH Stringer, JSA Sankaranarayanan, R Sahasrabuddhe, VV AF Parham, Groesbeck P. Mwanahamuntu, Mulindi H. Kapambwe, Sharon Muwonge, Richard Bateman, Allen C. Blevins, Meridith Chibwesha, Carla J. Pfaendler, Krista S. Mudenda, Victor Shibemba, Aaron L. Chisele, Samson Mkumba, Gracilia Vwalika, Bellington Hicks, Michael L. Vermund, Sten H. Chi, Benjamin H. Stringer, Jeffrey S. A. Sankaranarayanan, Rengaswamy Sahasrabuddhe, Vikrant V. TI Population-Level Scale-Up of Cervical Cancer Prevention Services in a Low-Resource Setting: Development, Implementation, and Evaluation of the Cervical Cancer Prevention Program in Zambia SO PLOS ONE LA English DT Article ID HIV-INFECTED WOMEN; VISUAL INSPECTION; ACETIC-ACID; MORTALITY; INDIA; CARE AB Background Very few efforts have been undertaken to scale-up low-cost approaches to cervical cancer prevention in low-resource countries. Methods In a public sector cervical cancer prevention program in Zambia, nurses provided visual-inspection with acetic acid (VIA) and cryotherapy in clinics co-housed with HIV/AIDS programs, and referred women with complex lesions for histopathologic evaluation. Low-cost technological adaptations were deployed for improving VIA detection, facilitating expert physician opinion, and ensuring quality assurance. Key process and outcome indicators were derived by analyzing electronic medical records to evaluate program expansion efforts. Findings Between 2006-2013, screening services were expanded from 2 to 12 clinics in Lusaka, the most-populous province in Zambia, through which 102,942 women were screened. The majority (71.7%) were in the target age-range of 25-49 years; 28% were HIV-positive. Out of 101,867 with evaluable data, 20,419 (20%) were VIA positive, of whom 11,508 (56.4%) were treated with cryotherapy, and 8,911 (43.6%) were referred for histopathologic evaluation. Most women (87%, 86,301 of 98,961 evaluable) received same-day services (including 5% undergoing same-visit cryotherapy and 82% screening VIA-negative). The proportion of women with cervical intraepithelial neoplasia grade 2 and worse (CIN2+) among those referred for histopathologic evaluation was 44.1% (1,735/3,938 with histopathology results). Detection rates for CIN2+ and invasive cervical cancer were 17 and 7 per 1,000 women screened, respectively. Women with HIV were more likely to screen positive, to be referred for histopathologic evaluation, and to have cervical precancer and cancer than HIV-negative women. Interpretation We creatively disrupted the 'no screening' status quo prevailing in Zambia and addressed the heavy burden of cervical disease among previously unscreened women by establishing and scaling-up public-sector screening and treatment services at a population level. Key determinants for successful expansion included leveraging HIV/AIDS program investments, and context-specific information technology applications for quality assurance and filling human resource gaps. C1 [Parham, Groesbeck P.; Mwanahamuntu, Mulindi H.; Kapambwe, Sharon; Bateman, Allen C.; Chibwesha, Carla J.; Pfaendler, Krista S.; Chi, Benjamin H.; Stringer, Jeffrey S. A.] Ctr Infect Dis Res Zambia, Lusaka, Zambia. [Parham, Groesbeck P.; Mwanahamuntu, Mulindi H.; Kapambwe, Sharon; Mudenda, Victor; Shibemba, Aaron L.; Chisele, Samson; Mkumba, Gracilia; Vwalika, Bellington] Univ Zambia, Lusaka, Zambia. [Parham, Groesbeck P.; Bateman, Allen C.; Chibwesha, Carla J.; Chi, Benjamin H.; Stringer, Jeffrey S. A.] Univ N Carolina, Chapel Hill, NC USA. [Parham, Groesbeck P.; Muwonge, Richard; Sankaranarayanan, Rengaswamy] Int Agcy Res Canc, F-69372 Lyon, France. [Blevins, Meridith; Vermund, Sten H.; Sahasrabuddhe, Vikrant V.] Vanderbilt Univ, Nashville, TN 37235 USA. [Hicks, Michael L.] Michigan Canc Inst, Pontiac, MI USA. [Sahasrabuddhe, Vikrant V.] NCI, Bethesda, MD 20892 USA. [Pfaendler, Krista S.] Univ Calif Irvine, Irvine, CA USA. RP Parham, GP (reprint author), Ctr Infect Dis Res Zambia, Lusaka, Zambia. EM professorparham@gmail.com RI Muwonge, Richard/P-6375-2015 FU Government of the Republic of Zambia's Ministry of Health; Ministry of Community Development, Mother and Child Health; United States Government through the President's Emergency Plan for AIDS Relief (PEPFAR) program through the United States Centers for Disease Control and Prevention (CDC); United States National Institutes of Health (NIH) [D43CA153784, D43TW001035, R24TW007988] FX The program was supported by funding from the Government of the Republic of Zambia's Ministry of Health and Ministry of Community Development, Mother and Child Health, as well as from the United States Government through the President's Emergency Plan for AIDS Relief (PEPFAR) program through the United States Centers for Disease Control and Prevention (CDC). Support for technical assistance and training for program personnel was received from the United States National Institutes of Health (NIH) grants to the University of North Carolina at Chapel Hill (grant number D43CA153784) and Vanderbilt University (grant numbers D43TW001035 and R24TW007988). Dr. Groesbeck Parham serves as a Senior Visiting Scientist at the International Agency for Research on Cancer (IARC)-World Health Organization (WHO), which also provided technical assistance for this evaluation. Dr. Parham had full access to all the data in the study and had final responsibility for the decision to submit for publication. The sponsors of this study had no role in study design, data collection, data analysis, data interpretation, writing of the report, or in the decision to submit the report for publication. NR 28 TC 13 Z9 13 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 17 PY 2015 VL 10 IS 4 AR e0122169 DI 10.1371/journal.pone.0122169 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1EX UT WOS:000353017000028 PM 25885821 ER PT J AU Tsuji, PA Carlson, BA Yoo, MH Naranjo-Suarez, S Xu, XM He, YW Asaki, E Seifried, HE Reinhold, WC Davis, CD Gladyshev, VN Hatfield, DL AF Tsuji, Petra A. Carlson, Bradley A. Yoo, Min-Hyuk Naranjo-Suarez, Salvador Xu, Xue-Ming He, Yiwen Asaki, Esther Seifried, Harold E. Reinhold, William C. Davis, Cindy D. Gladyshev, Vadim N. Hatfield, Dolph L. TI The 15kDa Selenoprotein and Thioredoxin Reductase 1 Promote Colon Cancer by Different Pathways SO PLOS ONE LA English DT Article ID SELENIUM SUPPLEMENTATION; HEPATOCELLULAR-CARCINOMA; NUTRITIONAL PREVENTION; 15-KDA SELENOPROTEIN; COLORECTAL-CANCER; REDOX HOMEOSTASIS; CELL-GROWTH; EXPRESSION; TRIAL; SEP15 AB Selenoproteins mediate much of the cancer-preventive properties of the essential nutrient selenium, but some of these proteins have been shown to also have cancer-promoting effects. We examined the contributions of the 15kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and formation of experimental metastases of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially interferon-gamma-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient, but not in TR1-deficient cells. Interestingly, components of the Wnt/beta-catenin signaling pathway were up-regulated in cells lacking both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, our results provide insights into new roles of selenoproteins in cancer. C1 [Tsuji, Petra A.] Towson Univ, Dept Biol Sci, Towson, MD 21252 USA. [Carlson, Bradley A.; Yoo, Min-Hyuk; Naranjo-Suarez, Salvador; Xu, Xue-Ming; Hatfield, Dolph L.] NIH, Mol Biol Selenium Sect, Mouse Canc Genet Program, Bethesda, MD 20892 USA. [He, Yiwen; Asaki, Esther] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. [Seifried, Harold E.] NIH, Nutr Sci Res Grp, Rockville, MD USA. [Reinhold, William C.] NIH, Genom & Informat Grp, Mol Pharmacol Lab, Bethesda, MD 20892 USA. [Davis, Cindy D.] NIH, Off Dietary Supplements, Rockville, MD USA. [Gladyshev, Vadim N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Tsuji, PA (reprint author), Towson Univ, Dept Biol Sci, Towson, MD 21252 USA. EM ptsuji@towson.edu FU Towson University's Fisher College of Science and Mathematics; National Cancer Institute Intramural support; National Cancer Institute Cancer Prevention Fellowship Program; National Institutes of Health [CA080946, GM065204] FX Funded by Towson University's Fisher College of Science and Mathematics (Endowed Chair, PAT), National Cancer Institute Intramural support, the National Cancer Institute Cancer Prevention Fellowship Program (PAT), and National Institutes of Health grants (CA080946, GM065204 to VNG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 4 Z9 5 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 17 PY 2015 VL 10 IS 4 AR e0124487 DI 10.1371/journal.pone.0124487 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1EX UT WOS:000353017000131 PM 25886253 ER PT J AU Wang, SJ Teng, ZG Huang, P Liu, DB Liu, Y Tian, Y Sun, J Li, YJ Ju, HX Chen, XY Lu, GM AF Wang, Shouju Teng, Zhaogang Huang, Peng Liu, Dingbin Liu, Ying Tian, Ying Sun, Jing Li, Yanjun Ju, Huangxian Chen, Xiaoyuan Lu, Guangming TI Reversibly Extracellular pH Controlled Cellular Uptake and Photothermal Therapy by PEGylated Mixed-Charge Gold Nanostars SO SMALL LA English DT Article DE controllable cellular uptake; PEGylated mixed-charge nanoparticles; photothermal therapy; reversibly pH responsive; tumor-targeted delivery ID DRUG-DELIVERY; CANCER-THERAPY; TUMOR HETEROGENEITY; SURFACE-CHARGE; NANOPARTICLES; NANORODS; SYSTEMS; PHOTOSENSITIZER; AGGREGATION; PEPTIDES AB Shielding nanoparticles from nonspecific interactions with normal cells/tissues before they reach and after they leave tumors is crucial for the selective delivery of NPs into tumor cells. By utilizing the reversible protonation of weak electrolytic groups to pH changes, long-chain amine/carboxyl-terminated polyethylene glycol (PEG) decorated gold nanostars (GNSs) are designed, exhibiting reversible, significant, and sensitive response in cell affinity and therapeutic efficacy to the extracellular pH (pHe) gradient between normal tissues and tumors. This smart nanosystem shows good dispersity and unimpaired photothermal efficacy in complex bioenvironment at pH 6.4 and 7.4 even when their surface charge is neutral. One PEGylated mixed-charge GNSs with certain surface composition, GNS-N/C 4, exhibits high cell affinity and therapeutic efficacy at pH 6.4, and low affinity and almost zero damage to cells at pH 7.4. Remarkably, this significant and sensitive response in cell affinity and therapeutic efficacy is reversible as local pH alternated. In vivo, GNS-N/C 4 shows higher accumulation in tumors and improved photothermal therapeutic efficacy than pH-insensitive GNSs. This newly developed smart nanosystem, whose cell affinity reversibly transforms in response to pHe gradient with unimpaired biostability, provides a novel effective means of tumor-selective therapy. C1 [Wang, Shouju; Teng, Zhaogang; Liu, Ying; Tian, Ying; Sun, Jing; Li, Yanjun; Lu, Guangming] Nanjing Univ, Sch Med, Jinling Hosp, Dept Med Imaging, Nanjing 210002, Jiangsu, Peoples R China. [Wang, Shouju; Teng, Zhaogang; Ju, Huangxian; Lu, Guangming] Nanjing Univ, Sch Chem & Chem Engn, State Key Lab Analyt Chem Life Sci, Nanjing 210093, Jiangsu, Peoples R China. [Huang, Peng; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Liu, Dingbin] Nankai Univ, State Key Lab Med Chem Biol, Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China. [Liu, Dingbin] Nankai Univ, Res Ctr Analyt Sci, Coll Chem, Tianjin 300071, Peoples R China. RP Lu, GM (reprint author), Nanjing Univ, Sch Med, Jinling Hosp, Dept Med Imaging, Nanjing 210002, Jiangsu, Peoples R China. EM cjr.luguangming@vip.163.com RI Ju, Huangxian/B-2265-2010; Huang, Peng/R-2480-2016 OI Huang, Peng/0000-0003-3651-7813 FU National Key Basic Research Program of the P.R. China [2014CB744504, 2011CB707700]; Major International (Regional) Joint Research Program of China [81120108013]; National Natural Science Foundation of China [30930028, 81201175]; Natural Science Foundation of Jiangsu Province [BK20140734] FX S.W. and T.Z. contributed equally to this work. This project is financially supported by the National Key Basic Research Program of the P.R. China (Program Nos. 2014CB744504 and 2011CB707700), the Major International (Regional) Joint Research Program of China (Program No. 81120108013), the National Natural Science Foundation of China (Program Nos. 30930028 and 81201175), and the Natural Science Foundation of Jiangsu Province (Program No. BK20140734). NR 41 TC 26 Z9 26 U1 15 U2 137 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1613-6810 EI 1613-6829 J9 SMALL JI Small PD APR 17 PY 2015 VL 11 IS 15 BP 1801 EP 1810 DI 10.1002/smll.201403248 PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CF8NV UT WOS:000352819700006 PM 25565411 ER PT J AU Takeuchi, N Cordero, OX Koonin, EV Kaneko, K AF Takeuchi, Nobuto Cordero, Otto X. Koonin, Eugene V. Kaneko, Kunihiko TI Gene-specific selective sweeps in bacteria and archaea caused by negative frequency-dependent selection SO BMC BIOLOGY LA English DT Article ID GENOMIC ISLANDS; ECOLOGICAL DIVERSITY; POPULATION GENOMICS; PERIODIC SELECTION; COHESIVE UNITS; EVOLUTION; PROCHLOROCOCCUS; DYNAMICS; RECOMBINATION; CONSEQUENCES AB Background: Fixation of beneficial genes in bacteria and archaea (collectively, prokaryotes) is often believed to erase pre-existing genomic diversity through the hitchhiking effect, a phenomenon known as genome-wide selective sweep. Recent studies, however, indicate that beneficial genes spread through a prokaryotic population via recombination without causing genome-wide selective sweeps. These gene-specific selective sweeps seem to be at odds with the existing estimates of recombination rates in prokaryotes, which appear far too low to explain such phenomena. Results: We use mathematical modeling to investigate potential solutions to this apparent paradox. Most microbes in nature evolve in heterogeneous, dynamic communities, in which ecological interactions can substantially impact evolution. Here, we focus on the effect of negative frequency-dependent selection (NFDS) such as caused by viral predation (kill-the-winner dynamics). The NFDS maintains multiple genotypes within a population, so that a gene beneficial to every individual would have to spread via recombination, hence a gene-specific selective sweep. However, gene loci affected by NFDS often are located in variable regions of microbial genomes that contain genes involved in the mobility of selfish genetic elements, such as integrases or transposases. Thus, the NFDS-affected loci are likely to experience elevated rates of recombination compared with the other loci. Consequently, these loci might be effectively unlinked from the rest of the genome, so that NFDS would be unable to prevent genome-wide selective sweeps. To address this problem, we analyzed population genetic models of selective sweeps in prokaryotes under NFDS. The results indicate that NFDS can cause gene-specific selective sweeps despite the effect of locally elevated recombination rates, provided NFDS affects more than one locus and the basal rate of recombination is sufficiently low. Although these conditions might seem to contradict the intuition that gene-specific selective sweeps require high recombination rates, they actually decrease the effective rate of recombination at loci affected by NFDS relative to the per-locus basal level, so that NFDS can cause gene-specific selective sweeps. Conclusion: Because many free-living prokaryotes are likely to evolve under NFDS caused by ubiquitous viruses, gene-specific selective sweeps driven by NFDS are expected to be a major, general phenomenon in prokaryotic populations. C1 [Takeuchi, Nobuto; Kaneko, Kunihiko] Univ Tokyo, Dept Basic Sci, Grad Sch Arts & Sci, Tokyo, Japan. [Cordero, Otto X.] ETH, Dept Environm Syst Sci, Zurich, Switzerland. [Koonin, Eugene V.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Takeuchi, N (reprint author), Univ Tokyo, Dept Basic Sci, Grad Sch Arts & Sci, Tokyo, Japan. EM takeuchi@complex.c.u-tokyo.ac.jp FU European Research Council [336938]; US Department of Health and Human Services; MEXT, Japan FX NT is a research fellow of the Japan Society for the Promotion of Science. OXC is funded by the European Research Council, under Starting Grant 336938. EVK is supported by the intramural funds of the US Department of Health and Human Services (to the National Library of Medicine). KK is supported in part by the Dynamic Approaches to the Living Systems from MEXT, Japan. NR 57 TC 9 Z9 9 U1 7 U2 23 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PD APR 16 PY 2015 VL 13 AR 20 DI 10.1186/s12915-015-0131-7 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CG8BT UT WOS:000353532900001 PM 25928466 ER PT J AU Lee, S Bhattacharya, S Tate, CG Grisshammer, R Vaidehi, N AF Lee, Sangbae Bhattacharya, Supriyo Tate, Christopher G. Grisshammer, Reinhard Vaidehi, Nagarajan TI Structural Dynamics and Thermostabilization of Neurotensin Receptor 1 SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID PROTEIN-COUPLED-RECEPTORS; RESOLUTION CRYSTAL-STRUCTURE; ADENOSINE A(2A) RECEPTOR; MEMBRANE-PROTEINS; SIMULATIONS; PEPTIDE; ANTAGONISTS; DETERMINES; MOLECULES; FAMILY AB The neurotensin receptor NTSR1 binds the peptide agonist neurotensin (NTS) and signals preferentially via the G(q) protein. Recently, Grisshammer and co-workers reported the crystal structure of a thermostable mutant NTSR1-GW5 with NTS bound. Understanding how the mutations thermostabilize the structure would allow efficient design of thermostable mutant GPCRs for protein purification, and subsequent biophysical studies. Using microsecond scale molecular dynamics simulations (4 mu s) of the thermostable mutant NTSR1-GW5 and wild type NTSR1, we have elucidated the structural and energetic factors that affect the thermostability and dynamics of NTSR1. The thermostable mutant NTSR1-GW5 is found to be less flexible and less dynamic than the wild type NTSR1. The point mutations confer thermostability by improving the interhelical hydrogen bonds, hydrophobic packing, and receptor interactions with the lipid bilayer, especially in the intracellular regions. During MD, NTSR1-GW5 becomes more hydrated compared to wild type NTSR1, with tight hydrogen bonded water clusters within the transmembrane core of the receptor, thus providing evidence that water plays an important role in improving helical packing in the thermostable mutant. Our studies provide valuable insights into the stability and functioning of NTSR1 that will be useful in future design of thermostable mutants of other peptide GPCRs. C1 [Lee, Sangbae; Bhattacharya, Supriyo; Vaidehi, Nagarajan] Beckman Res Inst City Hope, Div Immunol, Duarte, CA 91010 USA. [Tate, Christopher G.] MRC Lab Mol Biol, Cambridge CB2 0QH, England. [Grisshammer, Reinhard] NINDS, Membrane Prot Struct Funct Unit, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Vaidehi, N (reprint author), Beckman Res Inst City Hope, Div Immunol, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM NVaidehi@coh.org OI Tate, Christopher/0000-0002-2008-9183 FU National Center for Multiscale Modeling of Biological Systems (MMBioS) from the National Institutes of Health [P41GM103712-S1]; Medical Research Council [MRC U105197215]; Intramural Research Program of the National Institute of Neurological Disorders and Stroke, the National Institutes of Health; [NIH-RO1GM097261] FX Funding for this work to N.V. was provided by NIH-RO1GM097261. Anton computer time was provided by the National Center for Multiscale Modeling of Biological Systems (MMBioS) through Grant P41GM103712-S1 from the National Institutes of Health and the Pittsburgh Supercomputing Center (PSC). The Anton machine at PSC was generously made available by D.E. Shaw Research. C.G.T. is funded by the Medical Research Council (MRC U105197215), and the research of R.G. is supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, the National Institutes of Health. NR 45 TC 5 Z9 5 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 16 PY 2015 VL 119 IS 15 BP 4917 EP 4928 DI 10.1021/jp510735f PG 12 WC Chemistry, Physical SC Chemistry GA CG4IS UT WOS:000353249400002 PM 25807267 ER PT J AU Li, L Lyu, XW Hou, CH Takenaka, N Nguyen, HQ Ong, CT Cubenas-Potts, C Hu, M Lei, EP Bosco, G Qin, ZHS Corces, VG AF Li, Li Lyu, Xiaowen Hou, Chunhui Takenaka, Naomi Nguyen, Huy Q. Ong, Chin-Tong Cubenas-Potts, Caelin Hu, Ming Lei, Elissa P. Bosco, Giovanni Qin, Zhaohui S. Corces, Victor G. TI Widespread Rearrangement of 3D Chromatin Organization Underlies Polycomb-Mediated Stress-Induced Silencing SO MOLECULAR CELL LA English DT Article ID TRANSFER-RNA GENES; DROSOPHILA GENOME; DOMAINS; ARCHITECTURE; INSULATOR; CONDENSIN; TRANSCRIPTION; CHROMOSOMES; PRINCIPLES; EXPRESSION AB Chromosomes of metazoan organisms are partitioned in the interphase nucleus into discrete topologically associating domains (TADs). Borders between TADs are formed in regions containing active genes and clusters of architectural protein binding sites. The transcription of most genes is repressed after temperature stress in Drosophila. Here we show that temperature stress induces relocalization of architectural proteins from TAD borders to inside TADs, and this is accompanied by a dramatic rearrangement in the 3D organization of the nucleus. TAD border strength declines, allowing for an increase in long-distance inter-TAD interactions. Similar but quantitatively weaker effects are observed upon inhibition of transcription or depletion of individual architectural proteins. Heat shock-induced inter-TAD interactions result in increased contacts among enhancers and promoters of silenced genes, which recruit Pc and form Pc bodies in the nucleolus. These results suggest that the TAD organization of metazoan genomes is plastic and can be reconfigured quickly. C1 [Li, Li; Lyu, Xiaowen; Hou, Chunhui; Takenaka, Naomi; Ong, Chin-Tong; Cubenas-Potts, Caelin; Corces, Victor G.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA. [Li, Li; Qin, Zhaohui S.] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. [Nguyen, Huy Q.; Bosco, Giovanni] Geisel Sch Med Dartmouth, Dept Genet, Hanover, NH 03755 USA. [Hu, Ming] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA. [Lei, Elissa P.] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Corces, VG (reprint author), Emory Univ, Dept Biol, 1510 Clifton Rd NE, Atlanta, GA 30322 USA. EM vcorces@emory.edu OI Qin, Zhaohui/0000-0002-1583-146X; Hu, Ming/0000-0002-6062-8794 FU Intramural NIH HHS; NCI NIH HHS [P30 CA023108]; NHGRI NIH HHS [R01 HG005119]; NIDDK NIH HHS [DK015602]; NIGMS NIH HHS [R01 GM035463, R01 GM069462] NR 34 TC 43 Z9 45 U1 4 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD APR 16 PY 2015 VL 58 IS 2 BP 216 EP 231 DI 10.1016/j.molcel.2015.02.023 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CG4AR UT WOS:000353222900005 PM 25818644 ER PT J AU Williams, LH Fromm, G Gokey, NG Henriques, T Muse, GW Burkholder, A Fargo, DC Hu, G Adelman, K AF Williams, Lucy H. Fromm, George Gokey, Nolan G. Henriques, Telmo Muse, Ginger W. Burkholder, Adam Fargo, David C. Hu, Guang Adelman, Karen TI Pausing of RNA Polymerase II Regulates Mammalian Developmental Potential through Control of Signaling Networks SO MOLECULAR CELL LA English DT Article ID EMBRYONIC STEM-CELLS; POL-II; GROUND-STATE; SELF-RENEWAL; TRANSCRIPTION ELONGATION; P-TEFB; NELF; GENES; DROSOPHILA; PROMOTERS AB The remarkable capacity for pluripotency and self-enewal in embryonic stem cells (ESCs) requires a finely tuned transcriptional circuitry wherein the pathways and genes that initiate differentiation are suppressed, but poised to respond rapidly to developmental signals. To elucidate transcriptional control in mouse ESCs in the naive, ground state, we defined the distribution of engaged RNA polymerase II (Pol II) at high resolution. We find that promoter-roximal pausing of Pol II is most enriched at genes regulating cell cycle and signal transduction and not, as expected, at developmental or bivalent genes. Accordingly, ablation of the primary pause-nducing factor NELF does not increase expression of lineage markers, but instead causes proliferation defects, embryonic lethality, and dysregulation of ESC signaling pathways. Indeed, ESCs lacking NELF have dramatically attenuated FGF/ERK activity, rendering them resistant to differentiation. This work thus uncovers a key role for NELF-mediated pausing in establishing the responsiveness of stem cells to developmental cues. C1 [Williams, Lucy H.; Fromm, George; Gokey, Nolan G.; Henriques, Telmo; Muse, Ginger W.; Hu, Guang; Adelman, Karen] NIEHS, Lab Epigenet & Stem Cell Biol, Res Triangle Pk, NC 27709 USA. [Burkholder, Adam; Fargo, David C.] NIEHS, Ctr Integrat Bioinformat, Res Triangle Pk, NC 27709 USA. RP Adelman, K (reprint author), NIEHS, Lab Epigenet & Stem Cell Biol, POB 12233, Res Triangle Pk, NC 27709 USA. EM adelmank@niehs.nih.gov RI Hu, Guang/E-7474-2016 OI Hu, Guang/0000-0003-0437-4723 FU Intramural NIH HHS [ZIA ES101987-09]; NIEHS NIH HHS [Z01 ES101987, Z01ES101987] NR 39 TC 22 Z9 22 U1 4 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD APR 16 PY 2015 VL 58 IS 2 BP 311 EP 322 DI 10.1016/j.molcel.2015.02.003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CG4AR UT WOS:000353222900012 PM 25773599 ER PT J AU Mazzitello, KI Candia, J Albano, EV AF Mazzitello, Karina I. Candia, Julian Albano, Ezequiel V. TI Far-from-equilibrium growth of magnetic thin films with Blume-Capel impurities SO PHYSICAL REVIEW E LA English DT Article ID S ISING-MODEL; RENORMALIZATION-GROUP; MONTE-CARLO; 2 DIMENSIONS; PHASE-TRANSITIONS; BEHAVIOR; SURFACE; ORDER AB We investigate the irreversible growth of (2+1)-dimensional magnetic thin films. The spin variable can adopt three states (s(i) = +/- 1,0), and the system is in contact with a thermal bath of temperature T. The deposition process depends on the change of the configuration energy, which, by analogy to the Blume-Capel Hamiltonian in equilibrium systems, depends on Ising-like couplings between neighboring spins (J) and has a crystal field (D) term that controls the density of nonmagnetic impurities (s(i) = 0). Once deposited, particles are not allowed to flip, diffuse, or detach. By means of extensive Monte Carlo simulations, we obtain the phase diagram in the crystal field vs temperature parameter space. We show clear evidence of the existence of a tricritical point located at D-t/J = 1.145(10) and k(B)T(t)/J = 0.425(10), which separates a first-order transition curve at lower temperatures from a critical second-order transition curve at higher temperatures, in analogy with the previously studied equilibrium Blume-Capel model. Furthermore, we show that, along the second-order transition curve, the critical behavior of the irreversible growth model can be described by means of the critical exponents of the two-dimensional Ising model under equilibrium conditions. Therefore, our findings provide a link between well-known theoretical equilibrium models and nonequilibrium growth processes that are of great interest for many experimental applications, as well as a paradigmatic topic of study in current statistical physics. C1 [Mazzitello, Karina I.] Dept Fis UNMdP, Mar Del Plata, Buenos Aires, Argentina. [Candia, Julian; Albano, Ezequiel V.] UNLP, CONICET, Inst Fis Liquidos & Sistemas Biol, La Plata, Buenos Aires, Argentina. [Candia, Julian] Univ Maryland, Dept Phys, College Pk, MD 20742 USA. [Albano, Ezequiel V.] UNLP, Dept Fis, La Plata, Buenos Aires, Argentina. [Candia, Julian] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. RP Mazzitello, KI (reprint author), Dept Fis UNMdP, Mar Del Plata, Buenos Aires, Argentina. OI Candia, Julian/0000-0001-5793-8989 FU CONICET; UNLP; Agencia Nacional de Promocion Cientifica y Tecnologica de la Republica Argentina (Argentina) FX This work was financially supported by CONICET, UNLP, and Agencia Nacional de Promocion Cientifica y Tecnologica de la Republica Argentina (Argentina). NR 56 TC 0 Z9 0 U1 0 U2 7 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD APR 16 PY 2015 VL 91 IS 4 AR 042118 DI 10.1103/PhysRevE.91.042118 PG 9 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA CG0VN UT WOS:000352990000003 PM 25974450 ER PT J AU Zhang, DD Gao, ZG Zhang, KH Kiselev, E Crane, S Wang, J Paoletta, S Yi, CY Ma, LM Zhang, WR Han, GW Liu, H Cherezov, V Katritch, V Jiang, HL Stevens, RC Jacobson, KA Zhao, Q Wu, BL AF Zhang, Dandan Gao, Zhan-Guo Zhang, Kaihua Kiselev, Evgeny Crane, Steven Wang, Jiang Paoletta, Silvia Yi, Cuiying Ma, Limin Zhang, Wenru Han, Gye Won Liu, Hong Cherezov, Vadim Katritch, Vsevolod Jiang, Hualiang Stevens, Raymond C. Jacobson, Kenneth A. Zhao, Qiang Wu, Beili TI Two disparate ligand-binding sites in the human P2Y(1) receptor SO NATURE LA English DT Article ID PROTEIN-COUPLED RECEPTORS; CRYSTAL-STRUCTURE; NUCLEOTIDE RECEPTORS; PURINERGIC RECEPTORS; SMALL-MOLECULE; ANTAGONISTS; AGONIST; DISCOVERY; COMPLEX; RECOGNITION AB In response to adenosine 59-diphosphate, the P2Y(1) receptor (P2Y(1)R) facilitates platelet aggregation, and thus serves as an important antithrombotic drug target. Here we report the crystal structures of the human P2Y(1)R in complex with a nucleotide antagonist MRS2500 at 2.7 angstrom resolution, and with a non-nucleotide antagonist BPTU at 2.2 angstrom resolution. The structures reveal two distinct ligand-binding sites, providing atomic details of P2Y(1)R's unique ligand-binding modes. MRS2500 recognizes a binding site within the seven transmembrane bundle of P2Y(1)R, which is different in shape and location from the nucleotide binding site in the previously determined structure of P2Y(12)R, representative of another P2YR subfamily. BPTU binds to an allosteric pocket on the external receptor interface with the lipid bilayer, making it the first structurally characterized selective G-protein-coupled receptor (GPCR) ligand located entirely outside of the helical bundle. These high-resolutioninsights into P2Y(1)R should enable discovery of new orthosteric and allosteric antithrombotic drugs with reduced adverse effects. C1 [Zhang, Dandan; Zhang, Kaihua; Wang, Jiang; Yi, Cuiying; Ma, Limin; Zhang, Wenru; Liu, Hong; Zhao, Qiang; Wu, Beili] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China. [Gao, Zhan-Guo; Kiselev, Evgeny; Crane, Steven; Paoletta, Silvia; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Han, Gye Won; Cherezov, Vadim; Stevens, Raymond C.] Univ So Calif, Dept Chem, Bridge Inst, Los Angeles, CA 90089 USA. [Katritch, Vsevolod] Univ So Calif, Bridge Inst, Dept Biol Sci, Los Angeles, CA 90089 USA. [Jiang, Hualiang] Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China. [Stevens, Raymond C.] ShanghaiTech Univ, iHuman Inst, Shanghai 201203, Peoples R China. RP Wu, BL (reprint author), Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China. EM zhaoq@simm.ac.cn; beiliwu@simm.ac.cn RI Jacobson, Kenneth/A-1530-2009; Cherezov, Vadim/L-9812-2013; Katritch, Vsevolod/Q-8357-2016; OI Jacobson, Kenneth/0000-0001-8104-1493; Cherezov, Vadim/0000-0002-5265-3914; Zhang, Kaihua/0000-0003-3734-3624 FU National Basic Research Program of China [2012CB518000, 2014CB910400, 2012CB910400]; CAS Strategic Priority Research Program [XDB08020300]; National Science Foundation of China [31422017, 31370729, 91313000]; National Science and Technology Major Project [2013ZX09507001]; NIDDK; NIH Intramural Research Program [Z01 DK031116-26]; National Institutes of Health [U54 GM094618] FX This work was supported by the National Basic Research Program of China grants 2012CB518000, 2014CB910400 and 2012CB910400 (Q.Z., B.W.), CAS Strategic Priority Research Program XDB08020300 (B.W.), the National Science Foundation of China grants 31422017 (B.W.), 31370729 (Q.Z.) and 91313000 (H.J.), the National Science and Technology Major Project 2013ZX09507001 (H.J., Q.Z., B.W.), NIDDK, NIH Intramural Research Program grant Z01 DK031116-26 (K.A.J.), and the National Institutes of Health grant U54 GM094618 (V.C., V.K., R.C.S.). The authors thank A. Walker for assistance with manuscript preparation and S. M. Moss for technical assistance. The synchrotron radiation experiments were performed at the BL41XU of Spring-8 with approval of the Japan Synchrotron Radiation Research Institute (JASRI) (proposal no. 2014A1094 and 2014B1056). We thank the beamline staff members of the BL41XU for help with X-ray data collection. NR 37 TC 49 Z9 50 U1 2 U2 49 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 16 PY 2015 VL 520 IS 7547 BP 317 EP + DI 10.1038/nature14287 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG0RI UT WOS:000352974200031 PM 25822790 ER PT J AU Gundem, G Van Loo, P Kremeyer, B Alexandrov, LB Tubio, JMC Papaemmanuil, E Brewer, DS Kallio, HML Hoegnas, G Annala, M Kivinummi, K Goody, V Latimer, C O'Meara, S Dawson, KJ Isaacs, W Emmert-Buck, MR Nykter, M Foster, C Kote-Jarai, Z Easton, D Whitaker, HC Neal, DE Cooper, CS Eeles, RA Visakorpi, T Campbell, PJ McDermott, U Wedge, DC Bova, GS AF Gundem, Gunes Van Loo, Peter Kremeyer, Barbara Alexandrov, Ludmil B. Tubio, Jose M. C. Papaemmanuil, Elli Brewer, Daniel S. Kallio, Heini M. L. Hoegnas, Gunilla Annala, Matti Kivinummi, Kati Goody, Victoria Latimer, Calli O'Meara, Sarah Dawson, Kevin J. Isaacs, William Emmert-Buck, Michael R. Nykter, Matti Foster, Christopher Kote-Jarai, Zsofia Easton, Douglas Whitaker, Hayley C. Neal, David E. Cooper, Colin S. Eeles, Rosalind A. Visakorpi, Tapio Campbell, Peter J. McDermott, Ultan Wedge, David C. Bova, G. Steven CA ICGC Prostate UK Grp TI The evolutionary history of lethal metastatic prostate cancer SO NATURE LA English DT Article ID ANDROGEN DEPRIVATION THERAPY; PANCREATIC-CANCER; CLONAL EVOLUTION; HETEROGENEITY; PROGRESSION; RESISTANCE; PATHOGENESIS; MUTATIONS; SIGNATURE; PATTERNS AB Cancers emerge from an ongoing Darwinian evolutionary process, often leading to multiple competing subdones within a single primary tumour(1-4). This evolutionary process culminates in the formation of metastases, which is the cause of 90% of cancer-related deaths(5). However, despite its clinical importance, little is known about the principles governing the dissemination of cancer cells to distant organs. Although the hypothesis that each metastasis originates from a single tumour cell is generally supported(6-8), recent studies using mouse models of cancer demonstrated the existence of polyclonal seeding from and interclonal cooperation between multiple subdonee(9,10). Here we sought definitive evidence for the existence of polydonal seeding in human malignancy and to establish the clonal relationship among different metastases in the context of androgendeprived metastatic prostate cancer. Using whole-genome sequencing, we characterized multiple metastases arising from prostate tumours in ten patients. Integrated analyses of subdonal architecture revealed the patterns of metastatic spread in unprecedented detail. Metastasis-to-metastasis spread was found to be common, either through de novo monoclonal seeding of daughter metastases or, in five cases, through the transfer of multiple tumour clones between metastatic sites. Lesions affecting tumour suppressor genes usually occur as single events, whereas mutations in genes involved in androgen receptor signalling commonly involve multiple, convergent events in different metastases. Our results elucidate in detail the complex patterns of metastatic spread and further our understanding of the development of resistance to androgen-deprivation therapy in prostate cancer. C1 [Gundem, Gunes; Van Loo, Peter; Kremeyer, Barbara; Alexandrov, Ludmil B.; Tubio, Jose M. C.; Papaemmanuil, Elli; Goody, Victoria; Latimer, Calli; O'Meara, Sarah; Dawson, Kevin J.; Campbell, Peter J.; McDermott, Ultan; Wedge, David C.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. [Van Loo, Peter] Katholieke Univ Leuven, Dept Human Genet, B-3000 Leuven, Belgium. [Van Loo, Peter] Canc Res UK London Res Inst, London WC2A 3LY, England. [Brewer, Daniel S.; Cooper, Colin S.] Univ E Anglia, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England. [Brewer, Daniel S.; Cooper, Colin S.] Univ E Anglia, Dept Biol Sci, Norwich NR4 7TJ, Norfolk, England. [Brewer, Daniel S.] Genome Anal Ctr, Norwich NR4 7UH, Norfolk, England. [Kallio, Heini M. L.; Hoegnas, Gunilla; Annala, Matti; Kivinummi, Kati; Nykter, Matti; Visakorpi, Tapio; Bova, G. Steven] Univ Tampere, BioMediTech, Inst Biosci & Med Technol, FI-33520 Tampere, Finland. [Kallio, Heini M. L.; Hoegnas, Gunilla; Annala, Matti; Kivinummi, Kati; Nykter, Matti; Visakorpi, Tapio; Bova, G. Steven] Tampere Univ Hosp, Fimlab Labs, FI-33520 Tampere, Finland. [Isaacs, William] Johns Hopkins Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. [Emmert-Buck, Michael R.] NCI, Lab Pathol, NIH, Bethesda, MD 20892 USA. [Foster, Christopher] Univ Liverpool, London WC1E 6JA, England. [Foster, Christopher] HCA Pathol Labs, London WC1E 6JA, England. [Kote-Jarai, Zsofia; Cooper, Colin S.; Eeles, Rosalind A.] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England. [Easton, Douglas] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England. [Whitaker, Hayley C.; Neal, David E.] Canc Res UK Cambridge Inst, Urooncol Res Grp, Cambridge CB2 0RE, England. [Neal, David E.] Univ Cambridge, Addenbrookes Hosp, Dept Surg Oncol, Cambridge CB2 0QQ, England. [Eeles, Rosalind A.] Royal Marsden NHS Fdn Trust, London SW3 6JJ, England. [Eeles, Rosalind A.] Royal Marsden NHS Fdn Trust, Sutton SM2 5PT, Surrey, England. RP Bova, GS (reprint author), Univ Tampere, BioMediTech, Inst Biosci & Med Technol, FI-33520 Tampere, Finland. EM um1@sanger.ac.uk; dw9@sanger.ac.uk; g.steven.bova@uta.fi RI Tubio, Jose/H-5076-2015; OI Tubio, Jose/0000-0003-3540-2459; Eeles, Rosalind/0000-0002-3698-6241; Neal, David/0000-0002-6033-5086; Brewer, Daniel/0000-0003-4753-9794; Van Loo, Peter/0000-0003-0292-1949; McDermott, Ultan/0000-0001-9032-4700; Wedge, David/0000-0002-7572-3196; Massie, Charlie/0000-0003-2314-4843; Berney, Daniel/0000-0001-5474-8696 FU Cancer Research UK; NIH NCI Intramural Program; Academy of Finland; Cancer Society of Finland; PELICAN Autopsy Study family members and friends; John and Kathe Dyson; US National Cancer Institute [CA92234]; American Cancer Society; Johns Hopkins University Department of Pathology; Women's Board of Johns Hopkins Hospital; Grove Foundation; Association for the Cure of Cancer of the Prostate; American Foundation for Urologic Disease; Bob Champion Cancer Trust; Research Foundation - Flanders (FWO) [FWO-G.0687.12] FX We thank the men and their families who participated in the PELICAN (Project to ELIminate lethal CANcer) integrated clinical-molecular autopsy study of prostate cancer. We thank M. A. Eisenberger, M. A. Carducci, V. Sinibaldi, T. B. Smyth and G. J. Mamo for oncologic and urologic clinical support; T. Tolonen for uropathology support; P. Martikainen, M. Vaha-Jaakkola, M. Vakkuri, K. Leinonen, T. Vormisto, M. Rohrer, A. Koskenalho, J. Silander, T. Lahtinen, C. Hardy, G. Hutchins, B. Crain,S. Jhavar, C. Talbot, L. Kasch, M. Penno, A. Warner and Y. Golubeva for technical support; and M. R. Stratton and P.A. Futreal for their comments on the manuscript. This is an ICGC Prostate Cancer study funded by: Cancer Research UK(2011-present); NIH NCI Intramural Program (2013-2014); Academy of Finland (2011-present); Cancer Society of Finland (2013-present); PELICAN Autopsy Study family members and friends (1998-2004); John and Kathe Dyson (2000); US National Cancer Institute CA92234 (2000-2005); American Cancer Society (1998-2000); Johns Hopkins University Department of Pathology (1997-2011); Women's Board of Johns Hopkins Hospital (1998); The Grove Foundation (1998); Association for the Cure of Cancer of the Prostate (1994-1998); American Foundation for Urologic Disease (1991-1994); Bob Champion Cancer Trust (2013-present); Research Foundation - Flanders (FWO) [FWO-G.0687.12] (2012-present). E.P. is a European Hematology Association Research Fellow. NR 29 TC 170 Z9 172 U1 13 U2 68 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 16 PY 2015 VL 520 IS 7547 BP 353 EP + DI 10.1038/nature14347 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG0RI UT WOS:000352974200040 PM 25830880 ER PT J AU McCann, DJ Skolnick, P Bolash, RB AF McCann, David J. Skolnick, Phil Bolash, Robert B. TI Trends in Opioid Analgesic Abuse and Mortality in the United States SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [McCann, David J.; Skolnick, Phil] NIDA, Bethesda, MD 20892 USA. [Bolash, Robert B.] Cleveland Clin, Cleveland, OH 44106 USA. RP McCann, DJ (reprint author), NIDA, Bethesda, MD 20892 USA. EM dmccann@nih.gov NR 2 TC 0 Z9 0 U1 3 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 16 PY 2015 VL 372 IS 16 BP 1572 EP 1573 DI 10.1056/NEJMc1501822 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CF9BL UT WOS:000352856500021 PM 25875269 ER PT J AU Verma, M Lam, TK Hebert, E Divi, RL AF Verma, Mukesh Lam, Tram Kim Hebert, Elizabeth Divi, Rao L. TI Extracellular vesicles: potential applications in cancer diagnosis, prognosis, and epidemiology SO BMC CLINICAL PATHOLOGY LA English DT Review DE Cancer; Diagnosis; Epidemiology; Extracellular vesicles; Exosomes; Microvesicles ID CIRCULATING TUMOR-CELLS; IMMUNE-MODULATORY FEATURES; EXOSOMAL-LIKE VESICLES; PROSTATE-CANCER; BLADDER-CANCER; BREAST-CANCER; PROTEOMIC ANALYSIS; PANCREATIC-CANCER; OVARIAN-CANCER; SERUM EXOSOMES AB Both normal and diseased cells continuously shed extracellular vesicles (EVs) into extracellular space, and the EVs carry molecular signatures and effectors of both health and disease. EVs reflect dynamic changes that are occurring in cells and tissue microenvironment in health and at a different stage of a disease. EVs are capable of altering the function of the recipient cells. Trafficking and reciprocal exchange of molecular information by EVs among different organs and cell types have been shown to contribute to horizontal cellular transformation, cellular reprogramming, functional alterations, and metastasis. EV contents may include tumor suppressors, phosphoproteins, proteases, growth factors, bioactive lipids, mutant oncoproteins, oncogenic transcripts, microRNAs, and DNA sequences. Therefore, the EVs present in biofluids offer unprecedented, remote, and non-invasive access to crucial molecular information about the health status of cells, including their driver mutations, classifiers, molecular subtypes, therapeutic targets, and biomarkers of drug resistance. In addition, EVs may offer a non-invasive means to assess cancer initiation, progression, risk, survival, and treatment outcomes. The goal of this review is to highlight the current status of information on the role of EVs in cancer, and to explore the utility of EVs for cancer diagnosis, prognosis, and epidemiology. C1 [Verma, Mukesh; Lam, Tram Kim; Hebert, Elizabeth; Divi, Rao L.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD 20850 USA. RP Verma, M (reprint author), NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD 20850 USA. EM vermam@mail.nih.gov NR 112 TC 18 Z9 19 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6890 J9 BMC CLIN PATHOL JI BMC Clin. Pathol. PD APR 15 PY 2015 VL 15 AR 6 DI 10.1186/s12907-015-0005-5 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CQ2ZW UT WOS:000360472300001 PM 25883534 ER PT J AU Morens, DM Fauci, AS AF Morens, David M. Fauci, Anthony S. TI In Memoriam: Albert Z. Kapikian, MD, 1930-2014 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Biographical-Item DE electron microscopy; hepatitis A virus; infectious diseases; norovirus; rotavirus; vaccines; viral diseases; virology ID IMMUNE ELECTRON-MICROSCOPY; HEPATITIS; PARTICLE C1 [Morens, David M.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Bldg 31,Rm 7A-03,31 Ctr Dr, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2015 VL 211 IS 8 BP 1199 EP 1201 DI 10.1093/infdis/jiv034 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CI4LP UT WOS:000354720900001 PM 25737559 ER PT J AU Lionakis, MS Holland, SM AF Lionakis, Michail S. Holland, Steven M. TI Human Invasive Mycoses: Immunogenetics on the Rise SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material DE CARD9; invasive fungal infections; immunogenetics ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; CHRONIC GRANULOMATOUS-DISEASE; ANTIFUNGAL IMMUNITY; CARD9 DEFICIENCY; FUNGAL-INFECTION; STAT1 MUTATIONS; HOST-DEFENSE; KAPPA-B; MACROPHAGES; MECHANISMS C1 [Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Lionakis, MS (reprint author), NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike,Bldg 10,Rm 11C102, Bethesda, MD 20892 USA. EM lionakism@mail.nih.gov NR 31 TC 2 Z9 2 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2015 VL 211 IS 8 BP 1205 EP 1207 DI 10.1093/infdis/jiu411 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CI4LP UT WOS:000354720900003 PM 25057047 ER PT J AU Bliven, SE Bourne, PE Prlic, A AF Bliven, Spencer E. Bourne, Philip E. Prlic, Andreas TI Detection of circular permutations within protein structures using CE-CP SO BIOINFORMATICS LA English DT Article ID STRUCTURE ALIGNMENTS; EVOLUTION; DATABASE AB Motivation: Circular permutation is an important type of protein rearrangement. Natural circular permutations have implications for protein function, stability and evolution. Artificial circular permutations have also been used for protein studies. However, such relationships are difficult to detect for many sequence and structure comparison algorithms and require special consideration. Results: We developed a new algorithm, called Combinatorial Extension for Circular Permutations (CE-CP), which allows the structural comparison of circularly permuted proteins. CE-CP was designed to be user friendly and is integrated into the RCSB Protein Data Bank. It was tested on two collections of circularly permuted proteins. Pairwise alignments can be visualized both in a desktop application or on the web using Jmol and exported to other programs in a variety of formats. C1 [Bliven, Spencer E.] Univ Calif San Diego, Bioinformat & Syst Biol Program, La Jolla, CA 92093 USA. [Bliven, Spencer E.; Bourne, Philip E.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Bourne, Philip E.; Prlic, Andreas] Univ Calif San Diego, San Diego Supercomp Ctr, RCSB Prot Data Bank, La Jolla, CA 92093 USA. RP Bliven, SE (reprint author), Univ Calif San Diego, Bioinformat & Syst Biol Program, La Jolla, CA 92093 USA. EM sbliven@ucsd.edu OI Bliven, Spencer/0000-0002-1200-1698 FU National Science Foundation [DBI-1338415]; Intramural Research Program of National Center for Biotechnology Information, National Library of Medicine; National Institutes of Health [T32GM8806]; Department of Energy FX This work was supported by the National Science Foundation [grant number DBI-1338415]; the Intramural Research Program of the National Center for Biotechnology Information, National Library of Medicine; National Institutes of Health [grant number T32GM8806]; and the Department of Energy. NR 16 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD APR 15 PY 2015 VL 31 IS 8 BP 1316 EP 1318 DI 10.1093/bioinformatics/btu823 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA CI0UK UT WOS:000354453700028 PM 25505094 ER PT J AU Courtot, M Meskas, J Diehl, AD Droumeva, R Gottardo, R Jalali, A Taghiyar, MJ Maecker, HT McCoy, JP Ruttenberg, A Scheuermann, RH Brinkman, RR AF Courtot, Melanie Meskas, Justin Diehl, Alexander D. Droumeva, Radina Gottardo, Raphael Jalali, Adrin Taghiyar, Mohammad Jafar Maecker, Holden T. McCoy, J. Philip Ruttenberg, Alan Scheuermann, Richard H. Brinkman, Ryan R. TI flowCL: ontology-based cell population labelling in flow cytometry SO BIOINFORMATICS LA English DT Article AB Motivation: Finding one or more cell populations of interest, such as those correlating to a specific disease, is critical when analysing flow cytometry data. However, labelling of cell populations is not well defined, making it difficult to integrate the output of algorithms to external knowledge sources. Results: We developed flowCL, a software package that performs semantic labelling of cell populations based on their surface markers and applied it to labelling of the Federation of Clinical Immunology Societies Human Immunology Project Consortium lyoplate populations as a use case. Conclusion: By providing automated labelling of cell populations based on their immunopheno-type, flowCL allows for unambiguous and reproducible identification of standardized cell types. C1 [Courtot, Melanie] Simon Fraser Univ, Dept Biochem & Mol Biol, Burnaby, BC V5A 1S6, Canada. [Meskas, Justin; Droumeva, Radina; Jalali, Adrin; Taghiyar, Mohammad Jafar; Brinkman, Ryan R.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Diehl, Alexander D.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Neurol, Buffalo, NY 14203 USA. [Gottardo, Raphael] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Maecker, Holden T.] Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA. [McCoy, J. Philip] NHLBI, NIH, Bethesda, MD 20892 USA. [McCoy, J. Philip] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA. [Ruttenberg, Alan] SUNY Buffalo, Sch Dent Med, Buffalo, NY 14214 USA. [Scheuermann, Richard H.] J Craig Venter Inst, La Jolla, CA 92037 USA. [Scheuermann, Richard H.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92093 USA. RP Brinkman, RR (reprint author), British Columbia Canc Agcy, Terry Fox Lab, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM rbrinkman@bccrc.ca RI Brinkman, Ryan/B-1108-2008; Diehl, Alexander/G-9883-2016; OI Brinkman, Ryan/0000-0002-9765-2990; Diehl, Alexander/0000-0001-9990-8331; Courtot, Melanie/0000-0002-9551-6370 FU National Institutes of Health (NIH)/National Institute of Biomedical Imaging and Bioengineering (NIBIB) [R01 EB008400]; Human Immunology Project Consortium (HIPC) [U19 AI089986]; Natural Sciences and Engineering Research Council of Canada; National Institute of General Medical Sciences (NIGMS) [2R01GM080646-06, HHSN272201200028C] FX This work was supported by National Institutes of Health (NIH)/National Institute of Biomedical Imaging and Bioengineering (NIBIB) [R01 EB008400], Human Immunology Project Consortium (HIPC) [U19 AI089986], Natural Sciences and Engineering Research Council of Canada, National Institute of General Medical Sciences (NIGMS) 2R01GM080646-06 (Protein Ontology) and HHSN272201200028C (ImmPort). NR 6 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD APR 15 PY 2015 VL 31 IS 8 BP 1337 EP 1339 DI 10.1093/bioinformatics/btu807 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA CI0UK UT WOS:000354453700035 PM 25481008 ER PT J AU Forhan, SE Godfrey, CC Watts, DH Langley, CL AF Forhan, Sara E. Godfrey, Catherine C. Watts, D. Heather Langley, Carol L. TI A Systematic Review of the Effects of Visual Inspection With Acetic Acid, Cryotherapy, and Loop Electrosurgical Excision Procedures for Cervical Dysplasia in HIV-Infected Women in Low- and Middle-Income Countries SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE cervical cancer prevention; cervical dysplasia; HPV; HIV; LMIC ID SCREEN-AND-TREAT; CANCER PREVENTION; POSITIVE WOMEN; WESTERN KENYA; MORTALITY; CYTOLOGY; LESIONS; ZAMBIA AB Background:Cervical cancer, almost all of which is caused by human papillomavirus, accounts for 12% of female cancers worldwide and is more common among HIV-infected women. Nine of 10 deaths from cervical cancer occur in low- and middle-income countries (LMICs). Simple screening methods and outpatient treatment of precursor lesions save lives but the benefit of these interventions among HIV-infected women is uncertain.Objective:We reviewed evidence of the effects of screening with visual inspection with acetic acid (VIA), and outpatient treatment for cervical precancer among HIV-infected women in LMIC.Methods:A systematic review of articles published from January 1995 through July 2013 was conducted using key terms for VIA cervical screening, cervical precancer treatment with cryotherapy or loop electrosurgical excision procedure, HIV-infected women, low-resource settings, and outcomes, including morbidity and mortality.Results:Of 2159 articles screened, 14 met inclusion criteria; all considered only morbidity outcomes. No articles dealt with the long-term impact of screening/treatment on cervical cancer incidence or mortality among HIV-infected women. Articles reported on performance of VIA, prevalence of cervical dysplasia, and complications and rates of recurrent dysplasia after treatment.Conclusions:Dysplasia prevalence and recurrence were higher among HIV-infected compared with HIV-uninfected women but morbidity from treatment was similar. Few data exist on long-term outcomes of VIA, cryotherapy, or loop electrosurgical excision procedure interventions among HIV-infected women in LMIC; longer-term outcomes research is needed to assess the effects of VIA or other screening modalities and outpatient treatment on prevention of cervical cancer among HIV-infected women. C1 [Forhan, Sara E.] Ctr Dis Control & Prevent CDC, Div Global HIV AIDS, Atlanta, GA 30333 USA. [Godfrey, Catherine C.] NIAID, Div Aids, NIH, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. [Watts, D. Heather; Langley, Carol L.] US Dept State, Off US Global AIDS Coordinator & Hlth Diplomacy O, Washington, DC 20520 USA. RP Forhan, SE (reprint author), Ctr Dis Control & Prevent CDC, Div Global HIV AIDS, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. EM sforhan@cdc.gov FU US President's Emergency Plan for AIDS Relief (PEPFAR) FX Supported by the US President's Emergency Plan for AIDS Relief (PEPFAR). NR 26 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 15 PY 2015 VL 68 SU 3 BP S350 EP S356 DI 10.1097/QAI.0000000000000488 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CH6CN UT WOS:000354123500011 PM 25768874 ER PT J AU Louis, GMB Bloom, MS Gatto, NM Hogue, CR Westreich, DJ Zhang, CL AF Louis, Germaine M. Buck Bloom, Michael S. Gatto, Nicolle M. Hogue, Carol R. Westreich, Daniel J. Zhang, Cuilin TI Epidemiology's Continuing Contribution to Public Health: The Power of "Then and Now" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cancer; cardiovascular epidemiology; environment; infection; nutrition; perinatal epidemiology; social epidemiology; tobacco ID POLYUNSATURATED FATTY-ACIDS; MARGINAL STRUCTURAL MODELS; CORONARY-HEART-DISEASE; PRIMARY CARDIAC-ARREST; CARDIOVASCULAR-DISEASE; POOLED ANALYSIS; BREAST-CANCER; MYOCARDIAL-INFARCTION; MEDITERRANEAN DIET; RISK AB The 47th annual meeting of the Society for Epidemiologic Research hosted 17 invited speakers charged by the Executive Committee with presenting some of the many ways that epidemiologists have improved the health of the general population. There were 9 "Then and Now" sessions that were structured to focus on how early epidemiologists overcame research hurdles and advanced health through innovative strategies. For most topics, a longstanding expert was paired with an excellent contemporary epidemiologist working in the area, and both were given the freedom to deliver an integrated story about epidemiology's temporal role in protecting and promoting public health. Epidemiologic discoveries in cardiovascular, cancer, and perinatal epidemiology were discussed on day 1, followed by discussions of accomplishments in reducing exposures that adversely impact health (nutrition, environment/occupation, and tobacco use) on day 2. Topics with relevancy for many aspects of epidemiology were presented on day 3, including infectious diseases, social forces, and causal thinking in epidemiologic research. Given the large number of outstanding senior and junior epidemiologists that attended the meeting, choosing speakers was a unique challenge. What became evident from all sessions was the passion that epidemiologists have for population health, tempered with concerns for remaining true to epidemiologic principles, the timely adoption of innovative methods, and the responsible interpretation of research findings. C1 [Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Director, Div Intramural Populat Hlth Res, Rockville, MD 20854 USA. [Bloom, Michael S.] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Rensselaer, NY USA. [Bloom, Michael S.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Rensselaer, NY USA. [Gatto, Nicolle M.] Pfizer Inc, Epidemiol Worldwide Safety & Regulatory, New York, NY USA. [Gatto, Nicolle M.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Hogue, Carol R.] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Westreich, Daniel J.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Rockville, MD 20854 USA. RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Director, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20854 USA. EM gb156i@nih.gov OI Bloom, Michael/0000-0002-0028-5494 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (G.M.B.L. and C.Z.). NR 75 TC 2 Z9 2 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 2015 VL 181 IS 8 BP E1 EP E8 DI 10.1093/aje/kwv043 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH1XG UT WOS:000353815700001 ER PT J AU Okabe, M Miyazaki, Y Niimura, F Pastan, I Nishiyama, A Yokoo, T Ichikawa, I Matsusaka, T AF Okabe, Masahiro Miyazaki, Yoichi Niimura, Fumio Pastan, Ira Nishiyama, Akira Yokoo, Takashi Ichikawa, Iekuni Matsusaka, Taiji TI Unilateral ureteral obstruction attenuates intrarenal angiotensin II generation induced by podocyte injury SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE glomerulosclerosis; intrarenal angiotensin II; renin-angiotensin system; unilateral ureteral obstruction ID TYPE-2 DIABETIC-RATS; RENAL FIBROSIS; KIDNEY-DISEASE; RENIN; SYSTEM; NEPHROPATHY; BLOCKADE; MODEL AB The renal tissue renin-angiotensin system is activated in chronic kidney diseases. We previously demonstrated that intrarenal ANG II is synthesized primarily from liver-derived angiotensinogen filtered through the glomerulus and that podocyte injury increases the passage of angiotensinogen into the tubular lumen and generation of ANG II. In the present study, we tested the effect of cessation of glomerular filtration by ureteral obstruction on renal ANG II generation in kidneys with podocyte injury under two experimental conditions. Ureteral obstruction is known to activate the renin-angiotensin system in nonproteinuric kidneys. Transgenic mice expressing hCD25 in podocyte (NEP25) were injected with 1.25 or 10 ng/g body wt of LMB2, a hCD25-targeted immunotoxin, subjected to unilateral ureteral ligation on the following day, and euthanized 7 and 4 days later, respectively. In both experiments, compared with the kidney in untreated wild-type mice, renal angiotensinogen protein, as assessed by immunostaining and Western blot analysis, was increased in the contralateral unobstructed kidney. However, it was markedly decreased in the obstructed kidney. Whereas intrarenal ANG II content was increased in the contralateral kidney compared with the untreated kidney (248 +/- 83 vs. 106 +/- 21 and 298 +/- 185 vs. 64.8 +/- 20 fmol/g kidney, respectively), this increase was suppressed in the obstructed kidney (161 +/- 75 and 113 +/- 34 fmol/g kidney, respectively), a pattern opposite to what we expected in obstructed kidneys without podocyte injury. Thus, our study indicates that the major source of increased renal ANG II in podocyte 6injury is filtered angiotensinogen. C1 [Okabe, Masahiro; Miyazaki, Yoichi; Yokoo, Takashi] Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan. [Okabe, Masahiro; Matsusaka, Taiji] Tokai Univ, Sch Med, Dept Internal Med, Isehara, Kanagawa 2591193, Japan. [Niimura, Fumio] Tokai Univ, Sch Med, Dept Pediat, Isehara, Kanagawa 2591193, Japan. [Ichikawa, Iekuni] Tokai Univ, Sch Med, Isehara, Kanagawa 2591193, Japan. [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Nishiyama, Akira] Kagawa Univ, Sch Med, Dept Pharmacol, Takamatsu, Kagawa 760, Japan. [Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. [Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. RP Matsusaka, T (reprint author), Tokai Univ, Sch Med, Dept Internal Med, 143 Shimokasuya, Isehara, Kanagawa 2591193, Japan. EM taijim@is.icc.u-tokai.ac.jp FU Japan Society for the Promotion of Science, Ministry of Education, Culture, Sports, Science, and Technology (MEXT); MEXT-Supported Program for the Strategic Research Foundation at Private Universities; Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research; American Heart Association [12GRNT11630000] FX This study was supported by a Grant-in-Aid for Scientific Research of Japan Society for the Promotion of Science, Ministry of Education, Culture, Sports, Science, and Technology (MEXT), MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2009-2013), and in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and American Heart Association 12GRNT11630000. NR 29 TC 0 Z9 0 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR 15 PY 2015 VL 308 IS 8 BP F932 EP F937 DI 10.1152/ajprenal.00444.2014 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA CH3UZ UT WOS:000353957300016 PM 25673808 ER PT J AU Marciano, BE Spalding, C Fitzgerald, A Mann, D Brown, T Osgood, S Yockey, L Darnell, DN Barnhart, L Daub, J Boris, L Rump, AP Anderson, VL Haney, C Kuhns, DB Rosenzweig, SD Kelly, C Zelazny, A Mason, T DeRavin, SS Kang, E Gallin, JI Malech, HL Olivier, KN Uzel, G Freeman, AF Heller, T Zerbe, CS Holland, SM AF Marciano, Beatriz E. Spalding, Christine Fitzgerald, Alan Mann, Daphne Brown, Thomas Osgood, Sharon Yockey, Lynne Darnell, Dirk N. Barnhart, Lisa Daub, Janine Boris, Lisa Rump, Amy P. Anderson, Victoria L. Haney, Carissa Kuhns, Douglas B. Rosenzweig, Sergio D. Kelly, Corin Zelazny, Adrian Mason, Tamika DeRavin, Suk See Kang, Elizabeth Gallin, John I. Malech, Harry L. Olivier, Kenneth N. Uzel, Gulbu Freeman, Alexandra F. Heller, Theo Zerbe, Christa S. Holland, Steven M. TI Common Severe Infections in Chronic Granulomatous Disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE bacterial infection; fungal infection; CGD; superoxide production; survival ID FUNGAL-INFECTIONS; PATIENT; IMMUNODEFICIENCIES; POSACONAZOLE; PROPHYLAXIS; MANAGEMENT; REGISTRY; THERAPY AB Background. Chronic granulomatous disease (CGD) is due to defective nicotinamide adenine dinucleotide phosphate oxidase activity and characterized by recurrent infections with a limited spectrum of bacteria and fungi as well as inflammatory complications. To understand the impact of common severe infections in CGD, we examined the records of 268 patients followed at a single center over 4 decades. Methods. All patients had confirmed diagnoses of CGD, and genotype was determined where possible. Medical records were excerpted into a standard format. Microbiologic analyses were restricted to Staphylococcus, Burkholderia, Serratia, Nocardia, and Aspergillus. Results. Aspergillus incidence was estimated at 2.6 cases per 100 patient-years; Burkholderia, 1.06 per 100 patient-years; Nocardia, 0.81 per 100 patient-years; Serratia, 0.98 per 100 patient-years, and severe Staphylococcus infection, 1.44 per 100 patient-years. Lung infection occurred in 87% of patients, whereas liver abscess occurred in 32%. Aspergillus incidence was 55% in the lower superoxide-producing quartiles (quartiles 1 and 2) but only 41% in the higher quartiles (rate ratio, <0.0001). Aspergillus and Serratia were somewhat more common in lower superoxide producing gp91(phox) deficiency. The median age at death has increased from 15.53 years before 1990 to 28.12 years in the last decade. Fungal infection carried a higher risk of mortality than bacterial infection and was the most common cause of death (55%). Gastrointestinal complications were not associated with either infection or mortality. Conclusions. Fungal infections remain a major determinant of survival in CGD. X-linked patients generally had more severe disease, and this was generally in those with lower residual superoxide production. Survival in CGD has increased over the years, but infections are still major causes of morbidity and mortality. C1 [Marciano, Beatriz E.; Spalding, Christine; Fitzgerald, Alan; Osgood, Sharon; Yockey, Lynne; Darnell, Dirk N.; Barnhart, Lisa; Daub, Janine; Anderson, Victoria L.; Haney, Carissa; Mason, Tamika; Olivier, Kenneth N.; Uzel, Gulbu; Freeman, Alexandra F.; Zerbe, Christa S.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Mann, Daphne; Brown, Thomas; Boris, Lisa; Rump, Amy P.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA. [Kuhns, Douglas B.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Serv Program, Appl Dev Res Directorate, Frederick, MD USA. [Rosenzweig, Sergio D.; Zelazny, Adrian; Malech, Harry L.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Kelly, Corin; DeRavin, Suk See; Kang, Elizabeth; Gallin, John I.] NIAID, Lab Host Defenses, NIH, Rockville, MD USA. [Heller, Theo] NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov OI Malech, Harry/0000-0001-5874-5775 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH); National Cancer Institute, NIH [HHSN261200800001E]; National Cancer Institute, Center for Cancer Research, NIH FX This project was supported by Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) and the National Cancer Institute, NIH (contract number HHSN261200800001E) and the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, NIH. NR 36 TC 36 Z9 36 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2015 VL 60 IS 8 BP 1176 EP 1183 DI 10.1093/cid/ciu1154 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CH0MX UT WOS:000353715600007 PM 25537876 ER PT J AU Andre, P Song, H Kim, W Kispert, A Yang, YZ AF Andre, Philipp Song, Hai Kim, Wantae Kispert, Andreas Yang, Yingzi TI Wnt5a and Wnt11 regulate mammalian anterior-posterior axis elongation SO DEVELOPMENT LA English DT Article DE Convergent extension; EMT; Gastrulation; Notochord; Planar cell polarity; Wnt ID PLANAR-CELL-POLARITY; NEURAL-TUBE DEFECTS; EPITHELIAL-MESENCHYMAL TRANSITIONS; CONVERGENT EXTENSION MOVEMENTS; LEFT-RIGHT ASYMMETRY; MOUSE EMBRYO; STEM-CELLS; PARAXIAL MESODERM; ZEBRAFISH GASTRULATION; MATRIX ORGANIZATION AB Mesoderm formation and subsequent anterior-posterior (A-P) axis elongation are fundamental aspects of gastrulation, which is initiated by formation of the primitive streak (PS). Convergent extension (CE) movements and epithelial-mesenchymal transition(EMT) are important for A-P axis elongation in vertebrate embryos. The evolutionarily conserved planar cell polarity (PCP) pathway regulates CE, and Wnts regulate many aspects of gastrulation including CE and EMT. However, the Wnt ligands that regulate A-P axis elongation in mammalian development remain unknown. Wnt11 and Wnt5a regulate axis elongation in lower vertebrates, but only Wnt5a, not Wnt11, regulates mammalian PCP signaling and A-P axis elongation in development. Here, by generating Wnt5a; Wnt11 compound mutants, we show that Wnt11 and Wnt5a play redundant roles during mouse A-P axis elongation. Both genes regulate trunk notochord extension through PCP-controlled CE of notochord cells, establishing a role for Wnt11 in mammalian PCP. We show that Wnt5a and Wnt11 are required for proper patterning of the neural tube and somites by regulating notochord formation, and provide evidence that both genes are required for the generation and migration of axial and paraxial mesodermal precursor cells by regulating EMT. Axial and paraxial mesodermal precursors ectopically accumulate in the PS at late gastrula stages in Wnt5a(-/-); Wnt11(-/-) embryos and these cells ectopically express epithelial cell adhesion molecules. Our data suggest that Wnt5a and Wnt11 regulate EMT by inducing p38 (Mapk14) phosphorylation. Our findings provide new insights into the role of Wnt5a and Wnt11 in mouse early development and also in cancer metastasis, during which EMT plays a crucial role. C1 [Andre, Philipp; Song, Hai; Kim, Wantae; Yang, Yingzi] NHGRI, Genet Dis Res Branch, Bethesda, MD 20814 USA. [Kispert, Andreas] Hannover Med Sch, Inst Mol Biol, D-30625 Hannover, Germany. [Yang, Yingzi] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Yang, YZ (reprint author), NHGRI, Genet Dis Res Branch, Bethesda, MD 20814 USA. EM yingzi_yang@hsdm.harvard.edu FU National Institutes of Health; German Research Foundation (DFG) FX The work in the laboratory of Y.Y. (P.A., H.S., W.K. and Y.Y.) was funded by the Intramural Research Program of the National Institutes of Health. The work in the laboratory of A.K. was funded by grants from the German Research Foundation (DFG). Deposited in PMC for release after 12 months. NR 116 TC 8 Z9 8 U1 0 U2 11 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 APR 15 PY 2015 VL 142 IS 8 BP 1516 EP 1527 DI 10.1242/dev.119065 PG 12 WC Developmental Biology SC Developmental Biology GA CG8UW UT WOS:000353590900014 PM 25813538 ER PT J AU Butler, MG Iben, JR Marsden, KC Epstein, JA Granato, M Weinstein, BM AF Butler, Matthew G. Iben, James R. Marsden, Kurt C. Epstein, Jonathan A. Granato, Michael Weinstein, Brant M. TI SNPfisher: tools for probing genetic variation in laboratory-reared zebrafish SO DEVELOPMENT LA English DT Article DE Danio rerio; Zebrafish; Genome; SNP; Variation; Next-generation sequencing; Whole-genome sequencing ID DNA-SEQUENCING DATA; HUMAN GENOME; DANIO-RERIO; MUTATIONS; MAP; POLYMORPHISM; FRAMEWORK; ALIGNMENT; STRAINS; LINKAGE AB Single nucleotide polymorphisms (SNPs) are the benchmark molecular markers for modern genomics. Until recently, relatively few SNPs were known in the zebrafish genome. The use of next-generation sequencing for the positional cloning of zebrafish mutations has increased the number of known SNP positions dramatically. Still, the identified SNP variants remain under-utilized, owing to scant annotation of strain specificity and allele frequency. To address these limitations, we surveyed SNP variation in three common laboratory zebrafish strains using whole-genome sequencing. This survey identified an average of 5.04 million SNPs per strain compared with the Zv9 reference genome sequence. By comparing the three strains, 2.7 million variants were found to be strain specific, whereas the remaining variants were shared among all (2.3 million) or some of the strains. We also demonstrate the broad usefulness of our identified variants by validating most in independent populations of the same laboratory strains. We have made all of the identified SNPs accessible through 'SNPfisher', a searchable online database (snpfisher.nichd.nih.gov). The SNPfisher website includes the SNPfisher Variant Reporter tool, which provides the genomic position, alternate allele read frequency, strain specificity, restriction enzyme recognition site changes and flanking primers for all SNPs and Indels in a user-defined gene or region of the zebrafish genome. The SNPfisher site also contains links to display our SNP data in the UCSC genome browser. The SNPfisher tools will facilitate the use of SNP variation in zebrafish research as well as vertebrate genome evolution. C1 [Butler, Matthew G.; Weinstein, Brant M.] NICHHD, Sect Vertebrate Dev, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Iben, James R.; Epstein, Jonathan A.] NICHHD, Sect Mol Dysmorphol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Marsden, Kurt C.; Granato, Michael] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. RP Weinstein, BM (reprint author), NICHHD, Sect Vertebrate Dev, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM zebrafish321@gmail.com FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Fondation Leducq (Transatlantic Network of Excellence for the Identification of Novel Genetic Targets in Hemorrhagic Stroke); National Institutes of Health [MH092257] FX This work was supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and by the Fondation Leducq (Transatlantic Network of Excellence for the Identification of Novel Genetic Targets in Hemorrhagic Stroke) to B.M.W. This work was also supported by a National Institutes of Health grant [MH092257] to M.G. Deposited in PMC for release after 12 months. NR 42 TC 3 Z9 3 U1 1 U2 9 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 APR 15 PY 2015 VL 142 IS 8 BP 1542 EP 1552 DI 10.1242/dev.118786 PG 11 WC Developmental Biology SC Developmental Biology GA CG8UW UT WOS:000353590900016 PM 25813542 ER PT J AU Dabby, R Sadeh, M Hilton-Jones, D Plotz, P Hackman, P Vihola, A Udd, B Leshinsky-Silver, E AF Dabby, Ron Sadeh, Menachem Hilton-Jones, David Plotz, Paul Hackman, Peter Vihola, Anna Udd, Bjarne Leshinsky-Silver, Esther TI Adult onset limb-girdle muscular dystrophy - A recessive titinopathy masquerading as myositis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Titin; LGMD2J; Muscular dystrophy; Inflammatory myopathy ID EARLY RESPIRATORY-FAILURE; C-TERMINAL TITIN; DILATED CARDIOMYOPATHY; HEREDITARY MYOPATHY; TRUNCATING MUTATIONS; DISTAL MYOPATHY; INFLAMMATION; FAMILY; GENE; TTN AB Rarely, inflammation can be present in genetic myopathies, such as dysferlinopathies, facioscapulohumeral muscular dystrophy and GNE-myopathy (hereditary inclusion body myopathy). This may lead to erroneous initial diagnosis and unnecessary therapy which bear serious side effects. We report on an unusual case of mutations in the TEN gene presenting with inflammatory infiltrates in the muscle biopsy. Only after intensive immune-modulating therapies failed, a genetic myopathy was considered. Exome sequencing and search for mutated muscle protein-encoding genes disclosed compound heterozygous mutations in TTN: K26320T and A6135G. The parents carry one each of the mutations. Titinopathy could be considered also in patients presenting with inflammatory infiltrates resistant to therapy. (C) 2015 Elsevier B.V. All rights reserved. C1 [Dabby, Ron; Sadeh, Menachem] Tel Aviv Univ, Sackler Fac Med, Edith Wolfson Med Ctr, Dept Neurol, IL-69978 Tel Aviv, Israel. [Hilton-Jones, David] Radcliffe Infirm, Oxford, England. [Plotz, Paul] NIAMSD, NIH, Bethesda, MD 20892 USA. [Leshinsky-Silver, Esther] Tel Aviv Univ, Sackler Fac Med, Edith Wolfson Med Ctr, Dept Mol Genet Lab, IL-69978 Tel Aviv, Israel. [Hackman, Peter; Vihola, Anna; Udd, Bjarne] Univ Helsinki, Dept Med Genet, Folkhalsan Inst Genet, FIN-00014 Helsinki, Finland. [Udd, Bjarne] Tampere Univ, Neuromuscular Res Ctr, FIN-33101 Tampere, Finland. [Udd, Bjarne] Tampere Univ Hosp, Tampere, Finland. [Udd, Bjarne] Vasa Cent Hosp, Dept Neurol, Vaasa, Finland. RP Dabby, R (reprint author), Wolfson Med Ctr, Dept Neurol, IL-58100 Holon, Israel. EM ronda@post.tau.ac.il FU Finnish Academy of Sciences; Sigrid Juselius Foundation for the scientific research on human titinopathies FX BU is supported by research grants from the Finnish Academy of Sciences and the Sigrid Juselius Foundation for the scientific research on human titinopathies. There are no potential conflicts of interest for any of the authors. NR 23 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD APR 15 PY 2015 VL 351 IS 1-2 BP 120 EP 123 DI 10.1016/j.jns.2015.03.001 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH0UP UT WOS:000353738200021 PM 25772186 ER PT J AU Dubey, JP Howe, DK Furr, M Saville, WJ Marsh, AE Reed, SM Grigg, ME AF Dubey, J. P. Howe, D. K. Furr, M. Saville, W. J. Marsh, A. E. Reed, S. M. Grigg, M. E. TI An update on Sarcocystis neurona infections in animals and equine protozoal myeloencephalitis (EPM) SO VETERINARY PARASITOLOGY LA English DT Review DE Sarcocystis neurona; Equine protozoal myeloencephalitis; Marine mammals; Epidemiology; Life cycle; Prevention ID OPOSSUMS DIDELPHIS-VIRGINIANA; ENHYDRA-LUTRIS-NEREIS; RACCOONS PROCYON-LOTOR; GENE KNOCKOUT MICE; NUCLEOSIDE TRIPHOSPHATE HYDROLASE; CATS FELIS-DOMESTICUS; ARMADILLO DASYPUS-NOVEMCINCTUS; DISTEMPER VIRUS-INFECTION; FLUORESCENT-ANTIBODY TEST; PHOCA-VITULINA-RICHARDSI AB Equine protozoal myeloencephalitis (EPM) is a serious disease of horses, and its management continues to be a challenge for veterinarians. The protozoan Sarcocystis neurona is most commonly associated with EPM. S. neurona has emerged as a common cause of mortality in marine mammals, especially sea otters (Enhydra lutris). EPM-like illness has also been recorded in several other mammals, including domestic dogs and cats. This paper updates S. neurona and EPM information from the last 15 years on the advances regarding life cycle, molecular biology, epidemiology, clinical signs, diagnosis, treatment and control. Published by Elsevier B.V. C1 [Dubey, J. P.] ARS, USDA, Anim Parasit Dis Lab, Beltsville Agr Res Ctr, Beltsville, MD 20705 USA. [Howe, D. K.] Univ Kentucky, Dept Vet Sci, MH Gluck Equine Res Ctr, Lexington, KY 40546 USA. [Furr, M.] Virginia Maryland Reg Coll Vet Med, Marion du Pont Scott Equine Med Ctr, Leesburg, VA 20176 USA. [Saville, W. J.; Marsh, A. E.] Ohio State Univ, Dept Vet Prevent Med, Columbus, OH 43210 USA. [Reed, S. M.] Rood & Riddle Equine Hosp, Lexington, KY 40511 USA. [Grigg, M. E.] NIAID, Mol Parasitol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Dubey, JP (reprint author), ARS, USDA, Anim Parasit Dis Lab, Beltsville Agr Res Ctr, Bldg 1001, Beltsville, MD 20705 USA. EM Jitender.dubey@ars.usda.gov FU NIAID/Division of Intramural Research FX This research was partially funded by the NIAID/Division of Intramural Research to MEG. MEG is a scholar of the Integrated Microbial Biodiversity program of the Canadian Institute for Advanced Research (CIFAR). We are grateful for S.K. Verma and R. Calero-Bernal for their help with illustrations and to O.C.H. Kwok and Ana Beatriez Cassinelli for bibliography. NR 280 TC 10 Z9 11 U1 8 U2 42 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4017 EI 1873-2550 J9 VET PARASITOL JI Vet. Parasitol. PD APR 15 PY 2015 VL 209 IS 1-2 BP 1 EP 42 DI 10.1016/j.vetpar.2015.01.026 PG 42 WC Parasitology; Veterinary Sciences SC Parasitology; Veterinary Sciences GA CG9AX UT WOS:000353607900001 PM 25737052 ER PT J AU Luo, HC Dimaano, VL Kembro, JM Hilser, A Hurtado-de-Mendoza, D Pozios, I Tomas, MS Yalcin, H Dolores-Cerna, K Mormontoy, W Aon, MA Cameron, D Bluemke, DA Stewart, KJ Russell, SD Cordova, JG Abraham, TP Abraham, MR AF Luo, Hong-Chang Dimaano, Veronica L. Kembro, Jackelyn M. Hilser, Alex Hurtado-de-Mendoza, David Pozios, Iraklis Tomas, Miguel S. Yalcin, Hulya Dolores-Cerna, Ketty Mormontoy, Wilfredo Aon, Miguel A. Cameron, Duke Bluemke, David A. Stewart, Kerry J. Russell, Stuart D. Cordova, Jorge G. Abraham, Theodore P. Abraham, M. Roselle TI Exercise Heart Rates in Patients With Hypertrophic Cardiomyopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID IMPAIRED CHRONOTROPIC RESPONSE; RATE RECOVERY; SUDDEN-DEATH; PREDICTOR; INCOMPETENCE; ASSOCIATION; DYSFUNCTION; MORTALITY; ISCHEMIA; MODEL AB The exercise heart rate (HR) profile and its relation to cardiac function and arrhythmias were investigated in patients with hypertrophic cardiomyopathy (HC). Chronotropic response (CR) and heart rate recovery (HRR) were computed during and after treadmill exercise testing in 273 patients with HC and 95 age-matched healthy controls. Patients with HC had higher prevalence of chronotropic incompetence and lower HRR1-5min compared with controls. Exercise capacity, diastolic function (assessed by E/e') and left atrial volume index were associated with HRR1min and CR in HC. Septal myectomy was associated with reduction in chronotropic incompetence but did not affect HRR1min. In conclusion, impaired CR and HRR1min are associated with advanced disease and do not appear to be independent clinical markers indicating high-risk status in HC. Improving CR by titrating doses of negative chronotropic agents, myectomy, and atrial pacing may be useful to increase exercise capacity in patients with HC. (C) 2015 Elsevier Inc. All rights reserved. C1 [Luo, Hong-Chang] Huazhong Univ Sci & Technol, Dept Med Ultrasound, Tongji Hosp, Tongji Med,Coll, Wuhan 430074, Peoples R China. [Luo, Hong-Chang; Dimaano, Veronica L.; Kembro, Jackelyn M.; Hilser, Alex; Hurtado-de-Mendoza, David; Pozios, Iraklis; Tomas, Miguel S.; Yalcin, Hulya; Dolores-Cerna, Ketty; Mormontoy, Wilfredo; Aon, Miguel A.; Stewart, Kerry J.; Russell, Stuart D.; Abraham, Theodore P.; Abraham, M. Roselle] Johns Hopkins Univ, Div Cardiol, Baltimore, MD 21218 USA. [Cameron, Duke] Johns Hopkins Univ, Div Cardiac Surg, Baltimore, MD USA. [Hurtado-de-Mendoza, David; Cordova, Jorge G.] Cayetano Heredia Univ, Fac Sci, Dept Stat Demog Humanities & Social Sci, Lima, Peru. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Dept Radiol & Imaging Sci, NIH, Bethesda, MD USA. RP Abraham, MR (reprint author), Johns Hopkins Univ, Div Cardiol, Baltimore, MD 21218 USA. EM mabraha3@jhmi.edu RI Aon, Miguel/A-6564-2008; OI Aon, Miguel/0000-0002-4355-5431; Bluemke, David/0000-0002-8323-8086 FU John Taylor Babbit Foundation FX This study was supported in part by a grant from the John Taylor Babbit Foundation to MRA. NR 22 TC 1 Z9 1 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2015 VL 115 IS 8 BP 1144 EP 1150 DI 10.1016/j.amjcard.2015.01.548 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG2AQ UT WOS:000353077700022 PM 25746289 ER PT J AU Goldspiel, BR Dechristoforo, R Hoffman, JM AF Goldspiel, Barry R. Dechristoforo, Robert Hoffman, James M. TI Preventing chemotherapy errors: Updating guidelines to meet new challenges SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material C1 [Hoffman, James M.] St Jude Childrens Res Hosp, Pharmaceut Sci, Memphis, TN 38105 USA. RP Goldspiel, BR (reprint author), Care of Hawkins B, Natl Inst Hlth Clin Ctr, Pharm Dept, Bethesda, MD 20892 USA. EM bhawkins@ashp.org FU PHS HHS [NCICA21765] NR 2 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 EI 1535-2900 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD APR 15 PY 2015 VL 72 IS 8 BP 668 EP 669 DI 10.2146/sp150004 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG2BH UT WOS:000353079400017 PM 25825190 ER PT J AU Liskovykh, M Ponomartsev, S Popova, E Bader, M Kouprina, N Larionov, V Alenina, N Tomilin, A AF Liskovykh, Mikhail Ponomartsev, Sergey Popova, Elena Bader, Michael Kouprina, Natalay Larionov, Vladimir Alenina, Natalia Tomilin, Alexey TI Stable maintenance of de novo assembled human artificial chromosomes in embryonic stem cells and their differentiated progeny in mice SO CELL CYCLE LA English DT Article DE embryonic stem cells; human artificial chromosomes; gene therapy ID CONDITIONAL CENTROMERE; GENE DELIVERY; HAC; EXPRESSION; GENERATION; VECTOR AB De novo assembled alphoid(tetO)-type human artificial chromosomes (HACs) represent a novel promising generation of high capacity episomal vectors. Their function and persistence, and any adverse effects, in various cell types in live animals, have not, however, been explored. In this study we transferred the alphoid(tetO)-HAC into mouse ES cells and assessed whether the presence of this extra chromosome affects their pluripotent properties. Alphoid(tetO)-HAC-bearing ES cells were indistinguishable from their wild-type counterparts: they retained self-renewal potential and full capacity for multilineage differentiation during mouse development, whereas the HAC itself was mitotically and transcriptionally stable during this process. Our data provide the first example of fully synthetic DNA behaving like a normal chromosome in cells of living animals. It also opens a new perspective into functional genetic studies in laboratory animals as well as stem cell-based regenerative medicine. C1 [Liskovykh, Mikhail; Ponomartsev, Sergey; Tomilin, Alexey] Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia. [Liskovykh, Mikhail; Ponomartsev, Sergey; Tomilin, Alexey] Skolkovo Inst Sci & Technol, Skoltech Ctr Stem Cell Res, Moscow, Russia. [Liskovykh, Mikhail; Kouprina, Natalay; Larionov, Vladimir] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Popova, Elena; Bader, Michael; Alenina, Natalia] Max Delbruck Ctr Mol Med, Berlin, Germany. RP Tomilin, A (reprint author), Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia. EM mikhail.liskovykh@nih.gov; antom@mail.cytspb.rssi.ru RI Tomilin, Alexey/C-3361-2014 OI Tomilin, Alexey/0000-0002-1137-7167 FU International Academy of Life Science (IALS); Boehringer Ingelheim Fonds (BIF); President's stipend for young scientists [3805.2013.4]; DAAD [A/12/87445]; German Ministry for Education and Research (BMBF) [01DJ13012]; Russian Foundation for Basic Research [14-04-31556, 13-02-00923]; Russian Science Foundation [14-50-00068]; Federal Agency of Scientific Organizations (Russia) FX This work was supported by International Academy of Life Science (IALS) grant, Boehringer Ingelheim Fonds (BIF) grant, President's stipend for young scientists (3805.2013.4), DAAD (A/12/87445) to ML and NA, German Ministry for Education and Research (BMBF) grant to MB (01DJ13012), Russian Foundation for Basic Research grant to ML (14-04-31556) and to AT (13-02-00923). The part of the study dedicated to chromosome analysis was supported by the Russian Science Foundation (project No 14-50-00068) and the Federal Agency of Scientific Organizations (Russia). NR 27 TC 3 Z9 3 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD APR 15 PY 2015 VL 14 IS 8 BP 1268 EP 1273 DI 10.1080/15384101.2015.1014151 PG 6 WC Cell Biology SC Cell Biology GA CG3GZ UT WOS:000353168600022 PM 25695642 ER PT J AU Liyasova, MS Ma, K Lipkowitz, S AF Liyasova, Mariya S. Ma, Ke Lipkowitz, Stanley TI Molecular Pathways: Cbl Proteins in Tumorigenesis and Antitumor Immunity-Opportunities for Cancer Treatment SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; PHOSPHOTYROSINE-BINDING DOMAIN; ACQUIRED UNIPARENTAL DISOMY; UBIQUITIN LIGASE ACTIVITY; ACUTE MYELOID-LEUKEMIA; CD8(+) T-CELLS; C-CBL; DOWN-REGULATION; EGF-RECEPTOR; RING FINGER AB The Cbl proteins are a family of ubiquitin ligases (E3s) that regulate signaling through many tyrosine kinase-dependent pathways. A predominant function is to negatively regulate receptor tyrosine kinase (RTK) signaling by ubiquitination of active RTKs, targeting them for trafficking to the lysosome for degradation. Also, Cbl-mediated ubiquitination can regulate signaling protein function by altered cellular localization of proteins without degradation. In addition to their role as E3s, Cbl proteins play a positive role in signaling by acting as adaptor proteins that can recruit signaling molecules to the active RTKs. Cbl-b, a second family member, negatively regulates the costimulatory pathway of CD8 T cells and also negatively regulates natural killer cell function. The different functions of Cbl proteins and their roles both in the development of cancer and the regulation of immune responses provide multiple therapeutic opportunities. Mutations in Cbl that inactivate the negative E3 function while maintaining the positive adaptor function have been described in approximately 5% of myeloid neoplasms. An improved understanding of how the signaling pathways [e.g., Fms-like tyrosine kinase 3 (Flt3), PI3K, and signal transducer and activator of transcription (Stat)] are dysregulated by these mutations in Cbl has helped to identify potential targets for therapy of myeloid neoplasms. Conversely, the loss of Cbl-b leads to increased adaptive and innate antitumor immunity, suggesting that inhibiting Cbl-b may be a means to increase antitumor immunity across a wide variety of tumors. Thus, targeting the pathways regulated by Cbl proteins may provide attractive opportunities for treating cancer. (C)2014 AACR. C1 [Liyasova, Mariya S.; Ma, Ke; Lipkowitz, Stanley] NCI, Womens Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lipkowitz, S (reprint author), NCI, Womens Malignancies Branch, Ctr Canc Res, Bldg 37,Room 2066,Convent Dr, Bethesda, MD 20892 USA. EM lipkowis@mail.nih.gov FU Intramural Research Program of the NIH, NCI, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. NR 66 TC 8 Z9 9 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2015 VL 21 IS 8 BP 1789 EP 1794 DI 10.1158/1078-0432.CCR-13-2490 PG 6 WC Oncology SC Oncology GA CF9PJ UT WOS:000352897200004 PM 25477533 ER PT J AU Bates, SE AF Bates, Susan E. TI Targeting RAS: The Elusive Prize SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2015 VL 21 IS 8 BP 1796 EP 1796 DI 10.1158/1078-0432.CCR-14-2664 PG 1 WC Oncology SC Oncology GA CF9PJ UT WOS:000352897200005 PM 25878359 ER PT J AU McCormick, F AF McCormick, Frank TI KRAS as a Therapeutic Target SO CLINICAL CANCER RESEARCH LA English DT Article ID ONCOGENIC K-RAS; PANCREATIC-CANCER; MEK INHIBITION; LUNG-CANCER; IN-VIVO; N-RAS; ACTIVATION; DISCOVERY; MELANOMA; SURVIVAL AB KRAS proteins play a major role in human cancer, but have not yielded to therapeutic attack. New technologies in drug discovery and insights into signaling pathways that KRAS controls have promoted renewed efforts to develop therapies through direct targeting of KRAS itself, new ways of blocking KRAS processing, or by identifying targets that KRAS cancers depend on for survival. Although drugs that block the well-established downstream pathways, RAF-MAPK and PI3K, are being tested in the clinic, new efforts are under way to exploit previously unrecognized vulnerabilities, such as altered metabolic networks, or novel pathways identified through synthetic lethal screens. Furthermore, new ways of suppressing KRAS gene expression and of harnessing the immune system offer further hope that new ways of treating KRAS are finally coming into view. These issues are discussed in this edition of CCR Focus. (C)2015 AACR. C1 [McCormick, Frank] Frederick Natl Lab Canc Res, Frederick, MD USA. [McCormick, Frank] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA. RP McCormick, F (reprint author), Univ Calif San Francisco, 1450 3rd St, San Francisco, CA 94158 USA. EM mccormick@cc.ucsf.edu FU NCI NIH HHS [U01 CA168370] NR 40 TC 36 Z9 37 U1 4 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2015 VL 21 IS 8 BP 1797 EP 1801 DI 10.1158/1078-0432.CCR-14-2662 PG 5 WC Oncology SC Oncology GA CF9PJ UT WOS:000352897200006 PM 25878360 ER PT J AU Xi, Y Honeywell, C Zhang, D Schwartzentruber, J Beaulieu, CL Tetreault, M Hartley, T Marton, J Vidal, SM Majewski, J Aravind, L Gollob, M Boycott, KM Gow, RM AF Xi, Yanwei Honeywell, Christina Zhang, Dapeng Schwartzentruber, Jeremy Beaulieu, Chandree L. Tetreault, Martine Hartley, Taila Marton, Jennifer Vidal, Silvia M. Majewski, Jacek Aravind, L. Gollob, Michael Boycott, Kym M. Gow, Robert M. CA Care4Rare Canada Consortium TI Whole exome sequencing identifies the TNNI3K gene as a cause of familial conduction system disease and congenital junctional ectopic tachycardia SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Exome sequencing; TNNI3K; Junctional ectopic tachycardia ID MUTATION C1 [Xi, Yanwei; Boycott, Kym M.; Care4Rare Canada Consortium] Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada. [Honeywell, Christina; Beaulieu, Chandree L.; Hartley, Taila; Boycott, Kym M.; Gow, Robert M.] Childrens Hosp Eastern Ontario, Dept Pediat, Ottawa, ON K1H 8L1, Canada. [Zhang, Dapeng; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Schwartzentruber, Jeremy; Tetreault, Martine; Majewski, Jacek] McGill Univ, Montreal, PQ, Canada. [Schwartzentruber, Jeremy; Tetreault, Martine; Majewski, Jacek] Quebec Innovat Ctr, Montreal, PQ, Canada. [Tetreault, Martine; Marton, Jennifer; Vidal, Silvia M.; Majewski, Jacek] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Gollob, Michael] Univ Toronto, Toronto Gen Hosp, Dept Cardiol, Toronto, ON M5G 1L7, Canada. RP Boycott, KM (reprint author), Childrens Hosp Eastern Ontario, Div Cardiol, 401 Smyth Rd, Ottawa, ON K1H 8L1, Canada. EM kboycott@cheo.on.ca; rgow@cheo.on.ca OI Schwartzentruber, Jeremy/0000-0002-6183-2092 FU Canadian Institutes of Health Research [GPH-129346]; Intramural NIH HHS NR 10 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD APR 15 PY 2015 VL 185 BP 114 EP 116 DI 10.1016/j.ijcard.2015.03.130 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG3QR UT WOS:000353195200031 PM 25791106 ER PT J AU Richard, AC Tan, CY Hawley, ET Gomez-Rodriguez, J Goswami, R Yang, XP Cruz, AC Penumetcha, P Hayes, ET Pelletier, M Gabay, O Walsh, M Ferdinand, JR Keane-Myers, A Choi, YW O'Shea, JJ Al-Shamkhani, A Kaplan, MH Gery, I Siegel, RM Meylan, F AF Richard, Arianne C. Tan, Cuiyan Hawley, Eric T. Gomez-Rodriguez, Julio Goswami, Ritobrata Yang, Xiang-Ping Cruz, Anthony C. Penumetcha, Pallavi Hayes, Erika T. Pelletier, Martin Gabay, Odile Walsh, Matthew Ferdinand, John R. Keane-Myers, Andrea Choi, Yongwon O'Shea, John J. Al-Shamkhani, Aymen Kaplan, Mark H. Gery, Igal Siegel, Richard M. Meylan, Francoise TI The TNF-Family Ligand TL1A and Its Receptor DR3 Promote T Cell-Mediated Allergic Immunopathology by Enhancing Differentiation and Pathogenicity of IL-9-Producing T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INNATE LYMPHOID-CELLS; DOMAIN-CONTAINING RECEPTOR; NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; TRANSCRIPTION FACTOR PU.1; AIRWAY INFLAMMATION; LUNG INFLAMMATION; TH9 CELLS; RHEUMATOID-ARTHRITIS; IL-9 PRODUCTION AB The TNF family cytokine TL1A (Tnfsf15) costimulates T cells and type 2 innate lymphocytes (ILC2) through its receptor DR3 (Tnfrsf25). DR3-deficient mice have reduced T cell accumulation at the site of inflammation and reduced ILC2-dependent immune responses in a number of models of autoimmune and allergic diseases. In allergic lung disease models, immunopathology and local Th2 and ILC2 accumulation is reduced in DR3-deficient mice despite normal systemic priming of Th2 responses and generation of T cells secreting IL-13 and IL-4, prompting the question of whether TL1A promotes the development of other T cell subsets that secrete cytokines to drive allergic disease. In this study, we find that TL1A potently promotes generation of murine T cells producing IL-9 (Th9) by signaling through DR3 in a cell-intrinsic manner. TL1A enhances Th9 differentiation through an IL-2 and STAT5-dependent mechanism, unlike the TNF-family member OX40, which promotes Th9 through IL-4 and STAT6. Th9 differentiated in the presence of TL1A are more pathogenic, and endogenous TL1A signaling through DR3 on T cells is required for maximal pathology and IL-9 production in allergic lung inflammation. Taken together, these data identify TL1A-DR3 interactions as a novel pathway that promotes Th9 differentiation and pathogenicity. TL1A may be a potential therapeutic target in diseases dependent on IL-9. C1 [Richard, Arianne C.; Hawley, Eric T.; Cruz, Anthony C.; Penumetcha, Pallavi; Hayes, Erika T.; Pelletier, Martin; Gabay, Odile; Ferdinand, John R.; Siegel, Richard M.; Meylan, Francoise] NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Tan, Cuiyan; Gery, Igal] NEI, Expt Immunol Sect, NIH, Bethesda, MD 20892 USA. [Gomez-Rodriguez, Julio] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Gomez-Rodriguez, Julio; Kaplan, Mark H.] Indiana Univ Sch Med, Dept Pediat & Microbiol & Immunol, Indianapolis, IN 46202 USA. [Yang, Xiang-Ping; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Walsh, Matthew; Choi, Yongwon] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19102 USA. [Ferdinand, John R.; Al-Shamkhani, Aymen] Univ Southampton, Fac Med, Canc Sci Acad Unit, Southampton SO17 1BJ, Hants, England. [Keane-Myers, Andrea] Naval Med Res Ctr Frederick, Biol Def Res Directorate, Ft Detrick, MD 21702 USA. RP Siegel, RM (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 13C103A, Bethesda, MD 20892 USA. EM rsiegel@nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Eye Institute; National Institutes of Health-Oxford-Cambridge; National Institutes of Health-Wellcome Trust FX This work was supported by the intramural research programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Eye Institute, as well as the National Institutes of Health-Oxford-Cambridge and National Institutes of Health-Wellcome Trust Ph.D. programs. NR 75 TC 16 Z9 17 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 APR 15 PY 2015 VL 194 IS 8 BP 3567 EP 3582 DI 10.4049/jimmunol.1401220 PG 16 WC Immunology SC Immunology GA CG4HU UT WOS:000353247000007 PM 25786692 ER PT J AU Bin Dhuban, K d'Hennezel, E Nashi, E Bar-Or, A Rieder, S Shevach, EM Nagata, S Piccirillo, CA AF Bin Dhuban, Khalid d'Hennezel, Eva Nashi, Emil Bar-Or, Amit Rieder, Sadiye Shevach, Ethan M. Nagata, Satoshi Piccirillo, Ciriaco A. TI Coexpression of TIGIT and FCRL3 Identifies Helios(+) Human Memory Regulatory T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ROR-GAMMA-T; GENE-EXPRESSION; RHEUMATOID-ARTHRITIS; FUNCTIONAL VARIANT; FOXP3; TRANSCRIPTION; SUBSET; HETEROGENEITY; ACTIVATION; EXPANSION AB Two distinct subsets of CD4(+) Foxp3(+) regulatory T (Treg) cells have been described based on the differential expression of Helios, a transcription factor of the Ikaros family. Efforts to understand the origin and biological roles of these Treg populations in regulating immune responses have, however, been hindered by the lack of reliable surface markers to distinguish and isolate them for subsequent functional studies. Using a single-cell cloning strategy coupled with microarray analysis of different Treg functional subsets in humans, we identify the mRNA and protein expression of TIGIT and FCRL3 as a novel surface marker combination that distinguishes Helios(+) FOXP3+ from Helios(-)FOXP(3+) memory cells. Unlike conventional markers that are modulated on conventional T cells upon activation, we show that the TIGIT/FCRL3 combination allows reliable identification of Helios(+) Treg cells even in highly activated conditions in vitro as well as in PBMCs of autoimmune patients. We also demonstrate that the Helios(-)FOXP(3+) Treg subpopulation harbors a larger proportion of nonsuppressive clones compared with the Helios(+) FOXP3+ cell subset, which is highly enriched for suppressive clones. Moreover, we find that Helios 2 cells are exclusively responsible for the productions of the inflammatory cytokines IFN-gamma, IL-2, and IL-17 in FOXP3+ cells ex vivo, highlighting important functional differences between Helios(+) and Helios(-) Treg cells. Thus, we identify novel surface markers for the consistent identification and isolation of Helios(+) and Helios(-) memory Treg cells in health and disease, and we further reveal functional differences between these two populations. These new markers should facilitate further elucidation of the functional roles of Helios(-) based Treg heterogeneity. C1 [Bin Dhuban, Khalid; d'Hennezel, Eva; Piccirillo, Ciriaco A.] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3G 1A4, Canada. [Bin Dhuban, Khalid; d'Hennezel, Eva; Piccirillo, Ciriaco A.] McGill Univ, Ctr Hlth, Federat Clin Immunol Ctr Excellence, Res Inst, Montreal, PQ H3G 1A4, Canada. [Nashi, Emil] McGill Univ, Ctr Hlth, Div Allergy & Immunol, Montreal, PQ H2C 2P2, Canada. [Bar-Or, Amit] McGill Univ, Montreal Neurol Inst & Hosp, Neuroimmunol Unit, Montreal, PQ H3A 2B4, Canada. [Rieder, Sadiye; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Nagata, Satoshi] Sanford Res, Canc Biol Res Ctr, Sioux Falls, SD 57104 USA. RP Piccirillo, CA (reprint author), McGill Univ, Ctr Hlth, Ctr Translat Biol, Res Inst, Bloc E,Room E-M2-3248,1001 Blvd Decarie, Montreal, PQ H4A 3J1, Canada. EM Ciro.piccirillo@mcgill.ca FU Canadian Institutes for Health Research [MOP67211, MOP84041]; National Institutes of Health Centers of Biomedical Research Excellence Grant [P20 GM103548]; Research Institute of the McGill University Health Centre FX This work was supported by Canadian Institutes for Health Research Grant MOP67211 (to C.A.P.), as well as by Canadian Institutes for Health Research Grant MOP84041 from the New Emerging Team in "Clinical Autoimmunity: Immune Regulation and Biomarker Development in Pediatric and Adult Onset Autoimmune Diseases" (to C.A.P. and A.B.-O.). C.A.P. holds a Canada Research Chair. S.N. was supported by National Institutes of Health Centers of Biomedical Research Excellence Grant P20 GM103548. K.B.D. is the recipient of research fellowships from the Canadian Institutes for Health Research neuroinflammation training program and the Research Institute of the McGill University Health Centre. NR 41 TC 20 Z9 20 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2015 VL 194 IS 8 BP 3687 EP + DI 10.4049/jimmunol.1401803 PG 14 WC Immunology SC Immunology GA CG4HU UT WOS:000353247000018 PM 25762785 ER PT J AU Nakano, H Moran, TP Nakano, K Gerrish, KE Bortner, CD Cook, DN AF Nakano, Hideki Moran, Timothy P. Nakano, Keiko Gerrish, Kevin E. Bortner, Carl D. Cook, Donald N. TI Complement Receptor C5aR1/CD88 and Dipeptidyl Peptidase-4/CD26 Define Distinct Hematopoietic Lineages of Dendritic Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4 T-CELLS; AIRWAY INFLAMMATION; MEDIATED-IMMUNITY; LYMPHOID-TISSUE; MACROPHAGES; EXPRESSION; RESPONSES; ANTIGEN; ASTHMA; MICE AB Differential display of the integrins CD103 and CD11b are widely used to distinguish two major dendritic cell (DC) subsets in nonlymphoid tissues. CD103(+) DCs arise from FLT3-dependent DC precursors (preDCs), whereas CD11b(hi) DCs can arise either from preDCs or FLT3-independent monocytes. Functional characterization of these two lineages of CD11b(hi) DCs has been hindered by the lack of a widely applicable method to distinguish between them. We performed gene expression analysis of fractionated lung DCs from C57BL/6 mice and found that monocyte-derived DCs (moDCs), including CD11b(hi)Ly-6C(lo) tissue-resident and CD11b(hi)Ly-6C(hi) inflammatory moDCs, express the complement 5a receptor 1/CD88, whereas preDC-derived conventional DCs (cDCs), including CD103(+) and CD11b(hi) cDCs, express dipeptidyl peptidase-4/CD26. Flow cytometric analysis of multiple organs, including the kidney, liver, lung, lymph nodes, small intestine, and spleen, confirmed that reciprocal display of CD88 and CD26 can reliably distinguish FLT3-independent moDCs from FLT3-dependent cDCs in C57BL/6 mice. Similar results were obtained when DCs from BALB/c mice were analyzed. Using this novel approach to study DCs in mediastinal lymph nodes, we observed that most blood-derived lymph node-resident DCs, as well as tissue-derived migratory DCs, are cDCs. Furthermore, cDCs, but not moDCs, stimulated naive T cell proliferation. We anticipate that the use of Abs against CD88 and CD26 to distinguish moDCs and cDCs in multiple organs and mouse strains will facilitate studies aimed at assigning specific functions to distinct DC lineages in immune responses. C1 [Nakano, Hideki; Moran, Timothy P.; Nakano, Keiko; Cook, Donald N.] NIEHS, Immun Inflammat & Dis Lab, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Moran, Timothy P.] Duke Univ, Div Allergy & Immunol, Dept Pediat, Med Ctr, Durham, NC 27705 USA. [Gerrish, Kevin E.] NIEHS, Mol Genet Core Lab, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Bortner, Carl D.] NIEHS, Signal Transduct Lab, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Nakano, H (reprint author), NIEHS, Immun Inflammat & Dis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM nakanoh@niehs.nih.gov OI Moran, Timothy/0000-0002-6832-9772 FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [ES102025-09] FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences Grant ZIA ES102025-09. NR 53 TC 6 Z9 6 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2015 VL 194 IS 8 BP 3808 EP + DI 10.4049/jimmunol.1402195 PG 16 WC Immunology SC Immunology GA CG4HU UT WOS:000353247000029 PM 25769922 ER PT J AU Siciliano, CA Calipari, ES Carlson, VCC Helms, CM Lovinger, DM Grant, KA Jones, SR AF Siciliano, Cody A. Calipari, Erin S. Carlson, Verginia C. Cuzon Helms, Christa M. Lovinger, David M. Grant, Kathleen A. Jones, Sara R. TI Voluntary Ethanol Intake Predicts kappa-Opioid Receptor Supersensitivity and Regionally Distinct Dopaminergic Adaptations in Macaques SO JOURNAL OF NEUROSCIENCE LA English DT Article DE kappa-opioid receptor; caudate; dopamine; nonhuman primate; nucleus accumbens; voltammetry ID NUCLEUS-ACCUMBENS; DORSAL STRIATUM; INDUCED PLASTICITY; RAT-BRAIN; LONG-TERM; ALCOHOL; AGONISTS; COCAINE; DEPENDENCE; RELEASE AB The dopaminergic projections from the ventral midbrain to the striatum have long been implicated in mediating motivated behaviors and addiction. Previously it was demonstrated that kappa-opioid receptor (KOR) signaling in the striatum plays a critical role in the increased reinforcing efficacy of ethanol following ethanol vapor exposure in rodent models. Although rodents have been used extensively to determine the neurochemical consequences of chronic ethanol exposure, establishing high levels of voluntary drinking in these models has proven difficult. Conversely, nonhuman primates exhibit similar intake and pattern to humans in regard to drinking. Here we examine the effects of chronic voluntary ethanol self-administration on dopamine neurotransmission and the ability of KORs to regulate dopamine release in the dorsolateral caudate (DLC) and nucleus accumbens (NAc) core. Using voltammetry in brain slices from cynomolgus macaques after 6 months of ad libitum ethanol drinking, we found increased KOR sensitivity in both the DLC and NAc. The magnitude of ethanol intake predicted increases in KOR sensitivity in the NAc core, but not the DLC. Additionally, ethanol drinking increased dopamine release and uptake in the NAc, but decreased both of these measures in the DLC. These data suggest that chronic daily drinking may result in regionally distinct disruptions of striatal outputs. In concert with previous reports showing increased KOR regulation of drinking behaviors induced by ethanol exposure, the strong relationship between KOR activity and voluntary ethanol intake observed here gives further support to the hypothesis that KORs may provide a promising pharmacotherapeutic target in the treatment of alcoholism. C1 [Siciliano, Cody A.; Calipari, Erin S.; Jones, Sara R.] Wake Forest Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. [Carlson, Verginia C. Cuzon; Helms, Christa M.; Grant, Kathleen A.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA. [Lovinger, David M.] NIAAA, Lab Integrat Neurosci, Sect Synapt Pharmacol, NIH, Rockville, MD 20832 USA. RP Jones, SR (reprint author), Wake Forest Sch Med, Dept Physiol & Pharmacol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM srjones@wakehealth.edu OI Siciliano, Cody/0000-0001-9871-2089 FU NIH [U01 AA014091, P01 AA021099, F31 DA031533, F31 DA037710, T32 AA007565, P51 OD011092, R24 AA019431, P60 AA10760]; Division of Intramural Clinical and Biomedical Research; National Institute of Alcohol Abuse and Alcoholism; Integrative Neuroscience Initiative on Alcoholism [AA13510] FX This work was supported by NIH Grants U01 AA014091, P01 AA021099 (S.R.J.), F31 DA031533 (E.S.C.), F31 DA037710, T32 AA007565 (C.A.S.), P51 OD011092, R24 AA019431, and P60 AA10760 (K.A.G.); the Division of Intramural Clinical and Biomedical Research, National Institute of Alcohol Abuse and Alcoholism (D.M.L.), and Integrative Neuroscience Initiative on Alcoholism Grant AA13510 (K.A.G.). NR 50 TC 9 Z9 9 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 2015 VL 35 IS 15 BP 5959 EP 5968 DI 10.1523/JNEUROSCI.4820-14.2015 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CG1SZ UT WOS:000353055600008 PM 25878269 ER PT J AU Ford, A Castonguay, A Cottet, M Little, JW Chen, Z Symons-Liguori, AM Doyle, T Egan, TM Vanderah, TW De Konnick, Y Tosh, DK Jacobson, KA Salvemini, D AF Ford, Amanda Castonguay, Annie Cottet, Martin Little, Joshua W. Chen, Zhoumou Symons-Liguori, Ashley M. Doyle, Timothy Egan, Terrance M. Vanderah, Todd W. De Konnick, Yves Tosh, Dilip K. Jacobson, Kenneth A. Salvemini, Daniela TI Engagement of the GABA to KCC2 Signaling Pathway Contributes to the Analgesic Effects of A(3)AR Agonists in Neuropathic Pain SO JOURNAL OF NEUROSCIENCE LA English DT Article DE adenosine; adenosine receptors; GABA; KCC2; neuropathic pain ID CL-COTRANSPORTER KCC2; GAMMA-AMINOBUTYRIC-ACID; CATION-CHLORIDE-COTRANSPORTERS; PERIPHERAL-NERVE INJURY; SPINAL-CORD STIMULATION; ADENOSINE RECEPTOR; DORSAL-HORN; TYROSINE PHOSPHORYLATION; GABAERGIC INHIBITION; UP-REGULATION AB More than 1.5 billion people worldwide suffer from chronic pain, yet current treatment strategies often lack efficacy or have deleterious side effects in patients. Adenosine is an inhibitory neuromodulator that was previously thought to mediate antinociception through the A(1) and A(2A) receptor subtypes. We have since demonstrated that A(3)AR agonists have potent analgesic actions in preclinical rodent models of neuropathic pain and that A(3)AR analgesia is independent of adenosine A(1) or A(2A) unwanted effects. Herein, we explored the contribution of the GABA inhibitory system to A(3)AR-mediated analgesia using well-characterized mouse and rat models of chronic constriction injury (CCI)-induced neuropathic pain. The deregulation of GABA signaling in pathophysiological pain states is well established: GABA signaling can be hampered by a reduction in extracellular GABA synthesis by GAD65 and enhanced extracellular GABA reuptake via the GABA transporter, GAT-1. In neuropathic pain, GABA(A)R-mediated signaling can be further disrupted by the loss of the KCC2 chloride anion gradient. Here, we demonstrate that A(3)AR agonists (IB-MECA and MRS5698) reverse neuropathic pain via a spinal mechanism of action that modulates GABA activity. Spinal administration of the GABA(A) antagonist, bicuculline, disrupted A(3)AR-mediated analgesia. Furthermore, A(3)AR-mediated analgesia was associated with reductions in CCI-related GAD65 and GAT-1 serine dephosphorylation as well as an enhancement of KCC2 serine phosphorylation and activity. Our results suggest that A(3)AR-mediated reversal of neuropathic pain increases modulation of GABA inhibitory neurotransmission both directly and indirectly through protection of KCC2 function, underscoring the unique utility of A(3)AR agonists in chronic pain. C1 [Ford, Amanda; Chen, Zhoumou; Doyle, Timothy; Egan, Terrance M.; Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA. [Castonguay, Annie; Cottet, Martin; De Konnick, Yves] Inst Univ Sante Mentale Quebec, Quebec City, PQ G1J 2G3, Canada. [Castonguay, Annie; Cottet, Martin; De Konnick, Yves] Univ Laval, Dept Psychiat & Neurosci, Ste Foy, PQ G1K 7P4, Canada. [Little, Joshua W.] St Louis Univ, Sch Med, Dept Surg, Ctr Anat Sci & Educ, St Louis, MO 63104 USA. [Symons-Liguori, Ashley M.; Vanderah, Todd W.] Univ Arizona, Dept Pharmacol, Coll Med, Tucson, AZ 85724 USA. [Tosh, Dilip K.; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Salvemini, D (reprint author), St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, 1402 S Grand Blvd, St Louis, MO 63104 USA. EM salvemd@slu.edu RI Jacobson, Kenneth/A-1530-2009; De Koninck, Yves/C-2659-2008 OI Jacobson, Kenneth/0000-0001-8104-1493; De Koninck, Yves/0000-0002-5779-9330 FU National Cancer Institute [RO1CA169519]; St. Louis Cancer Center; Canadian Institutes of Health Research [MOP12942]; National Institute of Diabetes and Digestive and Kidney Diseases FX This study was supported by National Cancer Institute Grant RO1CA169519, the St. Louis Cancer Center, the Canadian Institutes of Health Research (MOP12942), and the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program. We thank Joe Henry Steinbach (Washington University, St. Louis) for the gift of plasmids encoding the GABA subunits. NR 74 TC 11 Z9 12 U1 2 U2 15 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 2015 VL 35 IS 15 BP 6057 EP 6067 DI 10.1523/JNEUROSCI.4495-14.2015 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CG1SZ UT WOS:000353055600018 PM 25878279 ER PT J AU Barbier, E Tapocik, JD Juergens, N Pitcairn, C Borich, A Schank, JR Sun, H Schuebel, K Zhou, ZF Yuan, QP Vendruscolo, LF Goldman, D Heilig, M AF Barbier, Estelle Tapocik, Jenica D. Juergens, Nathan Pitcairn, Caleb Borich, Abbey Schank, Jesse R. Sun, Hui Schuebel, Kornel Zhou, Zhifeng Yuan, Qiaoping Vendruscolo, Leandro F. Goldman, David Heilig, Markus TI DNA Methylation in the Medial Prefrontal Cortex Regulates Alcohol-Induced Behavior and Plasticity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE alcoholism; DNA methylation; DNMT; epigenetics; neurotransmitter release; plasticity ID EXPRESSION ANALYSIS; RNA-SEQ; DRINKING; ETHANOL; BRAIN; NEURONS; RATS; ACTIVATION; INHIBITORS; ADDICTION AB Recent studies have suggested an association between alcoholism and DNA methylation, a mechanism that can mediate long-lasting changes in gene transcription. Here, we examined the contribution of DNA methylation to the long-term behavioral and molecular changes induced by a history of alcohol dependence. In search of mechanisms underlying persistent rather than acute dependence-induced neuroadaptations, we studied the role of DNA methylation regulating medial prefrontal cortex (mPFC) gene expression and alcohol-related behaviors in rats 3 weeks into abstinence following alcohol dependence. Postdependent rats showed escalated alcohol intake, which was associated with increased DNA methylation as well as decreased expression of genes encoding synaptic proteins involved in neurotransmitter release in the mPFC. Infusion of the DNA methyltransferase inhibitor RG108 prevented both escalation of alcohol consumption and dependence-induced downregulation of 4 of the 7 transcripts modified in postdependent rats. Specifically, RG108 treatment directly reversed both downregulation of synaptotagmin 2 (Syt2) gene expression and hypermethylation on CpG#5 of its first exon. Lentiviral inhibition of Syt2 expression in the mPFC increased aversion-resistant alcohol drinking, supporting a mechanistic role of Syt2 in compulsive-like behavior. Our findings identified a functional role of DNA methylation in alcohol dependence-like behavioral phenotypes and a candidate gene network that may mediate its effects. Together, these data provide novel evidence for DNA methyltransferases as potential therapeutic targets in alcoholism. C1 [Barbier, Estelle; Heilig, Markus] Linkoping Univ, Fac Hlth Sci, Div Cell Biol, Dept Clin & Expt Med, SE-58185 Linkoping, Sweden. [Tapocik, Jenica D.; Juergens, Nathan; Pitcairn, Caleb; Borich, Abbey; Schank, Jesse R.; Sun, Hui; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. [Schuebel, Kornel; Zhou, Zhifeng; Yuan, Qiaoping; Goldman, David] NIAAA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. [Vendruscolo, Leandro F.] NIDA, Integrat Neurosci Res Branch, NIH, Baltimore, MD 21224 USA. RP Barbier, E (reprint author), NIAAA, Lab Clin & Translat Studies, 10 Ctr Dr,10-1E-5334, Bethesda, MD 20892 USA. EM estelle.barbier@liu.se RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 40 TC 10 Z9 10 U1 2 U2 13 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 2015 VL 35 IS 15 BP 6153 EP 6164 DI 10.1523/JNEUROSCI.4571-14.2015 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CG1SZ UT WOS:000353055600026 PM 25878287 ER PT J AU Hall, AM Throesch, BT Buckingham, SC Markwardt, SJ Peng, Y Wang, Q Hoffman, DA Roberson, ED AF Hall, Alicia M. Throesch, Benjamin T. Buckingham, Susan C. Markwardt, Sean J. Peng, Yin Wang, Qin Hoffman, Dax A. Roberson, Erik D. TI Tau-Dependent Kv4.2 Depletion and Dendritic Hyperexcitability in a Mouse Model of Alzheimer's Disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer; amyloid-beta; dendrites; excitability; Kv4.2; tau ID HIPPOCAMPAL PYRAMIDAL NEURONS; MENTAL-RETARDATION PROTEIN; POTASSIUM CHANNEL SUBUNITS; AMYLOID-BETA OLIGOMERS; LONG-TERM POTENTIATION; COGNITIVE IMPAIRMENTS; K+ CURRENT; PLAQUE-FORMATION; MESSENGER-RNAS; KNOCKOUT MICE AB Neuronal hyperexcitability occurs early in the pathogenesis of Alzheimer's disease (AD) and contributes to network dysfunction in AD patients. In other disorders with neuronal hyperexcitability, dysfunction in the dendrites often contributes, but dendritic excitability has notbeendirectly examined in AD models. We used dendritic patch-clamp recordings to measure dendritic excitability in the CA1 region of the hippocampus. We found that dendrites, more so than somata, of hippocampal neurons were hyperexcitable in mice overexpressing A beta. This dendritic hyperexcitability was associated with depletion of Kv4.2, a dendritic potassium channel important for regulating dendritic excitability and synaptic plasticity. The antiepileptic drug, levetiracetam, blocked Kv4.2 depletion. Tau was required, as crossing with tau knock-out mice also prevented both Kv4.2 depletion and dendritic hyperexcitability. Dendritic hyperexcitability induced by Kv4.2 deficiency exacerbated behavioral deficits and increased epileptiform activity in hAPP mice. We conclude that increased dendritic excitability, associated with changes in dendritic ion channels including Kv4.2, may contribute to neuronal dysfunction in early stages AD. C1 [Hall, Alicia M.; Roberson, Erik D.] Univ Alabama Birmingham, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA. [Hall, Alicia M.; Roberson, Erik D.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Hall, Alicia M.; Buckingham, Susan C.; Markwardt, Sean J.; Roberson, Erik D.] Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA. [Peng, Yin; Wang, Qin] Univ Alabama Birmingham, Dept Cel Dev & Integrat Biol, Birmingham, AL 35294 USA. [Throesch, Benjamin T.; Hoffman, Dax A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Mol Neurophysiol & Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Hoffman, DA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Mol Neurophysiol & Biophys Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hoffmand@mail.nih.gov; eroberson@uab.edu OI Throesch, Benjamin/0000-0001-6834-8263; Hoffman, Dax/0000-0001-6999-2157 FU National Institutes of Health [R01NS075487, R21NS052595, T32GM008111]; National Institute of Child Health and Human Development FX This work was supported by the National Institutes of Health Grants R01NS075487, R21NS052595, and T32GM008111 and the National Institute of Child Health and Human Development Intramural Research Program. We thank Dr. Dane Chetkovich for the gift of the HCN antibodies; Dr. Linda Overstreet-Wadiche for help with the dentate granule cell electrophysiology; Dr. Pascal Sanchez for advice on the levetiracetam treatment protocol; and James Black and Miriam Roberson for assistance with the mouse colony. NR 52 TC 15 Z9 16 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 2015 VL 35 IS 15 BP 6221 EP 6230 DI 10.1523/JNEUROSCI.2552-14.2015 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CG1SZ UT WOS:000353055600031 PM 25878292 ER PT J AU Leao, RM Cruz, FC Vendruscolo, LF de Guglielmo, G Logrip, ML Planeta, CS Hope, BT Koob, GF George, O AF Leao, Rodrigo M. Cruz, Fabio C. Vendruscolo, Leandro F. de Guglielmo, Giordano Logrip, Marian L. Planeta, Cleopatra S. Hope, Bruce T. Koob, George F. George, Olivier TI Chronic Nicotine Activates Stress/Reward-Related Brain Regions and Facilitates the Transition to Compulsive Alcohol Drinking SO JOURNAL OF NEUROSCIENCE LA English DT Article DE addiction; alcohol; compulsivity; Fos; neuronal ensembles; tobacco ID CONTEXT-SPECIFIC SENSITIZATION; CORTICOTROPIN-RELEASING-FACTOR; ACCUMBAL DOPAMINE OVERFLOW; CORTEX NEURONAL ENSEMBLES; VOLUNTARY ETHANOL INTAKE; ANXIETY-LIKE BEHAVIOR; NUCLEUS-ACCUMBENS; DRUG-ADDICTION; DEPENDENT RATS; PROTRACTED ABSTINENCE AB Alcohol and nicotine are the two most co-abused drugs in the world. Previous studies have shown that nicotine can increase alcohol drinking in nondependent rats, yet it is unknown whether nicotine facilitates the transition to alcohol dependence. We tested the hypothesis that chronic nicotine will speed up the escalation of alcohol drinking in rats and that this effect will be accompanied by activation of sparsely distributed neurons (neuronal ensembles) throughout the brain that are specifically recruited by the combination of nicotine and alcohol. Rats were trained to respond for alcohol and made dependent using chronic, intermittent exposure to alcohol vapor, while receiving daily nicotine (0.8 mg/kg) injections. Identification of neuronal ensembles was performed after the last operant session, using immunohistochemistry. Nicotine produced an early escalation of alcohol drinking associated with compulsive alcohol drinking in dependent, but not in nondependent rats (air exposed), as measured by increased progressive-ratio responding and increased responding despite adverse consequences. The combination of nicotine and alcohol produced the recruitment of discrete and phenotype-specific neuronal ensembles (similar to 4-13% of total neuronal population) in the nucleus accumbens core, dorsomedial prefrontal cortex, central nucleus of the amygdala, bed nucleus of stria terminalis, and posterior ventral tegmental area. Blockade of nicotinic receptors using mecamylamine (1 mg/kg) prevented both the behavioral and neuronal effects of nicotine in dependent rats. These results demonstrate that nicotine and activation of nicotinic receptors are critical factors in the development of alcohol dependence through the dysregulation of a set of interconnected neuronal ensembles throughout the brain. C1 [Leao, Rodrigo M.; Planeta, Cleopatra S.] Univ Estadual Paulista UNESP, Sch Pharmaceut Sci, Dept Nat Act Principles & Toxicol, Lab Pharmacol, BR-14801902 Sao Paulo, Brazil. [Leao, Rodrigo M.; Vendruscolo, Leandro F.; de Guglielmo, Giordano; Logrip, Marian L.; Koob, George F.; George, Olivier] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. [Leao, Rodrigo M.; Cruz, Fabio C.; Vendruscolo, Leandro F.; Hope, Bruce T.] NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP George, O (reprint author), Scripps Res Inst, Comm Neurobiol Addict Disorders, 10550 North Torrey Pines Rd,SP30-2400, La Jolla, CA 92037 USA. EM rodrigomolini@yahoo.com.br; ogeorge@scripps.edu RI George, Olivier/G-9921-2011; Hope, Bruce/A-9223-2010; koob, george/P-8791-2016 OI George, Olivier/0000-0002-3700-5003; Hope, Bruce/0000-0001-5804-7061; FU National Institutes of Health (NIH) [AA018914, AA020608, AA008459, AA006420, AA022977, DA023597]; National Institute on Drug Abuse, Intramural Research Program, NIH; Coordination for the Improvement of Higher Education Personnel (CAPES) [0093/11-4] FX This research was supported by National Institutes of Health (NIH) grants (AA018914, AA020608, AA008459, AA006420, AA022977, and DA023597); National Institute on Drug Abuse, Intramural Research Program, NIH; and Coordination for the Improvement of Higher Education Personnel (CAPES) PDEE fellowship 0093/11-4 (R.M.L.). NR 77 TC 16 Z9 16 U1 3 U2 12 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 2015 VL 35 IS 15 BP 6241 EP 6253 DI 10.1523/JNEUROSCI.3302-14.2015 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CG1SZ UT WOS:000353055600033 PM 25878294 ER PT J AU Changrob, S Leepiyasakulchai, C Tsuboi, T Cheng, Y Lim, CS Chootong, P Han, ET AF Changrob, Siriruk Leepiyasakulchai, Chaniya Tsuboi, Takafumi Cheng, Yang Lim, Chae Seung Chootong, Patchanee Han, Eun-Taek TI Naturally-acquired cellular immune response against Plasmodium vivax merozoite surface protein-1 paralog antigen SO MALARIA JOURNAL LA English DT Article DE Plasmodium vivax; PvMSP1P; Cellular immune response; Patients; Infection ID DUFFY-BINDING-PROTEIN; BLOOD-STAGE MALARIA; T-CELLS; VACCINE DEVELOPMENT; FALCIPARUM MALARIA; LIGAND DOMAIN; ENDEMIC AREA; MEMORY; IMMUNOGENICITY; INFECTION AB Background: Plasmodium vivax merozoite surface protein-1 paralog (PvMSP1P) is a glycosylphosphatidylinositol-anchored protein expressed on the merozoite surface. This molecule is a target of natural immunity, as high anti-MSP1P-19 antibody levels were detected during P. vivax infection and the antibody inhibited PvMSP1P-erythrocyte binding. Recombinant PvMSP1P antigen results in production of a significant Th1 cytokine response in immunized mice. The present study was performed to characterize natural cellular immunity against PvMSP1P-19 and PvDBP region II in acute and recovery P. vivax infection. Methods: Peripheral blood mononuclear cells (PBMCs) from acute and recovery P. vivax infection were obtained for lymphocyte proliferation assay upon PvMSP1P-19 and PvDBP region II antigen stimulation. The culture supernatant was examined for the presence of the cytokines IL-2, TNF, IFN-gamma and IL-10 by enzyme-linked immunosorbent assay (ELISA). To determine whether Th1 or Th2 have a memory response against PvMSP1P-19 and PvDBPII protein antigen, PBMCs from subjects who had recovered from P. vivax infection 8-10 weeks prior to the study were obtained for lymphocyte proliferation assay. Cytokine-producing cells were analysed by flow cytometry. Results: IL-2 was detected at high levels in lymphocyte cultures from acutely infected P. vivax patients upon PvMSP1P-19 stimulation. Analysis of the Th1 or Th2 memory response in PBMC cultures from subjects who had recovered from P. vivax infection showed significantly elevated levels of PvMSP1P-19 and PvDBPII-specific IFN-gamma-producing cells (P < 0.05). Interestingly, the response of IFN-gamma-producing cells in PvMSP1P stimulation was fourfold greater in recovered subjects than that in acute-infection patients. CD4(+) T cells were the major cell phenotype involved in the response to PvMSP1P-19 and PvDBPII antigen. Conclusions: PvMSP1P-19 strongly induces a specific cellular immune response for protection against P. vivax compared with PvDBPII as the antigen induces activation of IFN-gamma-producing effector cells following natural P. vivax exposure. Upon stimulation, PvMSP1P-19 has the potential to activate the recall response of Th1 effector memory cells that play a role in killing the parasite. C1 [Changrob, Siriruk; Leepiyasakulchai, Chaniya; Chootong, Patchanee] Mahidol Univ, Fac Med Technol, Dept Clin Microbiol & Appl Technol, Bangkok 10700, Thailand. [Tsuboi, Takafumi] Ehime Univ, Div Malaria Res, Proteosci Ctr, Matsuyama, Ehime 7908577, Japan. [Cheng, Yang; Han, Eun-Taek] Kangwon Natl Univ, Sch Med, Dept Med Environm Biol & Trop Med, Chunchon 200701, Gangwon Do, South Korea. [Cheng, Yang] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Lim, Chae Seung] Korea Univ, Guro Hosp, Dept Lab Med, Coll Med, Seoul 152703, South Korea. RP Chootong, P (reprint author), Mahidol Univ, Fac Med Technol, Dept Clin Microbiol & Appl Technol, Bangkok 10700, Thailand. EM pchooton@gmail.com; ethan@kangwon.ac.kr FU Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A121180] FX This work was supported by a grant of the Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A121180). We thank all the staff at Tha Sae and Malaria Clinic, Vector Borne Disease Control 11.4, Chumphon Province, Thailand for collection of the samples. NR 40 TC 1 Z9 1 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD APR 15 PY 2015 VL 14 AR 159 DI 10.1186/s12936-015-0681-8 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CG3SY UT WOS:000353201100001 PM 25889175 ER PT J AU Dominianni, C Sinha, R Goedert, JJ Pei, ZH Yang, LY Hayes, RB Ahn, JY AF Dominianni, Christine Sinha, Rashmi Goedert, James J. Pei, Zhiheng Yang, Liying Hayes, Richard B. Ahn, Jiyoung TI Sex, Body Mass Index, and Dietary Fiber Intake Influence the Human Gut Microbiome SO PLOS ONE LA English DT Article ID COLORECTAL-CANCER; FECAL MICROBIOTA; INTESTINAL MICROBIOME; COLONIC FUNCTION; HEALTHY HUMANS; OBESITY; ECOLOGY; DIVERSITY; BUTYRATE; TRANSIT AB Increasing evidence suggests that the composition of the human gut microbiome is important in the etiology of human diseases; however, the personal factors that influence the gut microbiome composition are poorly characterized. Animal models point to sex hormone-related differentials in microbiome composition. In this study, we investigated the relationship of sex, body mass index (BMI) and dietary fiber intake with the gut microbiome in 82 humans. We sequenced fecal 16S rRNA genes by 454 FLX technology, then clustered and classified the reads to microbial genomes using the QIIME pipeline. Relationships of sex, BMI, and fiber intake with overall gut microbiome composition and specific taxon abundances were assessed by permutational MANOVA and multivariate logistic regression, respectively. We found that sex was associated with the gut microbiome composition overall (p=0.001). The gut microbiome in women was characterized by a lower abundance of Bacteroidetes (p=0.03). BMI (>25 kg/m(2) vs. <25 kg/m(2)) was associated with the gut microbiome composition overall (p=0.05), and this relationship was strong in women (p=0.03) but not in men (p=0.29). Fiber from beans and from fruits and vegetables were associated, respectively, with greater abundance of Actinobacteria (p=0.006 and false discovery rate adjusted q=0.05) and Clostridia (p=0.009 and false discovery rate adjusted q=0.09). Our findings suggest that sex, BMI, and dietary fiber contribute to shaping the gut microbiome in humans. Better understanding of these relationships may have significant implications for gastrointestinal health and disease prevention. C1 [Dominianni, Christine; Hayes, Richard B.; Ahn, Jiyoung] NYU, Sch Med, Dept Populat Hlth, New York, NY 11201 USA. [Pei, Zhiheng; Hayes, Richard B.; Ahn, Jiyoung] NYU, Perlmutter Canc Ctr, New York, NY USA. [Sinha, Rashmi; Goedert, James J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Pei, Zhiheng] New York Vet Affairs Med Ctr, Dept Pathol & Lab Med, New York, NY USA. [Pei, Zhiheng] NYU, Sch Med, Dept Pathol, New York, NY USA. [Pei, Zhiheng; Yang, Liying] NYU, Sch Med, Dept Med, New York, NY USA. RP Ahn, JY (reprint author), NYU, Sch Med, Dept Populat Hlth, New York, NY 11201 USA. EM Jiyoung.Ahn@nyumc.org RI Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Yang, Liying/0000-0003-1442-4915; Pei, Zhiheng/0000-0001-8570-6747; Hayes, Richard/0000-0002-0918-661X FU National Cancer Institute [R03CA159414, R21CA183887, R01CA159036, UH3CA140233]; National Institutes of Health Human Microbiome Project; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This research was supported in part by grants R03CA159414, R21CA183887, R01CA159036 and UH3CA140233 from the National Cancer Institute (http://www.cancer.gov/researchandfunding) (JA) and National Institutes of Health Human Microbiome Project (http://grants.nih.gov/grants/oer.htm) and by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (http://www.research.va.gov/) (ZP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 15 Z9 15 U1 7 U2 58 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 15 PY 2015 VL 10 IS 4 AR e0124599 DI 10.1371/journal.pone.0124599 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1EL UT WOS:000353015800147 PM 25874569 ER PT J AU Munseri, PJ Kroidl, A Nilsson, C Joachim, A Geldmacher, C Mann, P Moshiro, C Aboud, S Lyamuya, E Maboko, L Missanga, M Kaluwa, B Mfinanga, S Podola, L Bauer, A Godoy-Ramirez, K Marovich, M Moss, B Hoelscher, M Gotch, F Stohr, W Stout, R McCormack, S Wahren, B Mhalu, F Robb, ML Biberfeld, G Sandstrom, E Bakari, M AF Munseri, Patricia. J. Kroidl, Arne Nilsson, Charlotta Joachim, Agricola Geldmacher, Christof Mann, Philipp Moshiro, Candida Aboud, Said Lyamuya, Eligius Maboko, Leonard Missanga, Marco Kaluwa, Bahati Mfinanga, Sayoki Podola, Lilly Bauer, Asli Godoy-Ramirez, Karina Marovich, Mary Moss, Bernard Hoelscher, Michael Gotch, Frances Stoehr, Wolfgang Stout, Richard McCormack, Sheena Wahren, Britta Mhalu, Fred Robb, Merlin L. Biberfeld, Gunnel Sandstrom, Eric Bakari, Muhammad TI Priming with a Simplified Intradermal HIV-1 DNA Vaccine Regimen followed by Boosting with Recombinant HIV-1 MVA Vaccine Is Safe and Immunogenic: A Phase IIa Randomized Clinical Trial SO PLOS ONE LA English DT Article ID HUMORAL IMMUNE-RESPONSES; VIRUS ANKARA; BROAD; PREVENTION; INFECTION; MULTIGENE AB Background Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools. Methods In this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 mu g total dose, (3 Env and 2 Gag encoding plasmids) compared to two "simplified" regimens of 2 injections of HIV-DNA, 600 mu g total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 10(8) pfu HIV-MVA at weeks 30 and 46. Results 129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-gamma ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%). There were no significant differences in the magnitude of Gag and/or Env IFN-gamma ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-gamma/IL-2 production by intracellular cytokine staining (ICS) or in response rates and median titers for binding antibodies to Env gp160 between study groups. Conclusions A simplified intradermal vaccination regimen with 2 injections of a total of 600 mu g with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 mu g with separated plasmid pools after boosting twice with HIV-MVA. C1 [Munseri, Patricia. J.; Bakari, Muhammad] MUHAS, Dept Internal Med, Dar Es Salaam, Tanzania. [Munseri, Patricia. J.; Sandstrom, Eric] Karolinska Inst, Stockholm, Sweden. [Kroidl, Arne; Mann, Philipp; Maboko, Leonard; Missanga, Marco; Kaluwa, Bahati; Podola, Lilly; Bauer, Asli; Hoelscher, Michael] Mbeya Med Res Ctr, Natl Inst Med Research, Mbeya, Tanzania. [Kroidl, Arne; Geldmacher, Christof; Mann, Philipp; Podola, Lilly; Bauer, Asli; Hoelscher, Michael] Klinikum Univ Munich, Dept Infect Dis & Trop Med, Munich, Germany. [Kroidl, Arne; Geldmacher, Christof; Hoelscher, Michael] German Ctr Infect Res DZIF, Munich, Germany. [Nilsson, Charlotta; Godoy-Ramirez, Karina; Biberfeld, Gunnel] Publ Hlth Agcy Sweden, Solna, Sweden. [Nilsson, Charlotta; Wahren, Britta; Biberfeld, Gunnel] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Nilsson, Charlotta] Karolinska Inst, Dept Lab Med, Huddinge, Sweden. [Joachim, Agricola; Aboud, Said; Lyamuya, Eligius; Mhalu, Fred] MUHAS, Dept Microbiol & Immunol, Dar Es Salaam, Tanzania. [Moshiro, Candida] MUHAS, Dept Epidemiol & Biostat, Dar Es Salaam, Tanzania. [Mfinanga, Sayoki] Muhimbili Med Res Ctr, Natl Inst Med Res, Dar Es Salaam, Tanzania. [Marovich, Mary; Robb, Merlin L.] WRAIR, Rockville, MD USA. [Marovich, Mary; Robb, Merlin L.] Henry M Jackson Fdn, Rockville, MD USA. [Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Gotch, Frances] Univ London Imperial Coll Sci Technol & Med, London, England. [Stoehr, Wolfgang; McCormack, Sheena] UCL, MRC, Clin Trials Unit, London, England. [Stout, Richard] Bioject Med Technol, Tigard, OR USA. RP Munseri, PJ (reprint author), MUHAS, Dept Internal Med, Dar Es Salaam, Tanzania. EM pmunseri@yahoo.com FU European and Developing Countries Clinical Trials Partnership (EDCTP) [CT.2006.33111.007]; Swedish International Development Cooperation Agency (Sida), in Tanzania; Regional HIV/AIDS Team for Africa at the Embassy of Sweden in Lusaka; German Ministry of Education and Research (BMBF), The Division of Intramural Research, NIAID; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]; U.S. Department of Defense (DOD) [W81XWH-07-2-0067] FX This work has been supported by the European and Developing Countries Clinical Trials Partnership (EDCTP) Grant CT.2006.33111.007, the Swedish International Development Cooperation Agency (Sida), in Tanzania and the Regional HIV/AIDS Team for Africa at the Embassy of Sweden in Lusaka jointly funded by Sweden and Norway, the German Ministry of Education and Research (BMBF), The Division of Intramural Research, NIAID, and by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD). The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the DOD. None of these organizations had any influence in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 6 Z9 7 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 15 PY 2015 VL 10 IS 4 AR e0119629 DI 10.1371/journal.pone.0119629 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1EL UT WOS:000353015800007 PM 25875843 ER PT J AU Tanner, K Gottesman, MM AF Tanner, Kandice Gottesman, Michael M. TI Beyond 3D culture models of cancer SO Science Translational Medicine LA English DT Article ID MAMMARY EPITHELIAL ACINI; TUMOR-CELL; DRUG-RESISTANCE; BREAST-CANCER; IN-VITRO; MICROENVIRONMENT; METASTASIS; MELANOMA; MORPHOGENESIS; PROGRESSION AB The mechanisms underlying the spatiotemporal evolution of tumor ecosystems present a challenge in evaluating drug efficacy. In this Perspective, we address the use of three-dimensional in vitro culture models to delineate the dynamic interplay between the tumor and the host microenvironment in an effort to attain realistic platforms for assessing pharmaceutical efficacy in patients. C1 [Tanner, Kandice; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Tanner, K (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kandice.tanner@nih.gov; mgottesman@nih.gov FU Intramural Research Program of NIH; National Cancer Institute FX The authors apologize to researchers whose work was not reflected in the references owing to space constraints. We thank A. Hoofring of the National Institutes of Health (NIH) Medical Arts for assistance with figure illustration. This effort was supported by the Intramural Research Program of NIH, the National Cancer Institute. NR 37 TC 14 Z9 14 U1 0 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 15 PY 2015 VL 7 IS 283 AR 283ps9 DI 10.1126/scitranslmed.3009367 PG 4 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CG6AJ UT WOS:000353377000001 PM 25877888 ER PT J AU Greytak, SR Engel, KB Bass, BP Moore, HM AF Greytak, Sarah R. Engel, Kelly B. Bass, B. Paige Moore, Helen M. TI Accuracy of Molecular Data Generated with FFPE Biospecimens: Lessons from the Literature SO CANCER RESEARCH LA English DT Review ID PARAFFIN-EMBEDDED TISSUE; GENOME GENE-EXPRESSION; TUMOR-TISSUES; COPY-NUMBER; MICROARRAY ANALYSIS; CLINICAL-SAMPLES; CANCER TISSUES; DNA; WIDE; PRESERVATION AB Formalin-fixed and paraffin-embedded (FFPE) tissue biospecimens are a valuable resource for molecular cancer research. Although much can be gained from their use, it remains unclear whether the genomic and expression profiles obtained from FFPE biospecimens accurately reflect the physiologic condition of the patient from which they were procured, or if such profiles are confounded by biologic effects from formalin fixation and processing. To assess the physiologic accuracy of genomic and expression data generated with FFPE specimens, we surveyed the literature for articles investigating genomic and expression endpoints in case-matched FFPE and fresh or frozen human biospecimens using the National Cancer Institute's Biospecimen Research Database (http://biospecimens.cancer.gov/brd). Results of the survey revealed that the level of concordance between differentially preserved biospecimens varied among analytical parameters and platforms but also among reports, genes/transcripts of interest, and tumor status. The identified analytical techniques and parameters that resulted in strong correlations between FFPE and frozen biospecimens may provide guidance when optimizing molecular protocols for FFPE use; however, discrepancies reported for similar assays also illustrate the importance of validating protocols optimized for use with FFPE specimens with a case-matched fresh or frozen cohort for each platform, gene or transcript, and FFPE processing regime. On the basis of evidence published to date, validation of analytical parameters with a properly handled frozen cohort is necessary to ensure a high degree of concordance and confidence in the results obtained with FFPE biospecimens. (C) 2015 AACR. C1 [Greytak, Sarah R.; Bass, B. Paige] Kelly Govt Solut, Rockville, MD USA. [Engel, Kelly B.] Preferred Solut Grp, Arlington, VA USA. [Moore, Helen M.] NCI, Biorepositories & Biospecimen Res Branch, Canc Diag Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Moore, HM (reprint author), NCI, Biorepositories & Biospecimen Res Branch, 9609 Med Ctr Dr,Room 3W422,MSC 9728, Bethesda, MD 20892 USA. EM moorehe@mail.nih.gov FU National Cancer Institute's Biorepositories; Biospecimen Research Branch FX This work was funded by the National Cancer Institute's Biorepositories and Biospecimen Research Branch. NR 41 TC 10 Z9 10 U1 0 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2015 VL 75 IS 8 BP 1541 EP 1547 DI 10.1158/0008-5472.CAN-14-2378 PG 7 WC Oncology SC Oncology GA CF9PH UT WOS:000352896900001 PM 25836717 ER PT J AU Debette, S Verbaas, CAI Bressler, J Schuur, M Smith, A Bis, JC Davies, G Wolf, C Gudnason, V Chibnik, LB Yang, Q Destefano, AL de Quervain, DJF Srikanth, V Lahti, J Grabe, HJ Smith, JA Priebe, L Yu, L Karbalai, N Hayward, C Wilson, JF Campbell, H Petrovic, K Fornage, M Chauhan, G Yeo, RB Boxall, R Becker, J Stegle, O Mather, KA Chouraki, V Sun, Q Rose, LM Resnick, S Oldmeadow, C Kirin, M Wright, AF Jonsdottir, MK Au, RD Becker, A Amin, N Nalls, MA Turner, ST Kardia, SLR Oostra, B Windham, G Coker, LH Zhao, W Knopman, DS Heiss, G Griswold, ME Gottesman, RF Vitart, V Hastie, ND Zgaga, L Rudan, I Polasek, O Holliday, EG Schofield, P Choi, SH Tanaka, T An, Y Perry, RT Kennedy, RE Sale, MM Wang, J Wadley, VG Liewald, DC Ridker, PM Gow, AJ Pattie, A Starr, JM Porteous, D Liu, X Thomson, R Armstrong, NJ Eiriksdottir, G Assareh, AA Kochan, NA Widen, E Palotie, A Hsieh, YC Eriksson, JG Vogler, C van Swieten, JC Shulman, JM Beiser, A Rotter, J Schmidt, CO Hoffmann, W Nothen, MM Ferrucci, L Attia, J Uitterlinden, AG Amouyel, P Dartigues, JF Amieva, H Raikkonen, K Garcia, M Wolf, PA Hofman, A Longstreth, WT Psaty, BM Boerwinkle, E DeJager, PL Sachdev, PS Schmidt, R Breteler, MMB Teumer, A Lopez, OL Cichon, S Chasman, DI Grodstein, F Muller-Myhsok, B Tzourio, C Papassotiropoulos, A Bennett, DA Ikram, MA Deary, IJ van Duijn, CM Launer, L Fitzpatrick, AL Seshadri, S Mosley, TH AF Debette, Stephanie Verbaas, Carla A. Ibrahim Bressler, Jan Schuur, Maaike Smith, Albert Bis, Joshua C. Davies, Gail Wolf, Christiane Gudnason, Vilmundur Chibnik, Lori B. Yang, Qiong deStefano, Anita L. de Quervain, Dominique J. F. Srikanth, Velandai Lahti, Jari Grabe, Hans J. Smith, Jennifer A. Priebe, Lutz Yu, Lei Karbalai, Nazanin Hayward, Caroline Wilson, James F. Campbell, Harry Petrovic, Katja Fornage, Myriam Chauhan, Ganesh Yeo, Robin Boxall, Ruth Becker, James Stegle, Oliver Mather, Karen A. Chouraki, Vincent Sun, Qi Rose, Lynda M. Resnick, Susan Oldmeadow, Christopher Kirin, Mirna Wright, Alan F. Jonsdottir, Maria K. Au, Rhoda Becker, Albert Amin, Najaf Nalls, Mike A. Turner, Stephen T. Kardia, Sharon L. R. Oostra, Ben Windham, Gwen Coker, Laura H. Zhao, Wei Knopman, David S. Heiss, Gerardo Griswold, Michael E. Gottesman, Rebecca F. Vitart, Veronique Hastie, Nicholas D. Zgaga, Lina Rudan, Igor Polasek, Ozren Holliday, Elizabeth G. Schofield, Peter Choi, Seung Hoan Tanaka, Toshiko An, Yang Perry, Rodney T. Kennedy, Richard E. Sale, Michele M. Wang, Jing Wadley, Virginia G. Liewald, David C. Ridker, Paul M. Gow, Alan J. Pattie, Alison Starr, John M. Porteous, David Liu, Xuan Thomson, Russell Armstrong, Nicola J. Eiriksdottir, Gudny Assareh, Arezoo A. Kochan, Nicole A. Widen, Elisabeth Palotie, Aarno Hsieh, Yi-Chen Eriksson, Johan G. Vogler, Christian van Swieten, John C. Shulman, Joshua M. Beiser, Alexa Rotter, Jerome Schmidt, Carsten O. Hoffmann, Wolfgang Noethen, Markus M. Ferrucci, Luigi Attia, John Uitterlinden, Andre G. Amouyel, Philippe Dartigues, Jean-Francois Amieva, Helene Raeikkoenen, Katri Garcia, Melissa Wolf, Philip A. Hofman, Albert Longstreth, W. T., Jr. Psaty, Bruce M. Boerwinkle, Eric DeJager, Philip L. Sachdev, Perminder S. Schmidt, Reinhold Breteler, Monique M. B. Teumer, Alexander Lopez, Oscar L. Cichon, Sven Chasman, Daniel I. Grodstein, Francine Mueller-Myhsok, Bertram Tzourio, Christophe Papassotiropoulos, Andreas Bennett, David A. Ikram, M. Arfan Deary, Ian J. van Duijn, Cornelia M. Launer, Lenore Fitzpatrick, Annette L. Seshadri, Sudha Mosley, Thomas H., Jr. CA Cohorts Heart & Aging Res in Genom TI Genome-wide Studies of Verbal Declarative Memory in Nondemented Older People: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Alzheimer disease; Dementia; Epidemiology; Genetics; Population-based; Verbal declarative memory ID ALZHEIMERS-DISEASE; IDENTIFIES VARIANTS; APOLIPOPROTEIN-E; ASSOCIATION; METAANALYSIS; SYSTEM; UBIQUITIN; INTELLIGENCE; PERFORMANCE; DECLINE AB BACKGROUND: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. METHODS: We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia-and stroke-free individuals of European descent, aged >= 45 years. Replication of suggestive associations (p < 5 x 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults. RESULTS: rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 55.7 x 10(-10)) and replication cohorts (p = 5.65 x 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 x 10(-8), and rs6813517 [SPOCK3], p = 2.58 x 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism. CONCLUSIONS: This largest study to date exploring the genetics of memory function in similar to 40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways. C1 [Debette, Stephanie; deStefano, Anita L.; Au, Rhoda; Beiser, Alexa; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Debette, Stephanie; Chauhan, Ganesh; Yeo, Robin; Dartigues, Jean-Francois; Amieva, Helene; Tzourio, Christophe] Epidemiol & Publ Hlth, INSERM, Unit 897, Bordeaux, France. [Debette, Stephanie; Chauhan, Ganesh; Yeo, Robin; Dartigues, Jean-Francois; Amieva, Helene; Tzourio, Christophe] Univ Bordeaux, Bordeaux, France. [Debette, Stephanie; Dartigues, Jean-Francois] Univ Hosp Bordeaux, Dept Neurol, Bordeaux, France. [Tzourio, Christophe] Univ Hosp Bordeaux, Dept Med Informat, Bordeaux, France. [Verbaas, Carla A. Ibrahim; Schuur, Maaike; Amin, Najaf; Oostra, Ben; van Duijn, Cornelia M.] Univ Med Ctr, Erasmus Med Ctr, Genet Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands. [Verbaas, Carla A. Ibrahim; Schuur, Maaike; van Swieten, John C.] Univ Med Ctr, Erasmus Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Bressler, Jan; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [Smith, Albert; Gudnason, Vilmundur; Jonsdottir, Maria K.; Eiriksdottir, Gudny] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA. [Davies, Gail; Boxall, Ruth; Liewald, David C.; Gow, Alan J.; Starr, John M.; Porteous, David; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland. [Davies, Gail; Liewald, David C.; Gow, Alan J.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland. [Davies, Gail; Porteous, David] Univ Edinburgh, Med Genet Sect, Mol Med Ctr, Inst Genet & Mol Med,Western Gen Hosp, Edinburgh, Midlothian, Scotland. [Wolf, Christiane; Karbalai, Nazanin; Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Chibnik, Lori B.; DeJager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Program Translat Neuro Psychiat Genom, Boston, MA 02115 USA. [Yang, Qiong; deStefano, Anita L.; Choi, Seung Hoan; Wang, Jing; Liu, Xuan; Beiser, Alexa; Seshadri, Sudha] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Yang, Qiong; deStefano, Anita L.; Au, Rhoda; Beiser, Alexa; Wolf, Philip A.; Seshadri, Sudha] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [de Quervain, Dominique J. F.] Univ Basel, Psychiat Univ Clin, Basel, Switzerland. [de Quervain, Dominique J. F.] Univ Basel, Div Cognit Neurosci, Dept Psychol, Basel, Switzerland. [Srikanth, Velandai] Monash Univ, Stroke & Ageing Res Ctr, Southern Clin Sch, Dept Med, Melbourne, Vic 3004, Australia. [Srikanth, Velandai; Thomson, Russell] Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas, Australia. [Lahti, Jari; Raeikkoenen, Katri] Univ Helsinki, Inst Behav Sci, FIN-00014 Helsinki, Finland. [Lahti, Jari; Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Grabe, Hans J.] Univ Med Greifswald, HELIOS Hosp Stralsund, Dept Psychiat & Psychotherapy, Stralsund, Germany. [Grabe, Hans J.; Hoffmann, Wolfgang; Breteler, Monique M. B.] German Ctr Neurodegenerat Dis, Greifswald, Germany. [Smith, Jennifer A.; Kardia, Sharon L. R.; Zhao, Wei] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Priebe, Lutz; Cichon, Sven] Univ Kilinikum Bonn, Inst Human Genet, Bonn, Germany. [Yu, Lei; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Hayward, Caroline; Wright, Alan F.; Vitart, Veronique; Hastie, Nicholas D.; Zgaga, Lina] Univ Edinburgh, MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland. [Wilson, James F.; Campbell, Harry; Kirin, Mirna; Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland. [Petrovic, Katja] Med Univ & Gen Hosp Graz, Div Gen Neurol, Dept Neurol, Graz, Austria. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA. [Becker, James; Lopez, Oscar L.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Becker, James; Lopez, Oscar L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Stegle, Oliver] Max Planck Inst Intelligent Syst, Tubingen, Germany. [Stegle, Oliver] Max Planck Inst Dev Biol, Tubingen, Germany. [Mather, Karen A.; Amin, Najaf; Assareh, Arezoo A.; Kochan, Nicole A.; Sachdev, Perminder S.] Univ New S Wales, Ctr Hlth Brain Ageing, Sch Psychiat, Sydney, NSW, Australia. [Chouraki, Vincent; Amouyel, Philippe] INSERM, Inst Pasteur Lille, Unit 744, F-59045 Lille, France. [Chouraki, Vincent; Amouyel, Philippe] Univ Lille Nord France, F-59045 Lille, France. [Sun, Qi] Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. [Sun, Qi; Grodstein, Francine] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Sun, Qi; Grodstein, Francine] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Sun, Qi; Ridker, Paul M.; Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA USA. [Rose, Lynda M.; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Resnick, Susan; An, Yang] NIA, Brain Aging & Behav Sect, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. [Oldmeadow, Christopher; Holliday, Elizabeth G.; Schofield, Peter; Attia, John] Univ Newcastle, Ctr Clin Epidemiol & Biostat, Sch Med & Publ Hlth, Fac Hlth, Newcastle, NSW 2300, Australia. [Oldmeadow, Christopher; Attia, John] Hunter Med Res Inst, Newcastle, NSW, Australia. [Becker, Albert] Univ Klinikum Bonn, Inst Neuropathol, Bonn, Germany. [Nalls, Mike A.] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Turner, Stephen T.] Mayo Clin, Dept Internal Med, Rochester, MN USA. [Oostra, Ben] Univ Med Ctr, Erasmus Med Ctr, Dept Clin Genet, Rotterdam, Netherlands. [Windham, Gwen] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA. [Coker, Laura H.] Wake Forest Sch Med, Div Publ Sci & Neurol, Winston Salem, NC USA. [Knopman, David S.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Heiss, Gerardo] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Griswold, Michael E.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA. [Gottesman, Rebecca F.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Polasek, Ozren] Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia. [Schofield, Peter; Attia, John] John Hunter Hosp, Dept Med, Newcastle, NSW, Australia. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Bethesda, MD 20892 USA. [Kennedy, Richard E.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Kennedy, Richard E.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Sale, Michele M.] Univ Virginia, Dept Med, Dept Biochem & Mol Genet, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Wadley, Virginia G.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Armstrong, Nicola J.] Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW, Australia. [Armstrong, Nicola J.] Univ New S Wales, Sch Math Stat, Sydney, NSW, Australia. [Armstrong, Nicola J.] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW, Australia. [Assareh, Arezoo A.] Univ New S Wales, Neurosci Res Australia & Primary Dementia Collabo, Sydney, NSW, Australia. [Kochan, Nicole A.; Sachdev, Perminder S.] Prince Wales Hosp, Inst Neuropsychiat, Randwick, NSW 2031, Australia. [Widen, Elisabeth; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland. [Palotie, Aarno] Wellcome Trust Sanger Inst, Cambridge, England. [Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Palotie, Aarno] Univ Helsinki, Univ Cent Hosp, Helsinki, Finland. [Hsieh, Yi-Chen] Taipei Med Univ, Neural Regenerat Med, Coll Med Sci & Technol, Taipei, Taiwan. [Eriksson, Johan G.] Natl Inst Hlth & Welf, Helsinki, Finland. Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. Vasa Cent Hosp, Vaasa, Finland. [Vogler, Christian; Papassotiropoulos, Andreas] Univ Basel, Psychiat Univ Clin, Basel, Switzerland. [Vogler, Christian; Papassotiropoulos, Andreas] Univ Basel, Psychiat Univ Clin, Div Mol Neurosci, Basel, Switzerland. [Shulman, Joshua M.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Shulman, Joshua M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Shulman, Joshua M.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA. [Rotter, Jerome] Harbor UCLA Med Ctr, Inst Translat Genom & Populaton Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Rotter, Jerome] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA. [Schmidt, Carsten O.] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Hoffmann, Wolfgang] Univ Med Greifswald, Sect Epidemiol Hlth Care & Community Hlth, Greifswald, Germany. [Noethen, Markus M.] Univ Bonn, Inst Human Genet, Dept Gen Life & Brain Res Ctr, Bonn, Germany. [Noethen, Markus M.] German Ctr Neurodegenerat Dis, Bonn, Germany. [Uitterlinden, Andre G.; Hofman, Albert; Breteler, Monique M. B.; Ikram, M. Arfan; van Duijn, Cornelia M.] Netherlands Consortium Hlth Ageing, Leiden, Netherlands. [Uitterlinden, Andre G.] Univ Med Ctr, Erasmus Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Amouyel, Philippe] Ctr Hosp Reg & Univ Lille, F-59037 Lille, France. [Garcia, Melissa; Launer, Lenore] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Hofman, Albert; Breteler, Monique M. B.; Ikram, M. Arfan] Univ Med Ctr, Erasmus Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Longstreth, W. T., Jr.; Psaty, Bruce M.; Fitzpatrick, Annette L.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Mueller-Myhsok, Bertram] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Mueller-Myhsok, Bertram] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med Prevent Human Dis, Houston, TX 77030 USA. [Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Div Neurogeriatr, Graz, Austria. [Breteler, Monique M. B.] Univ Bonn, Populat Hlth Sci, Bonn, Germany. [Breteler, Monique M. B.; Grodstein, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Teumer, Alexander] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Lopez, Oscar L.] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Pittsburgh, PA USA. [Cichon, Sven] Res Ctr Julich, Inst Neurosci & Med, Julich, Germany. [Cichon, Sven] Univ Basel, Dept Biomed, Div Med Genet, CH-4003 Basel, Switzerland. [Mueller-Myhsok, Bertram] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Mueller-Myhsok, Bertram] Univ Liverpool, Inst Translat Med, Liverpool L69 3BX, Merseyside, England. [Tzourio, Christophe] Univ Bordeaux Segalen, Bordeaux, France. [Papassotiropoulos, Andreas] Dept Biozentrum, Life Sci Training Facil, Basel, Switzerland. [Ikram, M. Arfan] Univ Med Ctr, Erasmus Med Ctr, Dept Radiol, Rotterdam, Netherlands. [van Duijn, Cornelia M.] Leiden Univ, Med Ctr, Netherlands Genom Initiat, Ctr Med Syst Biol, Leiden, Netherlands. [Mosley, Thomas H., Jr.] Univ Mississippi, Med Ctr, Dept Med & Neurol, Jackson, MS 39216 USA. RP Debette, S (reprint author), Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study, 72 East Concord St,B-622, Boston, MA 02118 USA. EM sdebette@bu.edu RI Gudnason, Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Smith, Albert/K-5150-2015; Karen, Mather/O-9795-2016; Tzourio, christophe/B-4015-2009; Thomson, Russell/H-5653-2012; OI Seshadri, Sudha/0000-0001-6135-2622; Gudnason, Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Smith, Albert/0000-0003-1942-5845; Karen, Mather/0000-0003-4143-8941; Tzourio, christophe/0000-0002-6517-2984; Thomson, Russell/0000-0003-4949-4120; Chouraki, Vincent/0000-0002-4698-1794; Stegle, Oliver/0000-0002-8818-7193; Zgaga, Lina/0000-0003-4089-9703; van Swieten, John /0000-0001-6278-6844; Nothen, Markus/0000-0002-8770-2464; Sachdev, Perminder/0000-0002-9595-3220; Beiser, Alexa/0000-0001-8551-7778; Smith, Jennifer/0000-0002-3575-5468; Gow, Alan/0000-0002-3320-4531; Lahti, Jari/0000-0002-4310-5297 FU National Institute on Aging [N01-AG-12100, AG08122, AG16495, AG033193, AG031287]; National Heart, Lung and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL70825, R01HL087641, R01HL59367, R01HL086694, HHSN268201200036C, HHSN268200800007C]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C, CA87969, CA49449, HL34594, U01HG004399, DK058845, CA65725, CA67262, CA50385, 5UO1CA098233, EY09611, EY015473, HG004728, HL35464, CA55075, CA134958, DK070756]; National Institutes of Health and National Institutes of Health Roadmap for Medical Research [UL1RR025005]; National Institute of Neurological Disorders and Stroke; NIA [R01AG023629, R01AG20098, R01AG05133]; National Center for Advancing Translational Sciences, Clinical and Translational Sciences Institute Grant [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center Grant [DK063491]; Medical Research Council (United Kingdom); European Commission Framework 6 project EUROSPAN [LSHG-CT-2006-018947]; Republic of Croatia Ministry of Science, Education and Sports research Grants [108-1080315-0302]; Netherlands Organization for Scientific Research; Internationale Stichting Alzheimer Onderzoek; Hersenstichting Nederland; Centre for Medical Systems Biology; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute of Neurological Disorders and Stroke [NS17950]; National Institute of Neurological Disorders and Stroke of the National Institutes of Health [NS041558]; Academy of Finland; Finnish Diabetes Research Society; Folkhalsan Research Foundation; Novo Nordisk Foundation; Finska Lakaresallskapet; Signe and Ane Gyllenberg Foundation; University of Helsinki; Ministry of Education; Ahokas Foundation; Emil Aaltonen Foundation; Juho Vainio Foundation; Wellcome Trust [WT089062]; Biotechnology and Biological Sciences Research Council; Royal Society; Chief Scientist Office of the Scottish Government; Research Into Ageing (continues as part of Age United Kingdom The Disconnected Mind project); United Kingdom Biotechnology and Biological Sciences Research Council; Engineering and Physical Sciences Research Council; Economic and Social Research Council; Medical Research Council; Medical Research Council Human Genetics Unit; Arthritis Research United Kingdom; European Union framework program 6 EUROSPAN project [LSHG-CT-2006-018947]; Netherlands Organisation of Scientific Research Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015, RIDE2]; Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research project [050-060-810]; National Institute on Aging Grants [P30AG10161, R01AG15819, R01AG17917, R01AG30146, K08AG34290, K25AG41906]; Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Siemens Healthcare; Erlangen, Germany; Federal State of Mecklenburg-West Pomerania; German Research Foundation (DFG) [GR 1912/5-1]; National Health and Medical Research Council (NHMRC) [403000, 491109, 606543]; Wicking Dementia Education and Research Centre, Hobart; National Health and Medical Research Council/National Heart Foundation Career Development Fellowship [606544]; National Health and Medical Research Council Principal Research Fellowship; Intramural Research Program of the National Institutes of Health, National Institute on Aging; University of Newcastle's Strategic Initiative Fund; Vincent Fairfax Family Foundation; Hunter Medical Research Institute; National Institutes of Health; Merck Research Laboratories; National Heart, Lung, and Blood Institute [K99HL098459, HL043851, HL080467]; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services [U01 NS041588]; National Health & Medical Research Council Grant [401184]; Australian National Health & Medical Research Council Program Grant [350833]; Capacity Building Grant [568940]; Australian Government-funded Dementia Collaborative Research Centre at the University of New South Wales; National Health & Medical Research Council Project Grant [525453]; Fondation pour la Recherche Medicale; Caisse Nationale Maladie des Travailleurs Salaries Direction Generale de la Sante; Mutuelle Generale de l'Education Nationale; Institut de la Longevite; Conseils Regionaux of Aquitaine and Bourgogne; Fondation de France; Ministry of Research-Institut National de la Sante et de la Recherche Medicale Programme "Cohortes et collections de donnees biologiques; Eisai; National Foundation for Alzheimer's Disease and Related Disorders; Institut Pasteur de Lille; Centre National de Genotypage; French national research agency (Agence Nationale de la Recherche); National Cancer Institute [CA047988]; Donald W. Reynolds Foundation; Fondation Leducq; Amgen; Swiss National Science Foundation [CRSI33_130080]; German Federal Ministry of Education and Research; National Heart, Lung and Blood Institute grant [N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, HL054464, HL054457, HL054481, HL071917, HL87660]; [R01 DK084350] FX Aging Gene-Environment Susceptibility-Reykjavik Study: The research has been funded by National Institute on Aging contract N01-AG-12100 with contributions from National Eye Institute, National Institute on Deafness and Other Communication Disorders, and National Heart, Lung and Blood Institute; the National Institute on Aging Intramural Research Program; Hjartavernd (the Icelandic Heart Association); and the Althingi (the Icelandic Parliament).; The Atherosclerosis Risk in Communities Study: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL70825, R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. We thank the staff and participants of the Atherosclerosis Risk in Communities Study for their important contributions. Infrastructure was partly supported by Grant number UL1RR025005, a component of the National Institutes of Health and National Institutes of Health Roadmap for Medical Research.; The Cardiovascular Health Study: This Cardiovascular Health Study research was supported by National Heart, Lung and Blood Institute contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and National Heart, Lung and Blood Institute Grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, and R01HL120393 with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through R01AG023629, R01AG20098 and R01AG05133 NIA. A full list of principal Cardiovascular Health Study investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported, in part, by the National Center for Advancing Translational Sciences, Clinical and Translational Sciences Institute Grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center Grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; Croatian Cohorts-Split and Korcula: The CROATIA-Korcula and CROATIA-Split studies were funded by Grants from the Medical Research Council (United Kingdom), European Commission Framework 6 project EUROSPAN (Contract No. LSHG-CT-2006-018947), and Republic of Croatia Ministry of Science, Education and Sports research Grants to IR (108-1080315-0302). We acknowledge the invaluable contributions of the recruitment teams in Korcula and Split, the administrative teams in Croatia and Edinburgh, and the people of Korcula and Split. The single nucleotide polymorphism genotyping for the CROATIA-Korcula cohort was performed in Helmholtz Zentrum Munchen, Neuherberg, Germany. The single nucleotide polymorphism genotyping for the CROATIA-Split cohort was performed by AROS Applied Biotechnology, Aarhus, Denmark.; Erasmus Rucphen Family Study: This study is financially supported by the Netherlands Organization for Scientific Research, the Internationale Stichting Alzheimer Onderzoek, the Hersenstichting Nederland, and the Centre for Medical Systems Biology (*1 and *2) in the framework of the Netherlands Genomics Initiative. We thank the participants from the Genetic Research in Isolated Populations, Erasmus Rucphen Family, who made this work possible.; Framingham Heart Study: From the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the Single Nucleotide Polymorphism Health Association Resource project. This study was also supported by Grants from the National Institute of Neurological Disorders and Stroke (NS17950) and the National Institute on Aging (AG08122, AG16495, AG033193, AG031287).; Genetic Epidemiology Network of Arteriopathy: Support for the Genetic Epidemiology Network of Arteriopathy was provided by the National Heart, Lung and Blood Institute (HL054464, HL054457, HL054481, HL071917, and HL87660) and the National Institute of Neurological Disorders and Stroke (NS041558) of the National Institutes of Health. Genotyping was performed at the Mayo Clinic (STT, Mariza de Andrade, Julie Cunningham) and was made possible by the University of Texas Health Sciences Center (EB, Megan L. Grove-Gaona). We also thank the families that participated in the Genetic Epidemiology Network of Arteriopathy study.; Helsinki Birth Cohort Study: We thank all study participants as well as everybody involved in the Helsinki Birth Cohort Study. The Helsinki Birth Cohort Study has been supported by Grants from the Academy of Finland, the Finnish Diabetes Research Society, Folkhalsan Research Foundation, Novo Nordisk Foundation, Finska Lakaresallskapet, Signe and Ane Gyllenberg Foundation, University of Helsinki, Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation, Juho Vainio Foundation, and Wellcome Trust (Grant number WT089062).; Lothian Birth Cohort 1921 and Lothian Birth Cohort 1936: We thank the cohort participants and team members who contributed to these studies. Phenotype collection in the Lothian Birth Cohort 1921 was supported by the Biotechnology and Biological Sciences Research Council, The Royal Society, and The Chief Scientist Office of the Scottish Government. Phenotype collection in the Lothian Birth Cohort 1936 was supported by Research Into Ageing (continues as part of Age United Kingdom The Disconnected Mind project). Genotyping of the cohorts was funded by the United Kingdom Biotechnology and Biological Sciences Research Council. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698). Funding from the Biotechnology and Biological Sciences Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, and Medical Research Council is gratefully acknowledged.; Orkney Complex Disease Study: Orkney Complex Disease Study was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, the Medical Research Council Human Genetics Unit, Arthritis Research United Kingdom, and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. We acknowledge the invaluable contributions of Lorraine Anderson and the research nurses in Orkney, the administrative team in Edinburgh, and the people of Orkney.; The Rotterdam Study: The generation and management of genome wide association study genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research project nr. 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera, and Marjolein Peters for their help in creating the genome-wide association study database and Karol Estrada and Maksim V. Struchalin for their support in creation and analysis of imputed data.; The Religious Order Study and Rush Memory and Aging Project: The Religious Order Study and Rush Memory and Aging Project Study are supported in part by National Institute on Aging Grants P30AG10161, R01AG15819, R01AG17917, R01AG30146, K08AG34290, and K25AG41906.; Study of Health in Pomerania: Study of Health in Pomerania is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (Grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (Grant no. 03ZIK012) and a joint Grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. The University of Greifswald is a member of the Center of Knowledge Interchange program of the Siemens AG. This work was also funded by the German Research Foundation (DFG: GR 1912/5-1).; The Tasmanian Study of Gait and Cognition is supported by Project Grants from the National Health and Medical Research Council (NHMRC IDs 403000, 491109, 606543) and a Grant from the Wicking Dementia Education and Research Centre, Hobart. Velandai Srikanth is supported by a National Health and Medical Research Council/National Heart Foundation Career Development Fellowship (ID 606544). Matthew Brown is supported by a National Health and Medical Research Council Principal Research Fellowship.; Baltimore Longitudinal Study of Aging: The Baltimore Longitudinal Study of Aging is supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging.; Hunter Community Study: We thank the men and women participating in the Hunter Community Study as well as all the staff, investigators, and collaborators who have supported or been involved in the project to date. The cohort was made possible with support from the University of Newcastle's Strategic Initiative Fund, the Vincent Fairfax Family Foundation, and the Hunter Medical Research Institute.; Nurses' Health Study: This study was supported by research Grants CA87969, CA49449, HL34594, U01HG004399, DK058845, CA65725, CA67262, CA50385, 5UO1CA098233, EY09611, EY015473, HG004728, HL35464, CA55075, CA134958, and DK070756 from the National Institutes of Health. The genotyping was partly supported by an unrestricted Grant from Merck Research Laboratories. Dr. Sun is supported by a career development award K99HL098459 from the National Heart, Lung, and Blood Institute.; REasons for Geographic and Racial Differences in Stroke: This research project is supported by a cooperative agreement U01 NS041588 (G. Howard, Principal Investigator) from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services. Genotyping was performed under Grant R01 DK084350 (Michele Sale, Principal Investigator). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke, the National Institute of Diabetes and Digestive and Kidney Diseases, or the National Institutes of Health. 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. We thank the other investigators, the staff, and the participants of the REasons for Geographic and Racial Differences in Stroke study for their valuable contributions. A full list of participating REasons for Geographic and Racial Differences in Stroke investigators and institutions can be found at http://www.regardsstudy.org.; Sydney Memory and Ageing Study: We acknowledge and thank the Sydney Memory and Ageing Study participants and the Sydney Memory and Ageing Study Research Team. DNA was extracted by Genetic Repositories Australia, an Enabling Facility, supported by National Health & Medical Research Council Grant 401184. Preparation of the DNA samples was undertaken in the laboratory of Peter Schofield and John Kwok, Neuroscience Research Australia. Genome-wide genotyping was performed by the Ramaciotti Centre, University of New South Wales. The Sydney Memory and Ageing Study is supported by Australian National Health & Medical Research Council Program Grant 350833 and Capacity Building Grant 568940. Henry Brodaty is supported by the Australian Government-funded Dementia Collaborative Research Centre at the University of New South Wales. Nicola Armstrong is supported by the National Health & Medical Research Council Project Grant 525453.; Three City Study: We thank the staff and the participants of the Three City Study for their important contributions. The Three City Study is conducted under a partnership agreement between the Institut National de la Sante et de la Recherche Medicale, the Victor Segalen-Bordeaux II University, and Sanofi-Aventis. The Fondation pour la Recherche Medicale funded the preparation and initiation of the study. The Three City Study is also supported by the Caisse Nationale Maladie des Travailleurs Salaries Direction Generale de la Sante, Mutuelle Generale de l'Education Nationale, Institut de la Longevite, Conseils Regionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research-Institut National de la Sante et de la Recherche Medicale Programme "Cohortes et collections de donnees biologiques." Lille Genopole received an unconditional Grant from Eisai. We thank A. Boland (Centre National de Genotypage) for her technical help in preparing the DNA samples for analyses. This work was supported by the National Foundation for Alzheimer's Disease and Related Disorders, the Institut Pasteur de Lille, and the Centre National de Genotypage. Stephanie Debette is a recipient of a Chaire d'Excellence Grant from the French national research agency (Agence Nationale de la Recherche).; Women's Genome Health Study: The Women's Genome Health Study is supported by HL043851 and HL080467 from the National Heart, Lung, and Blood Institute and CA047988 from the National Cancer Institute, the Donald W. Reynolds Foundation, and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen.; Swiss Memory Genetics Study: This work was funded by the Swiss National Science Foundation (Sinergia grant CRSI33_130080 to DQ and AP).; The hippocampal gene expression study was supported by the German Federal Ministry of Education and Research through the Integrated Genome Research Network MooDS (Systematic Investigation of the Molecular Causes of Major Mood Disorders and Schizophrenia, under the auspices of the National Genome Research Network plus). NR 45 TC 8 Z9 8 U1 3 U2 17 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 APR 15 PY 2015 VL 77 IS 8 BP 749 EP 763 DI 10.1016/j.biopsych.2014.08.027 PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CE8LB UT WOS:000352092700013 PM 25648963 ER PT J AU Koob, GF AF Koob, George F. TI The dark side of emotion: The addiction perspective SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Opponent process; Extended amygdala; Corticotropin-releasing factor; Dynorphin; Incentive salience; Allo stasis ID CORTICOTROPIN-RELEASING-FACTOR; KAPPA-OPIOID RECEPTOR; ANXIETY-LIKE BEHAVIOR; BRAIN REWARD FUNCTION; INTRACRANIAL SELF-STIMULATION; WITHDRAWAL-INDUCED ANXIETY; ETHANOL-DEPENDENT RATS; AMINOBUTYRIC-ACID RELEASE; PITUITARY-ADRENAL AXIS; PREFERRING P-RATS AB Emotions are "feeling" states and classic physiological emotive responses that are interpreted based on the history of the organism and the context. Motivation is a persistent state that leads to organized activity. Both are intervening variables and intimately related and have neural representations in the brain. The present thesis is that drugs of abuse elicit powerful emotions that can be interwoven conceptually into this framework. Such emotions range from pronounced euphoria to a devastating negative emotional state that in the extreme can create a break with homeostasis and thus an allostatic hedonic state that has been considered key to the etiology and maintenance of the pathophysiology of addiction. Drug addiction can be defined as a three-stage cycle-binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation-that involves allostatic changes in the brain reward and stress systems. Two primary sources of reinforcement, positive and negative reinforcement, have been hypothesized to play a role in this allostatic process. The negative emotional state that drives negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in the brain incentive salience and stress systems. Specific neurochemical elements in these structures include not only decreases in incentive salience system function in the ventral striatum (within-system opponent processes) but also recruitment of the brain stress systems mediated by corticotropin-releasing factor (CRF), dynorphin-kappa opioid systems, and norepinephrine, vasopressin, hypocretin, and substance P in the extended amygdala (between-system opponent processes). Neuropeptide Y, a powerful anti-stress neurotransmitter, has a profile of action on compulsive-like responding for drugs similar to a CRF1 receptor antagonist Other stress buffers include nociceptin and endocannabinoids, which may also work through interactions with the extended amygdala. The thesis argued here is that the brain has specific neurochemical neurocircuitry coded by the hedonic extremes of pleasant and unpleasant emotions that have been identified through the study of opponent processes in the domain of addiction. These neurochemical systems need to be considered in the context of the framework that emotions involve the specific brain regions now identified to differentially interpreting emotive physiological expression. Published by Elsevier B.V. C1 [Koob, George F.] Natl Inst Alcohol Abuse & Alcoholism, Washington, DC USA. RP Koob, GF (reprint author), Natl Inst Alcohol Abuse & Alcoholism, 5635 Fishers Lane,Room 2001,Suite 2000, Rockville, MD 20852 USA. EM goorge.koob@nih.gov RI koob, george/P-8791-2016 FU Intramural NIH HHS [Z99 AA999999] NR 205 TC 28 Z9 31 U1 4 U2 36 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 EI 1879-0712 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 15 PY 2015 VL 753 BP 73 EP 87 DI 10.1016/j.ejphar.2014.11.044 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CE6ND UT WOS:000351953200007 PM 25583178 ER PT J AU Metzger, DS Donnell, D Celentano, DD Jackson, JB Shao, YM Aramrattana, A Wei, L Fu, LP Ma, J Lucas, GM Chawarski, M Ruan, YH Richardson, P Shin, K Chen, RY Sugarman, J Dye, BJ Rose, SM Beauchamp, G Burns, DN AF Metzger, David S. Donnell, Deborah Celentano, David D. Jackson, J. Brooks Shao, Yiming Aramrattana, Apinun Wei, Liu Fu, Liping Ma, Jun Lucas, Gregory M. Chawarski, Marek Ruan, Yuhua Richardson, Paul Shin, Katherine Chen, Ray Y. Sugarman, Jeremy Dye, Bonnie J. Rose, Scott M. Beauchamp, Geetha Burns, David N. CA HPTN 058 Protocol Team TI Expanding Substance Use Treatment Options for HIV Prevention With Buprenorphine-Naloxone: HIV Prevention Trials Network 058 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV prevention; substance use treatment; buprenorphine/naloxone; medication-assisted treatment; PWID; opiates ID INJECTION-DRUG USERS; ANTIRETROVIRAL THERAPY; SUBSTITUTION TREATMENT; METHADONE TREATMENT; RISK REDUCTION; INFECTION; IMPACT; EPIDEMIOLOGY; TRANSMISSION; DEPENDENCE AB Background: Injection opioid use plays a significant role in the transmission of HIV infection in many communities and several regions of the world. Access to evidence-based treatments for opioid use disorders is extremely limited. Methods: HIV Prevention Trials Network 058 (HPTN 058) was a randomized controlled trial designed to compare the impact of 2 medication-assisted treatment (MAT) strategies on HIV incidence or death among opioid-dependent people who inject drugs (PWID). HIV-negative opioid-dependent PWID were recruited from 4 communities in Thailand and China with historically high prevalence of HIV among PWID. A total of 1251 participants were randomly assigned to either (1) a 1-year intervention consisting of 2 opportunities for a 15-day detoxification with buprenorphine/naloxone (BUP/NX) combined with up to 21 sessions of behavioral drug and risk counseling [short-term medication-assisted treatment (ST-MAT)] or (2) thrice-weekly dosing for 48 weeks with BUP/NX and up to 21 counseling sessions [long-term medication-assisted treatment (LT-MAT)] followed by dose tapering. All participants were followed for 52 weeks after treatment completion to assess durability of impact. Results: Although the study was stopped early due to lower than expected occurrence of the primary end points, sufficient data were available to assess the impact of the interventions on drug use and injection-related risk behavior. At week 26, 22% of ST-MAT participants had negative urinalyses for opioids compared with 57% in the LT-MAT (P< 0.001). Differences disappeared in the year after treatment: at week 78, 35% in ST-MAT and 32% in the LT-MAT had negative urinalyses. Injection-related risk behaviors were significantly reduced in both groups after randomization. Conclusions: Participants receiving BUP/NX 3 times weekly were more likely to reduce opioid injection while on active treatment. Both treatment strategies were considered safe and associated with reductions in injection-related risk behavior. These data support the use of thrice-weekly BUP/NX as a way to reduce exposure to HIV risk. Continued access to BUP/NX may be required to sustain reductions in opioid use. C1 [Metzger, David S.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Metzger, David S.] Treatment Res Inst, Philadelphia, PA USA. [Donnell, Deborah] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Celentano, David D.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Jackson, J. Brooks] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Jackson, J. Brooks] Univ Minnesota, Dept Pathol, Minneapolis, MN 55455 USA. [Shao, Yiming; Ruan, Yuhua] Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Natl Ctr AIDS STD Control & Prevent, Collaborat Innovat Ctr Diag & Treatment Infect Di, Beijing, Peoples R China. [Aramrattana, Apinun] Chiang Mai Univ, Fac Med, Dept Family Med, Chiang Mai, Thailand. [Wei, Liu] Guangxi Ctr HIV AIDS Prevent & Control, Guangxi Ctr Dis Control & Prevent, Nanning, Peoples R China. [Fu, Liping; Ma, Jun] Xinjiang Autonomous Reg Ctr Dis Control & Prevent, Xinjiang, Peoples R China. [Lucas, Gregory M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Chawarski, Marek] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Richardson, Paul] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Shin, Katherine] NIAID, Div AIDS, Pharmaceut Affairs Branch, Bethesda, MD USA. [Chen, Ray Y.] NIAID, Div Intramural Res, Bethesda, MD USA. [Sugarman, Jeremy] Johns Hopkins Univ, Berman Inst Bioeth, Baltimore, MD USA. [Dye, Bonnie J.; Rose, Scott M.] FHI 360, Hoan Kiem, Ha Noi, Vietnam. [Beauchamp, Geetha] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA USA. [Burns, David N.] NIAID, Div Aids, Prevent Sci Branch, Bethesda, MD USA. RP Metzger, DS (reprint author), Univ Penn, Perelman Sch Med, Dept Psychiat, 3535 Market St,Suite 4000, Philadelphia, PA 19104 USA. EM DSM@mail.med.upenn.edu RI Metzger, David/D-9499-2012; OI Chen, Ray/0000-0001-6344-1442; Donnell, Deborah/0000-0002-0587-7480 FU HIV Prevention Trials Network through NIH; National Institute of Allergy and Infectious Diseases [UM1 AI068619, UM1 AI069482, UM1 AI068613]; National Institute on Drug Abuse FX The research reported here was funded by the HIV Prevention Trials Network through a grant from the NIH. The HIV Prevention Trials Network was supported by award numbers UM1 AI068619, UM1 AI069482, and UM1 AI068613 from the National Institute of Allergy and Infectious Diseases. Funding support for this study was provided by the National Institute on Drug Abuse. Reckitt Benckiser Pharmaceuticals donated all medications used in this trial. NR 42 TC 4 Z9 4 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 15 PY 2015 VL 68 IS 5 BP 554 EP 561 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CE1RL UT WOS:000351589500015 PM 25564105 ER PT J AU Yao, WL Li, ZH Graubard, BI AF Yao, Wenliang Li, Zhaohai Graubard, Barry I. TI Estimation of ROC curve with complex survey data SO STATISTICS IN MEDICINE LA English DT Article DE receiver operating characteristic (ROC) curve; area under the ROC curve (AUC); jackknife variance; balanced repeated replication; survey sampling ID OPERATING CHARACTERISTIC CURVES; AREA; TESTS AB The receiver operating characteristic (ROC) curve can be utilized to evaluate the performance of diagnostic tests. The area under the ROC curve (AUC) is a widely used summary index for comparing multiple ROC curves. Both parametric and nonparametric methods have been developed to estimate and compare the AUCs. However, these methods are usually only applicable to data collected from simple random samples and not surveys and epidemiologic studies that use complex sample designs such as stratified and/or multistage cluster sampling with sample weighting. Such complex samples can inflate variances from intra-cluster correlation and alter the expectations of test statistics because of the use of sample weights that account for differential sampling rates. In this paper, we modify the nonparametric method to incorporate sampling weights to estimate the AUC and employ leaving-one-out jackknife methods along with the balanced repeated replication method to account for the effects of the complex sampling in the variance estimation of our proposed estimators of the AUC. The finite sample properties of our methods are evaluated using simulations, and our methods are illustrated by comparing the estimated AUC for predicting overweight/obesity using different measures of body weight and adiposity among sampled children and adults in the US Hispanic Health and Nutrition Examination Survey. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Yao, Wenliang; Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Yao, Wenliang] MedImmune LLC, Clin Biostat, Gaithersburg, MD 20878 USA. [Li, Zhaohai; Graubard, Barry I.] NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. RP Graubard, BI (reprint author), NCI, Biostat Branch, NIH, 9609 Med Ctr Dr,Rm 7-E140, Bethesda, MD 20892 USA. EM graubarb@exchange.nih.gov FU Intramural NIH HHS [Z01 CP010181-05] NR 23 TC 0 Z9 0 U1 1 U2 6 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 APR 15 PY 2015 VL 34 IS 8 BP 1293 EP 1303 DI 10.1002/sim.6405 PG 11 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 CD6NW UT WOS:000351207000003 PM 25546290 ER PT J AU Cao, GY Xu, W Yang, XW Gonzalez, FJ Li, F AF Cao, Gui-Yun Xu, Wei Yang, Xiu-Wei Gonzalez, Frank J. Li, Fei TI New neolignans from the seeds of Myristica fragrans that inhibit nitric oxide production SO FOOD CHEMISTRY LA English DT Article DE Myristica fragrans; Neolignans; Nitric oxide; Inhibition; iNOS mRNA ID ABSOLUTE-CONFIGURATION ASSIGNMENT; ENANTIOSELECTIVE SYNTHESIS; NUTMEG; LIGNANS; MACE; CONSTITUENTS; ANTIOXIDANT; MODEL; RAT AB Five new 8-0-4' type neolignans, named myrifralignan A-E (1-5), together with five known analogues (6-10), were isolated from the seeds of Myristica fragrans Houtt. Their chemical structures were determined using several spectroscopic methods. Compounds 3-10 exhibited potent inhibitory activity against the production of nitric oxide (NO) in the RAW264.7 cell line stimulated by lipopolysaccaride. Myrislignan (7) and machilin D (10) were the most potent inhibitors of NO production amongst these compounds. The IC50 values of myrislignan and machilin D were 21.2 and 18.5 mu M. And, their inhibitory activity was more than L-N-6-(1-iminoethyl)-lysine, a selective inhibitor of inducible nitric oxide synthase (IC50 = 27.1 mu M). Furthermore, real-time PCR analysis revealed that these neolignans could significantly suppress the expression of inducible nitric oxide synthase mRNA. These results demonstrated that the 8-0-4' type neolignans are promising candidates as anti-inflammatory agents. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Cao, Gui-Yun; Xu, Wei; Yang, Xiu-Wei] Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Dept Nat Med,State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. [Gonzalez, Frank J.; Li, Fei] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Yang, XW (reprint author), Peking Univ, Hlth Sci Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China. EM xwyang@bjmu.edu.cn; gonzalef@mail.nih.gov FU National Key Technologies R&D Program of China [2011BAI07B08]; National Natural Science Foundation of China [30973863, 81161120429] FX This research was partly supported by National Key Technologies R&D Program of China (2011BAI07B08) and the National Natural Science Foundation of China (30973863; 81161120429). NR 41 TC 18 Z9 18 U1 2 U2 44 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 EI 1873-7072 J9 FOOD CHEM JI Food Chem. PD APR 15 PY 2015 VL 173 BP 231 EP 237 DI 10.1016/j.foodchem.2014.09.170 PG 7 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA AY7RD UT WOS:000347755800030 PM 25466017 ER PT J AU Volkow, ND Wang, GJ Logan, J Alexoff, D Fowler, JS Thanos, PK Wong, C Casado, V Ferre, S Tomasi, D AF Volkow, N. D. Wang, G-J Logan, J. Alexoff, D. Fowler, J. S. Thanos, P. K. Wong, C. Casado, V. Ferre, S. Tomasi, D. TI Caffeine increases striatal dopamine D-2/D-3 receptor availability in the human brain SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID ADENOSINE A(2A) RECEPTORS; POSITRON-EMISSION-TOMOGRAPHY; PRIMARY DEMETHYLATED METABOLITES; CEREBRAL-BLOOD-FLOW; NUCLEUS-ACCUMBENS; COCAINE ABUSERS; D-3 RECEPTORS; AMPHETAMINE; SHELL; MICE AB Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A(2A) receptors (A(2A)R). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [C-11]raclopride (DA D-2/D-3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D-2/D-3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D-2/D-3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D-2/D-3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D-2/D-3 receptor availability. Instead, we interpret our findings to reflect an increase in D-2/D-3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D-2/D-3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D-2/D-3 receptors. C1 [Volkow, N. D.; Wang, G-J; Wong, C.; Tomasi, D.] NIAAA, Intramural Res Program, Bethesda, MD USA. [Logan, J.; Alexoff, D.; Fowler, J. S.; Thanos, P. K.] Brookhaven Natl Lab, Upton, NY 11973 USA. [Casado, V.] Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain. [Volkow, N. D.; Ferre, S.] NIDA, Intramural Res Program, Bethesda, MD 20892 USA. RP Volkow, ND (reprint author), NIDA, Intramural Res Program, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov RI Tomasi, Dardo/J-2127-2015; Casado, Vicent/K-1660-2014; Ferre, Sergi/K-6115-2014 OI Ferre, Sergi/0000-0002-1747-1779 FU NIH's Intramural Research Program (NIAAA) FX We thank Colleen Shea, Pauline Carter, Karen Apelskog and Ruben Baler for their contributions. This research was supported by NIH's Intramural Research Program (NIAAA). NR 58 TC 4 Z9 4 U1 5 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD APR 14 PY 2015 VL 5 AR e549 DI 10.1038/tp.2015.46 PG 6 WC Psychiatry SC Psychiatry GA DA2VS UT WOS:000367655500003 PM 25871974 ER PT J AU Przytycka, TM Levens, D AF Przytycka, Teresa M. Levens, David TI Shapely DNA attracts the right partner SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID TRANSCRIPTION; SPECIFICITIES; LIGANDS C1 [Przytycka, Teresa M.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Levens, David] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Przytycka, TM (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. EM przytyck@ncbi.nlm.nih.gov; levens@helix.nih.gov RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X FU Intramural NIH HHS NR 17 TC 1 Z9 1 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 14 PY 2015 VL 112 IS 15 BP 4516 EP 4517 DI 10.1073/pnas.1503951112 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF9BO UT WOS:000352856800026 PM 25848058 ER PT J AU Jeschke, A Zehethofer, N Lindner, B Krupp, J Schwudke, D Haneburger, I Jovic, M Backer, JM Balla, T Hilbi, H Haas, A AF Jeschke, Andreas Zehethofer, Nicole Lindner, Buko Krupp, Jessica Schwudke, Dominik Haneburger, Ina Jovic, Marko Backer, Jonathan M. Balla, Tamas Hilbi, Hubert Haas, Albert TI Phosphatidylinositol 4-phosphate and phosphatidylinositol 3-phosphate regulate phagolysosome biogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE phosphoinositides; cell-free membrane fusion; phagosome; lysosome; Legionella pneumophila ID INTERACTING LYSOSOMAL PROTEIN; MEMBRANE-FUSION; PHAGOSOME MATURATION; DISTINCT ROLES; RAB5 EFFECTORS; CLASS-I; TRAFFICKING; 3-KINASE; PHOSPHOINOSITIDES; PHAGOCYTOSIS AB Professional phagocytic cells ingest microbial intruders by engulfing them into phagosomes, which subsequently mature into microbicidal phagolysosomes. Phagosome maturation requires sequential fusion of the phagosome with early endosomes, late endosomes, and lysosomes. Although various phosphoinositides (PIPs) have been detected on phagosomes, it remained unclear which PIPs actually govern phagosome maturation. Here, we analyzed the involvement of PIPs in fusion of phagosomes with various endocytic compartments and identified phosphatidylinositol 4-phosphate [PI(4)P], phosphatidylinositol 3-phosphate [PI(3)P], and the lipid kinases that generate these PIPs, as mediators of phagosome-lysosome fusion. Phagosome-early endosome fusion required PI(3)P, yet did not depend on PI(4)P. Thus, PI(3)P regulates phagosome maturation at early and late stages, whereas PI(4)P is selectively required late in the pathway. C1 [Jeschke, Andreas; Krupp, Jessica; Haas, Albert] Univ Bonn, Inst Cell Biol, D-53121 Bonn, Germany. [Zehethofer, Nicole; Lindner, Buko; Schwudke, Dominik] Leibniz Ctr Med & Biosci, Dept Mol Infect Biol, Div Immunochem, D-23845 Borstel, Germany. [Haneburger, Ina; Hilbi, Hubert] Univ Munich, Max Von Pettenkofer Inst, Dept Med, D-80336 Munich, Germany. [Haneburger, Ina; Hilbi, Hubert] Univ Zurich, Inst Med Microbiol, CH-8006 Zurich, Switzerland. [Jovic, Marko] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Backer, Jonathan M.] Albert Einstein Coll Med, Belfer Inst Adv Biomed Sci, Mol Pharmacol, Bronx, NY 10461 USA. RP Haas, A (reprint author), Univ Bonn, Inst Cell Biol, D-53121 Bonn, Germany. EM albert.haas@uni-bonn.de RI Schwudke, Dominik/B-3478-2013; OI Schwudke, Dominik/0000-0002-1379-9451; Balla, Tamas/0000-0002-9077-3335 FU Deutsche Forschungsgemeinschaft [SFB 645, SPP 1580]; intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health, Bethesda, MD FX We thank all colleagues who generously contributed plasmids and antibodies. This study was supported by Deutsche Forschungsgemeinschaft Grants SFB 645 (to A.H.) and SPP 1580 (to A. H., B.L., and H. H.) and by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health, Bethesda, MD (to M.J. and T.B.). NR 55 TC 7 Z9 7 U1 4 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 14 PY 2015 VL 112 IS 15 BP 4636 EP 4641 DI 10.1073/pnas.1423456112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF9BO UT WOS:000352856800046 PM 25825728 ER PT J AU Li, XJ Wang, DW Chen, Z Lu, EM Wang, Z Duan, JJ Tian, W Wang, Y You, LJ Zou, YL Cheng, Y Zhu, QY Wan, XJ Xi, T Birnbaumerd, L Yang, Y AF Li, Xianjing Wang, Duowei Chen, Zhen Lu, Ermei Wang, Zhuo Duan, Jingjing Tian, Wei Wang, Yun You, Linjun Zou, Yulian Cheng, Yan Zhu, Qingyi Wan, Xiaojian Xi, Tao Birnbaumerd, Lutz Yang, Yong TI G alpha(i1) and G alpha(i3) regulate macrophage polarization by forming a complex containing CD14 and Gab1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE G alpha(i1); G alpha(i3); macrophage polarization; Toll-like receptor 4; endosome ID HETEROTRIMERIC G-PROTEINS; NF-KAPPA-B; IN-VIVO; ACTIVATION; KINASE; BETA; LIPOPOLYSACCHARIDE; ENDOCYTOSIS; TOLERANCE; CYTOKINES AB Heterotrimeric G proteins have been implicated in Toll-like receptor 4 (TLR4) signaling in macrophages and endothelial cells. However, whether guanine nucleotide-binding protein G(i) subunit alpha-1 and alpha-3 (G alpha(i1/3)) are required for LPS responses remains unclear, and if so, the underlying mechanisms need to be studied. In this study, we demonstrated that, in response to LPS, G alpha(i1/3) form complexes containing the pattern recognition receptor (PRR) CD14 and growth factor receptor binding 2 (Grb2)associated binding protein (Gab1), which are required for activation of PI3K-Akt signaling. G alpha(i1/3) deficiency decreased LPS-induced TLR4 endocytosis, which was associated with decreased phosphorylation of IFN regulatory factor 3 (IRF3). G alpha(i1/3) knockdown in bone marrow-derived macrophage cells (G alpha(i1/3) KD BMDMs) exhibited an M2-like phenotype with significantly suppressed production of TNF-alpha, IL-6, IL-12, and NO in response to LPS. The altered polarization coincidedwith decreased Akt activation. Further, G alpha(i1/3) deficiency caused LPS tolerance in mice. In vitro studies revealed that, in LPS-tolerant macrophages, G alpha(i1/3) were down-regulated partially by the proteasome pathway. Collectively, the present findings demonstrated that G alpha(i1/3) can interact with CD14/Gab1, which modulates macrophage polarization in vitro and in vivo. C1 [Li, Xianjing; Wang, Duowei; Chen, Zhen; Lu, Ermei; Wang, Zhuo; Duan, Jingjing; Tian, Wei; Wang, Yun; You, Linjun; Zou, Yulian; Cheng, Yan; Xi, Tao; Yang, Yong] China Pharmaceut Univ, State Key Lab Nat Med, Jiangsu Key Lab Drug Discovery Metab Dis, Ctr New Drug Safety Evaluat & Res, Nanjing 211198, Jiangsu, Peoples R China. [Zhu, Qingyi] Jiangsu Prov Hosp Tradit Chinese Med, Dept Urol, Nanjing 210029, Jiangsu, Peoples R China. [Wan, Xiaojian] Second Mil Med Univ, Changhai Hosp, Dept Anesthesiol & Intens Care Med, Shanghai 200433, Peoples R China. [Birnbaumerd, Lutz] Natl Inst Environm Hlth Sci, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. RP Birnbaumerd, L (reprint author), China Pharmaceut Univ, State Key Lab Nat Med, Jiangsu Key Lab Drug Discovery Metab Dis, Ctr New Drug Safety Evaluat & Res, Nanjing 211198, Jiangsu, Peoples R China. EM birbau1@gmail.com; yy@cpu.edu.cn FU NIH Intramural Research Program Project [Z01 ES101643]; National Science Foundation of China [81473230, 81403020, 81273547, 91129731]; Natural Science Foundation of Jiangsu Province [BK2012025, BK2011632] FX This work was supported in part by NIH Intramural Research Program Project Z01 ES101643 (to L.B.); National Science Foundation of China Grants 81473230, 81403020, 81273547, and 91129731; and Natural Science Foundation of Jiangsu Province Grants BK2012025 and BK2011632. NR 39 TC 4 Z9 4 U1 4 U2 24 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 14 PY 2015 VL 112 IS 15 BP 4731 EP 4736 DI 10.1073/pnas.1503779112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF9BO UT WOS:000352856800062 PM 25825741 ER PT J AU Gill, RL Castaing, JP Hsin, J Tan, IS Wang, XS Huang, KC Tian, F Ramamurthi, KS AF Gill, Richard L., Jr. Castaing, Jean-Philippe Hsin, Jen Tan, Irene S. Wang, Xingsheng Huang, Kerwyn Casey Tian, Fang Ramamurthi, Kumaran S. TI Structural basis for the geometry-driven localization of a small protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ArfGAP1; SpoIVA; DivIVA; curvature sensing; lipid packing ID SUBTILIS SPORE COAT; BACILLUS-SUBTILIS; MEMBRANE CURVATURE; SUBCELLULAR-LOCALIZATION; LIPID PACKING; MORPHOGENETIC PROTEIN; AMPHIPATHIC HELICES; MOLECULAR-DYNAMICS; ANCHORED PROTEINS; BAR DOMAINS AB In bacteria, certain shape-sensing proteins localize to differently curved membranes. During sporulation in Bacillus subtilis, the only convex (positively curved) surface in the cell is the forespore, an approximately spherical internal organelle. Previously, we demonstrated that SpoVM localizes to the forespore by preferentially adsorbing onto slightly convex membranes. Here, we used NMR and molecular dynamics simulations of SpoVM and a localization mutant (SpoVM(P9A)) to reveal that SpoVM's atypical amphipathic alpha-helix inserts deeply into the membrane and interacts extensively with acyl chains to sense packing differences in differently curved membranes. Based on binding to spherical supported lipid bilayers and Monte Carlo simulations, we hypothesize that SpoVM's membrane insertion, along with potential cooperative interactions with other SpoVM molecules in the lipid bilayer, drives its preferential localization onto slightly convex membranes. Such a mechanism, which is distinct from that used by high curvature-sensing proteins, may be widely conserved for the localization of proteins onto the surface of cellular organelles. C1 [Gill, Richard L., Jr.; Wang, Xingsheng; Tian, Fang] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. [Castaing, Jean-Philippe; Tan, Irene S.; Ramamurthi, Kumaran S.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Hsin, Jen; Huang, Kerwyn Casey] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Tan, Irene S.] Johns Hopkins Univ, NIH, Grad Partnerships Program, Baltimore, MD 21218 USA. [Huang, Kerwyn Casey] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. RP Huang, KC (reprint author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. EM kchuang@stanford.edu; ftian@psu.edu; ramamurthiks@mail.nih.gov RI Ramamurthi, Kumaran/P-3516-2015 FU National Institute of General Medical Sciences (NIGMS) National Center for Multiscale Modeling of Biological Systems [P41GM103712-S1]; National Science Foundation [OCI-1053575, TG-MCB110056]; NIH NIGMS [R01GM105963]; NIH Ruth L. Kirschstein National Research Service [1F32GM100677]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX We thank S. Lecuyer and J. Flanagan for discussion; S. Gottesman, R. Losick, A. Hitchcock-Camp, and members of the K.C.H., F.T., and K.S.R. laboratories for comments on the manuscript; Cordelia Weiss for construction of strain CW245; and A. Benesi and E. Hatzakis at the NMR facility of Pennsylvania State University for assistance with the 850-MHz instrument. Long time-scale MD simulations were carried out on the Anton supercomputer at the Pittsburgh Supercomputing Center, supported by National Institute of General Medical Sciences (NIGMS) National Center for Multiscale Modeling of Biological Systems Grant P41GM103712-S1. Access to the Anton supercomputer was granted through Proposal PSCA13052P (to K.C.H. and J.H.). Auxiliary simulations were conducted with computer time provided by the Extreme Science and Engineering Discovery Environment, supported by National Science Foundation Grant OCI-1053575, Allocation TG-MCB110056 (to K.C.H. and J.H.). This work was funded by NIH NIGMS Grant R01GM105963 (to F.T. and K.C.H.), NIH Ruth L. Kirschstein National Research Service Award 1F32GM100677 (to J.H.), and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (K.S.R.). NR 56 TC 7 Z9 7 U1 2 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 14 PY 2015 VL 112 IS 15 BP E1908 EP E1915 DI 10.1073/pnas.1423868112 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF9BO UT WOS:000352856800015 PM 25825747 ER PT J AU Wang, SJ Chu, CH Stewart, T Ginghina, C Wang, YF Nie, H Guo, MR Wilson, B Hong, JS Zhang, J AF Wang, Shijun Chu, Chun-Hsien Stewart, Tessandra Ginghina, Carmen Wang, Yifei Nie, Hui Guo, Mingri Wilson, Belinda Hong, Jau-Shyong Zhang, Jing TI alpha-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE alpha-Synuclein; microglial chemotaxis; neuroinflammation; Lyn; hydrogen peroxide ID PARKINSONS-DISEASE; IN-VITRO; INDUCED ACTIVATION; REDOX SENSOR; INFLAMMATION; NEUTROPHILS; INHIBITION; NEURONS; NEURODEGENERATION; REGENERATION AB Malformed alpha-Synuclein (alpha-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in alpha-synucleinopathies, such as Parkinson's disease. The mechanisms by which alpha-syn aggregates activate and recruit microglia remain unclear, however. Here we show that alpha-syn aggregates act as chemoattractants to direct microglia toward damaged neurons. In addition, we describe a mechanism underlying this directional migration of microglia. Specifically, chemotaxis occurs when alpha-syn binds to integrin CD11b, leading to H2O2 production by NADPH oxidase. H2O2 directly attracts microglia via a process in which extracellularly generated H2O2 diffuses into the cytoplasm and tyrosine protein kinase Lyn, phosphorylates the F-actin-associated protein cortactin after sensing changes in the microglial intracellular concentration of H2O2. Finally, phosphorylated cortactin mediates actin cytoskeleton rearrangement and facilitates directional cell migration. These findings have significant implications, given that alpha-syn-mediated microglial migration reaches beyond Parkinson's disease. C1 [Wang, Shijun; Stewart, Tessandra; Ginghina, Carmen; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Wang, Shijun; Chu, Chun-Hsien; Nie, Hui; Guo, Mingri; Wilson, Belinda; Hong, Jau-Shyong] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Wang, Yifei] East Chapel Hill High Sch, Chapel Hill, NC 27514 USA. [Wang, Yifei] Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA. [Zhang, Jing] Peking Univ, Hosp 3, Dept Pathol, Beijing 100191, Peoples R China. [Zhang, Jing] Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Beijing 100191, Peoples R China. RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. EM zhangj@u.washington.edu FU NIEHS; National Institutes of Health [R01 ES019277, R01 ES016873]; National Natural Science Foundation of China [81129018] FX We thank the Michael J. Fox Foundation for providing the AAV2 vectors. We appreciate the technical support from Dr. Negin Martin at the National Institute of Environmental Health Science (NIEHS) Laboratory of Neurobiology Viral Vector Core Facility and Mr. Jeff Tucker at the NIEHS Imaging Center. We are grateful to Drs. Keith Burridge and Zachary Hoffer for their critical reading of this manuscript. This study was supported by intramural funding from the NIEHS (to J.-S.H.), National Institutes of Health Grants R01 ES019277 and R01 ES016873 (to J.Z.), and Grant 81129018 from the National Natural Science Foundation of China (to J.Z.). NR 47 TC 17 Z9 17 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 14 PY 2015 VL 112 IS 15 BP E1926 EP E1935 DI 10.1073/pnas.1417883112 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF9BO UT WOS:000352856800017 PM 25825709 ER PT J AU Kratz, CP Franke, L Peters, H Kohlschmidt, N Kazmierczak, B Finckh, U Bier, A Eichhorn, B Blank, C Kraus, C Kohlhase, J Pauli, S Wildhardt, G Kutsche, K Auber, B Christmann, A Bachmann, N Mitter, D Cremer, FW Mayer, K Daumer-Haas, C Nevinny-Stickel-Hinzpeter, C Oeffner, F Schluter, G Gencik, M Uberlacker, B Lissewski, C Schanze, I Greene, MH Spix, C Zenker, M AF Kratz, C. P. Franke, L. Peters, H. Kohlschmidt, N. Kazmierczak, B. Finckh, U. Bier, A. Eichhorn, B. Blank, C. Kraus, C. Kohlhase, J. Pauli, S. Wildhardt, G. Kutsche, K. Auber, B. Christmann, A. Bachmann, N. Mitter, D. Cremer, F. W. Mayer, K. Daumer-Haas, C. Nevinny-Stickel-Hinzpeter, C. Oeffner, F. Schlueter, G. Gencik, M. Ueberlacker, B. Lissewski, C. Schanze, I. Greene, M. H. Spix, C. Zenker, M. TI Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes SO BRITISH JOURNAL OF CANCER LA English DT Article DE RASopathy; cancer risk; cancer risk variants ID JUVENILE MYELOMONOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; GERMLINE MUTATIONS; CHILDHOOD-CANCER; LEOPARD-SYNDROME; PTPN11 MUTATION; PHENOTYPE; DISEASE AB Background: Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These 'RASopathies' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown. Methods: We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry. Results: We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR) = 10.5, 95% confidence interval = 5.4-18.3). The specific cancers included juvenile myelomonocytic leukaemia = 4; brain tumour = 3; acute lymphoblastic leukaemia = 2; rhabdomyosarcoma = 2; and neuroblastoma = 1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4. Conclusions: These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours. C1 [Kratz, C. P.] Hannover Med Sch, Dept Pediat Hematol & Oncol, D-30625 Hannover, Germany. [Franke, L.; Lissewski, C.; Schanze, I.; Zenker, M.] Univ Hosp Magdeburg, Inst Human Genet, D-39120 Magdeburg, Germany. [Peters, H.] Inst Med & Human Genet, Charite Campus Virchow Klinikum, D-13353 Berlin, Germany. [Kohlschmidt, N.] Inst Klin Genet, D-53111 Bonn, Germany. [Kazmierczak, B.] Praxis Humangenet, D-28209 Bremen, Germany. [Finckh, U.] UBAG Med Versorgungszentrum Dr Eberhard & Par, D-44137 Dortmund, Germany. [Bier, A.] Gemeinschaftspraxis Humangenet, D-01307 Dresden, Germany. [Eichhorn, B.] Mitteldeutscher Praxisverbund Humangenet, D-01067 Dresden, Germany. [Blank, C.] Praenatal Med, D-40210 Dusseldorf, Germany. [Kraus, C.] Friedrich Alexander Univ Erlangen Nurnberg FAU, Univ Hosp Erlangen, Inst Human Genet, D-91054 Erlangen, Germany. [Kohlhase, J.] Ctr Human Genet Freiburg, D-79100 Freiburg, Germany. [Pauli, S.] Univ Gottingen, Inst Human Genet, D-37073 Gottingen, Germany. [Wildhardt, G.] Zentrum Humangenet, Biol, D-60438 Frankfurt, Germany. [Kutsche, K.] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, D-20246 Hamburg, Germany. [Auber, B.] MVZ GenteQ, D-20251 Hamburg, Germany. [Christmann, A.] Praxis Humangenet, D-66424 Homburg, Saar, Germany. [Bachmann, N.] Zentrum Humangenet, Biosci Ingelheim, D-55218 Ingelheim, Germany. [Mitter, D.] Univ Hosp Leipzig, Inst Human Genet, D-04103 Leipzig, Germany. [Cremer, F. W.] Zentrum Humangenet Mannheim, D-68163 Mannheim, Germany. [Mayer, K.] Zentrum Humangenet & Lab Diagnost MV, D-82152 Martinsried, Germany. [Daumer-Haas, C.] Pranatal Med Munchen, D-80639 Munich, Germany. [Nevinny-Stickel-Hinzpeter, C.] Praxis Humangenet Munchen, Synlab Medizin Versorgungszentrum Humane Genet, D-80337 Munich, Germany. [Oeffner, F.] Genetikum Neu Ulm, D-89231 Neu Ulm, Germany. [Schlueter, G.] Pranatalmed & Genet, D-90402 Nurnberg, Germany. [Gencik, M.] Diagenos, D-49076 Osnabruck, Germany. [Ueberlacker, B.] Inst Med Genet & Mol Med, D-50939 Cologne, Germany. [Greene, M. H.] Natl Canc Inst, Clin Genet Branch, Bethesda, MD 20850 USA. [Spix, C.] Univ Med Ctr Mainz, Inst Med Biostat Epidemiol & Informat, German Childhood Canc Registry, D-55131 Mainz, Germany. RP Kratz, CP (reprint author), Hannover Med Sch, Dept Pediat Hematol & Oncol, Carl Neuberg Str 1, D-30625 Hannover, Germany. RI Lissewski, Christina/K-1623-2015 OI Lissewski, Christina/0000-0002-5414-7126 FU National Institutes of Health; National Cancer Institute; Verein fur krebskranke Kinder Hannover e.V. FX This work was supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. The technical procedures ensuring encrypted matching were facilitated by Thomas Ziegler and Claudia Bremensdorfer (both GCCR). CPK is supported by the Verein fur krebskranke Kinder Hannover e.V. NR 24 TC 27 Z9 27 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD APR 14 PY 2015 VL 112 IS 8 BP 1392 EP 1397 DI 10.1038/bjc.2015.75 PG 6 WC Oncology SC Oncology GA CG0VM UT WOS:000352989900012 PM 25742478 ER PT J AU Xydakis, MS Mulligan, LP Smith, AB Olsen, CH Lyon, DM Belluscio, L AF Xydakis, Michael S. Mulligan, Lisa P. Smith, Alice B. Olsen, Cara H. Lyon, Dina M. Belluscio, Leonardo TI Olfactory impairment and traumatic brain injury in blast-injured combat troops A cohort study SO NEUROLOGY LA English DT Article ID GLASGOW COMA SCALE; MINOR HEAD-INJURY; DYSFUNCTION; DEFICITS; SMELL; MILD; TOMOGRAPHY; DEMENTIA; ANOSMIA; IMPACT AB Objective: To determine whether a structured and quantitative assessment of differential olfactory performance-recognized between a blast-injured traumatic brain injury (TBI) group and a demographically comparable blast-injured control group-can serve as a reliable antecedent marker for preclinical detection of intracranial neurotrauma. Methods: We prospectively and consecutively enrolled 231 polytrauma inpatients, acutely injured from explosions during combat operations in either Afghanistan or Iraq and requiring immediate stateside evacuation and sequential admission to our tertiary care medical center over a 21/2-year period. This study correlates olfactometric scores with both contemporaneous neuroimaging findings as well as the clinical diagnosis of TBI, tabulates population-specific incidence data, and investigates return of olfactory function. Results: Olfactometric score predicted abnormal neuroimaging significantly better than chance alone (area under the curve = 0.78, 95% confidence interval [CI] 0.70-0.87). Normosmia was present in all troops with mild TBI (i. e., concussion) and all control subjects. Troops with radiographic evidence of frontal lobe injuries were 3 times more likely to have olfactory impairment than troops with injuries to other brain regions (relative risk 3.0, 95% CI 0.98-9.14). Normalization of scores occurred in all anosmic troops available for follow-up testing. Conclusion: Quantitative identification olfactometry has limited sensitivity but high specificity as a marker for detecting acute structural neuropathology from trauma. When considering whether to order advanced neuroimaging, a functional disturbance with central olfactory impairment should be regarded as an important tool to inform the decision process. Classification of evidence: This study provides Class III evidence that central olfactory dysfunction identifies patients with TBI who have intracranial radiographic abnormalities with a sensitivity of 35% (95% CI 20.6%-51.7%) and specificity of 100% (95% CI 97.7%-100.0%). C1 [Xydakis, Michael S.] Walter Reed Natl Mil Med Ctr, Otorhinolaryngol Head & Neck Surg, Bethesda, MD 20889 USA. [Mulligan, Lisa P.] Walter Reed Natl Mil Med Ctr, Neurosurg, Bethesda, MD USA. [Smith, Alice B.] Walter Reed Natl Mil Med Ctr, Neuroradiol, Bethesda, MD USA. [Xydakis, Michael S.; Mulligan, Lisa P.; Lyon, Dina M.] Uniformed Serv Univ Hlth Sci, Traumat Brain Injury Surg Res Program, Bethesda, MD 20814 USA. [Xydakis, Michael S.] Uniformed Serv Univ Hlth Sci, Otorhinolaryngol Head & Neck Surg, Bethesda, MD 20814 USA. [Mulligan, Lisa P.] Uniformed Serv Univ Hlth Sci, Neurosurg, Bethesda, MD 20814 USA. [Smith, Alice B.] Uniformed Serv Univ Hlth Sci, Neuroradiol, Bethesda, MD 20814 USA. [Olsen, Cara H.] Uniformed Serv Univ Hlth Sci, Prevent Med & Biostat, Bethesda, MD 20814 USA. [Xydakis, Michael S.; Mulligan, Lisa P.; Smith, Alice B.; Lyon, Dina M.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Belluscio, Leonardo] NIH, Neurol Disorders & Stroke, Bethesda, MD 20892 USA. RP Xydakis, MS (reprint author), Walter Reed Natl Mil Med Ctr, Otorhinolaryngol Head & Neck Surg, Bethesda, MD 20889 USA. EM michael.xydakis@usuhs.edu FU US Department of Defense Combat Casualty Care Medical Research and Development Program [DMRDP: ID-D10-I-AR-J6-626] FX US Department of Defense Combat Casualty Care Medical Research and Development Program (DMRDP: ID-D10-I-AR-J6-626). NR 40 TC 1 Z9 2 U1 1 U2 13 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 APR 14 PY 2015 VL 84 IS 15 BP 1559 EP 1567 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CG1OH UT WOS:000353042100012 PM 25788559 ER PT J AU Joachim, A Nilsson, C Aboud, S Bakari, M Lyamuya, EF Robb, ML Marovich, MA Earl, P Moss, B Ochsenbauer, C Wahren, B Mhalu, F Sandstrom, E Biberfeld, G Ferrari, G Polonis, VR AF Joachim, Agricola Nilsson, Charlotta Aboud, Said Bakari, Muhammad Lyamuya, Eligius F. Robb, Merlin L. Marovich, Mary A. Earl, Patricia Moss, Bernard Ochsenbauer, Christina Wahren, Britta Mhalu, Fred Sandstrom, Eric Biberfeld, Gunnel Ferrari, Guido Polonis, Victoria R. TI Potent Functional Antibody Responses Elicited by HIV-I DNA Priming and Boosting with Heterologous HIV-1 Recombinant MVA in Healthy Tanzanian Adults SO PLOS ONE LA English DT Article ID CELL-MEDIATED CYTOTOXICITY; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; RHESUS MACAQUES; PROTECTIVE EFFICACY; IMMUNE-RESPONSES; VACCINE; VIRUS; INFECTION; CHALLENGE AB Vaccine-induced HIV antibodies were evaluated in serum samples collected from healthy Tanzanian volunteers participating in a phase I/II placebo-controlled double blind trial using multi-clade, multigene HIV-DNA priming and recombinant modified vaccinia Ankara (HIV-MVA) virus boosting (HIVIS03). The HIV-DNA vaccine contained plasmids expressing HIV-1 gp160 subtypes A, B, C, Rev B, Gag A, B and RTmut B, and the recombinant HIV-MVA boost expressed CRF01_AE HIV-1 Env subtype E and Gag-Pol subtype A. While no neutralizing antibodies were detected using pseudoviruses in the TZM-bl cell assay, this prime-boost vaccination induced neutralizing antibodies in 83% of HIVIS03 vaccinees when a peripheral blood mononuclear cell (PBMC) assay using luciferase reporter-infectious molecular clones (LucR-IMC) was employed. The serum neutralizing activity was significantly (but not completely) reduced upon depletion of natural killer (NK) cells from PBMC (p= 0.006), indicating a role for antibody-mediated Fcy-receptor function. High levels of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies against CRF01_AE and/or subtype B were subsequently demonstrated in 97% of the sera of vaccinees. The magnitude of ADCC-mediating antibodies against CM235 CRF01_AE IMC-infected cells correlated with neutralizing antibodies against CM235 in the IMC/PBMC assay. In conclusion, HIV-DNA priming, followed by two HIV-MVA boosts elicited potent ADCC responses in a high proportion of Tanzanian vaccinees. Our findings highlight the potential of HIV-DNA prime HIV-MVA boost vaccines for induction of functional antibody responses and suggest this vaccine regimen and ADCC studies as potentially important new avenues in HIV vaccine development. C1 [Joachim, Agricola; Aboud, Said; Lyamuya, Eligius F.; Mhalu, Fred] Muhimbili Univ Hlth & Allied Sci, Dept Microbiol & Immunol, Dar Es Salaam, Tanzania. [Joachim, Agricola; Nilsson, Charlotta; Wahren, Britta; Biberfeld, Gunnel] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Nilsson, Charlotta; Biberfeld, Gunnel] Publ Hlth Agcy Sweden, Solna, Sweden. [Nilsson, Charlotta] Karolinska Inst, Dept Lab Med, Huddinge, Sweden. [Bakari, Muhammad] Muhimbili Univ Hlth & Allied Sci, Dept Internal Med, Dar Es Salaam, Tanzania. [Robb, Merlin L.] Henry M Jackson Fdn Adv Mil Med, Mil HIV Res Program, Bethesda, MD USA. [Marovich, Mary A.; Polonis, Victoria R.] Walter Reed Army Inst Res, Mil HIV Res Program, Silver Spring, MD USA. [Earl, Patricia; Moss, Bernard] NIAID, NIH, Bethesda, MD 20892 USA. [Ochsenbauer, Christina] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Sandstrom, Eric] Karolinska Inst Sodersjukhuset, Venhalsan, Stockholm, Sweden. [Ferrari, Guido] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Joachim, A (reprint author), Muhimbili Univ Hlth & Allied Sci, Dept Microbiol & Immunol, Dar Es Salaam, Tanzania. EM agricolaj@muhas.ac.tz FU European Union; Swedish International Development Cooperation Agency (Sida); Swedish Embassy Tanzania; European & Developing Countries Clinical Trials Partnership (EDCTP) [CT.2006.33111.007]; Regional HIV/AIDS Team for Africa, Embassy of Sweden, Lusaka [2150012801]; Collaboration for AIDS Vaccine Discovery (CAVD) grant from the Bill & Melinda Gates Foundation [1032144]; Duke University Center for AIDS Research (CFAR) [P30 AI64518]; US Military HIV Research program; Walter Reed Army Institute of Research (WRAIR); Division of Intramural Research, NIAD, NIH FX This work was supported by the European Union, the Swedish International Development Cooperation Agency (Sida),Swedish Embassy Tanzania, the European & Developing Countries Clinical Trials Partnership (EDCTP, project code CT.2006.33111.007), and The Regional HIV/AIDS Team for Africa, Embassy of Sweden, Lusaka, jointly funded by Sweden and Norway (Sida contribution number 2150012801). Additional support was provided by the Collaboration for AIDS Vaccine Discovery (CAVD) grant from the Bill & Melinda Gates Foundation (Grant ID: 1032144), Duke University Center for AIDS Research (CFAR, grant P30 AI64518), the US Military HIV Research program, Walter Reed Army Institute of Research (WRAIR) and the Division of Intramural Research, NIAD, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 7 Z9 8 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 14 PY 2015 VL 10 IS 4 AR e0118486 DI 10.1371/journal.pone.0118486 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1EB UT WOS:000353014700001 PM 25874723 ER PT J AU Lagenaur, LA Swedek, I Lee, PP Parks, TP AF Lagenaur, Laurel A. Swedek, Iwona Lee, Peter P. Parks, Thomas P. TI Robust Vaginal Colonization of Macaques with a Novel Vaginally Disintegrating Tablet Containing a Live Biotherapeutic Product to Prevent HIV Infection in Women SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYANOVIRIN-N; BACTERIAL VAGINOSIS; PREEXPOSURE PROPHYLAXIS; MICROBICIDE DEVELOPMENT; MACACA-MULATTA; TENOFOVIR GEL; AFRICAN WOMEN; LACTOBACILLUS; ACQUISITION AB MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x10(11) CFU/g), and stable at 4 degrees C and 25 degrees C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody. C1 [Lagenaur, Laurel A.; Swedek, Iwona; Lee, Peter P.; Parks, Thomas P.] Osel Inc, Mountain View, CA 94043 USA. [Lagenaur, Laurel A.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. RP Lagenaur, LA (reprint author), Osel Inc, Mountain View, CA 94043 USA. EM llagenaur@mail.nih.gov FU National Institutes of Health (NIH) research grant [5R33AI071978]; Bill and Melinda Gates Foundation; Osel Inc. FX This work was supported by National Institutes of Health (NIH) research grant 5R33AI071978 and Phase 1 and Phase 2 Grand Challenges Explorations grants through the Bill and Melinda Gates Foundation (www.grandchallenges.org/). Osel Inc. played an indirect role through the participation of the co-authors and provided support in the form of salaries for authors LAL, TPP and IS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 0 Z9 0 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 14 PY 2015 VL 10 IS 4 AR e0122730 DI 10.1371/journal.pone.0122730 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1EB UT WOS:000353014700023 PM 25875100 ER PT J AU Song, N Choi, JY Sung, H Jeon, S Chung, S Song, M Park, SK Han, W Lee, JW Kim, MK Yoo, KY Ahn, SH Noh, DY Kang, D AF Song, Nan Choi, Ji-Yeob Sung, Hyuna Jeon, Sujee Chung, Seokang Song, Minkyo Park, Sue K. Han, Wonshik Lee, Jong Won Kim, Mi Kyung Yoo, Keun-Young Ahn, Sei-Hyun Noh, Dong-Young Kang, Daehee TI Tumor Subtype-Specific Associations of Hormone-Related Reproductive Factors on Breast Cancer Survival SO PLOS ONE LA English DT Article ID RISK-FACTORS; PROGNOSTIC FACTOR; RECEPTOR STATUS; YOUNG-WOMEN; LAST BIRTH; SHORT-TERM; PARITY; MORTALITY; PROLACTIN; DIAGNOSIS AB Purpose It is inconclusive whether reproductive factors, which are known as risk factors of breast cancer, also influence survival. We investigated overall and subtype-specific associations between reproductive factors and breast cancer survival. Methods Among 3,430 incident breast cancer patients who enrolled in the Seoul Breast Cancer Study, 269 patients (7.8%) died and 528 patients (15.4%) recurred. The overall and subtype-specific associations of reproductive factors including age at menarche and menopause, duration of estrogen exposure, menstrual cycle, parity, age at first full-term pregnancy, number of children, age at last birth, time since the last birth, and duration of breastfeeding, on overall and disease-free survival (OS and DFS) were estimated by hazard ratios (HRs) and 95% confidence intervals (95% CIs) using a multivariate Cox proportional hazard model. Results An older age at menarche (HR for OS=1.10, 95% CI=1.03-1.19), a greater number of children (>= 4 vs. 2, HR for DFS=1.58, 95% CI=1.11-2.26), and a shorter time since last birth (<5 vs. >= 20 years, HR for DFS=1.67, 95% CI=1.07-2.62) were associated with worse survival while longer duration of estrogen exposure with better survival (HR for DFS=0.97, 95% CI=0.96-0.99). In the stratified analyses by subtypes, those associations were more pronounced among women with hormone receptor and human epidermal growth factor 2 positive (HR+ HER2+) tumors. Conclusions It is suggested that reproductive factors, specifically age at menarche, number of children, time since last birth, and duration of estrogen exposure, could influence breast tumor progression, especially in the HR+ HER2+ subtype. C1 [Song, Nan; Choi, Ji-Yeob; Park, Sue K.; Han, Wonshik; Noh, Dong-Young; Kang, Daehee] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. [Choi, Ji-Yeob; Sung, Hyuna; Chung, Seokang; Song, Minkyo; Park, Sue K.; Kang, Daehee] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea. [Choi, Ji-Yeob; Jeon, Sujee; Song, Minkyo; Park, Sue K.; Yoo, Keun-Young; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Sung, Hyuna] NCI, Div Epidemiol & Genet, Rockville, MD USA. [Han, Wonshik; Noh, Dong-Young] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea. [Lee, Jong Won; Ahn, Sei-Hyun] Univ Ulsan, Coll Med, Dept Surg, Seoul, South Korea. [Lee, Jong Won] ASAN Med Ctr, Seoul, South Korea. [Kim, Mi Kyung] Natl Canc Ctr, Div Canc Epidemiol & Management, Goyang Si, Gyeonggi Do, South Korea. RP Choi, JY (reprint author), Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. EM jiyeob.choi@gmail.com RI Han, Wonshik/B-3699-2008 FU National Research Foundation of Korea (NRF) - Korea government (MSIP) [2010-0028631] FX This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2010-0028631). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 2 Z9 2 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 APR 14 PY 2015 VL 10 IS 4 AR e0123994 DI 10.1371/journal.pone.0123994 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1EB UT WOS:000353014700053 PM 25875532 ER PT J AU Wang, FQ Shi, ZY Cui, Y Guo, XG Shi, YB Chen, YL AF Wang, Fengqin Shi, Zhaoying Cui, Yan Guo, Xiaogang Shi, Yun-Bo Chen, Yonglong TI Targeted gene disruption in Xenopus laevis using CRISPR/Cas9 SO CELL AND BIOSCIENCE LA English DT Letter ID EFFECTOR NUCLEASES; EMBRYOS; TROPICALIS; ENDOCRINE; EXOCRINE; TALENS C1 [Wang, Fengqin] Anhui Univ, Sch Life Sci, Hefei 230601, Peoples R China. [Shi, Zhaoying; Chen, Yonglong] South Univ Sci & Technol China, Shenzhen Key Lab Cell Microenvironm, Dept Biol, Shenzhen 518055, Peoples R China. [Wang, Fengqin; Cui, Yan; Guo, Xiaogang; Chen, Yonglong] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, South China Inst Stem Cell Biol & Regenerat Med, CAS Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China. [Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Program Cellular Regulat & Metab, US NIH, Bethesda, MD USA. [Cui, Yan] Univ Chinese Acad Sci, Beijing 100049, Peoples R China. RP Chen, YL (reprint author), South Univ Sci & Technol China, Shenzhen Key Lab Cell Microenvironm, Dept Biol, Shenzhen 518055, Peoples R China. EM chenyl@sustc.edu.cn NR 10 TC 14 Z9 15 U1 7 U2 28 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2045-3701 J9 CELL BIOSCI JI Cell Biosci. PD APR 14 PY 2015 VL 5 AR 15 DI 10.1186/s13578-015-0006-1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CG2KF UT WOS:000353102700001 PM 25897376 ER PT J AU Jefferson, AL Beiser, AS Himali, JJ Seshadri, S O'Donnell, CJ Manning, WJ Wolf, PA Au, R Benjamin, EJ AF Jefferson, Angela L. Beiser, Alexa S. Himali, Jayandra J. Seshadri, Sudha O'Donnell, Christopher J. Manning, Warren J. Wolf, Philip A. Au, Rhoda Benjamin, Emelia J. TI Low Cardiac Index Is Associated With Incident Dementia and Alzheimer Disease The Framingham Heart Study SO CIRCULATION LA English DT Article DE Alzheimer disease; blood circulation; brain; cardiac output; dementia; hemodynamics ID VASCULAR RISK-FACTORS; MILD COGNITIVE IMPAIRMENT; MAGNETIC-RESONANCE; BLOOD-FLOW; CARDIOVASCULAR-DISEASE; INTERSTITIAL FLUID; APOLIPOPROTEIN-E; LIFETIME RISK; BRAIN; HYPERTENSION AB Background-Cross-sectional epidemiological and clinical research suggests that lower cardiac index is associated with abnormal brain aging, including smaller brain volumes, increased white matter hyperintensities, and worse cognitive performances. Lower systemic blood flow may have implications for dementia among older adults. Methods and Results-A total of 1039 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, and dementia formed our sample (age, 69 +/- 6 years; 53% women). Multivariable-adjusted proportional hazard models adjusting for Framingham Stroke Risk Profile score (age, sex, systolic blood pressure, antihypertensive medication, diabetes mellitus, cigarette smoking, cardiovascular disease history, atrial fibrillation), education, and apolipoprotein E4 status related cardiac magnetic resonance imaging-assessed cardiac index (cardiac output divided by body surface area) to incident all-cause dementia and Alzheimer disease (AD). Over the median 7.7-year follow-up period, 32 participants developed dementia, including 26 cases of AD. Each 1-SD unit decrease in cardiac index increased the relative risk of both dementia (hazard ratio [HR]=1.66; 95% confidence interval [CI], 1.11-2.47; P=0.013) and AD (HR=1.65; 95% CI, 1.07-2.54; P=0.022). Compared with individuals with normal cardiac index, individuals with clinically low cardiac index had a higher relative risk of dementia (HR=2.07; 95% CI, 1.02-4.19; P=0.044). If participants with clinically prevalent cardiovascular disease and atrial fibrillation were excluded (n=184), individuals with clinically low cardiac index had a higher relative risk of both dementia (HR=2.92; 95% CI, 1.34-6.36; P=0.007) and AD (HR=2.87; 95% CI, 1.21-6.80; P=0.016) compared with individuals with normal cardiac index. Conclusion-Lower cardiac index is associated with an increased risk for the development of dementia and AD. C1 [Jefferson, Angela L.] Vanderbilt Univ, Med Ctr, Dept Neurol, Vanderbilt Memory & Alzheimers Ctr, Nashville, TN USA. [Beiser, Alexa S.; Himali, Jayandra J.; Seshadri, Sudha; Wolf, Philip A.; Au, Rhoda] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Beiser, Alexa S.; Himali, Jayandra J.; Seshadri, Sudha; O'Donnell, Christopher J.; Wolf, Philip A.; Au, Rhoda; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Beiser, Alexa S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02215 USA. [Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. RP Jefferson, AL (reprint author), Vanderbilt Memory & Alzheimers Ctr, 2525 Wesr End Ave,12th Floor,Ste 1200, Nashville, TN 37203 USA. EM angela.jefferson@vanderbilt.edu OI Seshadri, Sudha/0000-0001-6135-2622; Benjamin, Emelia/0000-0003-4076-2336; Beiser, Alexa/0000-0001-8551-7778; /0000-0003-1391-9481 FU National Heart Lung Blood Institute [HC25195]; Paul B. Beeson Career Development Award in Aging Program; Alzheimer's Association [IIRG-08-88733, AG08122, NS017950, AG033040, AG16495, AG028321, HL092577, AG033193, AG031287, HL070279]; [HL111516]; [AG034962]; [AG046373]; [AG030962] FX The present research was supported by the National Heart Lung Blood Institute's Framingham Heart Study (HC25195); HL111516, AG034962, AG046373, AG030962, Paul B. Beeson Career Development Award in Aging Program, Alzheimer's Association IIRG-08-88733 (Dr Jefferson); AG08122, NS017950, AG033040, AG16495 (Dr Wolf); AG028321, HL092577 (Dr Benjamin); AG033193, AG031287 (Dr Seshadri); and HL070279 (Dr Manning). NR 47 TC 17 Z9 17 U1 1 U2 17 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 APR 14 PY 2015 VL 131 IS 15 BP 1333 EP 1339 DI 10.1161/CIRCULATIONAHA.114.012438 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CF7KH UT WOS:000352734600009 PM 25700178 ER PT J AU McDermott, MM Guralnik, JM Criqui, MH Liu, K Kibbe, M Ferrucci, L AF McDermott, Mary M. Guralnik, Jack M. Criqui, Michael H. Liu, Kiang Kibbe, Melina Ferrucci, Luigi TI Response to Letter Regarding Article, "Six-Minute Walk Is a Better Outcome Measure Than Treadmill Walking Tests in Therapeutic Trials of Patients With Peripheral Artery Disease" SO CIRCULATION LA English DT Letter ID INTERMITTENT CLAUDICATION; EXERCISE C1 [McDermott, Mary M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [McDermott, Mary M.; Liu, Kiang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Kibbe, Melina] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Ferrucci, Luigi] Natl Inst Aging, Longitudinal Studies Sect, Baltimore, MD USA. RP McDermott, MM (reprint author), Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. FU Intramural NIH HHS [ZIA AG000015-56] NR 5 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD APR 14 PY 2015 VL 131 IS 15 BP E407 EP E407 DI 10.1161/CIRCULATIONAHA.114.013268 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CF7KH UT WOS:000352734600003 PM 25869008 ER PT J AU Jayatunga, MKP Thompson, S McKee, TC Chan, MC Reece, KM Hardy, AP Sekirnik, R Seden, PT Cook, KM McMahon, JB Figg, WD Schofield, CJ Hamilton, AD AF Jayatunga, Madura K. P. Thompson, Sam McKee, Tawnya C. Chan, Mun Chiang Reece, Kelie M. Hardy, Adam P. Sekirnik, Rok Seden, Peter T. Cook, Kristina M. McMahon, James B. Figg, William D. Schofield, Christopher J. Hamilton, Andrew D. TI Inhibition of the HIF1 alpha-p300 interaction by quinone- and indandione-mediated ejection of structural Zn(II) SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Hypoxia; HIF; p300/CBP; Zinc ejection; Electrophile; Quinone ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ENDOTHELIAL GROWTH-FACTOR; TRANSCRIPTION FACTOR COMPLEX; PROTEIN-PROTEIN INTERACTIONS; SMALL-MOLECULE INHIBITOR; FACTOR 1-ALPHA; DNA-BINDING; FACTOR-I; CANCER CELLS; TUMOR-GROWTH AB Protein-protein interactions between the hypoxia inducible factor (HIF) and the transcriptional coactivators p300/CBP are potential cancer targets due to their role in the hypoxic response. A natural product based screen led to the identification of indandione and benzoquinone derivatives that reduce the tight interaction between a HIF-1 alpha fragment and the CH1 domain of p300. The indandione derivatives were shown to fragment to give ninhydrin, which was identified as the active species. Both the naphthoquinones and ninhydrin were observed to induce Zn(II) ejection from p300 and the catalytic domain of the histone demethylase KDM4A. Together with previous reports on the effects of related compounds on HIF-1 alpha and other systems, the results suggest that care should be taken in interpreting biological results obtained with highly electrophilic/thiol modifying compounds. (C) 2014 Elsevier Masson SAS. All rights reserved. C1 [Jayatunga, Madura K. P.; Thompson, Sam; Chan, Mun Chiang; Hardy, Adam P.; Sekirnik, Rok; Seden, Peter T.; Schofield, Christopher J.; Hamilton, Andrew D.] Univ Oxford, Chem Res Lab, Dept Chem, Oxford OX1 3TA, England. [McKee, Tawnya C.; McMahon, James B.] Ctr Canc Res, Mol Targets Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Reece, Kelie M.; Cook, Kristina M.; Figg, William D.] NCI, Mol Pharmacol Sect, Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Oncol Branch, Ctr Canc Res,NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sam.thompson@chem.ox.ac.uk; figgw@helix.nih.gov; andrew.hamilton@admin.ox.ac.uk RI Figg Sr, William/M-2411-2016; Thompson, Sam/I-5599-2013 OI Thompson, Sam/0000-0001-6267-5693 FU Cancer Research UK; Wellcome Trust; University of Oxford; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, MD, USA FX We thank Cancer Research UK (MKPJ), the Wellcome Trust, and the University of Oxford (ST) for funding. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, MD, USA. NR 63 TC 6 Z9 6 U1 2 U2 17 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 APR 13 PY 2015 VL 94 BP 509 EP 516 DI 10.1016/j.ejmech.2014.06.006 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CH0RU UT WOS:000353730900046 PM 25023609 ER PT J AU Cohen, AA Li, Q Milot, E Leroux, M Faucher, S Morissette-Thomas, V Legault, V Fried, LP Ferrucci, L AF Cohen, Alan A. Li, Qing Milot, Emmanuel Leroux, Maxime Faucher, Samuel Morissette-Thomas, Vincent Legault, Veronique Fried, Linda P. Ferrucci, Luigi TI Statistical Distance as a Measure of Physiological Dysregulation Is Largely Robust to Variation in Its Biomarker Composition SO PLOS ONE LA English DT Article ID ALLOSTATIC LOAD; OLDER-ADULTS; DEFICIT ACCUMULATION; STOCHASTIC-MODEL; ELDERLY-PEOPLE; MORTALITY; FRAILTY; HEALTH; POPULATION; AGE AB Physiological dysregulation may underlie aging and many chronic diseases, but is challenging to quantify because of the complexity of the underlying systems. Recently, we described a measure of physiological dysregulation, D-M, that uses statistical distance to assess the degree to which an individual's biomarker profile is normal versus aberrant. However, the sensitivity of D-M to details of the calculation method has not yet been systematically assessed. In particular, the number and choice of biomarkers and the definition of the reference population (RP, the population used to define a "normal" profile) may be important. Here, we address this question by validating the method on 44 common clinical biomarkers from three longitudinal cohort studies and one cross-sectional survey. D(M)s calculated on different biomarker subsets show that while the signal of physiological dysregulation increases with the number of biomarkers included, the value of additional markers diminishes as more are added and inclusion of 10-15 is generally sufficient. As long as enough markers are included, individual markers have little effect on the final metric, and even DMs calculated from mutually exclusive groups of markers correlate with each other at r similar to 0.4-0.5. We also used data subsets to generate thousands of combinations of study populations and RPs to address sensitivity to differences in age range, sex, race, data set, sample size, and their interactions. Results were largely consistent (but not identical) regardless of the choice of RP; however, the signal was generally clearer with a younger and healthier RP, and RPs too different from the study population performed poorly. Accordingly, biomarker and RP choice are not particularly important in most cases, but caution should be used across very different populations or for fine-scale analyses. Biologically, the lack of sensitivity to marker choice and better performance of younger, healthier RPs confirm an interpretation of D-M physiological dysregulation and as an emergent property of a complex system. C1 [Cohen, Alan A.; Li, Qing; Faucher, Samuel; Morissette-Thomas, Vincent; Legault, Veronique] Univ Sherbrooke, Dept Family Med, Grp Rech PRIMUS, Sherbrooke, PQ J1H 5N4, Canada. [Milot, Emmanuel] Univ Quebec Trois Rivieres, Dept Chem Biochem & Phys, Trois Rivieres, PQ G9A 5H7, Canada. [Leroux, Maxime] Univ Quebec, ESG, Dept Econ, Montreal, PQ H2X 3X2, Canada. [Fried, Linda P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Ferrucci, Luigi] MedStar Harbor Hosp, Translat Gerontol Branch, Longitudinal Studies Sect, NIA,NIH, Baltimore, MD USA. RP Cohen, AA (reprint author), Univ Sherbrooke, Dept Family Med, Grp Rech PRIMUS, 3001 12e Ave N, Sherbrooke, PQ J1H 5N4, Canada. EM Alan.Cohen@USherbrooke.ca FU FRQ-S; CIHR [110789, 120305, 119485]; NSERC Discovery Grant [402079-2011]; Intramural Research Program of the National Institute on Aging FX AAC is a member of the FRQ-S-supported Centre de recherche sur le vieillissement and Centre de recherche du CHUS, and is a funded Research Scholar of the FRQ-S. This research was supported by CIHR grant #s 110789, 120305, 119485 and by NSERC Discovery Grant # 402079-2011, as well as by the Intramural Research Program of the National Institute on Aging. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 5 Z9 5 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 APR 13 PY 2015 VL 10 IS 4 AR e0122541 DI 10.1371/journal.pone.0122541 PG 25 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF8XK UT WOS:000352845100081 PM 25875923 ER PT J AU Song, N Choi, JY Sung, H Jeon, S Chung, S Park, SK Han, W Lee, JW Kim, MK Lee, JY Yoo, KY Han, BG Ahn, SH Noh, DY Kang, D AF Song, Nan Choi, Ji-Yeob Sung, Hyuna Jeon, Sujee Chung, Seokang Park, Sue K. Han, Wonshik Lee, Jong Won Kim, Mi Kyung Lee, Ji-Young Yoo, Keun-Young Han, Bok-Ghee Ahn, Sei-Hyun Noh, Dong-Young Kang, Daehee TI Prediction of Breast Cancer Survival Using Clinical and Genetic Markers by Tumor Subtypes SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; ONE-CARBON METABOLISM; PROGNOSTIC-FACTORS; POLYMORPHISMS; WOMEN; CHEMOTHERAPY; SUSCEPTIBILITY; HETEROGENEITY; POPULATION; THERAPY AB Purpose To identify the genetic variants associated with breast cancer survival, a genome-wide association study (GWAS) was conducted of Korean breast cancer patients. Methods From the Seoul Breast Cancer Study (SEBCS), 3,226 patients with breast cancer (1,732 in the discovery and 1,494 in the replication set) were included in a two-stage GWAS on disease- free survival (DFS) by tumor subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2). The associations of the re-classified combined prognostic markers through recursive partitioning analysis (RPA) of DFS for breast cancer were assessed with the Cox proportional hazard model. The prognostic predictive values of the clinical and genetic models were evaluated by Harrell's C. Results In the two-stage GWAS stratified by tumor subtypes, rs166870 and rs10825036 were consistently associated with DFS in the HR+ HER2-and HR-HER2-breast cancer subtypes, respectively (P-rs166870= 2.88x10(-7) and P-rs10825036= 3.54x10(-7) in the combined set). When patients were classified by the RPA in each subtype, genetic factors contributed significantly to differentiating the high risk group associated with DFS inbreast cancer, specifically the HR+ HER2-(P-discovery= 1.18x10(-8) and P-replication= 2.08x10(-5)) and HR-HRE2-subtypes (P-discovery= 2.35x10(-4) and P-replication= 2.60x10(-2)). The inclusion of the SNPs tended to improve the performance of the prognostic models consisting of age, TNM stage and tumor subtypes based on ER, PR, and HER2 status. Conclusion Combined prognostic markers that include clinical and genetic factors by tumor subtypes could improve the prediction of survival in breast cancer. C1 [Song, Nan; Choi, Ji-Yeob; Park, Sue K.; Han, Wonshik; Noh, Dong-Young; Kang, Daehee] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. [Choi, Ji-Yeob; Sung, Hyuna; Chung, Seokang; Park, Sue K.; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea. [Choi, Ji-Yeob; Jeon, Sujee; Park, Sue K.; Yoo, Keun-Young; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Sung, Hyuna] Natl Canc Inst, Div Epidemiol & Genet, Rockville, MD USA. [Han, Wonshik; Noh, Dong-Young] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea. [Lee, Jong Won; Ahn, Sei-Hyun] Univ Ulsan, Coll Med, Dept Surg, Seoul, South Korea. [Lee, Jong Won; Ahn, Sei-Hyun] ASAN Med Ctr, Seoul, South Korea. [Kim, Mi Kyung] Natl Canc Ctr, Div Canc Epidemiol & Management, Goyang Si, Gyeonggi Do, South Korea. [Lee, Ji-Young] Yonsei Univ Hlth Syst, Cardiovasc Res Inst, Seoul, South Korea. [Lee, Ji-Young] Yonsei Univ Hlth Syst, Cardiovasc Genome Ctr, Seoul, South Korea. [Han, Bok-Ghee] Korea Natl Inst Hlth, Ctr Genome Sci, Osong, South Korea. RP Kang, D (reprint author), Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. EM dhkang@snu.ac.kr RI Han, Wonshik/B-3699-2008; OI Lee, Ji-Young/0000-0002-7784-1401 FU BRL (Basic Research Laboratory) program through the National Research Foundation of Korea - Ministry of Education, Science and Technology [2012-0000347]; Seoul National University Hospital FX This research was supported by the 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 Seoul National University Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript NR 59 TC 0 Z9 0 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 13 PY 2015 VL 10 IS 4 AR UNSP e0122413 DI 10.1371/journal.pone.0122413 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF8XK UT WOS:000352845100072 PM 25867717 ER PT J AU Weinberg, A Muresan, P Richardson, KM Fenton, T Dominguez, T Bloom, A Watts, DH Abzug, MJ Nachman, SA Levin, MJ AF Weinberg, Adriana Muresan, Petronella Richardson, Kelly M. Fenton, Terence Dominguez, Teresa Bloom, Anthony Watts, D. Heather Abzug, Mark J. Nachman, Sharon A. Levin, Myron J. CA P1086 Team TI Determinants of Vaccine Immunogenicity in HIV-Infected Pregnant Women: Analysis of B and T Cell Responses to Pandemic H1N1 Monovalent Vaccine SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEMAGGLUTINATION-INHIBITING ANTIBODY; MATERNAL INFLUENZA VACCINATION; BLOOD MONONUCLEAR-CELLS; ANTIRETROVIRAL THERAPY; YOUNG INFANTS; RESPIRATORY ILLNESS; IMMUNE ACTIVATION; UNITED-STATES; A H1N1 AB Influenza infections have high frequency and morbidity in HIV-infected pregnant women, underscoring the importance of vaccine-conferred protection. To identify the factors that determine vaccine immunogenicity in this group, we characterized the relationship of B-and T-cell responses to pandemic H1N1 (pH1N1) vaccine with HIV-associated immunologic and virologic characteristics. pH1N1 and seasonal-H1N1 (sH1N1) antibodies were measured in 119 HIV-infected pregnant women after two double-strength pH1N1 vaccine doses. pH1N1-IgG and IgA B-cell FluoroSpot, pH1N1-and sH1N1-interferon gamma (IFN gamma) and granzyme B (GrB) T-cell FluoroSpot, and flow cytometric characterization of B-and T-cell subsets were performed in 57 subjects. pH1N1-antibodies increased after vaccination, but less than previously described in healthy adults. pH1N1-IgG memory B cells (Bmem) increased, IFN gamma-effector T-cells (Teff) decreased, and IgA Bmem and GrB Teff did not change. pH1N1-antibodies and Teff were significantly correlated with each other and with sH1N1-HAI and Teff, respectively, before and after vaccination. pH1N1-antibody responses to the vaccine significantly increased with high proportions of CD4+, low CD8+ and low CD8+ HLADR+ CD38+ activated (Tact) cells. pH1N1-IgG Bmem responses increased with high proportions of CD19+ CD27+ CD21-activated B cells (Bact), high CD8+ CD39+ regulatory T cells (Treg), and low CD19+ CD27-CD21-exhausted B cells (Bexhaust). IFN gamma-Teff responses increased with low HIV plasma RNA, CD8+ HLADR+ CD38+ Tact, CD4+ FoxP3+ Treg and CD19+ IL10+ Breg. In conclusion, pre-existing antibody and Teff responses to sH1N1 were associated with increased responses to pH1N1 vaccination in HIV-infected pregnant women suggesting an important role for heterosubtypic immunologic memory. High CD4+% T cells were associated with increased, whereas high HIV replication, Tact and Bexhaust were associated with decreased vaccine immunogenicity. High Treg increased antibody responses but decreased Teff responses to the vaccine. The proportions of immature and transitional B cells did not affect the responses to vaccine. Increased Bact were associated with high Bmem responses to the vaccine. C1 [Weinberg, Adriana; Richardson, Kelly M.; Dominguez, Teresa; Abzug, Mark J.; Levin, Myron J.] Univ Colorado, Anschutz Med Ctr, Aurora, CO 80045 USA. [Muresan, Petronella; Fenton, Terence] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Bloom, Anthony] Frontier Sci & Technol Res Fdn Inc, Buffalo, NY USA. [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA. [Nachman, Sharon A.] SUNY Hlth Sci Ctr, Stony Brook, NY USA. RP Weinberg, A (reprint author), Univ Colorado, Anschutz Med Ctr, Aurora, CO 80045 USA. EM adriana.weinberg@ucdenver.edu FU National Institute of Allergy and Infectious Diseases [U01 AI068632, U01 AI41110, U01 AI068616]; National Institute of Child Health and Human Development; National Institute of Mental Health [AI068632, N01-DK-9-001/HHSN267200800001C, N01HD33162 (97-07)] FX Funding was provided by the National Institute of Allergy and Infectious Diseases, grant number U01 AI068632 & U01 AI41110 & U01 AI068616, http://www.niaid.nih.gov/Pages/default.aspx; and National Institute of Child Health and Human Development and the National Institute of Mental Health, grant number AI068632 & N01-DK-9-001/HHSN267200800001C & N01HD33162 (97-07), https://www.nichd.nih.gov/ Pages/index.aspx and http://www.nimh.nih.gov/index.shtml. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 86 TC 4 Z9 4 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 13 PY 2015 VL 10 IS 4 AR e0122431 DI 10.1371/journal.pone.0122431 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF8XK UT WOS:000352845100073 PM 25874544 ER PT J AU Tindana, P de Vries, J Campbell, M Littler, K Seeley, J Marshall, P Troyer, J Ogundipe, M Alibu, VP Yakubu, A Parker, M AF Tindana, Paulina de Vries, Jantina Campbell, Megan Littler, Katherine Seeley, Janet Marshall, Patricia Troyer, Jennifer Ogundipe, Morisola Alibu, Vincent Pius Yakubu, Aminu Parker, Michael CA H3A Working Grp Ethics TI Community engagement strategies for genomic studies in Africa: a review of the literature SO BMC MEDICAL ETHICS LA English DT Review DE Community engagement; Genetics; Genomic research; Africa ID INTERNATIONAL HEALTH RESEARCH; PARTICIPATORY RESEARCH CBPR; HIV PREVENTION TRIALS; SICKLE-CELL-DISEASE; SUB-SAHARAN AFRICA; ADVISORY BOARDS; DEVELOPING-COUNTRIES; INFORMED-CONSENT; RURAL UGANDA; CONSULTING COMMUNITIES AB Background: Community engagement has been recognised as an important aspect of the ethical conduct of biomedical research, especially when research is focused on ethnically or culturally distinct populations. While this is a generally accepted tenet of biomedical research, it is unclear what components are necessary for effective community engagement, particularly in the context of genomic research in Africa. Methods: We conducted a review of the published literature to identify the community engagement strategies that can support the successful implementation of genomic studies in Africa. Our search strategy involved using online databases, Pubmed (National Library of Medicine), Medline and Google scholar. Search terms included a combination of the following: community engagement, community advisory boards, community consultation, community participation, effectiveness, genetic and genomic research, Africa, developing countries. Results: A total of 44 articles and 1 thesis were retrieved of which 38 met the selection criteria. Of these, 21 were primary studies on community engagement, while the rest were secondary reports on community engagement efforts in biomedical research studies. 34 related to biomedical research generally, while 4 were specific to genetic and genomic research in Africa. Conclusion: We concluded that there were several community engagement strategies that could support genomic studies in Africa. While many of the strategies could support the early stages of a research project such as the recruitment of research participants, further research is needed to identify effective strategies to engage research participants and their communities beyond the participant recruitment stage. Research is also needed to address how the views of local communities should be incorporated into future uses of human biological samples. Finally, studies evaluating the impact of CE on genetic research are lacking. Systematic evaluation of CE strategies is essential to determine the most effective models of CE for genetic and genomic research conducted in African settings. C1 [Tindana, Paulina] Navrongo Hlth Res Ctr, Ghana Hlth Serv, Navrongo, Ghana. [de Vries, Jantina] Univ Cape Town, Groote Schuur Hosp, Dept Med, UCT Ctr Clin Res, ZA-7925 Cape Town, South Africa. [Campbell, Megan] Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa. [Littler, Katherine] Wellcome Trust Res Labs, London NW1 2BE, England. [Seeley, Janet] MRC UVRI Uganda Res Unit AIDS, Entebbe, Uganda. [Marshall, Patricia] Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. [Troyer, Jennifer] NHGRI, NIH, Bethesda, MD 20892 USA. [Ogundipe, Morisola] Ctr Bioeth, West African Bioeth Training Program, Ibadan, Oyo State, Nigeria. [Alibu, Vincent Pius] Makerere Univ, Coll Nat Sci, Dept Biochem & Sports Sci, Kampala, Uganda. [Yakubu, Aminu] Natl Hlth Res Eth Comm, Fed Minist Hlth, Abuja, Nigeria. [Parker, Michael] Univ Oxford, Ethox Ctr, Oxford, England. RP Tindana, P (reprint author), Navrongo Hlth Res Ctr, Ghana Hlth Serv, POB 114, Navrongo, Ghana. EM ptindana@gmail.com OI Yakubu, Aminu/0000-0002-7821-184X; Seeley, Janet/0000-0002-0583-5272 FU Wellcome Trust FX Funding for the H3Africa community engagement project was provided by the Wellcome Trust. We are extremely grateful to Dr. Ebony Madden, Quynh Nguyen and Dr. Nathalie Banner and the H3Africa Steering Committee for providing administrative support during this study and for their comments on earlier versions of the manuscript. NR 52 TC 9 Z9 9 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6939 J9 BMC MED ETHICS JI BMC Med. Ethics PD APR 12 PY 2015 VL 16 AR 24 DI 10.1186/s12910-015-0014-z PG 12 WC Ethics; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Biomedical Social Sciences GA CO8IX UT WOS:000359413000001 PM 25889051 ER PT J AU Wolff, AC Hammond, MEH Hicks, DG Allison, KH Bartlett, JMS Bilous, M Fitzgibbons, P Hanna, W Jenkins, RB Mangu, PB Paik, S Perez, EA Press, MF Spears, PA Vance, GH Viale, G Dowsett, M McShane, LM Hayes, DF AF Wolff, Antonio C. Hammond, M. Elizabeth H. Hicks, David G. Allison, Kimberly H. Bartlett, John M. S. Bilous, Michael Fitzgibbons, Patrick Hanna, Wedad Jenkins, Robert B. Mangu, Pamela B. Paik, Soonmyung Perez, Edith A. Press, Michael F. Spears, Patricia A. Vance, Gail H. Viale, Giuseppe Dowsett, Mitch McShane, Lisa M. Hayes, Daniel F. TI National Guidelines and Level of Evidence: Comments on Some of the New Recommendations in the American Society of Clinical Oncology and the College of American Pathologists Human Epidermal Growth Factor Receptor 2 Guidelines for Breast Cancer Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CORE NEEDLE-BIOPSY; HER2 STATUS; PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; EXCISIONAL BIOPSY; CARCINOMA; UPDATE; IMMUNOHISTOCHEMISTRY; SPECIMENS C1 [Wolff, Antonio C.] Johns Hopkins Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [Hammond, M. Elizabeth H.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Hammond, M. Elizabeth H.] Intermt Healthcare, Salt Lake City, UT USA. [Hicks, David G.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Allison, Kimberly H.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Bartlett, John M. S.] Ontario Inst Canc Res, Toronto, ON, Canada. [Bilous, Michael] Univ Western Sydney, Sydney, NSW, Australia. [Bilous, Michael] Healthscope Pathol, Sydney, NSW, Australia. [Fitzgibbons, Patrick] St Jude Med Ctr, Fullerton, CA USA. [Hanna, Wedad] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Jenkins, Robert B.] Mayo Clin, Rochester, MN USA. [Mangu, Pamela B.] Amer Soc Clin Oncol, Alexandria, VA USA. [Paik, Soonmyung] Natl Adjuvant Surg Breast & Bowel Project, Pittsburgh, PA USA. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. [Press, Michael F.] Univ So Calif, Los Angeles, CA USA. [Spears, Patricia A.] N Carolina State Univ, Raleigh, NC 27695 USA. [Vance, Gail H.] Indiana Univ, Med Ctr, Indianapolis, IN USA. [Viale, Giuseppe] Univ Milan, European Inst Oncol, Milan, Italy. [Dowsett, Mitch] Royal Marsden Hosp, London SW3 6JJ, England. [McShane, Lisa M.] NCI, Bethesda, MD 20892 USA. [Hayes, Daniel F.] Univ Michigan, Comprehens Canc Care Ctr, Ann Arbor, MI 48109 USA. RP Wolff, AC (reprint author), Johns Hopkins Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. OI Wolff, Antonio/0000-0003-3734-1063 NR 15 TC 5 Z9 5 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 10 PY 2015 VL 33 IS 11 BP 1302 EP 1304 DI 10.1200/JCO.2014.59.7559 PG 3 WC Oncology SC Oncology GA CK2RB UT WOS:000356058100018 PM 25753441 ER PT J AU Li, WD Saud, SM Young, MR Chen, GH Hua, BJ AF Li, Weidong Saud, Shakir M. Young, Matthew R. Chen, Guohong Hua, Baojin TI Targeting AMPK for cancer prevention and treatment SO ONCOTARGET LA English DT Article DE AMP activated kinase; cancer; prevention; treatment ID ACTIVATED PROTEIN-KINASE; AUTOPHAGIC CELL-DEATH; BREAST-CANCER; COLORECTAL-CANCER; SIGNALING PATHWAY; OVARIAN-CANCER; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; LEUKEMIA-CELLS; CYCLOOXYGENASE-2 INHIBITOR AB AMP-activated protein kinase (AMPK) is an important mediator in maintaining cellular energy homeostasis. AMPK is activated in response to a shortage of energy. Once activated, AMPK can promote ATP production and regulate metabolic energy. AMPK is a known target for treating metabolic syndrome and type-2 diabetes; however, recently AMPK is emerging as a possible metabolic tumor suppressor and target for cancer prevention and treatment. Recent epidemiological studies indicate that treatment with metformin, an AMPK activator reduces the incidence of cancer. In this article we review the role of AMPK in regulating inflammation, metabolism, and other regulatory processes with an emphasis on cancer, as well as, discuss the potential for targeting AMPK to treat various types of cancer. Activation of AMPK has been found to oppose tumor progression in several cancer types and offers a promising cancer therapy. This review evaluates the evidence linking AMPK with tumor suppressor function and analyzes the molecular mechanisms involved. AMPK activity opposes tumor development and progression in part by regulating inflammation and metabolism. C1 [Li, Weidong; Hua, Baojin] China Acad Chinese Med Sci, Guanganmen Hosp, Dept Oncol, Beijing, Peoples R China. [Saud, Shakir M.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Rockville, MD USA. [Li, Weidong; Saud, Shakir M.; Young, Matthew R.] NCI, Basic Res Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Chen, Guohong] China Acad Chinese Med Sci, Guanganmen Hosp, Dept Urinary Surg, Beijing, Peoples R China. RP Hua, BJ (reprint author), China Acad Chinese Med Sci, Guanganmen Hosp, Dept Oncol, Beijing, Peoples R China. EM cghdoctor@sina.com; dr.huabaojin@hotmail.com FU National Natural Science Foundation of China [81273718, 81102587]; China Postdoctoral Science Foundation [2012T50199] FX Weidong Li and Shakir M. Saud contributed equally to this work and should be considered co-first authors. This work was partly supported by National Natural Science Foundation of China (No.81273718 and 81102587) and China Postdoctoral Science Foundation (No. 2012T50199). NR 145 TC 29 Z9 30 U1 3 U2 16 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR 10 PY 2015 VL 6 IS 10 BP 7365 EP 7378 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CI6QJ UT WOS:000354885300002 PM 25812084 ER PT J AU Fagerholm, R Schmidt, MK Khan, S Rafiq, S Tapper, W Aittomaki, K Greco, D Heikkinen, T Muranen, TA Fasching, PA Janni, W Weinshilboum, R Loehberg, CR Hopper, JL Southey, MC Keeman, R Lindblom, A Margolin, S Mannermaa, A Kataja, V Chenevix-Trench, G Lambrechts, D Wildiers, H Chang-Claude, J Seibold, P Couch, FJ Olson, JE Andrulis, IL Knight, JA Garcia-Closas, M Figueroa, J Hooning, MJ Jager, A Shah, M Perkins, BJ Luben, R Hamann, U Kabisch, M Czene, K Hall, P Easton, DF Pharoah, PDP Liu, JJ Eccles, D Blomqvist, C Nevanlinna, H AF Fagerholm, Rainer Schmidt, Marjanka K. Khan, Sofia Rafiq, Sajjad Tapper, William Aittomaki, Kristiina Greco, Dario Heikkinen, Tuomas Muranen, Taru A. Fasching, Peter A. Janni, Wolfgang Weinshilboum, Richard Loehberg, Christian R. Hopper, John L. Southey, Melissa C. Keeman, Renske Lindblom, Annika Margolin, Sara Mannermaa, Arto Kataja, Vesa Chenevix-Trench, Georgia Lambrechts, Diether Wildiers, Hans Chang-Claude, Jenny Seibold, Petra Couch, Fergus J. Olson, Janet E. Andrulis, Irene L. Knight, Julia A. Garcia-Closas, Montserrat Figueroa, Jonine Hooning, Maartje J. Jager, Agnes Shah, Mitul Perkins, Barbara J. Luben, Robert Hamann, Ute Kabisch, Maria Czene, Kamila Hall, Per Easton, Douglas F. Pharoah, Paul D. P. Liu, Jianjun Eccles, Diana Blomqvist, Carl Nevanlinna, Heli CA kConFab Investigators TI The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients SO ONCOTARGET LA English DT Article DE breast cancer; survival; SNP; chemotherapy; cell cycle ID ESTROGEN-RECEPTOR-ALPHA; LARGE GENE LISTS; BRCA2 MUTATIONS; LUNG-CANCER; CELL-LINES; EXPRESSION; PROGNOSIS; OUTCOMES; REVEALS; SUSCEPTIBILITY AB We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p((adjusted))=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p((adjusted))=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p((interaction))=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway. C1 [Fagerholm, Rainer; Khan, Sofia; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A.; Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Fagerholm, Rainer; Khan, Sofia; Aittomaki, Kristiina; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A.; Blomqvist, Carl; Nevanlinna, Heli] Helsinki Univ Hosp, Helsinki, Hus, Finland. [Schmidt, Marjanka K.; Keeman, Renske] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. [Rafiq, Sajjad; Tapper, William; Eccles, Diana] Univ Southampton, Southampton Gen Hosp, Fac Med, Southampton, Hants, England. [Aittomaki, Kristiina] Univ Helsinki, Dept Clin Genet, Helsinki, Finland. [Fasching, Peter A.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, D-91054 Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90024 USA. [Janni, Wolfgang] Univ Hosp Ulm, Dept Gynecol & Obstet, Ulm, Germany. [Weinshilboum, Richard] Mayo Fdn, Mayo Med Sch, Coll Med,Mayo Clin, Div Clin Pharmacol,Dept Mol Pharmacol & Expt Ther, Rochester, MN USA. [Loehberg, Christian R.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Univ Breast Ctr Franconia,Dept Gynecol & Obstet, D-91054 Erlangen, Germany. [Hopper, John L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, Kuopio, Finland. [Mannermaa, Arto] Univ Eastern Finland, Canc Ctr Eastern Finland, Kuopio, Finland. [Mannermaa, Arto] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, SF-70210 Kuopio, Finland. [Kataja, Vesa] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland. [Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia. [kConFab Investigators] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Lambrechts, Diether] Vesalius Res Ctr, Leuven, Belgium. [Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium. [Wildiers, Hans] Univ Hosp Leuven, Med Oncol, Multidisciplinary Breast Ctr, Leuven, Belgium. [Chang-Claude, Jenny; Seibold, Petra] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Olson, Janet E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada. [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England. [Garcia-Closas, Montserrat] Inst Canc Res, Div Breast Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Figueroa, Jonine] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Hooning, Maartje J.; Jager, Agnes] Erasmus MC Canc Inst, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands. [Shah, Mitul; Perkins, Barbara J.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB2 1TN, England. [Luben, Robert] Univ Cambridge, Dept Publ Hlth & Primary Care, Clin Gerontol, Cambridge, England. [Hamann, Ute; Kabisch, Maria] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany. [Czene, Kamila; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England. [Liu, Jianjun] Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [Blomqvist, Carl] Univ Helsinki, Dept Oncol, Helsinki, Hus, Finland. RP Nevanlinna, H (reprint author), Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. EM heli.nevanlinna@hus.fi RI Garcia-Closas, Montserrat /F-3871-2015; Knight, Julia/A-6843-2012; Andrulis, Irene/E-7267-2013; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Muranen, Taru/0000-0002-5895-1808 FU Helsinki University Hospital Research Fund, Academy of Finland [266528]; Finnish Cancer Society; Nordic Cancer Union; Sigrid Juselius Foundation; Cancer Research UK [A7572, A11699, C22524, C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C490/A10124]; NHGRI Genomics and Randomized Trials Network [GARNET] [U01 HG005152]; NIH Genes, Environment and Health Initiative [GEI] [U01 HG005137]; European Community [223175, HEALTH-F2-2009-223175]; National Institutes of Health [CA128978]; Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund; National Cancer Institute (USA) [UM1 CA164920]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; Dutch Cancer Society [NKI 2007-3839, 2009 4363, DDHK 2004-3124, DDHK 2009-4318]; Dutch government [NWO 184.021.007]; Dutch National Genomics Initiative; Cancer Research UK; Breakthrough Breast Cancer; NHS; National Cancer Research Network (NCRN); Stockholm County Council; Karolinska Institutet; Swedish Cancer Society; Gustav V Jubilee foundation; Bert von Kantzows foundation; special Government Funding (EVO) of Kuopio University Hospital grants; Cancer Fund of North Savo; Finnish Cancer Organizations; University of Eastern Finland; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Council of Tasmania; Cancer Council of South Australia; Cancer Foundation of Western Australia; Stichting tegen Kanker [232-2008, 196-2010]; FWO; Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419]; Hamburg Cancer Society; German Cancer Research Center; Federal Ministry of Education and Research (BMBF) Germany [01KH0402]; NIH [CA128978, CA116167, CA176785]; NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA; Agency for Science, Technology and Research of Singapore (A*STAR); US National Institute of Health (NIH); Susan G. Komen Breast Cancer Foundation; UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge; DKFZ; [KULPFV/10/016-SymBioSysII] FX The HEBCS and HEBCS-GWS was financially supported by the Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation.; Funding for the POSH study cohort was provided by Cancer Research UK (grant refs A7572, A11699, C22524).; Funding support for the Genome-wide association study in breast cancer patients from the prospectively randomized SUCCESS-A trial was provided through the NHGRI Genomics and Randomized Trials Network [GARNET] (U01 HG005152). Funding support for genotyping, which was performed at the Center for Inherited Disease Research (CIDR) at Johns Hopkins University, was provided by the NIH Genes, Environment and Health Initiative [GEI] (U01 HG005137).; Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund.; The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. M.C.S. is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader.; The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]; BBMRI-NL, which is a Research Infrastructure financed by the Dutch government (NWO 184.021.007); and the Dutch National Genomics Initiative.; The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN).; Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and and Bert von Kantzows foundation.; The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland; kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia.; LMBC is supported by the 'Stichting tegen Kanker' (232-2008 and 196-2010). Diether Lambrechts is supported by the FWO and the KULPFV/10/016-SymBioSysII.; The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419], the Hamburg Cancer Society, the German Cancer Research Center and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402].; The MCBCS was supported by the NIH grants CA128978, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation; The Ontario Familial Breast Cancer Registry (OFBCR) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR.; The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA.; The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318).; The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation.; SEARCH is funded by a programme grant from Cancer Research UK [C490/A10124] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge.; SKKDKFZS is supported by the DKFZ. NR 45 TC 2 Z9 2 U1 0 U2 5 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR 10 PY 2015 VL 6 IS 10 BP 7390 EP 7407 PG 18 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CI6QJ UT WOS:000354885300004 PM 25823661 ER PT J AU Park, JW Zhao, L Willingham, M Cheng, SY AF Park, Jeong Won Zhao, Li Willingham, Mark Cheng, Sheue-yann TI Oncogenic mutations of thyroid hormone receptor beta SO ONCOTARGET LA English DT Article DE thyroid hormone receptors; oncogenes; protein-protein interactions; signaling transduction; thyroid hormone ID LIGAND-BINDING DOMAIN; BREAST-CANCER; MOUSE MODEL; TUMOR PROGRESSION; XENOGRAFT MODELS; GENE; RESISTANCE; CARCINOGENESIS; TUMORIGENESIS; SUPPRESSOR AB The C-terminal frame-shift mutant of the thyroid hormone receptor TR beta 1, PV, functions as an oncogene. An important question is whether the oncogenic activity of mutated TR beta 1 is uniquely dependent on the PV mutated sequence. Using four C-terminal frame-shift mutants-PV, Mkar, Mdbs, and AM-we examined that region in the oncogenic actions of TR beta 1 mutants. Remarkably, these C-terminal mutants induced similar growth of tumors in mouse xenograft models. Molecular analyses showed that they physically interacted with the p85 alpha regulatory subunit of PI3K similarly in cells. In vitro GST-binding assay showed that they bound to the C-terminal Src-homology 2 (CSH2) of p85a with markedly higher avidity. The sustained association of mutants with p85a led to activation of the common PI3-KAKT-ERK/STAT3 signaling to promote cell proliferation and invasion and to inhibit apoptosis. Thus, these results argue against the oncogenic activity of PV being uniquely dependent on the PV mutated sequence. Rather, these four mutants could favor a C-terminal conformation that interacted with the CSH2 domain of p85 alpha to initiate activation of PI3K to relay downstream signaling to promote tumorigenesis. Thus, we propose that the mutated C-terminal region of TR beta 1 could function as an "onco-domain" and TR beta 1 is a potential therapeutic target. C1 [Park, Jeong Won; Zhao, Li; Willingham, Mark; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural Research Program at the Center for Cancer Research; National Cancer Institute; National Institutes of Health FX The present research was supported by the Intramural Research Program at the Center for Cancer Research, National Cancer Institute, National Institutes of Health. We thank Ana Aranda for the parental MDA-MB-468 cells and Roy Weiss for the cDNA expression plasmids for Mkar, Mdbs, and AM. NR 48 TC 4 Z9 6 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 APR 10 PY 2015 VL 6 IS 10 BP 8115 EP 8131 PG 17 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CI6QJ UT WOS:000354885300055 PM 25924236 ER PT J AU Lauer, MS Gordon, D Olive, M AF Lauer, Michael S. Gordon, David Olive, Michelle TI Matching Taxpayer Funding to Population Health Needs Not so Simple SO CIRCULATION RESEARCH LA English DT Article DE burden of disease; policy; research funding ID BLOOD INSTITUTE; NATIONAL HEART; DISEASE; IMPACT; NHLBI; LUNG; PUBLICATION; INNOVATION; TRIALS; LDL C1 [Lauer, Michael S.; Gordon, David; Olive, Michelle] NHLBI, Div Cardiovasc Sci DCVS, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 21 TC 1 Z9 1 U1 1 U2 1 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 APR 10 PY 2015 VL 116 IS 8 BP 1301 EP 1303 DI 10.1161/CIRCRESAHA.114.305893 PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA CF4IH UT WOS:000352511600010 PM 25858063 ER PT J AU Jang, H Abraham, SJ Chavan, TS Hitchinson, B Khavrutskii, L Tarasova, NI Nussinov, R Gaponenko, V AF Jang, Hyunbum Abraham, Sherwin J. Chavan, Tanmay S. Hitchinson, Ben Khavrutskii, Lyuba Tarasova, Nadya I. Nussinov, Ruth Gaponenko, Vadim TI Mechanisms of Membrane Binding of Small GTPase K-Ras4B Farnesylated Hypervariable Region SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATOMIC-FORCE MICROSCOPY; PHOSPHOLIPID-BILAYER NANODISCS; MOLECULAR-DYNAMICS SIMULATIONS; FORMS ION CHANNELS; ALL-D-ENANTIOMER; K-RAS; PLASMA-MEMBRANE; LIPID RAFTS; H-RAS; ONCOGENIC KRAS AB K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. C1 [Jang, Hyunbum; Khavrutskii, Lyuba; Nussinov, Ruth] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Jang, Hyunbum; Khavrutskii, Lyuba; Tarasova, Nadya I.; Nussinov, Ruth] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA. [Abraham, Sherwin J.; Chavan, Tanmay S.] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. [Abraham, Sherwin J.; Hitchinson, Ben; Gaponenko, Vadim] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA. [Chavan, Tanmay S.; Gaponenko, Vadim] Univ Illinois, Dept Med Chem, Chicago, IL 60607 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Tarasova, NI (reprint author), NCI, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA. EM Nadya.Tarasova@nih.gov; NussinoR@helix.nih.gov; vadimg@uic.edu FU National Institutes of Health [R01 CA135341]; Frederick National Laboratory for Cancer Research [HHSN261200800001E]; Intramural Research Program, Frederick National Laboratory Center for Cancer Research; American Cancer Society [RGS-09-057-01-GMC] FX This work was supported, in whole or in part, by National Institutes of Health Grant R01 CA135341 (to V. G.), Frederick National Laboratory for Cancer Research Contract HHSN261200800001E, and by the Intramural Research Program, Frederick National Laboratory Center for Cancer Research. This work was also supported by American Cancer Society Grant RGS-09-057-01-GMC (to V. G.). NR 91 TC 29 Z9 29 U1 3 U2 20 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 10 PY 2015 VL 290 IS 15 BP 9465 EP 9477 DI 10.1074/jbc.M114.620724 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CF7IJ UT WOS:000352729400014 PM 25713064 ER PT J AU Rausch, JW Tian, MJ Li, YJ Angelova, L Bagaya, BS Krebs, KC Qian, F Zhu, CW Arts, EJ Le Grice, SFJ Gao, Y AF Rausch, Jason W. Tian, Meijuan Li, Yuejin Angelova, Lora Bagaya, Bernard S. Krebs, Kendall C. Qian, Feng Zhu, Chuanwu Arts, Eric J. Le Grice, Stuart F. J. Gao, Yong TI SiRNA-Induced Mutation in HIV-1 Polypurine Tract Region and Its Influence on Viral Fitness SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; STRAND DNA-SYNTHESIS; TYPE-1 REVERSE-TRANSCRIPTASE; SEQUENCE FEATURES IMPORTANT; RNASE-H ACTIVITY; RIBONUCLEASE-H; SUBSTRATE-SPECIFICITY; CLEAVAGE SPECIFICITY; INTEGRASE PROTEIN AB Converting single-stranded viral RNA into double stranded DNA for integration is an essential step in HIV-1 replication. Initial polymerization of minus-strand DNA is primed from a host derived tRNA, whereas subsequent plus-strand synthesis requires viral primers derived from the 3' and central polypurine tracts (3' and cPPTs). The 5' and 3' termini of these conserved RNA sequence elements are precisely cleaved by RT-associated RNase H to generate specific primers that are used to initiate plus-strand DNA synthesis. In this study, siRNA wad used to produce a replicative HIV-1 variant contained G(-1) A and T(-16) A substitutions within/adjacent to the 3'PPT sequence. Introducing either or both mutations into the 3'PPT region or only the G(-1) A substitution in the cPPT region of NL4-3 produced infectious virus with decreased fitness relative to the wild-type virus. In contrast, introducing the T(-16) A or both mutations into the cPPT rendered the virus(es) incapable of replication, most likely due to the F185L integrase mutation produced by this nucleotide substitution. Finally, the effects of G(-1) A and T(-16) A mutations on cleavage of the 3'PPT were examined using an in vitro RNase H cleavage assay. Substrate containing both mutations was miscleaved to a greater extent than either wild-type substrate or substrate containing the T(-16) A mutation alone, which is consistent with the observed effects of the equivalent nucleotide substitutions on the replication fitness of NL4-3 virus. In conclusion, siRNA targeting of the HIV-1 3'PPT region can substantially suppress virus replication, and this selective pressure can be used to generate infectious virus containing mutations within or near the HIV-1 PPT. Moreover, in-depth analysis of the resistance mutations demonstrates that although virus containing a G(-1) A mutation within the 3'PPT is capable of replication, this nucleotide substitution shifts the 3'-terminal cleavage site in the 3'PPT by one nucleotide (nt) and significantly reduces viral fitness. C1 [Rausch, Jason W.; Le Grice, Stuart F. J.] Frederick Natl Lab Canc Res, HIV Drug Resistance Program, Frederick, MD USA. [Tian, Meijuan; Li, Yuejin; Angelova, Lora; Krebs, Kendall C.; Gao, Yong] Case Western Reserve Univ, Dept Med, Div Infect Dis, Cleveland, OH 44106 USA. [Bagaya, Bernard S.; Gao, Yong] Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. [Qian, Feng; Zhu, Chuanwu] Suzhou Fifth Peoples Hosp, Suzhou, Jiangsu, Peoples R China. [Arts, Eric J.] Western Univ, Dept Microbiol & Immunol, London, ON, Canada. RP Gao, Y (reprint author), Case Western Reserve Univ, Dept Med, Div Infect Dis, Cleveland, OH 44106 USA. EM yong.gao@case.edu OI Bagaya Ssentalo, Bernard/0000-0002-3847-2615 FU National Institutes of Health [R01 AI49170, R01 AI84816] FX This work is funded by the National Institutes of Health (grant R01 AI49170 and grant R01 AI84816 to YG and EJA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 0 Z9 0 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 10 PY 2015 VL 10 IS 4 AR e0122953 DI 10.1371/journal.pone.0122953 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF5II UT WOS:000352590300070 PM 25860884 ER PT J AU Szalai, G Romero, R Chaiworapongsa, T Xu, Y Wang, B Ahn, H Xu, ZH Chiang, PJ Sundell, B Wang, R Jiang, Y Plazyo, O Olive, M Tarca, AL Dong, Z Qureshi, F Papp, Z Hassan, SS Hernandez-Andrade, E Than, NG AF Szalai, Gabor Romero, Roberto Chaiworapongsa, Tinnakorn Xu, Yi Wang, Bing Ahn, Hyunyoung Xu, Zhonghui Chiang, Po Jen Sundell, Birgitta Wang, Rona Jiang, Yang Plazyo, Olesya Olive, Mary Tarca, Adi L. Dong, Zhong Qureshi, Faisal Papp, Zoltan Hassan, Sonia S. Hernandez-Andrade, Edgar Than, Nandor Gabor TI Full-Length Human Placental sFlt-1-e15a Isoform Induces Distinct Maternal Phenotypes of Preeclampsia in Mice SO PLOS ONE LA English DT Article ID ENDOTHELIAL-GROWTH-FACTOR; FOR-GESTATIONAL-AGE; UTERINE PERFUSION-PRESSURE; CIRCULATING ANGIOGENIC FACTORS; FACTOR RECEPTOR-1 CONCENTRATION; HEALTHY NULLIPAROUS WOMEN; ARTERIAL-BLOOD-PRESSURE; LATE-ONSET PREECLAMPSIA; ELEVATED LIVER-ENZYMES; NITRIC-OXIDE SYNTHESIS AB Objective Most anti-angiogenic preeclampsiamodels in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsiamodels included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring. Methods Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia. Results Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (. MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 +/- 51.7 mu g/mg vs. 19.3 +/- 5.6 mu g/mg, p = 4.4x10(-2); GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10(-2)). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR). Conclusions A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the in vivo pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome. C1 [Szalai, Gabor; Romero, Roberto; Chaiworapongsa, Tinnakorn; Xu, Yi; Wang, Bing; Ahn, Hyunyoung; Xu, Zhonghui; Chiang, Po Jen; Sundell, Birgitta; Wang, Rona; Jiang, Yang; Plazyo, Olesya; Olive, Mary; Tarca, Adi L.; Dong, Zhong; Hassan, Sonia S.; Hernandez-Andrade, Edgar; Than, Nandor Gabor] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Hernandez-Andrade, Edgar; Than, Nandor Gabor] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Olive, Mary] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. [Tarca, Adi L.] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. [Tarca, Adi L.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Qureshi, Faisal] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Papp, Zoltan; Than, Nandor Gabor] Semmelweis Univ, Kutvolgyi Clin Block, Matern Private Dept, H-1085 Budapest, Hungary. [Than, Nandor Gabor] Hungarian Acad Sci, Inst Enzymol, Res Ctr Nat Sci, Budapest, Hungary. [Than, Nandor Gabor] Semmelweis Univ, Dept Pathol & Expt Canc 1, H-1085 Budapest, Hungary. RP Romero, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM romeror@mail.nih.gov; nthan@med.wayne.edu FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); Federal funds from NICHD, NIH [HHSN275201300006C]; NIH Center [P30CA22453]; Perinatology Research Branch (NICHD/NIH); Hungarian Academy of Sciences Momentum [LP2014-7/2014] FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); and, in part, with Federal funds from NICHD, NIH under Contract No. HHSN275201300006C. The Microscopy, Imaging and Cytometry Resources Core is supported, in part, by NIH Center grant P30CA22453 to the Karmanos Cancer Institute, Wayne State University, and the Perinatology Research Branch (NICHD/NIH). Manuscript writing was supported, in part, by the Hungarian Academy of Sciences Momentum Grant "LP2014-7/2014" (to NGT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 281 TC 4 Z9 4 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 10 PY 2015 VL 10 IS 4 AR e0119547 DI 10.1371/journal.pone.0119547 PG 42 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF5II UT WOS:000352590300008 PM 25860260 ER PT J AU Fauci, AS Collins, FS AF Fauci, Anthony S. Collins, Francis S. TI NIH research: Think globally SO SCIENCE LA English DT Editorial Material C1 [Fauci, Anthony S.] US Natl Inst Allergy & Infect Dis, NIH, Bethesda, MD 20892 USA. [Collins, Francis S.] US Natl Inst Hlth, Bethesda, MD USA. RP Fauci, AS (reprint author), US Natl Inst Allergy & Infect Dis, NIH, Bethesda, MD 20892 USA. EM afauci@niad.nih.gov; collinsf@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 35 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD APR 10 PY 2015 VL 348 IS 6231 BP 159 EP 159 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF5RD UT WOS:000352613700001 PM 25859018 ER PT J AU Allen, JD Torres, MI Tom, LS Rustan, S Leyva, B Negron, R Linnan, LA Jandorf, L Ospino, H AF Allen, Jennifer D. Torres, Maria Idali Tom, Laura S. Rustan, Sarah Leyva, Bryan Negron, Rosalyn Linnan, Laura A. Jandorf, Lina Ospino, Hosffman TI Enhancing organizational capacity to provide cancer control programs among Latino churches: design and baseline findings of the CRUZA Study SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Latinos; Hispanics; Faith-based organizations; Catholic; Cancer screening; Evidence-based interventions; Implementation science; Organizational capacity enhancement; Capacity building; Community-based participatory research ID AFRICAN-AMERICAN WOMEN; RE-AIM FRAMEWORK; HEALTH-PROMOTION INTERVENTIONS; PHYSICAL-ACTIVITY INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; SERVICES RESEARCH; VEGETABLE INTAKE; BLACK CHURCHES; IMPLEMENTATION; PREVENTION AB Background: Faith-based organizations (FBOs) have been successful in delivering health promotion programs for African Americans, though few studies have been conducted among Latinos. Even fewer have focused on organizational change, which is required to sustain community-based initiatives. We hypothesized that FBOs serving Latinos would be more likely to offer evidence-based strategies (EBS) for cancer control after receiving a capacity enhancement intervention to implement health programs, and designed the CRUZA trial to test this hypothesis. This paper describes the CRUZA design and baseline findings. Methods: We identified Catholic parishes in Massachusetts that provided Spanish-language mass (n = 65). A baseline survey assessed organizational characteristics relevant to adoption of health programs, including readiness for adoption, "fit" between innovation and organizational mission, implementation climate, and organizational culture. In the next study phase, parishes that completed the baseline assessment will be recruited to a randomized cluster trial, with the parish as the unit of analysis. Both groups will receive a Program Manual and Toolkit. Capacity Enhancement parishes will also be offered technical support, assistance forming health committees and building inter-institutional partnerships, and skills-based training. Results: Of the 49 parishes surveyed at baseline (75%), one-third (33%) reported having provided at least one health program in the prior year. However, only two program offerings were cancer-specific. Nearly one-fifth (18%) had an active health ministry. There was a high level of organizational readiness to adopt cancer control programs, high congruence between parish missions and CRUZA objectives, moderately conducive implementation climates, and organizational cultures supportive of CRUZA programming. Having an existing health ministry was significantly associated with having offered health programs within the past year. Relationships between health program offerings and other organizational characteristics were not statistically significant. Conclusions: Findings suggest that many parishes do not offer cancer control programs, yet many may be ready to do so. However, the perceptions about existing organizational practices and policies may not be conducive to program initiation. A capacity enhancement intervention may hold promise as a means of increasing health programming. The efficacy of such an intervention will be tested in phase two of this study. C1 [Allen, Jennifer D.; Tom, Laura S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Allen, Jennifer D.] Tufts Univ, Dept Publ Hlth & Community Med, Medford, MA 02155 USA. [Torres, Maria Idali; Rustan, Sarah; Negron, Rosalyn] Univ Massachusetts, Mauricio Gaston Inst Latino Community Dev & PublP, Boston, MA 02125 USA. [Leyva, Bryan] NCI, Bethesda, MD 20892 USA. [Linnan, Laura A.] Univ N Carolina, Chapel Hill, NC USA. [Jandorf, Lina] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Ospino, Hosffman] Boston Coll, Chestnut Hill, MA 02167 USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jennifer.allen@tufts.edu RI Allen, Jennifer/M-2113-2015 FU National Cancer Institute [U54CA156732]; National Institute on Minority Health and Health Disparities [R21MD005976]; Centers for Disease Control and Prevention with the National Cancer Institute [U48DP001946] FX This work was supported in part by the National Cancer Institute (U54CA156732, UMASS Boston/Dana-Farber Harvard Cancer Center Comprehensive Cancer Partnership Program), the National Institute on Minority Health and Health Disparities (R21MD005976), and through a cooperative agreement by the Centers for Disease Control and Prevention with the National Cancer Institute (U48DP001946, Massachusetts Cancer Prevention and Control Research Network). The authors gratefully acknowledge the time and insights provided by study participants. We also acknowledge the many contributions made by Milagros Abreu, Francisco Anzoategui, Amanda Bartholomew, Lois Biener, Deb Bowen, Melissa Colon, Daisy Diaz, Karen Emmons, Ana Galeas, Ericka Gonzalez, Elizabeth Gonzalez Suarez, Elizabeth Harden, Christina Hernandez, Alan Juarez, Robert Kickham, Ruth Lederman, Carol Lowenstein, Yolanda Martins, Angel Matos, Scott McInerney, Jane Mendez, Moraima Mendoza, Hannah Mills, Sean O'Malley, Aida Palencia, Beninson Pena, John Perez, Triniese Polk, Luciano Ramos, Lori-Anne Ramsey, Bianka Recinos, Rosa Robledo, Jeffrey Sanchez, Maria Sesma, Sarfaraz Shaikh, Ling Shi, Emeli Valverde, Bryan Weiner, David Wright, and the UMASS Boston Center for Survey Research. NR 63 TC 3 Z9 3 U1 5 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD APR 9 PY 2015 VL 15 AR 147 DI 10.1186/s12913-015-0735-1 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CH6UC UT WOS:000354170800001 PM 25889628 ER PT J AU Nguyen, TX Abdelmalak, M Marchand, C Agama, K Pommier, Y Cushman, M AF Trung Xuan Nguyen Abdelmalak, Monica Marchand, Christophe Agama, Keli Pommier, Yves Cushman, Mark TI Synthesis and Biological Evaluation of Nitrated 7-, 8-, 9-, and 10-Hydroxyindenoisoquinolines as Potential Dual Topoisomerase I (Top1)-Tyrosyl-DNA Phosphodiesterase I (TDP1) Inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TYROSYL-DNA PHOSPHODIESTERASE; COVALENT COMPLEXES; HUMAN-CELLS; INDENOISOQUINOLINES; IDENTIFICATION; ANTICANCER; REPAIR; ASSAY; OPTIMIZATION; RHODANINES AB The structureactivity relationships and hit-to-lead optimization of dual Top1-TDP1 inhibitors in the indenoisoquinoline drug class were investigated. A series of nitrated 7-, 8-, 9-, and 10-hydroxyindenoisoquinolines were synthesized and evaluated. Several compounds displayed potent dual Top1-TDP1 inhibition. The 9-hydroxy series exhibited potencies and cytotoxicities vs Top1 that surpassed those of camptothecin (CPT), the natural alkaloid that is being used as a standard in the Top1-mediated DNA cleavage assay. One member of this series was a more potent Top1 inhibitor at a concentration of 5 nM and produced a more stable ternary drugDNATop1 cleavage complex than CPT. C1 [Trung Xuan Nguyen; Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, W Lafayette, IN 47907 USA. [Trung Xuan Nguyen; Cushman, Mark] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA. [Abdelmalak, Monica; Marchand, Christophe; Agama, Keli; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Abdelmalak, Monica; Marchand, Christophe; Agama, Keli; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, 575 Stadium Mall Dr, W Lafayette, IN 47907 USA. EM cushman@purdue.edu RI Marchand, Christophe/D-8559-2016 FU National Institutes of Health (NIH) [U01CA089566, P30CA023168]; Purdue Research Foundation Grant; NIH, National Cancer Institute, Center for Cancer Research [Z01-BC006161]; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was made possible by the National Institutes of Health (NIH) through support with research grants U01CA089566 and P30CA023168 and by a Purdue Research Foundation Grant. This research was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (Z01-BC006161). This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 53 TC 9 Z9 10 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD APR 9 PY 2015 VL 58 IS 7 BP 3188 EP 3208 DI 10.1021/acs.jmedchem.5b00136 PG 21 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CG2FW UT WOS:000353091300019 PM 25811317 ER PT J AU Romagnoli, R Baraldi, PG Salvador, MK Prencipe, F Lopez-Cara, C Ortega, SS Brancale, A Hamel, E Castagliuolo, I Mitola, S Ronca, R Bortolozzi, R Porcu, E Basso, G Viola, G AF Romagnoli, Romeo Baraldi, Pier Giovanni Salvador, Maria Kimatrai Prencipe, Filippo Lopez-Cara, Carlota Schiaffino Ortega, Santiago Brancale, Andrea Hamel, Ernest Castagliuolo, Ignazio Mitola, Stefania Ronca, Roberto Bortolozzi, Roberta Porcu, Elena Basso, Giuseppe Viola, Giampietro TI Design, Synthesis, in Vitro, and in Vivo Anticancer and Antiangiogenic Activity of Novel 3-Arylaminobenzofuran Derivatives Targeting the Colchicine Site on Tubulin SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID VASCULAR DISRUPTING AGENTS; POLYMERIZATION INHIBITOR; BIOLOGICAL EVALUATION; MICROTUBULE DYNAMICS; ANTIMITOTIC AGENTS; CANCER-THERAPY; APOPTOSIS; BINDING; CELLS; PHOSPHATE AB A new series of compounds characterized by the presence of a 2-methoxy/ethoxycarbonyl group, combined with either no substituent or a methoxy group at each of the four possible positions of the benzene portion of the 3-(3',4',5'-trimethoxyanilino)benzo[b]furan skeleton, were evaluated for antiproliferative activity against cancer cells in culture and, for selected, highly active compounds, inhibition of tubulin polymerization, cell cycle effects, and in vivo potency. The greatest antiproliferative activity occurred with a methoxy group introduced at the C-6 position, the least with this substituent at C-4. Thus far, the most promising compound in this series was 2-methoxycarbonyl-3-(3',4',5'-trimethoxyanilino)-6-methoxybenzo[b]furan (3g), which inhibited cancer cell growth at nanomolar concentrations (IC50 values of 0.3-27 nM), bound to the colchicine site of tubulin, induced apoptosis, and showed, both in vitro and in vivo, potent vascular disrupting properties derived from the effect of this compound on vascular endothelial cells. Compound 3g had in vivo antitumor activity in a murine model comparable to the activity obtained with combretastatin A-4 phosphate. C1 [Romagnoli, Romeo; Baraldi, Pier Giovanni; Salvador, Maria Kimatrai; Prencipe, Filippo] Univ Ferrara, Dipartimento Sci Farmaceut, I-44121 Ferrara, Italy. [Lopez-Cara, Carlota; Schiaffino Ortega, Santiago] Univ Granada, Fac Farm, Dept Quim Organ & Farmaceut, E-18071 Granada, Spain. [Brancale, Andrea] Cardiff Univ, Sch Pharm & Pharmaceut Sci, Cardiff CF10 3NB, S Glam, Wales. [Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Natl Lab Canc Res,NIH, Frederick, MD 21702 USA. [Mitola, Stefania; Ronca, Roberto] Univ Brescia, Dipartimento Med Mol & Traslaz, Unita Oncol Sperimentale & Immunol, I-25121 Brescia, Italy. [Castagliuolo, Ignazio] Univ Padua, Dipartimento Med Mol, I-35121 Padua, Italy. [Bortolozzi, Roberta; Porcu, Elena; Basso, Giuseppe; Viola, Giampietro] Univ Padua, Lab Oncoematol, Dipartimento Salute Donna & Bambino, I-35131 Padua, Italy. RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, I-44121 Ferrara, Italy. EM rmr@unife.it; pgb@unife.it; giampietro.viola1@unipd.it RI Viola, Giampietro/I-4095-2012; Bortolozzi, Roberta/D-4950-2015; LOPEZ-CARA, LUISA CARLOTA/F-9686-2014; Baraldi, Pier Giovanni/B-7933-2017; CASTAGLIUOLO, IGNAZIO/K-9963-2016; OI Viola, Giampietro/0000-0001-9329-165X; Bortolozzi, Roberta/0000-0002-3357-4815; LOPEZ-CARA, LUISA CARLOTA/0000-0003-1142-6448; CASTAGLIUOLO, IGNAZIO/0000-0001-9888-7030; MITOLA, Stefania Maria Filomena/0000-0002-5557-738X FU PRIN [2010W7YRLZ_007]; Consejeria de Economia, Innovacion, Ciencia y Empleo, Junta de Andalucia [P12-CTS-696] FX The research was supported by PRIN 2010-2011 (Grant 2010W7YRLZ_007) and "Consejeria de Economia, Innovacion, Ciencia y Empleo, Junta de Andalucia" (Grant P12-CTS-696). The authors thank Dr. Alberto Casolari for excellent technical assistance. NR 53 TC 7 Z9 7 U1 4 U2 38 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD APR 9 PY 2015 VL 58 IS 7 BP 3209 EP 3222 DI 10.1021/acs.jmedchem.5b00155 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CG2FW UT WOS:000353091300020 PM 25785605 ER PT J AU Jiang, ZP Hess, SK Heinrich, F Lee, JC AF Jiang, Zhiping Hess, Sara K. Heinrich, Frank Lee, Jennifer C. TI Molecular Details of alpha-Synuclein Membrane Association Revealed by Neutrons and Photons SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID PULSED ESR MEASUREMENTS; CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE; LIPID VESICLES; TRYPTOPHAN FLUORESCENCE; ALZHEIMERS-DISEASE; N-TERMINUS; IN-VIVO; PROTEIN; BINDING AB alpha-Synuclein (alpha-syn) is an abundant neuronal protein associated with Parkinson's disease that is disordered in solution, but it exists in equilibrium between a bent-helix and an elongated-helix on negatively charged membranes. Here, neutron reflectometry (NR) and fluorescence spectroscopy were employed to uncover molecular details of the interaction between alpha-syn and two anionic lipids, phosphatidic acid (PA) and phosphatidylserine (PS). Both NR and site-specific Trp measurements indicate that penetration depth of alpha-syn is similar for either PA- or PS-containing membranes (similar to 9-11 A from bilayer center) even though there is a preference for alpha-syn binding to PA. However, closer examination of the individual Trp quenching profiles by brominated lipids reveals differences into local membrane interactions especially at position 39 where conformational heterogeneity was observed. The data also indicate that while W94 penetrates the bilayer as deeply as W4, W94 resides in a more polar surrounding. Taken together, we suggest the N- and C-terminal regions near positions 4 and 94 are anchored to the membrane, while the putative linker spanning residue 39 samples multiple conformations, which are sensitive to the chemical nature of the membrane surface. This flexibility may enable alpha-syn to bind diverse biomembranes in vivo. C1 [Jiang, Zhiping; Hess, Sara K.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Heinrich, Frank] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. [Heinrich, Frank] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. RP Lee, JC (reprint author), Lab Mol Biophys, 50 South Dr,MSC 8013, Bethesda, MD 20892 USA. EM leej4@mail.nih.gov RI Lee, Jennifer/E-9658-2015; Heinrich, Frank/A-5339-2010 OI Lee, Jennifer/0000-0003-0506-8349; Heinrich, Frank/0000-0002-8579-553X FU Intramural Research Program at the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI); NIST IMS program "Precision Measurements for Integral Membrane Proteins" FX This work was supported by the Intramural Research Program at the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI) and by the NIST IMS program "Precision Measurements for Integral Membrane Proteins". Research was performed in part at the National Institute of Standards and Technology (NIST) Center for Nanoscale Science and Technology. We thank the NHLBI Electron Microscopy, Biophysics, and Biochemistry Cores for the use of equipment and technical expertise. Certain commercial materials, equipment, and instruments are identified in this work to describe the experimental procedure as completely as possible. In no case does such an identification imply a recommendation or endorsement by NIST, nor does it imply that the materials, equipment, or instrument identified are necessarily the best available for the purpose. NR 85 TC 6 Z9 6 U1 4 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 9 PY 2015 VL 119 IS 14 BP 4812 EP 4823 DI 10.1021/jp512499r PG 12 WC Chemistry, Physical SC Chemistry GA CF8PB UT WOS:000352823200002 PM 25790164 ER PT J AU Bhadra, S Jiang, YS Kumar, MR Johnson, RF Hensley, LE Ellington, AD AF Bhadra, Sanchita Jiang, Yu Sherry Kumar, Mia R. Johnson, Reed F. Hensley, Lisa E. Ellington, Andrew D. TI Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) SO PLOS ONE LA English DT Article ID RECOMBINASE POLYMERASE AMPLIFICATION; STRAND DISPLACEMENT CASCADES; SAUDI-ARABIA; CLINICAL-FEATURES; CARE DIAGNOSTICS; DNA-SEQUENCES; RT-LAMP; INFECTION; PCR; QUANTIFICATION AB The Middle East respiratory syndrome coronavirus (MERS-CoV),an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF) 1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens. C1 [Bhadra, Sanchita; Jiang, Yu Sherry; Ellington, Andrew D.] Univ Texas Austin, Inst Cellular & Mol Biol, Ctr Syst & Synthet Biol, Dept Chem & Biochem, Austin, TX 78712 USA. [Kumar, Mia R.; Johnson, Reed F.] NIAID, Emerging Viral Pathogens Sect, NIH, Ft Detrick, MD USA. [Hensley, Lisa E.] NIAID, Integrated Res Facil, NIH, Ft Detrick, MD USA. RP Ellington, AD (reprint author), Univ Texas Austin, Inst Cellular & Mol Biol, Ctr Syst & Synthet Biol, Dept Chem & Biochem, Austin, TX 78712 USA. EM ellingtonlab@gmail.com FU Welch Foundation [F-1654]; Defense Advanced Research Projects Agency [HR0011-11-2-0018]; Division of Intramural Research of the National Institute of Allergy and Infectious Diseases (NIAID); Integrated Research Facility (NIAID, Division of Clinical Research) FX This work was supported by the Welch Foundation (F-1654) and by the Defense Advanced Research Projects Agency (HR0011-11-2-0018). This work was also supported, in part, by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases (NIAID) the Integrated Research Facility (NIAID, Division of Clinical Research). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 7 Z9 9 U1 3 U2 28 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2015 VL 10 IS 4 AR e0123126 DI 10.1371/journal.pone.0123126 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF5HQ UT WOS:000352588500077 PM 25856093 ER PT J AU Maduna, PH Dolan, M Kondlo, L Mabuza, H Dlamini, JN Polis, M Mnisi, T Orsega, S Maja, P Ledwaba, L Molefe, T Sangweni, P Malan, L Matchaba, G Khabo, P Grandits, G Neaton, JD AF Maduna, Patrick H. Dolan, Matt Kondlo, Lwando Mabuza, Honey Dlamini, Judith N. Polis, Mike Mnisi, Thabo Orsega, Susan Maja, Patrick Ledwaba, Lotty Molefe, Thuthukile Sangweni, Phumelele Malan, Lisette Matchaba, Gugu Khabo, Paul Grandits, Greg Neaton, James D. TI Morbidity and Mortality According to Latest CD4+Cell Count among HIV Positive Individuals in South Africa Who Enrolled in Project Phidisa SO PLOS ONE LA English DT Article ID NON-AIDS EVENTS; CD4 CELL COUNT; SHORT-TERM RISK; STARTING ANTIRETROVIRAL THERAPY; INFECTED ADULTS; COTE-DIVOIRE; VIRAL LOAD; FOLLOW-UP; NONFATAL AIDS; ALL-CAUSE AB Background Short-term morbidity and mortality rates for HIV positive soldiers in the South African National Defence Force (SANDF) would inform decisions about deployment and HIV disease management. Risks were determined according to the latest CD4+ cell count and use of antiretroviral therapy (ART) for HIV positive individuals in the SANDF and their dependents. Methods and Findings A total of 7,114 participants were enrolled and followed for mortality over a median of 4.7 years (IQR: 1.9, 7.1 years). For a planned subset (5,976), progression of disease (POD) and grade 4, potentially life-threatening events were also ascertained. CD4+ count and viral load were measured every 3 to 6 months. Poisson regression was used to compare event rates by latest CD4+ count (<50, 50-99, 100-199, 200-349, 350-499, 500+) with a focus on upper three strata, and to estimate relative risks (RRs) (ART/no ART). Median entry CD4+ was 207 cells/mm(3). During follow-up over 70% were prescribed ART. Over follow-up 1,226 participants died; rates ranged from 57.6 (<50 cells) to 0.8 (500+ cells) per 100 person years (py). Compared to those with latest CD4+ 200-349 (2.2/100py), death rates were significantly lower (p<0.001), as expected, for those with 350-499 (0.9/100py) and with 500+ cells (0.8/100py). The composite outcome of death, POD or grade 4 events occurred in 2,302 participants (4,045 events); rates were similar in higher CD4+ count strata (9.4 for 350-499 and 7.9 for 500+ cells) and lower than those with counts 200-349 cells (13.5) (p<0.001). For those with latest CD4+ 350+ cells, 63% of the composite outcomes (680 of 1,074) were grade 4 events. Conclusion Rates of morbidity and mortality are lowest among those with CD4+ count of 350 or higher and rates do not differ for those with counts of 350-499 versus 500+ cells. Grade 4 events are the predominant morbidity for participants with CD4+ counts of 350+ cells. C1 [Maduna, Patrick H.; Mabuza, Honey; Mnisi, Thabo; Malan, Lisette] South African Natl Def Forces, South Africa Mil Hlth Serv, Pretoria, South Africa. [Dolan, Matt] Henry M Jackson Fdn Adv Mil Med Inc, Bethesda, MD USA. [Kondlo, Lwando; Dlamini, Judith N.; Maja, Patrick; Ledwaba, Lotty; Molefe, Thuthukile; Sangweni, Phumelele; Matchaba, Gugu; Khabo, Paul] Charisma Healthcare Solut, Pretoria, South Africa. [Polis, Mike; Orsega, Susan] NIAID, NIH, Bethesda, MD 20892 USA. [Grandits, Greg; Neaton, James D.] Univ Minnesota, Div Biostat, Minneapolis, MN 55455 USA. RP Neaton, JD (reprint author), Univ Minnesota, Div Biostat, Minneapolis, MN 55455 USA. EM jim@ccbr.umn.edu FU Phidisa Project; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; South African National Defence Force; United States National Institutes of Health; United States Department of Defense FX Funding for the Phidisa Project, the Phidisa I and II studies, and this substudy were provided by the South African National Defence Force, the United States National Institutes of Health and the United States Department of Defense. SAIC-Frederick, Inc. helped fund the study through the employment of Beth Basseler and Xiao Liu who contributed to the study. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The funders had a role in study design, data collection and analysis, decision to publish, and preparation of the manuscript. NR 43 TC 2 Z9 2 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2015 VL 10 IS 4 AR e0121843 DI 10.1371/journal.pone.0121843 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF5HQ UT WOS:000352588500026 PM 25856495 ER PT J AU Rosenberg, SA AF Rosenberg, Steven A. TI Personalized Immunotherapy SO CELL LA English DT News Item C1 NCI, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 3 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD APR 9 PY 2015 VL 161 IS 2 BP 186 EP 186 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CF7AL UT WOS:000352708300005 ER PT J AU Ridaura, V Belkaid, Y AF Ridaura, Vanessa Belkaid, Yasmine TI Gut Microbiota: The Link to Your Second Brain SO CELL LA English DT Editorial Material ID TRANSIT AB Serotonin is a highly ubiquitous signaling molecule that plays a role in the regulation of various physiological functions. Several lines of evidence, including the present work from Hsiao and colleagues, demonstrate that, in the gut, microbial-derived metabolites affect the production of serotonin that in turn impacts host physiological functions. C1 [Ridaura, Vanessa; Belkaid, Yasmine] NIAID, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA. [Ridaura, Vanessa; Belkaid, Yasmine] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Belkaid, Y (reprint author), NIAID, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov NR 8 TC 11 Z9 12 U1 2 U2 47 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD APR 9 PY 2015 VL 161 IS 2 BP 193 EP 194 DI 10.1016/j.cell.2015.03.033 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CF7AL UT WOS:000352708300010 PM 25860600 ER PT J AU Roederer, M Quaye, L Mangino, M Beddall, MH Mahnke, Y Chattopadhyay, P Tosi, I Napolitano, L Barberio, MT Menni, C Villanova, F Di Meglio, P Spector, TD Nestle, FO AF Roederer, Mario Quaye, Lydia Mangino, Massimo Beddall, Margaret H. Mahnke, Yolanda Chattopadhyay, Pratip Tosi, Isabella Napolitano, Luca Barberio, Manuela Terranova Menni, Cristina Villanova, Federica Di Meglio, Paola Spector, Tim D. Nestle, Frank O. TI The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis SO CELL LA English DT Article ID GENOME-WIDE ASSOCIATION; CHRONIC HEPATITIS-B; REGULATORY T-CELLS; SUSCEPTIBILITY LOCI; JAPANESE POPULATION; HIV-1 CONTROL; RISK LOCI; VARIANTS; INFECTION; DENSITY AB Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. C1 [Roederer, Mario; Beddall, Margaret H.; Mahnke, Yolanda; Chattopadhyay, Pratip] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Quaye, Lydia; Mangino, Massimo; Menni, Cristina; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England. [Tosi, Isabella; Napolitano, Luca; Barberio, Manuela Terranova; Villanova, Federica; Di Meglio, Paola; Nestle, Frank O.] Kings Coll London, St Johns Inst Dermatol, Cutaneous Med Unit, London SE1 9RT, England. [Mangino, Massimo; Tosi, Isabella; Villanova, Federica; Nestle, Frank O.] Guys & St Thomas NHS Fdn Trust, NIHR Biomed Res Ctr, London SE1 9RT, England. RP Roederer, M (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM roederer@nih.gov; tim.spector@kcl.ac.uk RI mangino, massimo/F-5134-2011; OI mangino, massimo/0000-0002-2167-7470; Menni, Cristina/0000-0001-9790-0571; Chattopadhyay, Pratip/0000-0002-5457-9666 FU Vaccine Research Center (NIAID, NIH); Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre; Wellcome Trust; ERC FX This work was supported by the Vaccine Research Center (NIAID, NIH) intramural research program and by the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, King's College Hospital NHS Foundation (guysbrc-2012-1) Trust, and Dunhill Medical Trust. TwinsUK is also supported by the Wellcome Trust, and TDS is an ERC Advanced Researcher. We wish to thank Kaimei Song, Steve Perfetto, Richard Nguyen, Lynda Myles, Gabriela Surdulescu, Dylan Hodgkiss, and Ayrun Nessa for technical help with the samples, as well as the TwinsUK volunteers for participation. NR 62 TC 40 Z9 40 U1 3 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD APR 9 PY 2015 VL 161 IS 2 BP 387 EP 403 DI 10.1016/j.cell.2015.02.046 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CF7AL UT WOS:000352708300029 PM 25772697 ER PT J AU Sahu, T Lambert, L Herrod, J Conteh, S Orr-Gonzalez, S Carter, D Duffy, PE AF Sahu, Tejram Lambert, Lynn Herrod, Jessica Conteh, Solomon Orr-Gonzalez, Sachy Carter, Dariyen Duffy, Patrick E. TI Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model SO FRONTIERS IN MICROBIOLOGY LA English DT Article DE Plasmodium; chloroquine; liver-stage; CVac; prepatent ID PROTECTIVE IMMUNITY; PLASMODIUM-BERGHEI; SPOROZOITE INOCULATION; MALARIA; IMMUNIZATION; MICE; HYDROXYCHLOROQUINE; PHARMACOKINETICS AB Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites (SPZ) under drug cover. CVac using the drug chloroquine (CQ) induces pre- erythrocytic immunity in humans that includes antibody to SPZ and T-cell responses to liver stage (LS) parasites. The mechanism by which CVac with CO induces strong protective immunity is not understood as untreated infections do not confer protection. CO kills blood stage parasites, but its effect on LS parasites is poorly studied. Here we hypothesized that CO may prolong or perturb LS development of Plasmodium, as a potential explanation for enhanced pre-erythrocytic immune responses. Balb/c mice with or without CQ prophylaxis were infected with sporozoite forms of a luciferase-expressing rodent parasite, Plasmodium yoelii-Luc (Py-Luc). Mice that received primaquine, a drug that kills LS parasites, served as a positive control of drug effect. Parasite burden in liver was measured both by bioluminescence and by qRT-PCR quantification of parasite transcript. Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates LS parasites nor delays their development. Further investigations into the mechanism of CO-induced protection after CVac are required, and may give insights relevant to drug and vaccine development. C1 [Sahu, Tejram; Lambert, Lynn; Herrod, Jessica; Conteh, Solomon; Orr-Gonzalez, Sachy; Carter, Dariyen; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA. RP Duffy, PE (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, 5640 Fishers Lane,Room-1111, Rockville, MD 20852 USA. EM sahut@mail.nih.gov; duffype@niaid.nih.gov FU Intramural Research Program, NIAID, NIH FX We thank Prof. Jean Langhorne for her comments and sugestions on this work. We thank Dr. Stephan H. Kappe from Seattle Biomedical Research Institute, Seattle for providing the Py-Luc parasite line. Technical help by Yvette Robbins during experiments and Dr. Ankur Sharma during manuscript preparation is duly acknowledged. This work was funded by the Intramural Research Program, NIAID, NIH. NR 25 TC 1 Z9 1 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PD APR 9 PY 2015 VL 6 AR 233 DI 10.3389/fmicb.2015.00233 PG 6 WC Microbiology SC Microbiology GA CF4WM UT WOS:000352553900004 ER PT J AU Gillinov, AM Gelijns, AC Parides, MK DeRose, JJ Moskowitz, AJ Voisine, P Ailawadi, G Bouchard, D Smith, PK Mack, MJ Acker, MA Mullen, JC Rose, EA Chang, HL Puskas, JD Couderc, JP Gardner, TJ Varghese, R Horvath, KA Bolling, SF Michler, RE Geller, NL Ascheim, DD Miller, MA Bagiella, E Moquete, EG Williams, P Taddei-Peters, WC O'Gara, PT Blackstone, EH Argenziano, M AF Gillinov, A. Marc Gelijns, Annetine C. Parides, Michael K. DeRose, Joseph J., Jr. Moskowitz, Alan J. Voisine, Pierre Ailawadi, Gorav Bouchard, Denis Smith, Peter K. Mack, Michael J. Acker, Michael A. Mullen, John C. Rose, Eric A. Chang, Helena L. Puskas, John D. Couderc, Jean-Philippe Gardner, Timothy J. Varghese, Robin Horvath, Keith A. Bolling, Steven F. Michler, Robert E. Geller, Nancy L. Ascheim, Deborah D. Miller, Marissa A. Bagiella, Emilia Moquete, Ellen G. Williams, Paula Taddei-Peters, Wendy C. O'Gara, Patrick T. Blackstone, Eugene H. Argenziano, Michael CA CTSN Investigators TI Surgical Ablation of Atrial Fibrillation during Mitral-Valve Surgery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RADIOFREQUENCY ABLATION; PULMONARY VEINS; LESION SET; FOLLOW-UP; DISEASE; TRIAL; MAZE; APPENDAGE; CLOSURE; MULTICENTER AB Background Among patients undergoing mitral-valve surgery, 30 to 50% present with atrial fibrillation, which is associated with reduced survival and increased risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted, but evidence regarding its safety and effectiveness is limited. Methods We randomly assigned 260 patients with persistent or long-standing persistent atrial fibrillation who required mitral-valve surgery to undergo either surgical ablation (ablation group) or no ablation (control group) during the mitral-valve operation. Patients in the ablation group underwent further randomization to pulmonary-vein isolation or a biatrial maze procedure. All patients underwent closure of the left atrial appendage. The primary end point was freedom from atrial fibrillation at both 6 months and 12 months (as assessed by means of 3-day Holter monitoring). Results More patients in the ablation group than in the control group were free from atrial fibrillation at both 6 and 12 months (63.2% vs. 29.4%, P< 0.001). There was no significant difference in the rate of freedom from atrial fibrillation between patients who underwent pulmonary-vein isolation and those who underwent the biatrial maze procedure (61.0% and 66.0%, respectively; P = 0.60). One-year mortality was 6.8% in the ablation group and 8.7% in the control group (hazard ratio with ablation, 0.76; 95% confidence interval, 0.32 to 1.84; P = 0.55). Ablation was associated with more implantations of a permanent pacemaker than was no ablation (21.5 vs. 8.1 per 100 patient-years, P = 0.01). There were no significant between-group differences in major cardiac or cerebrovascular adverse events, overall serious adverse events, or hospital readmissions. Conclusions The addition of atrial fibrillation ablation to mitral-valve surgery significantly increased the rate of freedom from atrial fibrillation at 1 year among patients with persistent or long-standing persistent atrial fibrillation, but the risk of implantation of a permanent pacemaker was also increased. C1 [Gillinov, A. Marc; Blackstone, Eugene H.] Cleveland Clin Fdn, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44195 USA. [Gelijns, Annetine C.; Parides, Michael K.; Moskowitz, Alan J.; Chang, Helena L.; Ascheim, Deborah D.; Bagiella, Emilia; Moquete, Ellen G.; Williams, Paula] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, Int Ctr Hlth Outcomes & Innovat Res, New York, NY 10029 USA. [DeRose, Joseph J., Jr.; Michler, Robert E.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Cardiothorac Surg, New York, NY USA. [Rose, Eric A.; Puskas, John D.; Varghese, Robin] Mt Sinai Hlth Syst, Dept Cardiac Surg, New York, NY USA. [Argenziano, Michael] Columbia Univ Coll Phys & Surg, Dept Surg, Div Cardiothorac Surg, New York, NY 10032 USA. [Couderc, Jean-Philippe] Univ Rochester, Med Ctr, Dept Cardiol, Heart Res Follow Up Program, Rochester, NY 14642 USA. [Voisine, Pierre] Hop Laval, Inst Univ Cardiol Quebec, Quebec City, PQ, Canada. [Bouchard, Denis] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Mullen, John C.] Univ Alberta, Div Cardiac Surg, Edmonton, AB, Canada. [Ailawadi, Gorav] Univ Virginia, Sch Med, Div Thorac & Cardiovasc Surg, Charlottesville, VA 22908 USA. [Smith, Peter K.] Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA. [Mack, Michael J.] Baylor Hlth Care Syst, Baylor Res Inst, Div Cardiothorac Surg, Plano, TX USA. [Acker, Michael A.] Univ Penn, Sch Med, Dept Surg, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. [Gardner, Timothy J.] Christiana Care Hlth Syst, Ctr Heart & Vasc Hlth, Newark, DE USA. [Horvath, Keith A.] Suburban Hosp, Ctr Heart, NIH, Dept Cardiothorac Surg, Bethesda, MD USA. [Geller, Nancy L.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Miller, Marissa A.; Taddei-Peters, Wendy C.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Bolling, Steven F.] Univ Michigan Hlth Syst, Dept Cardiac Surg, Ann Arbor, MI USA. [O'Gara, Patrick T.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Gelijns, AC (reprint author), Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, 1 Gustave L Levy Pl,Box 1077, New York, NY 10029 USA. EM annetine.gelijns@mssm.edu OI Moskowitz, Alan/0000-0002-4412-9450 FU National Institutes of Health; Canadian Institutes of Health Research FX Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00903370. NR 37 TC 45 Z9 47 U1 1 U2 15 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 9 PY 2015 VL 372 IS 15 BP 1399 EP 1409 DI 10.1056/NEJMoa1500528 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CF2ZV UT WOS:000352417900004 PM 25853744 ER PT J AU Weng, MT Tung, TH Lee, JH Wei, SC Lin, HL Huang, YJ Wong, JM Luo, J Sheu, JC AF Weng, Meng-Tzu Tung, Tzu-Hsun Lee, Jih-Hsiang Wei, Shu-Chen Lin, Hang-Li Huang, Yu-Jung Wong, Jau-Min Luo, Ji Sheu, Jin-Chuan TI Enhancer of rudimentary homolog regulates DNA damage response in hepatocellular carcinoma SO SCIENTIFIC REPORTS LA English DT Article ID CHECKPOINT KINASE INHIBITOR; PERIPHERAL-BLOOD LYMPHOCYTES; HEPATITIS-B; OXIDATIVE STRESS; CHK1 INHIBITION; CANCER-CELLS; COMET ASSAY; REPAIR; PHOSPHORYLATION; CYTOTOXICITY AB We previously demonstrated that the enhancer of rudimentary homolog (ERH) gene is required for the expression of multiple cell cycle and DNA damage response (DDR) genes. The present study investigated the role of ERH and its target DNA damage repair genes in hepatocellular carcinoma cells. We observed positive correlation between ERH and ataxia telangiectasia and Rad3 related (ATR) expression in liver tissues. Expression of ERH, ATR as well as checkpoint kinase 1 (CHK1) were higher in HCCs than in normal liver tissues. Knocking-down ERH augmented ultraviolet light induced DNA damage in HepG2 cells. ATR protein level is reduced upon ERH depletion as a result of defect in the splicing of ATR mRNA. Consequently, the ATR effector kinase Chk1 failed to be phosphorylated upon ultraviolet light or hydroxyurea treatment in ERH knocked-down HepG2 cells. Finally, we observed Chk1 inhibitor AZD7762 enhanced the effect of doxorubicin on inhibiting growth of HCC cells in vitro and in vivo. This study suggested that ERH regulates the splicing of the DNA damage response proteins ATR in HCC cells, and targeting DNA damage response by Chk1 inhibitor augments chemotherapy to treat HCC cells. C1 [Weng, Meng-Tzu] Natl Taiwan Univ Hosp, Grad Inst Clin Med, Taipei 100, Taiwan. [Weng, Meng-Tzu] Far Eastern Mem Hosp, New Taipei 220, Taiwan. [Tung, Tzu-Hsun; Huang, Yu-Jung] Liver Dis Prevent & Treatment Res Fdn, Taipei 100, Taiwan. [Lee, Jih-Hsiang] Clin Trial Ctr, Taipei 100, Taiwan. [Wei, Shu-Chen; Lin, Hang-Li; Wong, Jau-Min; Sheu, Jin-Chuan] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Wei, Shu-Chen; Lin, Hang-Li; Wong, Jau-Min; Sheu, Jin-Chuan] Coll Med, Taipei 100, Taiwan. [Luo, Ji] NCI, Canc Syst Biol Sect, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Sheu, JC (reprint author), Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. EM jcsheu@ntu.edu.tw OI SHEU, JIN-CHUAN/0000-0002-2503-7139 FU Liver Disease Prevention and Treatment Research Foundation, Taiwan FX We thank Yin-Wen Shiue for comet assay technique assistance. The study was supported partly by the Liver Disease Prevention and Treatment Research Foundation, Taiwan. NR 48 TC 3 Z9 3 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD APR 9 PY 2015 VL 5 AR 9357 DI 10.1038/srep09357 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3SB UT WOS:000352467700001 PM 25880358 ER PT J AU Ran, FA Cong, L Yan, WX Scott, DA Gootenberg, JS Kriz, AJ Zetsche, B Shalem, O Wu, XB Makarova, KS Koonin, EV Sharp, PA Zhang, F AF Ran, F. Ann Cong, Le Yan, Winston X. Scott, David A. Gootenberg, Jonathan S. Kriz, Andrea J. Zetsche, Bernd Shalem, Ophir Wu, Xuebing Makarova, Kira S. Koonin, Eugene V. Sharp, Phillip A. Zhang, Feng TI In vivo genome editing using Staphylococcus aureus Cas9 SO NATURE LA English DT Article ID OFF-TARGET SITES; GUIDE RNA; NUCLEASE SPECIFICITY; DNA CLEAVAGE; CRISPR RNA; GENE; IMMUNITY; SYSTEMS; ENDONUCLEASE; SEQUENCE AB The RNA-guided endonuclease Cas9 has emerged as a versatile genom-editing platform. However, the size of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for basic research and therapeutic applications that use the highly versatileaderio-assolated virus (AAV) delivery vehicle. Here, we we characterize six smaller Cas9 ortholocgues and show that Cas9 from Staphylococcus aureus (SaCas9) can edit the genome with efficiencies similar to those of spcas9, while being more than 1 kilobase shorter. We packaged SaCas9 and its single guide RNA expression cassette into a single AAV vector and targeted the cholesterol regulatory gene Pcsk9 in the mouse liver. Within one week of injection we observed >40%. gene modification, accompanied by significant reductions in serum Pcsk9 and total cholesterol le; Is We further assess the genome -wide targeting specificity of SaCas9 and SpCas9 using BLESS, and demonstrate that SaCas9-mediated in vivo genome editing has the potential to be efficient and specific. C1 [Ran, F. Ann; Cong, Le; Yan, Winston X.; Scott, David A.; Gootenberg, Jonathan S.; Zetsche, Bernd; Shalem, Ophir; Zhang, Feng] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Ran, F. Ann] Harvard Univ, Soc Fellows, Cambridge, MA 02138 USA. [Cong, Le; Kriz, Andrea J.; Sharp, Phillip A.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Yan, Winston X.] Harvard Univ, Sch Med, Grad Program Biophys, Boston, MA 02115 USA. [Yan, Winston X.] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02115 USA. [Scott, David A.; Zhang, Feng] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Scott, David A.; Zhang, Feng] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Gootenberg, Jonathan S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Wu, Xuebing; Sharp, Phillip A.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Wu, Xuebing] MIT, Computat & Syst Biol Grad Program, Cambridge, MA 02139 USA. [Makarova, Kira S.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Zhang, Feng] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP Zhang, F (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM zhang@broadinstitute.org RI Cong, Le/M-9981-2013 OI Cong, Le/0000-0003-4725-8714 FU National Institute of General Medical Sciences [T32GM007753]; Paul and Daisy Soros Fellowship; US Department of Energy Computational Science Graduate Fellowship; United States Public Health Service from the National Institutes of Health [RO1-GM34277, R01-CA133404]; United States Public Health Service from the National Cancer Institute [PO1-CA42063]; Cancer Center from the National Cancer Institute [P30-CA14051]; National Institutes of Health through NIMH [5DP1-MH100706]; National Institutes of Health through NIDDK [5R01DK097768-03]; Waterman Award from the National Science Foundation; Keck Foundation; New York Stem Cell Foundation; Damon Runyon Foundation; Searle Scholars Foundation; Merkin Foundation; Vallee Foundation; NIH core grant [5P30EY012196-17] FX We thank E. Charpentier, I. Fonfara and K. Chylinski for discussions; A. Scherer-Hoock, B. Clear and the MIT Division of Comparative Medicine for assistance with animal experiments; Boston Children's Hospital Viral Core and R. Xiao for assistance with AAV production; N. Crosetto for advice on BLESS; C.-Y. Lin and I. Slaymaker for experimental assistance; and the entire Zhang laboratory for support and advice. F.A.R. is a Junior Fellow at the Harvard Society of Fellows. W.X.Y. is supported by T32GM007753 from the National Institute of General Medical Sciences and a Paul and Daisy Soros Fellowship. J.S.G. is supported by a US Department of Energy Computational Science Graduate Fellowship. X.W. is a Howard Hughes Medical Institute International Student Research Fellow. P.A.S. is supported by United States Public Health Service grants RO1-GM34277, R01-CA133404 from the National Institutes of Health, and PO1-CA42063 from the National Cancer Institute, and partially by Cancer Center Support (core) grant P30-CA14051 from the National Cancer Institute. F.Z. is supported by the National Institutes of Health through NIMH (5DP1-MH100706) and NIDDK (5R01DK097768-03), a Waterman Award from the National Science Foundation, the Keck, New York Stem Cell, Damon Runyon, Searle Scholars, Merkin, and Vallee Foundations, and B. Metcalfe. F.Z. is a New York Stem Cell Foundation Robertson Investigator. The Children's Hospital virus core is supported by an NIH core grant (5P30EY012196-17). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. CRISPR reagents are available to the academic community through Addgene, and information about the protocols, plasmids, and reagents can be found at the Zhang laboratory website http://www.genome-engineering.org. NR 50 TC 324 Z9 338 U1 65 U2 247 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 9 PY 2015 VL 520 IS 7546 BP 186 EP U98 DI 10.1038/nature14299 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3NA UT WOS:000352454600031 PM 25830891 ER PT J AU Hibar, DP Stein, JL Renteria, ME Arias-Vasquez, A Desrivieres, S Jahanshad, N Toro, R Wittfeld, K Abramovic, L Andersson, M Aribisala, BS Armstrong, NJ Bernard, M Bohlken, MM Boks, MP Bralten, J Brown, AA Chakravarty, MM Chen, Q Ching, CRK Cuellar-Partida, G den Braber, A Giddaluru, S Goldman, AL Grimm, O Guadalupe, T Hass, J Woldehawariat, G Holmes, AJ Hoogman, M Janowitz, D Jia, TY Kim, S Klein, M Kraemer, B Lee, PH Loohuis, LMO Luciano, M Macare, C Mather, KA Mattheisen, M Milaneschi, Y Nho, K Papmeyer, M Ramasamy, A Risacher, SL Roiz-Santianez, R Rose, EJ Salami, A Samann, PG Schmaal, L Schork, AJ Shin, J Strike, LT Teumer, A van Donkelaar, MMJ van Eijk, KR Walters, RK Westlye, LT Whelan, CD Winkler, AM Zwiers, MP Alhusaini, S Athanasiu, L Ehrlich, S Hakobjan, MMH Hartberg, CB Haukvik, UK Heister, AJGAM Hoehn, D Kasperaviciute, D Liewald, DCM Lopez, LM Makkinje, RRR Matarin, M Naber, MAM Mckay, DR Needham, M Nugent, AC Putz, B Royle, NA Shen, L Sprooten, E Trabzuni, D van der Marel, SSL van Hulzen, KJE Walton, E Wolf, C Almasy, L Ames, D Arepalli, S Assareh, AA Bastin, ME Brodaty, H Bulayeva, KB Carless, MA Cichon, S Corvin, A Curran, JE Czisch, M de Zubicaray, GI Dillman, A Duggirala, R Dyer, TD Erk, S Fedko, IO Ferrucci, L Foroud, TM Fox, PT Fukunaga, M Gibbs, JR Goring, HHH Green, RC Guelfi, S Hansell, NK Hartman, CA Hegenscheid, K Heinz, A Hernandez, DG Heslenfeld, DJ Hoekstra, PJ Holsboer, F Homuth, G Hottenga, JJ Ikeda, M Jack, CR Jenkinson, M Johnson, R Kanai, R Keil, M Kent, JW Kochunov, P Kwok, JB Lawrie, SM Liu, XM Longo, DL McMahon, KL Meisenzah, E Melle, I Mahnke, S Montgomery, GW Mostert, JC Muhleisen, TW Nalls, MA Nichols, TE Nilsson, LG Nothen, MM Ohi, K Olvera, RL Perez-Iglesias, R Pike, GB Potkin, SG Reinvang, I Reppermund, S Rietschel, M Romanczuk-Seiferth, N Rosen, GD Rujescu, D Schnell, K Schofield, PR Smith, C Steen, VM Sussmann, JE Thalamuthu, A Toga, AW Traynor, BJ Troncoso, J Turner, JA Hernandez, MCV van't Ent, D van der Brug, M van der Wee, NJA van Tol, MJ Veltman, DJ Wassink, TH Westman, E Zielke, RH Zonderman, AB Ashbrook, DG Hager, R Lu, L McMahon, FJ Morris, DW Williams, RW Brunner, HG Buckner, RL Buitelaar, JK Cahn, W Calhoun, VD Cavalleri, GL Crespo-Facorro, B Dale, AM Davies, GE Delanty, N Depondt, C Djurovic, S Drevets, WC Espeseth, T Gollub, RL Ho, BC Hoffman, W Hosten, N Kahn, RS Le Hellard, S Meyer-Lindenberg, A Muller-Myhsok, B Nauck, M Nyberg, L Pandolfo, M Penninx, BWJH Roffman, JL Sisodiya, SM Smoller, JW van Bokhoven, H van Haren, NEM Volzke, H Walter, H Weiner, MW Wen, W White, T Agartz, I Andreassen, OA Blangero, J Boomsma, DI Brouwer, RM Cannon, DM Cookson, MR de Geus, EJC Deary, IJ Donohoe, G Fernandez, G Fisher, SE Francks, C Glahn, DC Grabe, HJ Gruber, O Hardy, J Hashimoto, R Pol, HEH Jonsson, EG Kloszewska, I Lovestone, S Mattay, VS Mecocci, P McDonald, C McIntosh, AM Ophoff, RA Paus, T Pausova, Z Ryten, M Sachdev, PS Saykin, AJ Simmons, A Singleton, A Soininen, H Wardlaw, JM Weale, ME Weinberger, DR Adams, HHH Launer, LJ Seiler, S Schmidt, R Chauhan, G Satizabal, CL Becker, JT Yanek, L van der Lee, SJ Ebling, M Fischl, B Longstreth, WT Greve, D Schmidt, H Nyquist, P Vinke, LN van Duijn, CM Xue, LT Mazoyer, B Bis, JC Gudnason, V Seshadri, S Ikram, MA Martin, NG Wright, MJ Schumann, G Franke, B Thompson, PM Medland, SE AF Hibar, Derrek P. Stein, Jason L. Renteria, Miguel E. Arias-Vasquez, Alejandro Desrivieres, Sylvane Jahanshad, Neda Toro, Roberto Wittfeld, Katharina Abramovic, Lucija Andersson, Micael Aribisala, Benjamin S. Armstrong, Nicola J. Bernard, Manon Bohlken, Marc M. Boks, Marco P. Bralten, Janita Brown, Andrew A. Chakravarty, M. Mallar Chen, Qiang Ching, Christopher R. K. Cuellar-Partida, Gabriel den Braber, Anouk Giddaluru, Sudheer Goldman, Aaron L. Grimm, Oliver Guadalupe, Tulio Hass, Johanna Woldehawariat, Girma Holmes, Avram J. Hoogman, Martine Janowitz, Deborah Jia, Tianye Kim, Sungeun Klein, Marieke Kraemer, Bernd Lee, Phil H. Loohuis, Loes M. Olde Luciano, Michelle Macare, Christine Mather, Karen A. Mattheisen, Manuel Milaneschi, Yuri Nho, Kwangsik Papmeyer, Martina Ramasamy, Adaikalavan Risacher, Shannon L. Roiz-Santianez, Roberto Rose, Emma J. Salami, Alireza Saemann, Philipp G. Schmaal, Lianne Schork, Andrew J. Shin, Jean Strike, Lachlan T. Teumer, Alexander van Donkelaar, Marjolein M. J. van Eijk, Kristel R. Walters, Raymond K. Westlye, Lars T. Whelan, Christopher D. Winkler, Anderson M. Zwiers, Marcel P. Alhusaini, Saud Athanasiu, Lavinia Ehrlich, Stefan Hakobjan, Marina M. H. Hartberg, Cecilie B. Haukvik, Unn K. Heister, Angelien J. G. A. M. Hoehn, David Kasperaviciute, Dalia Liewald, David C. M. Lopez, Lorna M. Makkinje, Remco R. R. Matarin, Mar Naber, Marlies A. M. McKay, D. Reese Needham, Margaret Nugent, Allison C. Puetz, Benno Royle, Natalie A. Shen, Li Sprooten, Emma Trabzuni, Daniah van der Marel, Saskia S. L. van Hulzen, Kimm J. E. Walton, Esther Wolf, Christiane Almasy, Laura Ames, David Arepalli, Sampath Assareh, Amelia A. Bastin, Mark E. Brodaty, Henry Bulayeva, Kazima B. Carless, Melanie A. Cichon, Sven Corvin, Aiden Curran, Joanne E. Czisch, Michael de Zubicaray, Greig I. Dillman, Allissa Duggirala, Ravi Dyer, Thomas D. Erk, Susanne Fedko, Iryna O. Ferrucci, Luigi Foroud, Tatiana M. Fox, Peter T. Fukunaga, Masaki Gibbs, J. Raphael Goering, Harald H. H. Green, Robert C. Guelfi, Sebastian Hansell, Narelle K. Hartman, Catharina A. Hegenscheid, Katrin Heinz, Andreas Hernandez, Dena G. Heslenfeld, Dirk J. Hoekstra, Pieter J. Holsboer, Florian Homuth, Georg Hottenga, Jouke-Jan Ikeda, Masashi Jack, Clifford R., Jr. Jenkinson, Mark Johnson, Robert Kanai, Ryota Keil, Maria Kent, Jack W., Jr. Kochunov, Peter Kwok, John B. Lawrie, Stephen M. Liu, Xinmin Longo, Dan L. McMahon, Katie L. Meisenzah, Eva Melle, Ingrid Mahnke, Sebastian Montgomery, Grant W. Mostert, Jeanette C. Muehleisen, Thomas W. Nalls, Michael A. Nichols, Thomas E. Nilsson, Lars G. Noethen, Markus M. Ohi, Kazutaka Olvera, Rene L. Perez-Iglesias, Rocio Pike, G. Bruce Potkin, Steven G. Reinvang, Ivar Reppermund, Simone Rietschel, Marcella Romanczuk-Seiferth, Nina Rosen, Glenn D. Rujescu, Dan Schnell, Knut Schofield, Peter R. Smith, Colin Steen, Vidar M. Sussmann, Jessika E. Thalamuthu, Anbupalam Toga, Arthur W. Traynor, Bryan J. Troncoso, Juan Turner, Jessica A. Valdes Hernandez, Maria C. van't Ent, Dennis van der Brug, Marcel van der Wee, Nic J. A. van Tol, Marie-Jose Veltman, Dick J. Wassink, Thomas H. Westman, Eric Zielke, Ronald H. Zonderman, Alan B. Ashbrook, David G. Hager, Reinmar Lu, Lu McMahon, Francis J. Morris, Derek W. Williams, Robert W. Brunner, Han G. Buckner, Randy L. Buitelaar, Jan K. Cahn, Wiepke Calhoun, Vince D. Cavalleri, Gianpiero L. Crespo-Facorro, Benedicto Dale, Anders M. Davies, Gareth E. Delanty, Norman Depondt, Chantal Djurovic, Srdjan Drevets, Wayne C. Espeseth, Thomas Gollub, Randy L. Ho, Beng-Choon Hoffman, Wolfgang Hosten, Norbert Kahn, Rene S. Le Hellard, Stephanie Meyer-Lindenberg, Andreas Mueller-Myhsok, Bertram Nauck, Matthias Nyberg, Lars Pandolfo, Massimo Penninx, Brenda W. J. H. Roffman, Joshua L. Sisodiya, Sanjay M. Smoller, Jordan W. van Bokhoven, Hans van Haren, Neeltje E. M. Voelzke, Henry Walter, Henrik Weiner, Michael W. Wen, Wei White, Tonya Agartz, Ingrid Andreassen, Ole A. Blangero, John Boomsma, Dorret I. Brouwer, Rachel M. Cannon, Dara M. Cookson, Mark R. de Geus, Eco J. C. Deary, Ian J. Donohoe, Gary Fernandez, Guillen Fisher, Simon E. Francks, Clyde Glahn, David C. Grabe, Hans J. Gruber, Oliver Hardy, John Hashimoto, Ryota Pol, Hilleke E. Hulshoff Joensson, Erik G. Kloszewska, Iwona Lovestone, Simon Mattay, Venkata S. Mecocci, Patrizia McDonald, Colm McIntosh, Andrew M. Ophoff, Roel A. Paus, Tomas Pausova, Zdenka Ryten, Mina Sachdev, Perminder S. Saykin, Andrew J. Simmons, Andy Singleton, Andrew Soininen, Hilkka Wardlaw, Joanna M. Weale, Michael E. Weinberger, Daniel R. Adams, Hieab H. H. Launer, Lenore J. Seiler, Stephan Schmidt, Reinhold Chauhan, Ganesh Satizabal, Claudia L. Becker, James T. Yanek, Lisa van der Lee, Sven J. Ebling, Maritza Fischl, Bruce Longstreth, W. T., Jr. Greve, Douglas Schmidt, Helena Nyquist, Paul Vinke, Louis N. van Duijn, Cornelia M. Xue, Luting Mazoyer, Bernard Bis, Joshua C. Gudnason, Vilmundur Seshadri, Sudha Ikram, M. Arfan Martin, Nicholas G. Wright, Margaret J. Schumann, Gunter Franke, Barbara Thompson, Paul M., Jr. Medland, Sarah E. CA Alzheimers Dis Neuroimaging CHARGE Consortium EPIGEN IMAGEN SYS TI Common genetic variants influence human subcortical brain structures SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; BASAL GANGLIA; NERVOUS-SYSTEM; EXPRESSION; CHROMATIN; KINECTIN; IDENTIFICATION; ORGANIZATION; SEGMENTATION; HIPPOCAMPAL AB The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume(5) and intracranial volume(6). These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 X 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. C1 [Hibar, Derrek P.; Stein, Jason L.; Jahanshad, Neda; Ching, Christopher R. K.; Whelan, Christopher D.; Thompson, Paul M., Jr.] Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Imaging Genet Ctr, Los Angeles, CA 90292 USA. [Stein, Jason L.; Ching, Christopher R. K.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Neurogenet Program, Los Angeles, CA 90095 USA. [Renteria, Miguel E.; Cuellar-Partida, Gabriel; Strike, Lachlan T.; Hansell, Narelle K.; Montgomery, Grant W.; Martin, Nicholas G.; Wright, Margaret J.; Medland, Sarah E.] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia. [Arias-Vasquez, Alejandro; Bralten, Janita; Hoogman, Martine; Klein, Marieke; van Donkelaar, Marjolein M. J.; Hakobjan, Marina M. H.; Heister, Angelien J. G. A. M.; Makkinje, Remco R. R.; Naber, Marlies A. M.; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Mostert, Jeanette C.; Brunner, Han G.; van Bokhoven, Hans; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [Arias-Vasquez, Alejandro; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6500 HB Nijmegen, Netherlands. [Arias-Vasquez, Alejandro; Bralten, Janita; Buitelaar, Jan K.; Fernandez, Guillen] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6500 HB Nijmegen, Netherlands. [Arias-Vasquez, Alejandro; Bralten, Janita; Ching, Christopher R. K.; Hoogman, Martine; Klein, Marieke; van Donkelaar, Marjolein M. J.; Zwiers, Marcel P.; Hakobjan, Marina M. H.; Heister, Angelien J. G. A. M.; Makkinje, Remco R. R.; Naber, Marlies A. M.; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Mostert, Jeanette C.; Brunner, Han G.; Buitelaar, Jan K.; van Bokhoven, Hans; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Franke, Barbara] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6500 GL Nijmegen, Netherlands. [Desrivieres, Sylvane; Jia, Tianye; Macare, Christine; Schumann, Gunter] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London SE5 8AF, England. [Toro, Roberto] Inst Pasteur, Lab Human Genet & Cognit Funct, F-75015 Paris, France. [Toro, Roberto] Inst Pasteur, CNRS, URA Genes Synapses & Cognit 2182, F-75015 Paris, France. [Toro, Roberto] Univ Paris Diderot, Sorbonne Paris Cite, F-75015 Paris, France. [Wittfeld, Katharina; Hoffman, Wolfgang] German Ctr Neurodegenerat Dis DZNE, D-17487 Greifswald, Germany. [Wittfeld, Katharina; Janowitz, Deborah; Grabe, Hans J.] Univ Med Greifswald, Dept Psychiat, D-17489 Greifswald, Germany. [Abramovic, Lucija; Bohlken, Marc M.; Boks, Marco P.; van Eijk, Kristel R.; Cahn, Wiepke; Kahn, Rene S.; van Haren, Neeltje E. M.; Brouwer, Rachel M.; Pol, Hilleke E. Hulshoff; Ophoff, Roel A.] Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, NL-3584 CX Utrecht, Netherlands. [Andersson, Micael; Salami, Alireza; Nilsson, Lars G.; Nyberg, Lars] Umea Univ, Ctr Funct Brain Imaging UFBI, S-90187 Umea, Sweden. [Aribisala, Benjamin S.; Royle, Natalie A.; Wardlaw, Joanna M.] Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh EH4 2XU, Midlothian, Scotland. [Aribisala, Benjamin S.; Royle, Natalie A.; Wardlaw, Joanna M.] Lagos State Univ, Dept Comp Sci, Lagos, Nigeria. [Aribisala, Benjamin S.; Royle, Natalie A.; Bastin, Mark E.; Wardlaw, Joanna M.] Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh EH4 2XU, Midlothian, Scotland. [Armstrong, Nicola J.; Mather, Karen A.; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Reppermund, Simone; Thalamuthu, Anbupalam; Wen, Wei; Sachdev, Perminder S.] Univ New S Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW 2052, Australia. [Armstrong, Nicola J.] Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia. [Bernard, Manon; Shin, Jean; Pausova, Zdenka] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Brown, Andrew A.; Athanasiu, Lavinia; Hartberg, Cecilie B.; Haukvik, Unn K.; Melle, Ingrid; Djurovic, Srdjan; Agartz, Ingrid; Andreassen, Ole A.; Joensson, Erik G.] Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, N-0316 Oslo, Norway. [Brown, Andrew A.; Westlye, Lars T.; Athanasiu, Lavinia; Melle, Ingrid; Espeseth, Thomas; Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, N-0424 Oslo, Norway. [Chakravarty, M. Mallar] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Montreal, PQ H4H 1R3, Canada. [Chakravarty, M. Mallar] McGill Univ, Dept Psychiat & Biomed Engn, Montreal, PQ H3A 2B4, Canada. [Chen, Qiang; Goldman, Aaron L.; Mattay, Venkata S.; Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Ching, Christopher R. K.] Univ Calif Los Angeles, Sch Med, Interdept Neurosci Grad Program, Los Angeles, CA 90095 USA. [den Braber, Anouk; Fedko, Iryna O.; Hottenga, Jouke-Jan; van't Ent, Dennis; Boomsma, Dorret I.; de Geus, Eco J. C.] Vrije Univ Amsterdam, Biol Psychol, NL-1081 BT Amsterdam, Netherlands. [den Braber, Anouk; Fedko, Iryna O.; Hottenga, Jouke-Jan; van't Ent, Dennis; Boomsma, Dorret I.; de Geus, Eco J. C.] Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 BT Amsterdam, Netherlands. [den Braber, Anouk; Fedko, Iryna O.; Hottenga, Jouke-Jan; van't Ent, Dennis; Boomsma, Dorret I.; de Geus, Eco J. C.] Vrije Univ Amsterdam Med Ctr, NL-1081 BT Amsterdam, Netherlands. [Giddaluru, Sudheer; Steen, Vidar M.; Le Hellard, Stephanie] Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5021 Bergen, Norway. [Giddaluru, Sudheer; Steen, Vidar M.; Le Hellard, Stephanie] Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, N-5021 Bergen, Norway. [Grimm, Oliver; Rietschel, Marcella; Meyer-Lindenberg, Andreas] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, D-68159 Mannheim, Germany. [Guadalupe, Tulio; Fisher, Simon E.; Francks, Clyde] Max Planck Inst Psycholinguist, Language & Genet Dept, NL-6525 XD Nijmegen, Netherlands. [Guadalupe, Tulio] Int Max Planck Res Sch Language, NL-6525 XD Nijmegen, Netherlands. [Hass, Johanna; Ehrlich, Stefan; Walton, Esther] Tech Univ Dresden, Fac Med, Dept Child & Adolescent Psychiat, D-01307 Dresden, Germany. [Woldehawariat, Girma; Nugent, Allison C.; Liu, Xinmin; McMahon, Francis J.; Drevets, Wayne C.; Cannon, Dara M.] NIMH, Human Genet Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Woldehawariat, Girma; Nugent, Allison C.; Liu, Xinmin; McMahon, Francis J.; Drevets, Wayne C.; Cannon, Dara M.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Holmes, Avram J.] Yale Univ, Dept Psychol, New Haven, CT 06511 USA. [Holmes, Avram J.; Lee, Phil H.; Ehrlich, Stefan; Buckner, Randy L.; Gollub, Randy L.; Roffman, Joshua L.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Shen, Li; Saykin, Andrew J.] Indiana Univ Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN 46202 USA. [Kim, Sungeun; Nho, Kwangsik; Shen, Li] Indiana Univ Sch Med, Ctr Computat Biol & Bloinformat, Indianapolis, IN 46202 USA. [Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Shen, Li; Foroud, Tatiana M.; Saykin, Andrew J.] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA. [Kraemer, Bernd; Keil, Maria; Gruber, Oliver] Univ Med Ctr, Dept Psychiat & Psychotherapy, Ctr Translat Res Syst Neurosci & Psychiat, D-37075 Gottingen, Germany. [Lee, Phil H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02115 USA. [Lee, Phil H.; Smoller, Jordan W.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA 02141 USA. [Lee, Phil H.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Loohuis, Loes M. Olde; Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. [Luciano, Michelle; Liewald, David C. M.; Lopez, Lorna M.; Royle, Natalie A.; Bastin, Mark E.; Deary, Ian J.; McIntosh, Andrew M.; Wardlaw, Joanna M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland. [Mattheisen, Manuel] Aarhus Univ Hosp, Dept Biomed, DK-8000 Aarhus, Denmark. [Mattheisen, Manuel] iPSYCH, Ludbeck Fdn Initiat Integrat Psychiat Res, DK-8000 Aarhus, Denmark. [Mattheisen, Manuel] iPSYCH, Ludbeck Fdn Initiat Integrat Psychiat Res, DK-8000 Copenhagen, Denmark. [Mattheisen, Manuel] Aarhus Univ, iSEQ, Ctr Integrated Sequencing, DK-8000 Aarhus, Denmark. [Milaneschi, Yuri; Schmaal, Lianne; Veltman, Dick J.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam, Med Ctr GGZ InGeest, Dept Psychiat, NL-1081 HL Amsterdam, Netherlands. [Papmeyer, Martina; Sprooten, Emma; Lawrie, Stephen M.; Sussmann, Jessika E.; McIntosh, Andrew M.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland. [Ramasamy, Adaikalavan; Ryten, Mina; Weale, Michael E.] Kings Coll London, Dept Med & Mol Genet, London SE1 9RT, England. [Ramasamy, Adaikalavan; Trabzuni, Daniah; Gibbs, J. Raphael; Guelfi, Sebastian; Hernandez, Dena G.; Hardy, John; Ryten, Mina] UCL, Inst Neurol, Reta Lila Weston Inst, London WC1N 3BG, England. [Ramasamy, Adaikalavan; Trabzuni, Daniah; Gibbs, J. Raphael; Guelfi, Sebastian; Hernandez, Dena G.; Hardy, John; Ryten, Mina] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Roiz-Santianez, Roberto; Crespo-Facorro, Benedicto] Univ Cantabria, IDIVAL, Sch Med, Dept Psychiat,Univ Hosp Marques de Valdecilla, Santander 39008, Spain. [Roiz-Santianez, Roberto; Perez-Iglesias, Rocio; Crespo-Facorro, Benedicto] Cibersam Ctr Invest Biomed Red Salud Mental, Madrid 28029, Spain. [Rose, Emma J.; Needham, Margaret; Corvin, Aiden; Morris, Derek W.; Donohoe, Gary] Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dublin 2, Ireland. [Rose, Emma J.; Needham, Margaret; Corvin, Aiden; Morris, Derek W.; Donohoe, Gary] Univ Dublin Trinity Coll, Dept Psychiat, Trinity Coll Inst Psychiat, Dublin 2, Ireland. [Rose, Emma J.] Univ Maryland, Sch Med, Dept Psychiat, Translat Res Advers Neurodev & Subst Abuse C TRAN, Columbia, MD 21045 USA. [Salami, Alireza] Karolinska Inst, Aging Res Ctr, S-11330 Stockholm, Sweden. [Salami, Alireza] Stockholm Univ, S-11330 Stockholm, Sweden. [Saemann, Philipp G.; Hoehn, David; Puetz, Benno; Wolf, Christiane; Czisch, Michael; Holsboer, Florian; Mueller-Myhsok, Bertram; Gruber, Oliver] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Schork, Andrew J.] Univ Calif San Diego, Dept Neurosci, Multimodal Imaging Lab, La Jolla, CA 92093 USA. [Schork, Andrew J.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92161 USA. [Strike, Lachlan T.; de Zubicaray, Greig I.; Wright, Margaret J.] Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. [Strike, Lachlan T.; McMahon, Katie L.] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld 4072, Australia. [Teumer, Alexander; Hoffman, Wolfgang; Voelzke, Henry] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany. [Walters, Raymond K.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Walters, Raymond K.] Broad Inst Harvard & MIT, Med & Populat Genet Program, Boston, MA 02142 USA. [Westlye, Lars T.; Reinvang, Ivar; Espeseth, Thomas] Univ Oslo, Dept Psychol, N-0373 Oslo, Norway. [Winkler, Anderson M.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford Ctr Funct MRI Brain, Oxford OX3 9DU, England. [Winkler, Anderson M.; McKay, D. Reese; Sprooten, Emma; Glahn, David C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Alhusaini, Saud] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. [Alhusaini, Saud; Cavalleri, Gianpiero L.; Delanty, Norman] Royal Coll Surg, Mol & Cellular Therapeut, Dublin 2, Ireland. [Ehrlich, Stefan; Gollub, Randy L.; Ebling, Maritza; Fischl, Bruce; Greve, Douglas; Vinke, Louis N.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Hartberg, Cecilie B.; Agartz, Ingrid] Diakonhjemmet Hosp, Dept Psychiat Res & Dev, N-0319 Oslo, Norway. [Kasperaviciute, Dalia; Sisodiya, Sanjay M.] UCL, Inst Neurol, London, England. [Kasperaviciute, Dalia; Sisodiya, Sanjay M.] Epilepsy Soc, London WC1N 3BG, England. [Kasperaviciute, Dalia] Univ London Imperial Coll Sci Technol & Med, Dept Med, London W12 0NN, England. [Matarin, Mar] UCL, Inst Neurol, Dept Clin & Expt Epilepsy, London WC1N 3BG, England. [McKay, D. Reese; Sprooten, Emma; Glahn, David C.] Hartford Hosp, Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT 06106 USA. [Trabzuni, Daniah] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [Almasy, Laura; Carless, Melanie A.; Curran, Joanne E.; Duggirala, Ravi; Dyer, Thomas D.; Goering, Harald H. H.; Kent, Jack W., Jr.; Blangero, John] Texas Biomed Res Inst, San Antonio, TX 78245 USA. [Almasy, Laura; Dyer, Thomas D.; Fox, Peter T.; Blangero, John] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Ames, David] Royal Melbourne Hosp, Natl Ageing Res Inst, Melbourne, Vic 3052, Australia. [Ames, David; Gibbs, J. Raphael; Hernandez, Dena G.] Univ Melbourne, Acad Unit Psychiat Old Age, Melbourne, Vic 3101, Australia. [Arepalli, Sampath; Dillman, Allissa; Nalls, Michael A.; Traynor, Bryan J.; Cookson, Mark R.; Singleton, Andrew] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. [Bastin, Mark E.; Valdes Hernandez, Maria C.; Wardlaw, Joanna M.] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH4 2XU, Midlothian, Scotland. [Bulayeva, Kazima B.] Russian Acad Sci, IN Vavilov Inst Gen Genet, Moscow 119333, Russia. [Cichon, Sven] Univ Basel, Dept Biomed, Div Med Genet, CH-4055 Basel, Switzerland. [Cichon, Sven; Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany. [Cichon, Sven; Muehleisen, Thomas W.] Forschungszentrum Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany. [Cichon, Sven; Heinz, Andreas; Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Dept Genom, D-53127 Bonn, Germany. [Cichon, Sven; Heinz, Andreas; Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, D-53127 Bonn, Germany. [Erk, Susanne; Mahnke, Sebastian; Romanczuk-Seiferth, Nina; Walter, Henrik; Saykin, Andrew J.] Charite, CCM, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 20892 USA. [Foroud, Tatiana M.; Olvera, Rene L.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Fukunaga, Masaki] Osaka Univ, Immunol Frontier Res Ctr, Biofunct Imaging, Osaka 5650871, Japan. [Green, Robert C.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Green, Robert C.; Gollub, Randy L.; Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hartman, Catharina A.; Hoekstra, Pieter J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 GZ Groningen, Netherlands. [Hegenscheid, Katrin; Hosten, Norbert] Univ Med Greifswald, Inst Diagnost Radiolou & Neuroradiol, D-17475 Greifswald, Germany. [Heslenfeld, Dirk J.] Vrije Univ Amsterdam, Dept Cognit, NL-1081 BT Amsterdam, Netherlands. [Heslenfeld, Dirk J.] Vrije Univ Amsterdam, Dept Clin Neuropsychol, NL-1081 BT Amsterdam, Netherlands. [Homuth, Georg] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17489 Greifswald, Germany. [Ikeda, Masashi] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 4701192, Japan. [Jack, Clifford R., Jr.] Mayo Clin, Radiol, Rochester, MN 55905 USA. [Jenkinson, Mark; Nichols, Thomas E.] Univ Oxford, FMRIB Ctr, Oxford OX3 9DU, England. [Johnson, Robert; Zielke, Ronald H.] Univ Maryland, Sch Med, NICHD Brain & Tissue Bank Dev Disorders, Baltimore, MD 21201 USA. [Kanai, Ryota] Univ Sussex, Sch Psychol, Brighton BN1 9QH, E Sussex, England. [Kanai, Ryota] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. [Kochunov, Peter] Univ Maryland, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA. [Kwok, John B.; Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW 2031, Australia. [Kwok, John B.; Schofield, Peter R.] UNSW, Sch Med Sci, Sydney, NSW 2052, Australia. [Liu, Xinmin] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Longo, Dan L.] NIA, Lymphocyte Cell Biol Unit, Genet Lab, NIH, Baltimore, MD 21224 USA. [Meisenzah, Eva; Rujescu, Dan] Univ Munich, Dept Psychiat, D-80336 Munich, Germany. [Nichols, Thomas E.] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England. [Nichols, Thomas E.] Univ Warwick, WMG, Coventry CV4 7AL, W Midlands, England. [Ohi, Kazutaka] Osaka Univ, Dept Psychiat, Grad Sch Med, Osaka 5650871, Japan. [Perez-Iglesias, Rocio] Kings Coll London, Inst Psychiat, London SE5 8AF, England. [Pike, G. Bruce] Univ Calgary, Dept Neurol, Calgary, AB T2N 2T9, Canada. [Pike, G. Bruce] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 2T9, Canada. [Potkin, Steven G.] Univ Calif Irvine, Psychiat & Human Behav, Irvine, CA 92617 USA. [Rosen, Glenn D.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Rosen, Glenn D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schnell, Knut] Heidelberg Univ Hosp, Dept Gen Psychiat, D-69115 Heidelberg, Germany. [Smith, Colin] Univ Edinburgh, MRC, Sudden Death Brain Bank Project, Dept Neuropathol, Edinburgh EH8 9AG, Midlothian, Scotland. [Toga, Arthur W.] Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Lab Neuro Imaging, Los Angeles, CA 90033 USA. [Troncoso, Juan] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21287 USA. [Turner, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. [Turner, Jessica A.] Georgia State Univ, Neurosci Inst, Atlanta, GA 30302 USA. [van der Brug, Marcel] Genentech Inc, San Francisco, CA 94080 USA. [van der Wee, Nic J. A.] Leiden Univ, Med Ctr, Psychiat, NL-2333 ZA Leiden, Netherlands. [van der Wee, Nic J. A.] Leiden Univ, Med Ctr, Leiden Inst Brain & Cogniton, NL-2333 ZA Leiden, Netherlands. [van Tol, Marie-Jose] Univ Groningen, Univ Med Ctr Groningen, Neuroimaging Ctr, NL-9713 AW Groningen, Netherlands. [Wassink, Thomas H.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Westman, Eric] Karolinska Inst, Dept Neurobiol Care Sci & Soc, SE-14183 Stockholm, Sweden. [Zonderman, Alan B.] NIA, Behav Epidemiol Sect, Intramural Res Program, Bethesda, MD 20892 USA. [Ashbrook, David G.; Hager, Reinmar] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. [Lu, Lu; Williams, Robert W.] Univ Tennessee, Hlth Sci Ctr, Ctr Integrat & Translat Genom, Memphis, TN 38163 USA. [Lu, Lu; Williams, Robert W.] Univ Tennessee, Hlth Sci Ctr, Dept Genet Genom & Informat, Memphis, TN 38163 USA. [Lu, Lu] Nantong Univ, Coll Med, Jiangsu Prov Key Lab Inflammat & Mol Drug Target, Nantong 226001, Peoples R China. [Morris, Derek W.; Donohoe, Gary] Natl Univ Ireland Galway, Sch Psychol, Cognit Genet & Therapy Grp, Galway, Ireland. [Morris, Derek W.; Donohoe, Gary] Natl Univ Ireland Galway, Discipline Biochem, Galway, Ireland. [Brunner, Han G.] Maastricht Univ, Med Ctr, Dept Clin Genet, NL-6200 MD Maastricht, Netherlands. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Dept Psychol, Boston, MA 02138 USA. [Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Karakter Child & Adolescent Psychiat, NL-6500 HB Nijmegen, Netherlands. [Calhoun, Vince D.] Mind Res Network, Albuquerque, NM 87106 USA. [Calhoun, Vince D.] LBERI, Albuquerque, NM 87106 USA. [Calhoun, Vince D.] Univ New Mexico, Dept ECE, Albuquerque, NM 87131 USA. [Dale, Anders M.] Univ Calif San Diego, Ctr Translat Imaging & Personalized Med, La Jolla, CA 92093 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92093 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92093 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92093 USA. [Davies, Gareth E.] Avera Inst Human Genet, Sioux Falls, SD 57108 USA. [Delanty, Norman] Beaumont Hosp, Neurol Div, Dublin 9, Ireland. [Depondt, Chantal; Pandolfo, Massimo] Univ Libre Bruxelles, Hop Erasme, Dept Neurol, B-1070 Brussels, Belgium. [Djurovic, Srdjan] Oslo Univ Hosp, Dept Med Genet, N-0450 Oslo, Norway. [Drevets, Wayne C.] Johnson & Johnson, Janssen Res & Dev, Titusville, NJ 08560 USA. [Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Mueller-Myhsok, Bertram] Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany. [Mueller-Myhsok, Bertram] Univ Liverpool, Inst Translat Med, Liverpool L69 3BX, Merseyside, England. [Nauck, Matthias] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany. [Weiner, Michael W.] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [White, Tonya] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, NL-3000 CB Rotterdam, Netherlands. [White, Tonya; Adams, Hieab H. H.; Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Radiol, NL-3015 CN Rotterdam, Netherlands. [Agartz, Ingrid; Joensson, Erik G.] Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, SE-17176 Stockholm, Sweden. [Cannon, Dara M.; McDonald, Colm] Natl Univ Ireland Galway, Coll Med Nursing & Hlth Sci, Clin Neuroimaging Lab, Galway, Ireland. [Grabe, Hans J.] HELIOS Hosp, Dept Psychiat & Psychotherapy, D-18435 Stralsund, Germany. [Hashimoto, Ryota] Osaka Univ, United Grad Sch Child Dev, Mol Res Ctr Childrens Mental Dev, Osaka 5650871, Japan. [Kloszewska, Iwona] Med Univ Lodz, PL-90419 Lodz, Poland. [Lovestone, Simon] Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England. [Lovestone, Simon] Kings Coll London, NIHR Dementia Biomed Res Unit, London SE5 8AF, England. [Mattay, Venkata S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Mecocci, Patrizia] Univ Perugia, Dept Med, Sect Gerontol & Geriat, I-06156 Perugia, Italy. [Paus, Tomas] Univ Toronto, Rotman Res Inst, Toronto, ON M6A 2E1, Canada. [Paus, Tomas] Univ Toronto, Dept Psychol, Toronto, ON M5T 1R8, Canada. [Paus, Tomas] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada. [Pausova, Zdenka] Univ Toronto, Dept Physiol, Toronto, ON M5S 3E2, Canada. [Pausova, Zdenka] Univ Toronto, Dept Nutr Sci, Toronto, ON M5S 3E2, Canada. [Sachdev, Perminder S.] Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW 2031, Australia. [Simmons, Andy] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London SE5 8AF, England. [Simmons, Andy] Kings Coll London, Biomed Res Ctr Mental Hlth, London SE5 8AF, England. [Simmons, Andy] Kings Coll London, Biomed Res Unit Dementia, London SE5 8AF, England. [Soininen, Hilkka] Univ Eastern Finland, Inst Clin Med, Neurol, FI-70211 Kuopio, Finland. [Soininen, Hilkka] Kuopio Univ Hosp, Neuroctr Neurol, FI-70211 Kuopio, Finland. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA. [Adams, Hieab H. H.; van der Lee, Sven J.; van Duijn, Cornelia M.; Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands. [Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA. [Seiler, Stephan; Schmidt, Reinhold] Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, A-8010 Graz, Austria. [Chauhan, Ganesh] Univ Bordeaux, INSERM, U897, F-33076 Bordeaux, France. [Satizabal, Claudia L.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Satizabal, Claudia L.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Becker, James T.; Seshadri, Sudha] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. [Becker, James T.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Becker, James T.] Univ Pittsburgh, Dept Psychol, Dietrich Sch Arts & Sci, Pittsburgh, PA 15260 USA. [Yanek, Lisa] Johns Hopkins Sch Med, Gen Internal Med, Baltimore, MD 21205 USA. [Ebling, Maritza; Fischl, Bruce; Greve, Douglas; Vinke, Louis N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fischl, Bruce] MIT, Comp Sci & Al Lab, Boston, MA 02141 USA. [Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Schmidt, Helena] Med Univ, Inst Mol Biol & Biochem, A-8010 Graz, Austria. [Nyquist, Paul] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21205 USA. [Xue, Luting] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Mazoyer, Bernard] CEA, Grp Imagerie Neurofonct, UMR5296, CNRS, F-33076 Bordeaux, France. [Mazoyer, Bernard] Univ Bordeaux, F-33076 Bordeaux, France. [Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Gudnason, Vilmundur] Univ Iceland, Fac Med, Iceland Heart Assoc, IS-101 Reykjavik, Iceland. RP Thompson, PM (reprint author), Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Imaging Genet Ctr, Los Angeles, CA 90292 USA. EM pthomp@usc.edu; Sarah.Medland@qimrberghofer.edu.au RI Karen, Mather/O-9795-2016; Winkler, Anderson/P-7773-2016; Luciano, Michelle/F-7277-2010; Tzourio, christophe/B-4015-2009; Meyer-Lindenberg, Andreas/H-1076-2011; Cuellar Partida, Gabriel/C-6686-2017; Poustka, Luise/D-9299-2017; Montgomery, Grant/B-7148-2008; Makkinje, Remco/Q-2406-2015; Mattheisen, Manuel/B-4949-2012; Hager, Reinmar/F-8659-2012; Hansell, Narelle/A-4553-2016; Wright, Margaret/A-4560-2016; Hakobjan, Marina/A-5594-2016; Arias Vasquez, Alejandro/E-4762-2012; Kowall, Neil/G-6364-2012; Weale, Michael/F-2587-2010; McMahon, Katie/C-6440-2009; Matarin, Mar/F-1771-2016; Melle, Ingrid /B-4858-2011; Walter, Henrik/O-2612-2013; Pike, Bruce/K-5562-2014; Fernandez, Guillen/B-3771-2009; Franke, Barbara/D-4836-2009; Zwiers, Marcel/D-2968-2009; Gudnason, Vilmundur/K-6885-2015; Singleton, Andrew/C-3010-2009; Brunner, Han/C-9928-2013; Arias Vasquez, A./L-4175-2015; Williams, Steve/D-6979-2011; Bokhoven, J.H.L.M./H-8015-2014; Cavalleri, Gianpiero/A-6632-2010; McDonald, Colm/C-1430-2009; Westman, Eric/H-5771-2011; Fisher, Simon/E-9130-2012; Hardy, John/C-2451-2009; Mostert, Jeanette/E-4745-2015; Bralten, Janita/D-4647-2011; Hoogman, Martine/G-8958-2015; Roiz-Santianez, Roberto/H-6462-2015; Lubbe, Steven/L-8261-2013; Simmons, Andrew/B-8848-2008; de Zubicaray, Greig/B-1763-2008; Jack, Clifford/F-2508-2010; OI Desrivieres, Sylvane/0000-0002-9120-7060; Preda, Adrian /0000-0003-3373-2438; Ashbrook, David/0000-0002-7397-8910; Boks, Marco/0000-0001-6163-7484; Satizabal, Claudia/0000-0002-1115-4430; Westman, Eric/0000-0002-3115-2977; Cavalleri, Gianpiero/0000-0002-9802-0506; Jonsson, Erik/0000-0001-8368-6332; Brown, Andrew/0000-0002-8087-3033; Nothen, Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; Sachdev, Perminder/0000-0002-9595-3220; McMahon, Francis/0000-0002-9469-305X; Jenkinson, Mark/0000-0001-6043-0166; Seshadri, Sudha/0000-0001-6135-2622; Corvin, Aiden/0000-0001-6717-4089; Walton, Esther/0000-0002-0935-2200; Nyberg, Lars/0000-0002-3367-1746; Delaney, Norman/0000-0002-3953-9842; Romanczuk-Seiferth, Nina/0000-0002-6931-269X; Whelan, Christopher/0000-0003-0308-5583; Nugent, Allison/0000-0003-2569-2480; Karen, Mather/0000-0003-4143-8941; Winkler, Anderson/0000-0002-4169-9781; Luciano, Michelle/0000-0003-0935-7682; Tzourio, christophe/0000-0002-6517-2984; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Cuellar Partida, Gabriel/0000-0001-7648-4097; Ehrlich, Stefan/0000-0003-2132-4445; Nees, Frauke/0000-0002-7796-8234; Montgomery, Grant/0000-0002-4140-8139; Mattheisen, Manuel/0000-0002-8442-493X; Hansell, Narelle/0000-0002-8229-9741; Wright, Margaret/0000-0001-7133-4970; Arias Vasquez, Alejandro/0000-0002-4786-0169; Kowall, Neil/0000-0002-6624-0213; Weale, Michael/0000-0003-4593-1186; McMahon, Katie/0000-0002-6357-615X; Matarin, Mar/0000-0002-4717-5735; Melle, Ingrid /0000-0002-9783-548X; Pike, Bruce/0000-0001-8924-683X; Fernandez, Guillen/0000-0002-5522-0604; Franke, Barbara/0000-0003-4375-6572; Zwiers, Marcel/0000-0001-5483-2935; Gudnason, Vilmundur/0000-0001-5696-0084; Williams, Steve/0000-0003-4299-1941; Fisher, Simon/0000-0002-3132-1996; Mostert, Jeanette/0000-0002-0033-1622; Hoogman, Martine/0000-0002-1261-7628; Roiz-Santianez, Roberto/0000-0002-5176-2983; Simmons, Andrew/0000-0003-2306-5811; de Zubicaray, Greig/0000-0003-4506-0579; Jack, Clifford/0000-0001-7916-622X; de Geus, Eco/0000-0001-6022-2666; Kanai, Ryota/0000-0002-0186-2687; McIntosh, Andrew/0000-0002-0198-4588; Flor, Herta/0000-0003-4809-5398; Shen, Li/0000-0002-5443-0503; Zonderman, Alan B/0000-0002-6523-4778; Vaidya, Dhananjay/0000-0002-7164-1601; Beiser, Alexa/0000-0001-8551-7778; Medland, Sarah/0000-0003-1382-380X; Westlye, Lars T./0000-0001-8644-956X; Williams, Robert/0000-0001-8924-4447 FU Biotechnology and Biological Sciences Research Council [BB/F019394/1]; Chief Scientist Office [ETM/84]; Medical Research Council [G0700704, G0701120, G0802462, G0900908, G1001245, MR/K026992/1, MR/L016400/1]; NCATS NIH HHS [TL1 TR000096, UL1 TR001108, UL1 TR001120]; NIA NIH HHS [P50 AG005133, P50 AG005134, P50 AG005146, R01 AG033193, R01 AG040060, RF1 AG041915, U01 AG049505, U24 AG021886]; NIBIB NIH HHS [P41 EB015922, R01 EB005846, R01 EB015611, U54 EB020403]; NIMH NIH HHS [K01 MH099232, K99 MH101367]; NINDS NIH HHS [R01 NS017950, T32 NS048004]; NLM NIH HHS [K99 LM011384, R00 LM011384]; Wellcome Trust [100309, 104036] NR 57 TC 108 Z9 109 U1 25 U2 123 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 9 PY 2015 VL 520 IS 7546 BP 224 EP U216 DI 10.1038/nature14101 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3NA UT WOS:000352454600040 PM 25607358 ER PT J AU Fillmore, CM Xu, CX Desai, PT Berry, JM Rowbotham, SP Lin, YJ Zhang, HK Marquez, VE Hammerman, PS Wong, KK Kim, CF AF Fillmore, Christine M. Xu, Chunxiao Desai, Pooja T. Berry, Joanne M. Rowbotham, Samuel P. Lin, Yi-Jang Zhang, Haikuo Marquez, Victor E. Hammerman, Peter S. Wong, Kwok-Kin Kim, Carla F. TI EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors SO NATURE LA English DT Article ID GENE-EXPRESSION PROFILES; CANCER CELL-LINES; DRUG-COMBINATION; MICROARRAY DATA; ADENOCARCINOMA; MUTATIONS; COMPLEXES; POLYCOMB; SURVIVAL; SWI/SNF AB Non-small-cell lung cancer is the leading cause of cancer-related death worldwide(1). Chemotherapies such as the topoisomerase II (TopoII) inhibitor etoposide effectively reduce disease in a minority of patients with this cancer(2,3); therefore, alternative drug targets, including epigenetic enzymes, are under consideration for therapeutic intervention(4). A promising potential epigenetic target is the methyltransferase EZH2, which in the context of the polycomb repressive complex 2 (PRC2) is well known to tri-methylate histone H3 at lysine 27 (H3K27me3) and elicit gene silencing(5). Here we demonstrate that EZH2 inhibition has differential effects on the TopoII inhibitor response of non-small-cell lung cancers in vitro and in vivo. EGFR and BRG1 mutations are genetic biomarkers that predict enhanced sensitivity to TopoII inhibitor in response to EZH2 inhibition. BRG1 loss-of-function mutant tumours respond to EZH2 inhibition with increased S phase, anaphase bridging, apoptosis and TopoII inhibitor sensitivity. Conversely, EGFR and BRG1 wild-type tumours upregulate BRG1 in response to EZH2 inhibition and ultimately become more resistant to TopoII inhibitor. EGFR gain-of-function mutant tumours are also sensitive to dual EZH2 inhibition and TopoII inhibitor, because of genetic antagonism between EGFR and BRG1. These findings suggest an opportunity for precision medicine in the genetically complex disease of non-small-cell lung cancer. C1 [Fillmore, Christine M.; Desai, Pooja T.; Berry, Joanne M.; Rowbotham, Samuel P.; Kim, Carla F.] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Fillmore, Christine M.; Rowbotham, Samuel P.; Lin, Yi-Jang; Kim, Carla F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Fillmore, Christine M.; Rowbotham, Samuel P.; Kim, Carla F.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Xu, Chunxiao; Zhang, Haikuo; Hammerman, Peter S.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xu, Chunxiao; Zhang, Haikuo; Wong, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Marquez, Victor E.] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA. RP Kim, CF (reprint author), Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. EM carla.kim@childrens.harvard.edu FU Ladies Auxiliary to the Veterans of Foreign Wars; American Cancer Society [PF-12-151-01-DMC]; Uniting Against Lung Cancer Young Investigator Award; Boston University Undergraduate Research Opportunities Program; American Cancer Society Research Scholar Grant [RSG-08-082-01-MGO]; V Foundation for Cancer Research; Basil O'Conner March of Dimes Starter Award; Harvard Stem Cell Institute; Lung Cancer Research Foundation; National Institutes of Health (NIH) [CA122794, CA140594, CA163896, CA166480, CA154303, CA120964]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; NIH [K08 CA163677]; [RO1 HL090136]; [U01 HL100402 RFA-HL-09-004] FX We thank the Kim laboratory, F. Luo, P. Louis, K. Harrington, X. Wang and J. Brainson for technical assistance and discussions, and J. Crabtree, D. Hargreaves, C. Kadoch, L. Zon, K. Cichowski, M. Enos, S. Orkin, A. Gutierrez and C. Roberts for discussions. This work was supported in part by the Ladies Auxiliary to the Veterans of Foreign Wars, PF-12-151-01-DMC from the American Cancer Society, and the Uniting Against Lung Cancer Young Investigator Award supported by Meryl Bralower (C. M. F.), Boston University Undergraduate Research Opportunities Program (P.T.D.), RO1 HL090136, U01 HL100402 RFA-HL-09-004, American Cancer Society Research Scholar Grant RSG-08-082-01-MGO, the V Foundation for Cancer Research, a Basil O'Conner March of Dimes Starter Award, the Harvard Stem Cell Institute, and the Lung Cancer Research Foundation (C. F. K.), the National Institutes of Health (NIH) grants CA122794, CA140594, CA163896, CA166480, CA154303 and CA120964 (K.K.W.), the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (V.E.M.), and the NIH grant K08 CA163677 (P.S.H.). NR 51 TC 55 Z9 57 U1 13 U2 57 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 9 PY 2015 VL 520 IS 7546 BP 239 EP U261 DI 10.1038/nature14122 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3NA UT WOS:000352454600043 PM 25629630 ER PT J AU Grover, S Balogun, OD Yamoah, K Groen, R Shah, M Rodin, D Martei, Y Olson, AC Slone, JS Shulman, LN Coleman, CN Hahn, SM AF Grover, Surbhi Balogun, Onyinye D. Yamoah, Kosj Groen, Reinou Shah, Mira Rodin, Danielle Martei, Yehoda Olson, Adam C. Slone, Jeremy S. Shulman, Lawrence N. Coleman, C. Norman Hahn, Stephen M. TI Training global oncologists: addressing the global cancer control problem SO FRONTIERS IN ONCOLOGY LA English DT Editorial Material DE global health; oncology training; radiation oncology; surgical oncology; medical oncology ID MIDDLE-INCOME-COUNTRIES; RADIATION ONCOLOGY; BREAST-CANCER; HEALTH; RESIDENTS; RADIOTHERAPY; EXPERIENCES; THERAPY; PROGRAM; WOMEN C1 [Grover, Surbhi; Hahn, Stephen M.] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Balogun, Onyinye D.] NYU, Perlmutter Canc Ctr, Dept Radiat Oncol, New York, NY USA. [Yamoah, Kosj] Thomas Jefferson Univ, Dept Radiat Oncol, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Groen, Reinou] Johns Hopkins Univ Hosp, Dept Gynecol & Obstet, Baltimore, MD 21287 USA. [Shah, Mira] Henry Ford Hlth Syst, Dept Radiat Oncol, Detroit, MI USA. [Rodin, Danielle] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada. [Martei, Yehoda] Hosp Univ Penn, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Olson, Adam C.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Slone, Jeremy S.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Shulman, Lawrence N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Coleman, C. Norman] NIH, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Coleman, C. Norman] Int Canc Expert Corps, Chevy Chase, MD USA. RP Grover, S (reprint author), Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. EM surbhi.grover@uphs.upenn.edu NR 33 TC 11 Z9 11 U1 0 U2 0 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2234-943X J9 FRONT ONCOL JI Front. Oncol. PD APR 8 PY 2015 VL 5 AR 80 DI 10.3389/fonc.2015.00080 PG 4 WC Oncology SC Oncology GA CO3UU UT WOS:000359086800001 PM 25905040 ER PT J AU Yepes, AJJ Plaza, L Carrillo-de-Albornoz, J Mork, JG Aronson, AR AF Yepes, Antonio Jose Jimeno Plaza, Laura Carrillo-de-Albornoz, Jorge Mork, James G. Aronson, Alan R. TI Feature engineering for MEDLINE citation categorization with MeSH SO BMC BIOINFORMATICS LA English DT Article DE Text categorization; Feature engineering; Biomedical literature; MeSH indexing ID TEXT CATEGORIZATION; SENTENCE SELECTION; BIOMEDICAL TEXT; UMLS; ABSTRACTS; RULES AB Background: Research in biomedical text categorization has mostly used the bag-of-words representation. Other more sophisticated representations of text based on syntactic, semantic and argumentative properties have been less studied. In this paper, we evaluate the impact of different text representations of biomedical texts as features for reproducing the MeSH annotations of some of the most frequent MeSH headings. In addition to unigrams and bigrams, these features include noun phrases, citation meta-data, citation structure, and semantic annotation of the citations. Results: Traditional features like unigrams and bigrams exhibit strong performance compared to other feature sets. Little or no improvement is obtained when using meta-data or citation structure. Noun phrases are too sparse and thus have lower performance compared to more traditional features. Conceptual annotation of the texts by MetaMap shows similar performance compared to unigrams, but adding concepts from the UMLS taxonomy does not improve the performance of using only mapped concepts. The combination of all the features performs largely better than any individual feature set considered. In addition, this combination improves the performance of a state-of-the-art MeSH indexer. Concerning the machine learning algorithms, we find that those that are more resilient to class imbalance largely obtain better performance. Conclusions: We conclude that even though traditional features such as unigrams and bigrams have strong performance compared to other features, it is possible to combine them to effectively improve the performance of the bag-of-words representation. We have also found that the combination of the learning algorithm and feature sets has an influence in the overall performance of the system. Moreover, using learning algorithms resilient to class imbalance largely improves performance. However, when using a large set of features, consideration needs to be taken with algorithms due to the risk of over-fitting. Specific combinations of learning algorithms and features for individual MeSH headings could further increase the performance of an indexing system. C1 [Yepes, Antonio Jose Jimeno] Univ Melbourne, Dept Comp & Informat Syst, Parkville, Vic 3010, Australia. [Yepes, Antonio Jose Jimeno; Mork, James G.; Aronson, Alan R.] Natl Lib Med, Bethesda, MD 20894 USA. [Plaza, Laura; Carrillo-de-Albornoz, Jorge] UNED NLP & IR Grp, Madrid 28040, Spain. RP Yepes, AJJ (reprint author), Univ Melbourne, Dept Comp & Informat Syst, Parkville, Vic 3010, Australia. EM antonio.jimeno@gmail.com OI Jimeno Yepes, Antonio Jose/0000-0002-6581-094X FU NIH; National Library of Medicine; Spanish Ministry of Science and Innovation [TIN2010-21128-C02-01, TIN2013-47090-C3-1-P]; University of Melbourne FX In carrying out this research, we have received funding from the University of Melbourne. This work was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. This research was partially supported by the Spanish Ministry of Science and Innovation (Holopedia Project, TIN2010-21128-C02-01, VoxPopuli Project, TIN2013-47090-C3-1-P). NR 50 TC 2 Z9 2 U1 0 U2 1 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 APR 8 PY 2015 VL 16 AR 113 DI 10.1186/s12859-015-0539-7 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA CG4MO UT WOS:000353260300001 ER PT J AU McMahon, DBT Russ, BE Elnaiem, HD Kurnikova, AI Leopold, DA AF McMahon, David B. T. Russ, Brian E. Elnaiem, Heba D. Kurnikova, Anastasia I. Leopold, David A. TI Single-Unit Activity during Natural Vision: Diversity, Consistency, and Spatial Sensitivity among AF Face Patch Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE eigenneurons; fMRI; macaque; movies; natural vision; single units ID MONKEY INFEROTEMPORAL CORTEX; SUPERIOR TEMPORAL SULCUS; MACAQUE MONKEY; RHESUS-MONKEY; PARAHIPPOCAMPAL CORTICES; FUNCTIONAL MRI; BODY PARTS; LOBE; RESPONSES; FMRI AB Several visual areas within the STS of the macaque brain respond strongly to faces and other biological stimuli. Determining the principles that govern neural responses in this region has proven challenging, due in part to the inherently complex stimulus domain of dynamic biological stimuli that are not captured by an easily parameterized stimulus set. Here we investigated neural responses in one fMRI-defined face patch in the anterior fundus (AF) of the STS while macaques freely view complex videos rich with natural social content. Longitudinal single-unit recordings allowed for the accumulation of each neuron's responses to repeated video presentations across sessions. We found that individual neurons, while diverse in their response patterns, were consistently and deterministically driven by the video content. We used principal component analysis to compute a family of eigenneurons, which summarized 24% of the shared population activity in the first two components. We found that the most prominent component of AF activity reflected an interaction between visible body region and scene layout. Close-up shots of faces elicited the strongest neural responses, whereas far away shots of faces or close-up shots of hindquarters elicited weak or inhibitory responses. Sensitivity to the apparent proximity of faces was also observed in gamma band local field potential. This category-selective sensitivity to spatial scale, together with the known exchange of anatomical projections of this area with regions involved in visuospatial analysis, suggests that the AF face patch may be specialized in aspects of face perception that pertain to the layout of a social scene. C1 [McMahon, David B. T.; Russ, Brian E.; Elnaiem, Heba D.; Kurnikova, Anastasia I.; Leopold, David A.] NIMH, Lab Neuropsychol, NIH, Bethesda, MD 20892 USA. [McMahon, David B. T.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Leopold, David A.] NEI, Neurophysiol Imaging Facil, NIMH, Bethesda, MD 20892 USA. [Leopold, David A.] NINDS, NIH, Bethesda, MD 20982 USA. RP McMahon, DBT (reprint author), NEI, Sensorimotor Res Lab, Bldg 49,Room 2A5049,49 Convent Dr, Bethesda, MD 20892 USA. EM mcmahond@mail.nih.gov OI Leopold, David/0000-0002-1345-6360 FU Intramural Research Programs of the National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Eye Institute and by National Institutes of Health Grant [EY018028] FX This work was supported by the Intramural Research Programs of the National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and National Eye Institute and by National Institutes of Health Grant EY018028 (to D.B.T.M.). We thank Kadharbatcha S. Saleem for helpful discussions and Hannah Johnson for assistance with data collection. NR 48 TC 7 Z9 7 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 8 PY 2015 VL 35 IS 14 BP 5537 EP 5548 DI 10.1523/JNEUROSCI.3825-14.2015 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CG1SS UT WOS:000353054900009 PM 25855170 ER PT J AU Rubio, FJ Liu, QR Li, X Cruz, FC Leao, RM Warren, BL Kambhampati, S Babin, KR McPherson, KB Cimbro, R Bossert, JM Shaham, Y Hope, BT AF Rubio, F. Javier Liu, Qing-Rong Li, Xuan Cruz, Fabio C. Leao, Rodrigo M. Warren, Brandon L. Kambhampati, Sarita Babin, Klil R. McPherson, Kylie B. Cimbro, Raffaello Bossert, Jennifer M. Shaham, Yavin Hope, Bruce T. TI Context-Induced Reinstatement of Methamphetamine Seeking Is Associated with Unique Molecular Alterations in Fos-Expressing Dorsolateral Striatum Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE extinction; neuroadaptations; neuronal ensembles; renewal; self-administration ID NUCLEUS-ACCUMBENS SHELL; MEDIAL PREFRONTAL CORTEX; DOPAMINE D-1-FAMILY RECEPTORS; EXTINGUISHED ALCOHOL-SEEKING; CUE-INDUCED RELAPSE; COCAINE-SEEKING; DRUG-SEEKING; HEROIN-SEEKING; C-FOS; DORSAL STRIATUM AB Context-induced reinstatement of drug seeking is a well established animal model for assessing the neural mechanisms underlying context-induced drug relapse, a major factor in human drug addiction. Neural activity in striatum has previously been shown to contribute to context-induced reinstatement of heroin, cocaine, and alcohol seeking, but not yet for methamphetamine seeking. In this study, we found that context-induced reinstatement of methamphetamine seeking increased expression of the neural activity marker Fos in dorsal but not ventral striatum. Reversible inactivation of neural activity in dorsolateral but not dorsomedial striatum using the GABA agonists muscimol and baclofen decreased context-induced reinstatement. Based on our previous findings that Fos-expressing neurons play a critical role in conditioned drug effects, we assessed whether context-induced reinstatement was associated with molecular alterations selectively induced within context-activated Fos-expressing neurons. We used fluorescence-activated cell sorting to isolate reinstatement-activated Fos-positive neurons from Fos-negative neurons in dorsal striatum and used quantitative PCR to assess gene expression within these two populations of neurons. Context-induced reinstatement was associated with increased expression of the immediate early genes Fos and FosB and the NMDA receptor subunit gene Grin2a in only Fos-positive neurons. RNAscope in situ hybridization confirmed that Grin2a, as well as Grin2b, expression were increased in only Fos-positive neurons from dorsolateral, but not dorsomedial, striatum. Our results demonstrate an important role of dorsolateral striatum in context-induced reinstatement of methamphetamine seeking and that this reinstatement is associated with unique gene alterations in Fos-expressing neurons. C1 [Rubio, F. Javier; Liu, Qing-Rong; Li, Xuan; Cruz, Fabio C.; Leao, Rodrigo M.; Warren, Brandon L.; Kambhampati, Sarita; Babin, Klil R.; McPherson, Kylie B.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Cimbro, Raffaello] Johns Hopkins Sch Med, Div Rheumatol, Baltimore, MD 21224 USA. RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. EM bhope@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012; Hope, Bruce/A-9223-2010; OI Liu, Qing-Rong/0000-0001-8477-6452; Hope, Bruce/0000-0001-5804-7061; McPherson, Kylie/0000-0002-5196-098X; Cimbro, Raffaello/0000-0002-6251-5160 FU National Institute on Drug Abuse Intramural Research Program, National Institutes of Health; National Institutes of Health; Becas-Chile Scholarship; Universidad de los Andes, Santiago, Chile; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institute of Health [P30AR053503] FX This work was supported by the National Institute on Drug Abuse Intramural Research Program, National Institutes of Health. F.J.R. was supported by an appointment to the National Institute on Drug Abuse Research Participation Program sponsored by the National Institutes of Health and administered by the Oak Ridge Institute for Science and Education, and received additional financial support from Becas-Chile Scholarship managed by the Comision Nacional de Investigacion Cientifica y Tecnologica and the Universidad de los Andes, Santiago, Chile. The Johns Hopkins FACS Core facility was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institute of Health under Award Number P30AR053503. NR 75 TC 12 Z9 13 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 8 PY 2015 VL 35 IS 14 BP 5625 EP 5639 DI 10.1523/JNEUROSCI.4997-14.2015 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CG1SS UT WOS:000353054900016 PM 25855177 ER PT J AU Hage, TA Khaliq, ZM AF Hage, Travis A. Khaliq, Zayd M. TI Tonic Firing Rate Controls Dendritic Ca2+ Signaling and Synaptic Gain in Substantia Nigra Dopamine Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE action potential; backpropagation; calcium imaging; dendrite; dopamine; substantia nigra ID VENTRAL TEGMENTAL AREA; BACKPROPAGATING ACTION-POTENTIALS; PYRAMIDAL NEURONS; MITRAL CELLS; IN-VIVO; GRANULE CELLS; CALCIUM; PROPAGATION; ATTENUATION; CHANNELS AB Substantia nigra dopamine neurons fire tonically resulting in action potential backpropagation and dendritic Ca2+ influx. Using Ca2+ imaging in acute mouse brain slices, we find a surprisingly steep relationship between tonic firing rate and dendritic Ca2+. Increasing the tonic rate from 1 to 6 Hz generated Ca2+ signals up to fivefold greater than predicted by linear summation of single spike-evoked Ca2+-transients. This "Ca2+ supralinearity" was produced largely by depolarization of the interspike voltage leading to activation of subthreshold Ca2+ channels and was present throughout the proximal and distal dendrites. Two-photon glutamate uncaging experiments show somatic depolarization enhances NMDA receptor-mediated Ca2+ signals >400 mu m distal to the soma, due to unusually tight electrotonic coupling of the soma to distal dendrites. Consequently, we find that fast tonic firing intensifies synaptically driven burst firing output in dopamine neurons. These results show that modulation of background firing rate precisely tunes dendritic Ca2+ signaling and provides a simple yet powerful mechanism to dynamically regulate the gain of synaptic input. C1 [Hage, Travis A.; Khaliq, Zayd M.] NINDS, Cellular Neurophysiol Unit, NIH, Bethesda, MD 20892 USA. RP Khaliq, ZM (reprint author), NINDS, Cellular Neurophysiol Unit, NIH, Bethesda, MD 20892 USA. EM Zayd.khaliq@nih.gov FU National Institute of Neurological Disorders and Stroke Intramural Research Program [NS003135] FX This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program Grant NS003135 to Z.M.K. We thank Dr Chris McBain for helpful discussions, and Dr Jeffery Diamond and members of the Khaliq laboratory for helpful comments on the paper. NR 58 TC 9 Z9 9 U1 0 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 8 PY 2015 VL 35 IS 14 BP 5823 EP 5836 DI 10.1523/JNEUROSCI.3904-14.2015 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CG1SS UT WOS:000353054900030 PM 25855191 ER PT J AU Hoggarth, A McLaughlin, AJ Ronellenfitch, K Trenholm, S Vasandani, R Sethuramanujam, S Schwab, D Briggman, KL Awatramani, GB AF Hoggarth, Alex McLaughlin, Amanda J. Ronellenfitch, Kara Trenholm, Stuart Vasandani, Rishi Sethuramanujam, Santhosh Schwab, David Briggman, Kevin L. Awatramani, Gautam B. TI Specific Wiring of Distinct Amacrine Cells in the Directionally Selective Retinal Circuit Permits Independent Coding of Direction and Size SO NEURON LA English DT Article ID RECEPTIVE-FIELD PROPERTIES; GANGLION-CELLS; RABBIT RETINA; MOUSE RETINA; LATERAL INHIBITION; MAMMALIAN RETINA; FUNCTIONAL CIRCUITRY; AXON TERMINALS; INNER RETINA; MECHANISMS AB Local and global forms of inhibition controlling directionally selective ganglion cells (DSGCs) in the mammalian retina are well documented. It is established that local inhibition arising from GABAergic starburst amacrine cells (SACs) strongly contributes to direction selectivity. Here, we demonstrate that increasing ambient illumination leads to the recruitment of GABAergic wide-field amacrine cells (WACs) endowing the DS circuit with an additional feature: size selectivity. Using a combination of electrophysiology, pharmacology, and light/electron microscopy, we show that WACs predominantly contact presynaptic bipolar cells, which drive direct excitation and feedforward inhibition (through SACs) to DSGCs, thus maintaining the appropriate balance of inhibition/excitation required for generating DS. This circuit arrangement permits high-fidelity direction coding over a range of ambient light levels, over which size selectivity is adjusted. Together, these results provide novel insights into the anatomical and functional arrangement of multiple inhibitory interneurons within a single computational module in the retina. C1 [Hoggarth, Alex; McLaughlin, Amanda J.; Ronellenfitch, Kara; Trenholm, Stuart; Vasandani, Rishi; Sethuramanujam, Santhosh; Awatramani, Gautam B.] Univ Victoria, Dept Biol, Victoria, BC V8W 3N5, Canada. [Schwab, David] Northwestern Univ, Dept Phys & Astron, Evanston, IL 60208 USA. [Briggman, Kevin L.] NIH, Circuit Dynam & Connect Unit, Bethesda, MD 20892 USA. RP Awatramani, GB (reprint author), Univ Victoria, Dept Biol, Victoria, BC V8W 3N5, Canada. EM gautam@uvic.ca FU Marguerite Adamson Estate Fund; Foundation Fighting Blindness (Canada); Canadian Institutes for Health Research [CIHR- 130268-2013] FX We thank K. Delaney and B. Chow for their useful discussions, J. Boyd (University of British Columbia) for help with 2-photon imaging software, A. Sullivan and A. Nanda for providing helpful technical support, and T. MacKellar for help with morphological reconstructions. This work was supported by the Marguerite Adamson Estate Fund (A.H. and A.J.M.) and operating grants from the Foundation Fighting Blindness (Canada) and Canadian Institutes for Health Research (CIHR- 130268-2013) awarded to G.B.A. NR 69 TC 18 Z9 18 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD APR 8 PY 2015 VL 86 IS 1 BP 276 EP 291 DI 10.1016/j.neuron.2015.02.035 PG 16 WC Neurosciences SC Neurosciences & Neurology GA CF4WE UT WOS:000352552900027 PM 25801705 ER PT J AU Ebshiana, AA Snowden, SG Thambisetty, M Parsons, R Hye, A Legido-Quigley, C AF Ebshiana, Amera A. Snowden, Stuart G. Thambisetty, Madhav Parsons, Richard Hye, Abdul Legido-Quigley, Cristina TI Metabolomic Method: UPLC-q-ToF Polar and Non-Polar Metabolites in the Healthy Rat Cerebellum Using an In-Vial Dual Extraction SO PLOS ONE LA English DT Article ID MASS-SPECTROMETRY; ALZHEIMERS-DISEASE; LIQUID-CHROMATOGRAPHY; ION SUPPRESSION; ELECTROSPRAY-IONIZATION; LC-MS; DIAGNOSIS; DISORDERS; PLASMA; PHASE AB Unbiased metabolomic analysis of biological samples is a powerful and increasingly commonly utilised tool, especially for the analysis of bio-fluids to identify candidate biomarkers. To date however only a small number of metabolomic studies have been applied to studying the metabolite composition of tissue samples, this is due, in part to a number of technical challenges including scarcity of material and difficulty in extracting metabolites. The aim of this study was to develop a method for maximising the biological information obtained from small tissue samples by optimising sample preparation, LC-MS analysis and metabolite identification. Here we describe an in-vial dual extraction (IVDE) method, with reversed phase and hydrophilic liquid interaction chromatography (HILIC) which reproducibly measured over 4,000 metabolite features from as little as 3mg of brain tissue. The aqueous phase was analysed in positive and negative modes following HILIC separation in which 2,838 metabolite features were consistently measured including amino acids, sugars and purine bases. The non-aqueous phase was also analysed in positive and negative modes following reversed phase separation gradients respectively from which 1,183 metabolite features were consistently measured representing metabolites such as phosphatidylcholines, sphingolipids and triacylglycerides. The described metabolomics method includes a database for 200 metabolites, retention time, mass and relative intensity, and presents the basal metabolite composition for brain tissue in the healthy rat cerebellum. C1 [Ebshiana, Amera A.; Parsons, Richard; Legido-Quigley, Cristina] Kings Coll London, Inst Pharmaceut Sci, London SE1 9NH, England. [Snowden, Stuart G.; Hye, Abdul] Kings Coll London, Inst Psychiat, Dept Old Age Psychiat, London SE5 8AF, England. [Thambisetty, Madhav] Natl Inst Aging, Lab Behav Neurosci, Clin & Translat Neurosci Unit, Baltimore, MD USA. RP Legido-Quigley, C (reprint author), Kings Coll London, Inst Pharmaceut Sci, Franklin Wilkins Bldg,150 Stamford St, London SE1 9NH, England. EM cristina.legido_quigley@kcl.ac.uk FU Butterfield Trust; Libyan Cultural Bureau London FX This work has been supported by grants from the Butterfield Trust and the Libyan Cultural Bureau London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 3 Z9 3 U1 2 U2 27 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 8 PY 2015 VL 10 IS 4 AR e0122883 DI 10.1371/journal.pone.0122883 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3WA UT WOS:000352478400083 PM 25853858 ER PT J AU Zhang, FQ Xu, Y Cao, HB Jin, CH Cheng, ZH Wang, GQ Shugart, YY AF Zhang, Fuquan Xu, Yong Cao, Hongbao Jin, Chunhui Cheng, Zaohuo Wang, Guoqiang Shugart, Yin Yao TI Mapsnp: An R Package to Plot a Genomic Map for Single Nucleotide Polymorphisms SO PLOS ONE LA English DT Article ID BROWSER; SOFTWARE; DATABASE; DATASETS AB Single-nucleotide polymorphism (SNP) is one of the most common sources of genetic variations of the genome. Currently, SNPs are a main target for most genetic association studies. Visualizing genomic coordinates of SNPs, including their physical location relative to their host gene, and the structure of the relevant transcripts, may provide intuitive supplements to the understanding of their functions. Nevertheless, to date, no such easy-to-use programming tools exist. Therefore, we developed an R package, "mapsnp", to plot genomic map for a panel of SNPs within a genome region of interest, including the relative chromosome location and the transcripts in the region. mapsnp is a simple and flexible software package which can be used to visualize a genomic map for SNPs, integrating a chromosome ideogram, genomic coordinates, SNP locations and SNP labels. C1 [Zhang, Fuquan; Jin, Chunhui; Cheng, Zaohuo; Wang, Guoqiang] Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi, Jiangsu, Peoples R China. [Zhang, Fuquan; Cao, Hongbao; Shugart, Yin Yao] NIMH, Intramural Res Program, Unit Stat Genom, NIH, Bethesda, MD 20892 USA. [Xu, Yong] Shanxi Med Univ, Hosp 1, Dept Psychiat, Taiyuan, Peoples R China. RP Wang, GQ (reprint author), Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi, Jiangsu, Peoples R China. EM wuwangguoqiang@126.com; kay1yao@mail.nih.gov FU Wuxi Hospital Management Center key joint scientific and technical project in medicine [YGZXL1315]; National Natural Science Foundation of China [81000583, 81278412]; China Postdoctoral Science Foundation [2013M541207]; Program for New Century Excellent Talents in University; Program for the Top Young Academic Leaders of Higher Learning Institutions of Shanxi FX This work was supported by Wuxi Hospital Management Center key joint scientific and technical project in medicine (YGZXL1315), the National Natural Science Foundation of China (81000583, 81278412), China Postdoctoral Science Foundation (2013M541207), Program for New Century Excellent Talents in University (YX), and Program for the Top Young Academic Leaders of Higher Learning Institutions of Shanxi (YX). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 14 TC 2 Z9 2 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 8 PY 2015 VL 10 IS 4 AR e0123609 DI 10.1371/journal.pone.0123609 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3WA UT WOS:000352478400107 PM 25853637 ER PT J AU Byrd, AL Segre, JA AF Byrd, Allyson L. Segre, Julia A. TI Integrating host gene expression and the microbiome to explore disease pathogenesis SO GENOME BIOLOGY LA English DT Article ID SINGULAR-VALUE DECOMPOSITION; COMPONENT ANALYSIS AB In a recent study, rich clinical assessment and longitudinal study design are combined with host gene expression and microbial sequencing analyses to develop a framework for exploring disease etiology and outcomes in the context of human inflammatory disease. C1 [Byrd, Allyson L.; Segre, Julia A.] NHGRI, Microbial Genom Sect, Translat & Funct Genom Branch, Bethesda, MD 20892 USA. RP Segre, JA (reprint author), NHGRI, Microbial Genom Sect, Translat & Funct Genom Branch, Bethesda, MD 20892 USA. EM jsegre@nhgri.nih.gov NR 10 TC 1 Z9 1 U1 4 U2 12 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 APR 8 PY 2015 VL 16 AR 70 DI 10.1186/s13059-015-0625-1 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CF0XG UT WOS:000352267100001 PM 25887564 ER PT J AU Aiba, I Noebels, JL AF Aiba, Isamu Noebels, Jeffrey L. TI Spreading depolarization in the brainstem mediates sudden cardiorespiratory arrest in mouse SUDEP models SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID UNEXPECTED DEATH; DRAVET SYNDROME; GABAERGIC INTERNEURONS; EPILEPTIFORM ACTIVITY; EPILEPSY; DEPRESSION; SEIZURES; MICE; MECHANISMS; MIGRAINE AB Cardiorespiratory collapse after a seizure is the leading cause of sudden unexpected death in epilepsy (SUDEP) in young persons, but why only certain individuals are at risk is unknown. To identify a mechanism for this lethal cardiorespiratory failure, we examined whether genes linked to increased SUDEP risk lower the threshold for spreading depolarization (SD), a self-propagating depolarizing wave that silences neuronal networks. Mice carrying mutations in Kv1.1 potassium channels (-/-) and Scn1a sodium ion channels (+/R1407X) phenocopy many aspects of human SUDEP. In mutant, but not wild-type mice, seizures initiated by topical application of 4-aminopyridine to the cortex led to a slow, negative DC potential shift recorded in the dorsal medulla, a brainstem region that controls cardiorespiratory pacemaking. This irreversible event slowly depolarized cells and inactivated synaptic activity, producing cardiorespiratory arrest. Local initiation of SD in this region by potassium chloride microinjection also elicited electroencephalographic suppression, apnea, bradycardia, and asystole, similar to the events seen in monitored human SUDEP. In vitro study of brainstem slices confirmed that mutant mice had a lower threshold for SD elicited by metabolic substrate depletion and that immature mice were at greater risk than adults. Deletion of the gene encoding tau, which prolongs life in these mutants, also restored the normal SD threshold in Kv1.1-mutant mouse brainstem. Thus, brainstem SD may be a critical threshold event linking seizures and SUDEP. C1 [Aiba, Isamu; Noebels, Jeffrey L.] Baylor Coll Med, Dept Neurol, Dev Neurogenet Lab, Houston, TX 77030 USA. [Aiba, Isamu; Noebels, Jeffrey L.] Baylor Coll Med, NIH, NINDS, Ctr SUDEP Res, Houston, TX 77030 USA. [Noebels, Jeffrey L.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Noebels, Jeffrey L.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Noebels, JL (reprint author), Baylor Coll Med, Dept Neurol, Dev Neurogenet Lab, Houston, TX 77030 USA. EM jnoebels@bcm.edu OI Noebels, Jeffrey /0000-0002-2887-0839 FU American Heart Association [14POST20130031]; NINDS [NS029709, NS090340]; Blue Bird Circle Foundation FX This work was supported by a Postdoctoral Fellowship award (14POST20130031) from the American Heart Association (I.A.), NINDS NS029709 and NS090340 (J.L.N.), and the Blue Bird Circle Foundation. NR 41 TC 22 Z9 22 U1 0 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 8 PY 2015 VL 7 IS 282 AR 282ra46 DI 10.1126/scitranslmed.aaa4050 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CF4QK UT WOS:000352535200003 PM 25855492 ER PT J AU He, SS Lin, B Chu, V Hu, ZY Hu, X Xiao, JB Wang, AQ Schweitzer, CJ Li, QS Imamura, M Hiraga, N Southall, N Ferrer, M Zheng, W Chayama, K Marugan, JJ Liang, TJ AF He, Shanshan Lin, Billy Chu, Virginia Hu, Zongyi Hu, Xin Xiao, Jingbo Wang, Amy Q. Schweitzer, Cameron J. Li, Qisheng Imamura, Michio Hiraga, Nobuhiko Southall, Noel Ferrer, Marc Zheng, Wei Chayama, Kazuaki Marugan, Juan J. Liang, T. Jake TI Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of hepatitis C virus infection SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID LIFE-CYCLE; IN-VITRO; HALF-LIFE; ENTRY; DRUGS; IDENTIFICATION; REPLICATION; INHIBITORS; DISCOVERY; THERAPIES AB Hepatitis C virus (HCV) infection affects an estimated 185 million people worldwide, with chronic infection often leading to liver cirrhosis and hepatocellular carcinoma. Although HCV is curable, there is an unmet need for the development of effective and affordable treatment options. Through a cell-based high-throughput screen, we identified chlorcyclizine HCl (CCZ), an over-the-counter drug for allergy symptoms, as a potent inhibitor of HCV infection. CCZ inhibited HCV infection in human hepatoma cells and primary human hepatocytes. The mode of action of CCZ is mediated by inhibiting an early stage of HCV infection, probably targeting viral entry into host cells. The in vitro antiviral effect of CCZ was synergistic with other anti-HCV drugs, including ribavirin, interferon-alpha, telaprevir, boceprevir, sofosbuvir, daclatasvir, and cyclosporin A, without significant cytotoxicity, suggesting its potential in combination therapy of hepatitis C. In the mouse pharmacokinetic model, CCZ showed preferential liver distribution. In chimeric mice engrafted with primary human hepatocytes, CCZ significantly inhibited infection of HCV genotypes 1b and 2a, without evidence of emergence of drug resistance, during 4 and 6 weeks of treatment, respectively. With its established clinical safety profile as an allergy medication, affordability, and a simple chemical structure for optimization, CCZ represents a promising candidate for drug repurposing and further development as an effective and accessible agent for treatment of HCV infection. C1 [He, Shanshan; Lin, Billy; Chu, Virginia; Hu, Zongyi; Schweitzer, Cameron J.; Li, Qisheng; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Hu, Xin; Xiao, Jingbo; Wang, Amy Q.; Southall, Noel; Ferrer, Marc; Zheng, Wei; Marugan, Juan J.] Natl Ctr Adv Translat Sci, NIH, Rockville, MD 20850 USA. [Imamura, Michio; Hiraga, Nobuhiko; Chayama, Kazuaki] Hiroshima Univ, Grad Sch Biomed Sci, Dept Med & Mol Sci, Hiroshima 7300053, Japan. RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. EM jliang@nih.gov RI Southall, Noel/H-8991-2012; OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757 FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases and Molecular Libraries FX The Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases and Molecular Libraries funding. NR 49 TC 9 Z9 9 U1 1 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 8 PY 2015 VL 7 IS 282 AR 282ra49 DI 10.1126/scitranslmed.3010286 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CF4QK UT WOS:000352535200006 PM 25855495 ER PT J AU Sheets, RL Rangavajhula, V Pullen, JK Butler, C Mehra, V Shapiro, S Pensiero, M AF Sheets, Rebecca L. Rangavajhula, Vijaya Pullen, Jeffrey K. Butler, Chris Mehra, Vijay Shapiro, Stuart Pensiero, Michael TI Now that you want to take your HIV/AIDS vaccine/biological product research concept into the clinic: What are the "cGMP"? SO VACCINE LA English DT Review DE Vaccine; Manufacturing; Clinical trial; Investigational product; Good Manufacturing Practices ID GLYCOSYLATION AB The Division of AIDS Vaccine Research Program funds the discovery and development of HIV/AIDS vaccine candidates. Basic researchers, having discovered a potential vaccine in the laboratory, next want to take that candidate into the clinic to test the concept hi humans, to see if it translates. Many of them have heard of "cGMP" and know that they are supposed to make a "GMP product" to take into the clinic, but often they are not very familiar with what "cGMP" means and why these good practices are so important. As members of the Vaccine Translational Research Branch, we frequently get asked "can't we use the material we made in the lab in the clinic?" or "aren't Phase 1 studies exempt from cGMP?" Over the years, we have had many experiences where researchers or their selected contract manufacturing organizations have not applied an appropriate degree of compliance with cGMP suitable for the clinical phase of development. We share some of these experiences and the lessons learned, along with explaining the importance of cGMP, just what cGMP means, and what they can assure, in an effort to de-mystify this subject and facilitate the rapid and safe translational development of HIV vaccines. Published by Elsevier Ltd. C1 [Sheets, Rebecca L.; Rangavajhula, Vijaya; Pullen, Jeffrey K.; Butler, Chris; Mehra, Vijay; Shapiro, Stuart; Pensiero, Michael] NIAID, NIH, Div Aids, Vaccine Res Program, Rockville, MD 20892 USA. RP Pensiero, M (reprint author), NIAID, NIH, Div Aids, Vaccine Res Program, 5601 Fishers Lane, Rockville, MD 20892 USA. EM Michael.Pensiero@nih.hhs.gov FU Intramural NIH HHS [Z99 AI999999] NR 9 TC 0 Z9 0 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD APR 8 PY 2015 VL 33 IS 15 BP 1757 EP 1766 DI 10.1016/j.vaccine.2015.02.003 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CF6PL UT WOS:000352678500001 PM 25698494 ER PT J AU Pinsky, PF Gierada, DS Black, W Munden, R Nath, H Aberle, D Kazerooni, E AF Pinsky, Paul F. Gierada, David S. Black, William Munden, Reginald Nath, Hrudaya Aberle, Denise Kazerooni, Ella TI Performance of Lung-RADS in the National Lung Screening Trial A Retrospective Assessment SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID FLEISCHNER-SOCIETY; CANCER; STATEMENT; MANAGEMENT; CT AB Background: Lung cancer screening with low-dose computed tomography (LDCT) has been recommended, based primarily on the results of the NLST (National Lung Screening Trial). The American College of Radiology recently released Lung-RADS, a classification system for LDCT lung cancer screening. Objective: To retrospectively apply the Lung-RADS criteria to the NLST. Design: Secondary analysis of a group from a randomized trial. Setting: 33 U.S. screening centers. Patients: Participants were randomly assigned to the LDCT group of the NLST, were aged 55 to 74 years, had at least a 30-pack-year history of smoking, and were current smokers or had quit within the past 15 years. Intervention: 3 annual LDCT lung cancer screenings. Measurements: Lung-RADS classifications for LDCT screenings. Lung-RADS categories 1 to 2 constitute negative screening results, and categories 3 to 4 constitute positive results. Results: Of 26 722 LDCT group participants, 26 455 received a baseline screening; 48 671 screenings were done after baseline. At baseline, the false-positive result rate (1 minus the specificity rate) for Lung-RADS was 12.8% (95% CI, 12.4% to 13.2%) versus 26.6% (CI, 26.1% to 27.1%) for the NLST; after baseline, the falsepositive result rate was 5.3% (CI, 5.1% to 5.5%) for Lung-RADS versus 21.8% (CI, 21.4% to 22.2%) for the NLST. Baseline sensitivity was 84.9% (CI, 80.8% to 89.0%) for Lung-RADS versus 93.5% (CI, 90.7% to 96.3%) for the NLST, and sensitivity after baseline was 78.6% (CI, 74.6% to 82.6%) for Lung-RADS versus 93.8% (CI, 91.4% to 96.1%) for the NLST. Limitation: Lung-RADS criteria were applied retrospectively. Conclusion: Lung-RADS may substantially reduce the falsepositive result rate; however, sensitivity is also decreased. The effect of using Lung-RADS criteria in clinical practice must be carefully studied. C1 [Pinsky, Paul F.] NCI, Bethesda, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO USA. Geisel Sch Med Dartmouth, Hanover, NH USA. Houston Methodist Hosp, Houston, TX USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Pinsky, PF (reprint author), NCI, 9609 Med Ctr Dr,Room 5E108, Bethesda, MD 20892 USA. EM pp4f@nih.gov OI Aberle, Denise/0000-0002-8858-3401 FU [U01-CA-80098]; [U01-CA-79778]; [N01-CN-25522]; [N01-CN-25511]; [N01-CN-25512]; [N01-CN-25513]; [N01-CN-25514]; [N01-CN-25515]; [N01-CN-25516]; [N01-CN-25518]; [N01-CN-25524]; [N01-CN-75022]; [N01-CN-25476]; [N02-CN-63300] FX The NLST was supported by the following grants and contracts: U01-CA-80098, U01-CA-79778, N01-CN-25522, N01-CN-25511, N01-CN-25512, N01-CN-25513, N01-CN-25514, N01-CN-25515, N01-CN-25516, N01-CN-25518, N01-CN-25524, N01-CN-75022, N01-CN-25476, and N02-CN-63300. NR 14 TC 38 Z9 38 U1 2 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 7 PY 2015 VL 162 IS 7 BP 485 EP U154 DI 10.7326/M14-2086 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CG4UT UT WOS:000353283400003 PM 25664444 ER PT J AU Wilson, RL Frisz, JF Klitzing, HA Zimmerberg, J Weber, PK Kraft, ML AF Wilson, Robert L. Frisz, Jessica F. Klitzing, Haley A. Zimmerberg, Joshua Weber, Peter K. Kraft, Mary L. TI Hemagglutinin Clusters in the Plasma Membrane Are Not Enriched with Cholesterol and Sphingolipids SO BIOPHYSICAL JOURNAL LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; GPI-ANCHORED PROTEINS; LIPID RAFT MICRODOMAINS; LIVING CELL-MEMBRANES; MASS-SPECTROMETRY; QUANTITATIVE-ANALYSIS; TRANSMEMBRANE DOMAIN; SURFACE; CERAMIDE; ORGANIZATION AB The clusters of the influenza envelope protein, hemagglutinin, within the plasma membrane are hypothesized to be enriched with cholesterol and sphingolipids. Here, we directly tested this hypothesis by using high-resolution secondary ion mass spectrometry to image the distributions of antibody-labeled hemagglutinin and isotope-labeled cholesterol and sphingolipids in the plasma membranes of fibroblast cells that stably express hemagglutinin. We found that the hemagglutinin clusters were neither enriched with cholesterol nor colocalized with sphingolipid domains. Thus, hemagglutinin clustering and localization in the plasma membrane is not controlled by cohesive interactions between hemagglutinin and liquid-ordered domains enriched with cholesterol and sphingolipids, or from specific binding interactions between hemagglutinin, cholesterol, and/or the majority of sphingolipid species in the plasma membrane. C1 [Wilson, Robert L.; Frisz, Jessica F.; Klitzing, Haley A.; Kraft, Mary L.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA. [Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular & Membrane Biophys, NIH, Bethesda, MD USA. [Weber, Peter K.] Lawrence Livermore Natl Lab, Glenn T Seaborg Inst, Livermore, CA USA. [Kraft, Mary L.] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA. RP Kraft, ML (reprint author), Univ Illinois, Dept Chem, 1209 W Calif St, Urbana, IL 61801 USA. EM mlkraft@illinois.edu FU CASI from the Burroughs Wellcome Fund; Intramural Program of the National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH); NIH Training Program in the Chemistry-Biology Interface [T32 GM070421]; National Science Foundation (NSF) [CHE-1058809]; Lab Directed Research and Development funding; U.S. DOE [DE-AC52-07NA27344] FX This work was partially supported by a CASI from the Burroughs Wellcome Fund (to M.L.K.), the Intramural Program of the National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), the NIH Training Program in the Chemistry-Biology Interface T32 GM070421 (to J.F.F.), the National Science Foundation (NSF) under CHE-1058809, and Lab Directed Research and Development funding (to Lawrence Livermore National Laboratory (LLNL)). We thank Kaiyan Lou for the synthesis of the 15 N-sphingolipid precursors and 18O-cholesterol. Work at LLNL was performed under the auspices of the U.S. DOE under contract DE-AC52-07NA27344. NR 67 TC 11 Z9 11 U1 1 U2 16 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 APR 7 PY 2015 VL 108 IS 7 BP 1652 EP 1659 DI 10.1016/j.bpj.2015.02.026 PG 8 WC Biophysics SC Biophysics GA CF4DF UT WOS:000352498100013 PM 25863057 ER PT J AU Berezhkovskii, AM Dagdug, L Bezrukov, SM AF Berezhkovskii, Alexander M. Dagdug, Leonardo Bezrukov, Sergey M. TI Biased diffusion in three-dimensional comb-like structures SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID BRAIN EXTRACELLULAR-SPACE; FACILITATED MEMBRANE-TRANSPORT; DEAD-END PORES; ANOMALOUS DIFFUSION; VENTRICULAR MYOCARDIUM; BOUNDARY-CONDITIONS; AGGREGATED MEDIA; DENDRITIC SPINES; POROUS-MEDIA; DISPERSION AB In this paper, we study biased diffusion of point Brownian particles in a three-dimensional comb-like structure formed by a main cylindrical tube with identical periodic cylindrical dead ends. It is assumed that the dead ends are thin cylinders whose radius is much smaller than both the radius of the main tube and the distance between neighboring dead ends. It is also assumed that in the main tube, the particle, in addition to its regular diffusion, moves with a uniform constant drift velocity. For such a system, we develop a formalism that allows us to derive analytical expressions for the Laplace transforms of the first two moments of the particle displacement along the main tube axis. Inverting these Laplace transforms numerically, one can find the time dependences of the two moments for arbitrary values of both the drift velocity and the dead-end length, including the limiting case of infinitely long dead ends, where the unbiased diffusion becomes anomalous at sufficiently long times. The expressions for the Laplace transforms are used to find the effective drift velocity and diffusivity of the particle as functions of its drift velocity in the main tube and the tube geometric parameters. As might be expected from common-sense arguments, the effective drift velocity monotonically decreases from the initial drift velocity to zero as the dead-end length increases from zero to infinity. The effective diffusivity is a more complex, non-monotonic function of the dead-end length. As this length increases from zero to infinity, the effective diffusivity first decreases, reaches a minimum, and then increases approaching a plateau value which is proportional to the square of the particle drift velocity in the main tube. (C) 2015 AIP Publishing LLC. C1 [Berezhkovskii, Alexander M.; Dagdug, Leonardo; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Berezhkovskii, Alexander M.; Dagdug, Leonardo] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Phys, Mexico City 09340, DF, Mexico. RP Berezhkovskii, AM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. FU NIH, Center for Information Technology; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Consejo Nacional de Ciencia y Tecnologia (CONACyT) [176452] FX This study was supported by the Intramural Research Program of the NIH, Center for Information Technology and Eunice Kennedy Shriver National Institute of Child Health and Human Development. L.D. thanks Consejo Nacional de Ciencia y Tecnologia (CONACyT) for partial support under Grant No. 176452. NR 58 TC 4 Z9 4 U1 0 U2 12 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 APR 7 PY 2015 VL 142 IS 13 AR UNSP 134101 DI 10.1063/1.4916310 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA CF6DG UT WOS:000352646300005 PM 25854222 ER PT J AU Zonderman, AB Grimmer, T AF Zonderman, Alan B. Grimmer, Timo TI Risk of mild cognitive impairment The Olmsted County MCI Risk Score SO NEUROLOGY LA English DT Editorial Material ID PREDICTION; VALIDATION C1 [Zonderman, Alan B.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Grimmer, Timo] Tech Univ Munich, Klinikum Rechts Isar, Dept Psychiat & Psychotherapy, D-80290 Munich, Germany. RP Zonderman, AB (reprint author), NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM zondermana@mail.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS NR 8 TC 1 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD APR 7 PY 2015 VL 84 IS 14 BP 1392 EP 1393 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CF4BP UT WOS:000352493700005 PM 25788556 ER PT J AU Kim, SYH Karlawish, J Berkman, BE AF Kim, Scott Y. H. Karlawish, Jason Berkman, Benjamin E. TI Ethics of genetic and biomarker test disclosures in neurodegenerative disease prevention trials SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; HUNTINGTON-DISEASE; DECISION-MAKING; PRESYMPTOMATIC TREATMENTS; PSYCHOLOGICAL IMPACT; CLINICAL-RESEARCH; APOE GENOTYPE; RISK; RECOMMENDATIONS; DISCRIMINATION AB Objective: Prevention trials for neurodegenerative diseases use genetic or other risk marker tests to select participants but there is concern that this could involve coercive disclosure of unwanted information. This has led some trials to use blinded enrollment (participants are tested but not told of their risk marker status). We examined the ethics of blinded vs transparent enrollment using well-established criteria for assessing the ethics of clinical research. Methods: Normative analysis applying 4 key ethical criteria-favorable risk-benefit ratio, informed consent, fair subject selection, and scientific validity-to blinded vs transparent enrollment, using current evidence and state of Alzheimer disease (AD) and other prevention trials. Results: Current evidence on the psychosocial impact of risk marker disclosure and considerations of scientific benefit do not support an obligation to use blinded enrollment in prevention trials. Nor does transparent enrollment coerce or involve undue influence of potential participants. Transparent enrollment does not unfairly exploit vulnerable participants or limit generalizability of scientific findings of prevention trials. However, if the preferences of a community of potential participants would affect the rigor or feasibility of a prevention trial using transparent enrollment, then investigators are required by considerations of scientific validity to use blinded enrollment. Conclusions: Considerations of risks and benefits, informed consent, and fair subject selection do not require the use of blinded enrollment for AD prevention trials. Blinded enrollment in AD prevention trials may sometimes be necessary because of the need for scientific validity, not because it prevents coercion or undue influence. C1 [Kim, Scott Y. H.; Berkman, Benjamin E.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Karlawish, Jason] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Karlawish, Jason] Univ Penn, Dept Med Eth & Hlth Policy, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Kim, SYH (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM scott.kim@nih.gov FU NIH Intramural Program; NIA [P30-AG10124] FX Supported by the NIH Intramural Program. Dr. Karlawish was supported by NIA P30-AG10124. NR 40 TC 4 Z9 4 U1 1 U2 12 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 APR 7 PY 2015 VL 84 IS 14 BP 1488 EP 1494 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CF4BP UT WOS:000352493700017 PM 25762713 ER PT J AU Bharucha-Goebel, DX Neil, E Donkervoort, S Dastgir, J Wiggs, E Winder, TL Moore, SA Iannaccone, ST Bonnemann, CG AF Bharucha-Goebel, Diana X. Neil, Erin Donkervoort, Sandra Dastgir, Jahannaz Wiggs, Edythe Winder, Thomas L. Moore, Steven A. Iannaccone, Susan T. Boennemann, Carsten G. TI INTRAFAMILIAL VARIABILITY IN GMPPB-ASSOCIATED DYSTROGLYCANOPATHY: BROADENING OF THE PHENOTYPE SO NEUROLOGY LA English DT Editorial Material ID MUSCULAR-DYSTROPHIES; ALPHA-DYSTROGLYCAN; GLYCOSYLATION; MUTATIONS C1 [Bharucha-Goebel, Diana X.; Donkervoort, Sandra; Wiggs, Edythe; Boennemann, Carsten G.] NIH, Bethesda, MD 20892 USA. [Bharucha-Goebel, Diana X.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Neil, Erin] Univ Michigan, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA. [Dastgir, Jahannaz] Columbia Univ, Med Ctr, New York, NY USA. [Winder, Thomas L.] Prevent Genet, Marshfield, WI USA. [Moore, Steven A.] Univ Iowa, Iowa City, IA USA. [Iannaccone, Susan T.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Bonnemann, CG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM carsten.bonnemann@nih.gov FU NIAMS NIH HHS [T32 AR056993]; NINDS NIH HHS [U54 NS053672] NR 6 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD APR 7 PY 2015 VL 84 IS 14 BP 1495 EP 1497 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA CF4BP UT WOS:000352493700018 PM 25770200 ER PT J AU Huang, BL Mackem, S AF Huang, Bau-Lin Mackem, Susan TI Tamoxifen-Dependent, Inducible Bmp2CreER Drives Selective Recombinase Activity in Early Interdigital Mesenchyme and Digit Collateral Ligaments SO PLOS ONE LA English DT Article ID PROGRAMMED CELL-DEATH; VERTEBRATE LIMB; MOUSE; EXPRESSION; IDENTITY; TENDONS; MICE AB During limb development, the interdigital mesenchyme has been proposed to play a signaling role instructing morphogenesis of different digit types, as well as undergoing programmed cell death necessary to free digits in animals not adapted for swimming or flying. We have generated a conditional, tamoxifen-dependent Cre line, Bmp2CreER, which drives highly selective recombination restricted to the distal limb mesoderm, largely restricted to the interdigits, and selectively active in digit ligament but not tendon progenitors at later stages. The Bmp2CreER provides a valuable new tool to dissect roles of interdigital mesenchyme and potentially investigate divergence of ligament and tendon lineages. C1 [Huang, Bau-Lin; Mackem, Susan] NCI Frederick, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Mackem, S (reprint author), NCI Frederick, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM mackems@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX This research was supported by the Center for Cancer Research, National Cancer Institute, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 2 Z9 2 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 7 PY 2015 VL 10 IS 4 AR e0123325 DI 10.1371/journal.pone.0123325 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3VU UT WOS:000352477800224 PM 25850076 ER PT J AU Maillard, S Damiola, F Clero, E Pertesi, M Robinot, N Rachedi, F Boissin, JL Sebbag, J Shan, L Bost-Bezeaud, F Petitdidier, P Doyon, F Xhaard, C Rubino, C Blanche, H Drozdovitch, V Lesueur, F de Vathaire, F AF Maillard, Stephane Damiola, Francesca Clero, Enora Pertesi, Maroulio Robinot, Nivonirina Rachedi, Frederique Boissin, Jean-Louis Sebbag, Joseph Shan, Larrys Bost-Bezeaud, Frederique Petitdidier, Patrick Doyon, Francoise Xhaard, Constance Rubino, Carole Blanche, Helene Drozdovitch, Vladimir Lesueur, Fabienne de Vathaire, Florent TI Common Variants at 9q22.33, 14q13.3, and ATM Loci, and Risk of Differentiated Thyroid Cancer in the French Polynesian Population SO PLOS ONE LA English DT Article ID BREAST-CANCER; DNA-DAMAGE; POOLED ANALYSIS; CARCINOMA; RADIATION; FOXE1; SUSCEPTIBILITY; ASSOCIATION; GENE; RADIOSENSITIVITY AB Background French Polynesia has one of the highest incidence rates of thyroid cancer worldwide. Relationships with the atmospheric nuclear weapons tests and other environmental, biological, or behavioral factors have already been reported, but genetic susceptibility has yet to be investigated. We assessed the contribution of polymorphisms at the 9q22.33 and 14q13.3 loci identified by GWAS, and within the DNA repair gene ATM, to the risk of differentiated thyroid cancer (DTC) in 177 cases and 275 matched controls from the native population. Principal Findings For the GWAS SNP rs965513 near FOXE1, an association was found between genotypes G/A and A/A, and risk of DTC. A multiplicative effect of allele A was even noted. An excess risk was also observed in individuals carrying two long alleles of the poly-alanine tract expansion in FOXE1, while no association was observed with rs1867277 falling in the promoter region of the gene. In contrast, the GWAS SNP rs944289 (NKX2-1) did not show any significant association. Although the missense substitution D1853N (rs1801516) in ATM was rare in the population, carriers of the minor allele (A) also showed an excess risk. The relationships between these five polymorphisms and the risk of DTC were not contingent on the body surface area, body mass index, ethnicity or dietary iodine intake. However, an interaction was evidenced between the thyroid radiation dose and rs944289. Significance A clear link could not be established between the high incidence in French Polynesia and the studied polymorphisms, involved in susceptibility to DTC in other populations. Important variation in allele frequencies was observed in the Polynesian population as compared to the European populations. For FOXE1 rs965513, the direction of association and the effect size was similar to that observed in other populations, whereas for ATM rs1801516, the minor allele was associated to an increased risk in the Polynesian population and with a decreased risk in the European population. C1 [Maillard, Stephane; Clero, Enora; Doyon, Francoise; Xhaard, Constance; Rubino, Carole; de Vathaire, Florent] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, U1018, Radiat Epidemiol Grp, F-94800 Villejuif, France. [Maillard, Stephane; Clero, Enora; Doyon, Francoise; Xhaard, Constance; Rubino, Carole; de Vathaire, Florent] Univ Paris Sud, UMRS 1018, F-94807 Villejuif, France. [Maillard, Stephane; Clero, Enora; Doyon, Francoise; Xhaard, Constance; Rubino, Carole; de Vathaire, Florent] Inst Gustave Roussy, F-94800 Villejuif, France. [Damiola, Francesca; Pertesi, Maroulio; Robinot, Nivonirina; Lesueur, Fabienne] Int Agcy Res Canc, Genet Canc Susceptibil, F-69372 Lyon, France. [Damiola, Francesca] Ctr Leon Berard, INSERM, U1052, CRCL,CNRS,UMR5286, F-69373 Lyon, France. [Rachedi, Frederique; Bost-Bezeaud, Frederique] Terr Hosp Taaone, Papeete, Fr Polynesia. [Boissin, Jean-Louis] 10 IPRAME, Papeete, Fr Polynesia. [Sebbag, Joseph] Paofai Clin, Papeete, Fr Polynesia. [Petitdidier, Patrick] Lab Boz, Papeete, Fr Polynesia. [Blanche, Helene] Fdn Jean Dausset CEPH, F-75010 Paris, France. [Drozdovitch, Vladimir] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Lesueur, Fabienne] Mines ParisTech, Inst Curie, INSERM, U900, F-75248 Paris, France. RP de Vathaire, F (reprint author), INSERM, Ctr Res Epidemiol & Populat Hlth CESP, U1018, Radiat Epidemiol Grp, F-94800 Villejuif, France. EM florent.devathaire@igr.fr RI de Vathaire, Florent/L-2983-2016 FU Agence Nationale pour la Recherche (ANR); Ligue Nationale Contre le Cancer (LNCC); Direction Generale de la Sante; Agence Francaise de Securite Sanitaire de l'alimentation, de l'environnement et du travail (ANSES); CHILDTHYREEC program; Fondation de France FX This study was supported by the Agence Nationale pour la Recherche (ANR), the Ligue Nationale Contre le Cancer (LNCC), the Direction Generale de la Sante, the Agence Francaise de Securite Sanitaire de l'alimentation, de l'environnement et du travail (ANSES), CHILDTHYREEC program, and the Fondation de France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 6 Z9 6 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 7 PY 2015 VL 10 IS 4 AR UNSP e0123700 DI 10.1371/journal.pone.0123700 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF3VU UT WOS:000352477800253 PM 25849217 ER PT J AU Cook, PR Jones, CE Furano, AV AF Cook, Pamela R. Jones, Charles E. Furano, Anthony V. TI Phosphorylation of ORF1p is required for L1 retrotransposition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE proline-directed protein kinase; LINE-1; peptidyl prolyl isomerase 1; retrotransposon; Pin1 ID OPEN READING FRAME; RNA CHAPERONE ACTIVITY; LINE-1 RETROTRANSPOSITION; PROTEIN-PHOSPHORYLATION; RIBONUCLEOPROTEIN-PARTICLES; MULTISITE PHOSPHORYLATION; STRUCTURAL VARIATION; LTR-RETROTRANSPOSON; SOMATIC MOSAICISM; MASS-SPECTROMETRY AB Although members of the L1 (LINE-1) clade of non-LTR retrotransposons can be deleterious, the L1 clade has remained active in most mammals for similar to 100 million years and generated almost 40% of the human genome. The details of L1-host interaction are largely unknown, however. Here we report that L1 activity requires phosphorylation of the protein encoded by the L1 ORF1 (ORF1p). Critical phospho-acceptor residues (two serines and two threonines) reside in four conserved proline-directed protein kinase (PDPK) target sites. The PDPK family includes mitogen-activated protein kinases and cyclin-dependent kinases. Mutation of any PDPK phospho-acceptor inhibits L1 retrotransposition. The phosphomimetic aspartic acid can restore activity at the two serine sites, but not at either threonine site, where it is strongly inhibitory. ORF1p also contains conserved PDPK docking sites, which promote specific interaction of PDPKs with their targets. As expected, mutations in these sites also inhibit L1 activity. PDPK mutations in ORF1p that inactivate L1 have no significant effect on the ability of ORF1p to anneal RNA in vitro, an important biochemical property of the protein. We show that phosphorylated PDPK sites in ORF1p are required for an interaction with the peptidyl prolyl isomerase 1 (Pin1), a critical component of PDPK-mediated regulation. Pin1 acts via isomerization of proline side chains at phosphorylated PDPK motifs, thereby affecting substrate conformation and activity. Our demonstration that L1 activity is dependent on and integrated with cellular phosphorylation regulatory cascades significantly increases our understanding of interactions between L1 and its host. C1 [Cook, Pamela R.; Jones, Charles E.; Furano, Anthony V.] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Furano, AV (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. EM avf@helix.nih.gov FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Cesar Perez-Gonzalez for help in constructing the precursor of the pRTC2-puro plasmid, Dr. John Moran for the generous gifts of JM102 (the L1.3-containing retrotransposition cassette) and HeLa cells, Dr. Sandy Martin for advice, and Deborah Hinton for useful comments on the paper. We also thank TuKiet T. Lam, Jean E. Kanyo, and Mary LoPresti from the W.M. Keck Foundation Biotechnology Resource Laboratory at Yale University for the LC-MS/MS phospho site verification, data collection, and sample preparation, respectively. This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 76 TC 10 Z9 10 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 7 PY 2015 VL 112 IS 14 BP 4298 EP 4303 DI 10.1073/pnas.1416869112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF1EZ UT WOS:000352287800043 PM 25831499 ER PT J AU Yu, B Swatkoski, S Holly, A Lee, LC Giroux, V Lee, CS Hsu, D Smith, JL Yuen, G Yue, JQ Ann, DK Simpson, RM Creighton, CJ Figg, WD Gucek, M Luo, J AF Yu, Bing Swatkoski, Stephen Holly, Alesia Lee, Liam C. Giroux, Valentin Lee, Chih-Shia Hsu, Dennis Smith, Jordan L. Yuen, Garmen Yue, Junqiu Ann, David K. Simpson, R. Mark Creighton, Chad J. Figg, William D. Gucek, Marjan Luo, Ji TI Oncogenesis driven by the Ras/Raf pathway requires the SUMO E2 ligase Ubc9 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE KRAS; SUMO; Ubc9; transformation; colorectal cancer ID TRANSCRIPTIONAL REPRESSION; CANCER PROGRESSION; LUNG-CANCER; IN-VIVO; SUMOYLATION; RAS; CELLS; ADDICTION; SURVIVAL; SCREEN AB The small GTPase KRAS is frequently mutated in human cancer and currently there are no targeted therapies for KRAS mutant tumors. Here, we show that the small ubiquitin-like modifier (SUMO) pathway is required for KRAS-driven transformation. RNAi depletion of the SUMO E2 ligase Ubc9 suppresses 3D growth of KRAS mutant colorectal cancer cells in vitro and attenuates tumor growth in vivo. In KRAS mutant cells, a subset of proteins exhibit elevated levels of SUMOylation. Among these proteins, KAP1, CHD1, and EIF3L collectively support anchorage-independent growth, and the SUMOylation of KAP1 is necessary for its activity in this context. Thus, the SUMO pathway critically contributes to the transformed phenotype of KRAS mutant cells and Ubc9 presents a potential target for the treatment of KRAS mutant colorectal cancer. C1 [Yu, Bing; Lee, Liam C.; Giroux, Valentin; Lee, Chih-Shia; Hsu, Dennis; Smith, Jordan L.; Yuen, Garmen; Yue, Junqiu; Simpson, R. Mark; Luo, Ji] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Holly, Alesia] NCI, Genitourol Canc Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Swatkoski, Stephen; Figg, William D.; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. [Ann, David K.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Pharmacol, Duarte, CA 91010 USA. [Creighton, Chad J.] Baylor Coll Med, Dan L Duncan Canc Ctr, Div Biostat, Houston, TX 77030 USA. RP Luo, J (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM ji.luo@nih.gov RI Figg Sr, William/M-2411-2016; OI Smith , Jordan /0000-0003-0460-0647 FU National Cancer Institute [P30 CA125123, ZIABC011303] FX We thank Drs. Tom Misteli, Mary Dasso, Anne DeJean, and John Schneekloth for critical discussion and feedback. This study was supported by National Cancer Institute Grant P30 CA125123 (to C.J.C.); a National Cancer Institute Director's Intramural Career Development Innovation award (to B.Y.); and National Cancer Institute Intramural Program Grant ZIABC011303 (to J.L.). NR 43 TC 6 Z9 6 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 7 PY 2015 VL 112 IS 14 BP E1724 EP E1733 DI 10.1073/pnas.1415569112 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF1EZ UT WOS:000352287800008 PM 25805818 ER PT J AU Marosi, K Mattson, MP AF Marosi, Krisztina Mattson, Mark P. TI Hold the Salt: Vasopressor Role for BDNF SO CELL METABOLISM LA English DT Editorial Material ID DOWN-REGULATION; INHIBITION; MECHANISM; NEURONS; BRAIN; KCC2 AB In a recent publication in Neuron, Choe et al. (2015) demonstrate that brain-derived neurotrophic factor (BDNF) signaling mediates salt-induced blood pressure elevation by increasing the excitability of hypothalamic vasopressin-secreting neurons. These findings suggest complex roles for BDNF in adaptive cardiovascular responses to physiological challenges and in the pathogenesis of hypertension. C1 [Marosi, Krisztina; Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA. EM mark.mattson@nih.gov FU Intramural NIH HHS NR 10 TC 1 Z9 1 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD APR 7 PY 2015 VL 21 IS 4 BP 509 EP 510 DI 10.1016/j.cmet.2015.03.015 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CF4EF UT WOS:000352500800004 PM 25863241 ER PT J AU Kolodin, D van Panhuys, N Li, CR Magnuson, AM Cipolletta, D Miller, CM Wagers, A Germain, RN Benoist, C Mathis, D AF Kolodin, Dmitriy van Panhuys, Nicolas Li, Chaoran Magnuson, Angela M. Cipolletta, Daniela Miller, Christine M. Wagers, Amy Germain, Ronald N. Benoist, Christophe Mathis, Diane TI Antigen- and Cytokine-Driven Accumulation of Regulatory T Cells in Visceral Adipose Tissue of Lean Mice SO CELL METABOLISM LA English DT Article ID LYMPH-NODES; REG CELLS; INFLAMMATION; OBESITY; IL-33; DIFFERENTIATION; MACROPHAGES; POPULATION; MOLECULES; GENE AB A unique population of Foxp3(+)CD4(+) regulatory T (Treg) cells, with a distinct transcriptome and antigen-receptor repertoire, resides in visceral adipose tissue (VAT) of lean individuals. These cells regulate local inflammation and both local and systemic metabolic indices. Here we focus on expansion of the VAT Treg compartment in aging lean mice-assessing these cells' phenotypic conversion from conventional CD4(+) T cells, influx from lymphoid organs, and local population dynamics. Our findings establish that the VAT Treg compartment is seeded from thymocytes generated during the first weeks of life and expands beyond 10 weeks of age due to indolent proliferation, of certain clones in particular, coupled with enhanced survival. Accumulation of VAT Tregs depends on the antigen(s) presented by MHC class-II molecules and soluble mediators, notably interleukin(IL)-33. Addressing such factors therapeutically promises novel approaches for harnessing Tregs to stem the growing epidemic of obesity and consequent metabolic abnormalities. C1 [Kolodin, Dmitriy; Li, Chaoran; Magnuson, Angela M.; Cipolletta, Daniela; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [van Panhuys, Nicolas; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Miller, Christine M.; Wagers, Amy] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wagers, Amy] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Wagers, Amy] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA. [Benoist, Christophe; Mathis, Diane] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. EM cbdm@hms.harvard.edu RI van Panhuys, Nicholas/E-1812-2011; OI van Panhuys, Nicholas/0000-0003-2199-852X FU NIH [R01DK092541, RO1HL088582]; JPB Foundation; NIAID, NIH; National Science Foundation; Juvenile Diabetes Research Foundation FX We thank K. Hattori, N. Asinovski, A. Ortiz-Lopez, K. Leatherbee, D. Jepson, K. Rothamel, S. Davis, H. Paik, R. Cruse, J. LaVecchio, and G. Buruzula for experimental support; C. Shu and D. Burzyn for valuable discussions; and A Rudensky, V. Kuchroo, O. Kanagawa, R. Lee, and A. MacKenzie for mouse lines. This work was supported by NIH R01DK092541 and the JPB Foundation to D.M., NIH RO1HL088582 to A.J.W., and in part by the Intramural Research Program of NIAID, NIH. Cell sorting was performed at the HSCI/DRC Flow Core (NIH P30DK036836). D.K. and A.M. were supported by fellowships from the National Science and Juvenile Diabetes Research Foundations, respectively. Content is solely the responsibility of the authors and does not represent the official view of the NIH or other funding agencies. NR 29 TC 48 Z9 48 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD APR 7 PY 2015 VL 21 IS 4 BP 543 EP 557 DI 10.1016/j.cmet.2015.03.005 PG 15 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CF4EF UT WOS:000352500800010 PM 25863247 ER PT J AU Ortega-Molina, A Lopez-Guadamillas, E Mattison, JA Mitchell, SJ Munoz-Martin, M Iglesias, G Gutierrez, VM Vaughan, KL Szarowicz, MD Gonzalez-Garcia, I Lopez, M Cebrian, D Martinez, S Pastor, J de Cabo, R Serrano, M AF Ortega-Molina, Ana Lopez-Guadamillas, Elena Mattison, Julie A. Mitchell, Sarah J. Munoz-Martin, Maribel Iglesias, Gema Gutierrez, Vincent M. Vaughan, Kelli L. Szarowicz, Mark D. Gonzalez-Garcia, Ismael Lopez, Miguel Cebrian, David Martinez, Sonia Pastor, Joaquin de Cabo, Rafael Serrano, Manuel TI Pharmacological Inhibition of PI3K Reduces Adiposity and Metabolic Syndrome in Obese Mice and Rhesus Monkeys SO CELL METABOLISM LA English DT Article ID CALORIC RESTRICTION; INSULIN-RESISTANCE; ENERGY-EXPENDITURE; HUMANS; THERMOGENESIS; HOMEOSTASIS; PI3K-GAMMA; GENETICS; PATHWAY; DRIVE AB Genetic inhibition of PI3K signaling increases energy expenditure, protects from obesity and metabolic syndrome, and extends longevity. Here, we show that two pharmacological inhibitors of PI3K, CNIO-PI3Ki and GDC-0941, decrease the adiposity of obese mice without affecting their lean mass. Longterm treatment of obese mice with low doses of CNIO-PI3Ki reduces body weight until reaching a balance that is stable for months as long as the treatment continues. CNIO-PI3Ki treatment also ameliorates liver steatosis and decreases glucose serum levels. The above observations have been recapitulated in independent laboratories and using different oral formulations of CNIO-PI3Ki. Finally, daily oral treatment of obese rhesus monkeys for 3 months with low doses of CNIO-PI3Ki decreased their adiposity and lowered their serum glucose levels, in the absence of detectable toxicities. Therefore, pharmacological inhibition of PI3K is an effective and safe anti-obesity intervention that could reverse the negative effects of metabolic syndrome in humans. C1 [Ortega-Molina, Ana; Lopez-Guadamillas, Elena; Munoz-Martin, Maribel; Iglesias, Gema; Serrano, Manuel] Spanish Natl Canc Res Ctr CNIO, Tumor Suppress Grp, Madrid 28029, Spain. [Mattison, Julie A.; Mitchell, Sarah J.; Gutierrez, Vincent M.; Vaughan, Kelli L.; Szarowicz, Mark D.; de Cabo, Rafael] NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Vaughan, Kelli L.; Szarowicz, Mark D.] SoBran Inc, Burtonsville, MD 20866 USA. [Gonzalez-Garcia, Ismael; Lopez, Miguel] Univ Santiago de Compostela, CIBER Fisiopatol Obesidad & Nutr CIBERobn, Inst Invest Sanitaria, Dept Physiol,CIMUS, Santiago De Compostela 15782, Spain. [Cebrian, David; Martinez, Sonia; Pastor, Joaquin] Spanish Natl Canc Res Ctr CNIO, Expt Therapeut Programme, Madrid 28029, Spain. RP Serrano, M (reprint author), Spanish Natl Canc Res Ctr CNIO, Tumor Suppress Grp, Madrid 28029, Spain. EM mserrano@cnio.es RI Pastor, Joaquin/I-4567-2015; Martinez Gonzalez, Sonia/I-4616-2015; Serrano, Manuel/H-2634-2015; de Cabo, Rafael/J-5230-2016; OI Pastor, Joaquin/0000-0003-0553-8021; Martinez Gonzalez, Sonia/0000-0003-2230-7794; Serrano, Manuel/0000-0001-7177-9312; de Cabo, Rafael/0000-0002-3354-2442; Vaughan, Kelli/0000-0001-5274-582X; , rafael/0000-0003-2830-5693 FU CNIO; Spanish Ministry of Economy (SAF); European Research Council (ERC); Regional Government of Madrid; Botin Foundation; Banco Santander (Santander Universities Global Division); Ramon Areces Foundation; AXA Foundation; NIA (NIH); Xunta de Galicia; Spanish Ministry of Education FX We are grateful to Francisca Mulero for the DXA analyses and Marta Canamero for histology. Work in the laboratory of M.S. was funded by the CNIO and by grants from the Spanish Ministry of Economy (SAF), the European Research Council (ERC Advanced Grant), the Regional Government of Madrid, the Botin Foundation and Banco Santander (Santander Universities Global Division), the Ramon Areces Foundation, and the AXA Foundation. Work in the laboratory of R.d.C. was funded, in part, by the Intramural Research Program of the NIA (NIH). Work in the laboratory of M.L. was funded by the European Research Council (ERC Starting Grant) and Xunta de Galicia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. A.O.-M. was recipient of a predoctoral contract from the Regional Government of Madrid. E.L.-G. and I.G.-G. were recipients of a predoctoral contract from the Spanish Ministry of Education. Some of the authors (A.O.-M., S.M., J.P., and M.S.) are inventors in patents covering CNIO-PI3Ki and the use of PI3K inhibitors for obesity. NR 30 TC 11 Z9 11 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD APR 7 PY 2015 VL 21 IS 4 BP 558 EP 570 DI 10.1016/j.cmet.2015.02.017 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CF4EF UT WOS:000352500800011 PM 25817535 ER PT J AU Alegana, VA Atkinson, PM Pezzulo, C Sorichetta, A Weiss, D Bird, T Erbach-Schoenberg, E Tatem, AJ AF Alegana, V. A. Atkinson, P. M. Pezzulo, C. Sorichetta, A. Weiss, D. Bird, T. Erbach-Schoenberg, E. Tatem, A. J. TI Fine resolution mapping of population age-structures for health and development applications SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE demography; geo-statistics; mapping ID SYSTEMATIC ANALYSIS; CHILDBEARING AGE; PUBLIC-HEALTH; GLOBAL BURDEN; CHILDREN; AFRICA; MODELS; MORTALITY; PROGRESS; DISEASE AB The age-group composition of populations varies considerably across the world, and obtaining accurate, spatially detailed estimates of numbers of children under 5 years is important in designing vaccination strategies, educational planning or maternal healthcare delivery. Traditionally, such estimates are derived from population censuses, but these can often be unreliable, outdated and of coarse resolution for resource-poor settings. Focusing on Nigeria, we use nationally representative household surveys and their cluster locations to predict the proportion of the under-five population in 1 x 1 km using a Bayesian hierarchical spatio-temporal model. Results showed that land cover, travel time to major settlements, night-time lights and vegetation index were good predictors and that accounting for fine-scale variation, rather than assuming a uniform proportion of under 5 year olds can result in significant differences in health metrics. The largest gaps in estimated bednet and vaccination coverage were in Kano, Katsina and Jigawa. Geolocated household surveys are a valuable resource for providing detailed, contemporary and regularly updated population age-structure data in the absence of recent census data. By combining these with covariate layers, age-structure maps of unprecedented detail can be produced to guide the targeting of interventions in resource-poor settings. C1 [Alegana, V. A.; Atkinson, P. M.; Pezzulo, C.; Sorichetta, A.; Bird, T.; Erbach-Schoenberg, E.; Tatem, A. J.] Univ Southampton, Ctr Geog Hlth Res Geog & Environm, Highfield Southampton, England. [Weiss, D.] Univ Oxford, Dept Zool, Oxford, England. [Tatem, A. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Tatem, A. J.] Flowminder Fdn, Stockholm, Sweden. RP Alegana, VA (reprint author), Univ Southampton, Ctr Geog Hlth Res Geog & Environm, Highfield Southampton, England. EM vaalg10@soton.ac.uk OI Alegana, Victor/0000-0001-5177-9227 FU Commonwealth fellowship [KECS-2012-601]; NIH/NIAID [U19AI089674]; Bill & Melinda Gates Foundation [OPP110642749446, 1032350]; RAPIDD programme of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX V.A.A. is supported by a Commonwealth fellowship (KECS-2012-601). A.J.T. is supported by funding from NIH/NIAID (U19AI089674), the Bill & Melinda Gates Foundation (OPP110642749446, 1032350) and the RAPIDD programme of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. This work forms part of the WorldPop Project (www.worldpop.org.uk) and Flowminder Foundation (www.flowminder.org). NR 75 TC 4 Z9 4 U1 5 U2 12 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 EI 1742-5662 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD APR 6 PY 2015 VL 12 IS 105 AR 20150073 DI 10.1098/rsif.2015.0073 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD6WK UT WOS:000351230700019 ER PT J AU Wu, TJ Schriml, LM Chen, QR Colbert, M Crichton, DJ Finney, R Hu, Y Kibbe, WA Kincaid, H Meerzaman, D Mitraka, E Pan, Y Smith, KM Srivastava, S Ward, S Yan, C Mazumder, R AF Wu, Tsung-Jung Schriml, Lynn M. Chen, Qing-Rong Colbert, Maureen Crichton, Daniel J. Finney, Richard Hu, Ying Kibbe, Warren A. Kincaid, Heather Meerzaman, Daoud Mitraka, Elvira Pan, Yang Smith, Krista M. Srivastava, Sudhir Ward, Sari Yan, Cheng Mazumder, Raja TI Generating a focused view of disease ontology cancer terms for pan-cancer data integration and analysis SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID PROGRAMMED CELL-DEATH; MOLECULAR CLASSIFICATION; GENE ONTOLOGY; APOPTOSIS; NOMENCLATURE; MUTATIONS; NECROSIS; BIOLOGY AB Bio-ontologies provide terminologies for the scientific community to describe biomedical entities in a standardized manner. There are multiple initiatives that are developing biomedical terminologies for the purpose of providing better annotation, data integration and mining capabilities. Terminology resources devised for multiple purposes inherently diverge in content and structure. A major issue of biomedical data integration is the development of overlapping terms, ambiguous classifications and inconsistencies represented across databases and publications. The disease ontology (DO) was developed over the past decade to address data integration, standardization and annotation issues for human disease data. We have established a DO cancer project to be a focused view of cancer terms within the DO. The DO cancer project mapped 386 cancer terms from the Catalogue of Somatic Mutations in Cancer (COSMIC), The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium, Therapeutically Applicable Research to Generate Effective Treatments, Integrative Oncogenomics and the Early Detection Research Network into a cohesive set of 187 DO terms represented by 63 top-level DO cancer terms. For example, the COSMIC term 'kidney, NS, carcinoma, clear_cell_renal_cell_carcinoma' and TCGA term 'Kidney renal clear cell carcinoma' were both grouped to the term 'Disease Ontology Identification (DOID): 4467 / renal clear cell carcinoma' which was mapped to the TopNodes_DOcancerslim term 'DOID: 263 / kidney cancer'. Mapping of diverse cancer terms to DO and the use of top level terms (DO slims) will enable pan-cancer analysis across datasets generated from any of the cancer term sources where pan-cancer means including or relating to all or multiple types of cancer. The terms can be browsed from the DO web site (http://www.disease-ontology.org) and downloaded from the DO's Apache Subversion or GitHub repositories. C1 [Wu, Tsung-Jung; Pan, Yang; Smith, Krista M.; Yan, Cheng; Mazumder, Raja] George Washington Univ, Dept Biochem & Mol Med, Washington, DC 20037 USA. [Schriml, Lynn M.; Mitraka, Elvira] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Chen, Qing-Rong; Finney, Richard; Hu, Ying; Kibbe, Warren A.; Meerzaman, Daoud] NCI, Ctr Bioinformat & Informat Technol, Rockville, MD 20892 USA. [Colbert, Maureen; Crichton, Daniel J.; Kincaid, Heather] NASA, Jet Prop Lab, Pasadena, CA USA. [Srivastava, Sudhir] NCI, Canc Prevent Div, Rockville, MD 20892 USA. [Ward, Sari] Wellcome Trust Sanger Inst, Cambridge, England. [Mazumder, Raja] George Washington Univ, McCormick Genom & Prote Ctr, Washington, DC 20037 USA. RP Mazumder, R (reprint author), George Washington Univ, Dept Biochem & Mol Med, Washington, DC 20037 USA. EM mazumder@gwu.edu OI Mitraka, Elvira/0000-0003-0719-3485; Schriml, Lynn/0000-0001-8910-9851; Pan, Yang/0000-0003-3487-7233 FU National Cancer Institute EDRN (NCI) [156620] FX This project was partially funded by National Cancer Institute EDRN (NCI) Associate Member, agreement (156620) to R.M. Funding for open access charge: EDRN (NCI) Associate Member, agreement #156620 to R.M. NR 47 TC 1 Z9 1 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PD APR 4 PY 2015 AR bav032 DI 10.1093/database/bav032 PG 10 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA CR0XX UT WOS:000361048100002 ER PT J AU Danis, M AF Danis, Marion TI Weighing the Importance of Palliation of Symptoms for Ebola Patients During the Epidemic in West Africa SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID VIRUS DISEASE; CARE C1 [Danis, Marion] NIH, Bethesda, MD 20892 USA. RP Danis, M (reprint author), NIH, Dept Bioeth, Ctr Clin, Builiding 10,Room 1C118,10 Ctr Dr,MSC 1156, Bethesda, MD 20892 USA. EM mdanis@cc.nih.gov FU Department of Bioethics, an intramural program of the National Institutes of Health FX This work was supported by the Department of Bioethics, an intramural program of the National Institutes of Health. NR 8 TC 0 Z9 0 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD APR 3 PY 2015 VL 15 IS 4 BP 70 EP 72 DI 10.1080/15265161.2015.1011000 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA CF5RO UT WOS:000352614900022 ER PT J AU Alnaeeli, M Noguchi, CT AF Alnaeeli, Mawadda Noguchi, Constance Tom TI Erythropoietin and obesity-induced white adipose tissue inflammation: redefining the boundaries of the immunometabolism territory SO ADIPOCYTE LA English DT Article DE cytokines; chemokines; white adipose tissue; chemokines; macrophages; erythropoietin; erythropoietin receptor; adipocytes; obesity-induced inflammation; immunometabolism ID DIET-INDUCED OBESITY; INSULIN-RESISTANCE; MACROPHAGE RECRUITMENT; RECEPTOR; CELLS; ALPHA; HYPOXIA; GLUCOSE AB The adipose tissue represents a critical and predominant site for the interaction between metabolic and inflammatory responses during health and disease. In the white adipose tissue microenvironment, macrophages/adipocytes cross-talk have been shown to influence the metabolic and inflammatory states of both cell types, and contribute to the development of systemic insulin resistance during obesity. Indeed, the existence of paracrine loops between mature adipocytes and macrophages, especially during obesity-induced stress, involving the release of, and response to, an array of cytokines and regulatory factors, have been extensively studied using several in vitro and in vivo model systems. Published evidence together with recent observations, brought to light the unexpected role of erythropoietin and its receptor in the regulation of white adipose tissue mass, energy homeostasis, and inflammation as demonstrated by erythropoietin effects on adipocyte development and metabolic profile, and macrophage infiltration, cytokine responses, and activation state during diet-induced obesity. In this commentary, we discuss the newly added elements and perspectives to our understanding of the erythropoietin/erythropoietin-receptor axis as a regulator of obesity-induced white adipose tissue inflammation, providing insight into its effects on cytokine responses of macrophages and adipocytes, and possible links to glucose metabolism and insulin resistance. C1 [Alnaeeli, Mawadda] Ohio Univ, Dept Biol Sci, Zanesville, OH USA. [Alnaeeli, Mawadda] Ohio Univ, Inst Diabet, Athens, OH 45701 USA. [Noguchi, Constance Tom] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Noguchi, CT (reprint author), NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. EM connien@helix.nih.gov FU NIDDK NIH HHS [ZIA DK025102] NR 36 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-3945 EI 2162-397X J9 ADIPOCYTE JI Adipocyte PD APR 3 PY 2015 VL 4 IS 2 BP 153 EP 157 DI 10.4161/21623945.2014.978654 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CM4MR UT WOS:000357659300011 PM 26167420 ER PT J AU DeMets, DL Wittes, JT Geller, NL AF DeMets, David L. Wittes, Janet Turk Geller, Nancy L. TI The Influence of Biostatistics at the National Heart, Lung, and Blood Institute SO AMERICAN STATISTICIAN LA English DT Article ID SEQUENTIAL CLINICAL TRIALS; SAMPLE-SIZE; HYPERTENSION PREVENTION; MYOCARDIAL-INFARCTION; MORTALITY; DISEASE; SURVIVAL; TIME; EFFICIENCY; PRESSURE AB Since the early 1950s, the National Heart, Lung, and Blood Institute (NHBLI) has conducted a long series of influential randomized clinical trials in heart, lung, and blood diseases. The biostatisticians at the Institute have been central to the design, conduct, monitoring, and final analyses of these trials. The uniquely favorable deck of cards the group of biostatisticians at the Institute has been dealt over the six and half decades of the group's life has led to contributions that have had a major impact on the fields of biostatistics and clinical trials. The leaders of the NHLBI and its several Divisions have valued the independence, creativity, and collaborative interactions of statisticians within the Institute. The medical problems the Institute faced impelled the statisticians to develop methodology that would address questions of great public importance. Perhaps most importantly, the individual members of the group had a collective vision passed from member to member over time that new methodology must fit the questions being asked. The group has always had the technical ability to develop new methods and the conviction that they were responsible for ensuring that they could explain their methods to the clinicians with whom they worked. C1 [DeMets, David L.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. [Wittes, Janet Turk] Stat Collaborat Inc, Washington, DC 20036 USA. [Geller, Nancy L.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP DeMets, DL (reprint author), Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. EM demets@biostat.wisc.edu; janet@statcollab.com; ng@helix.nih.gov NR 94 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0003-1305 EI 1537-2731 J9 AM STAT JI Am. Stat. PD APR 3 PY 2015 VL 69 IS 2 BP 108 EP 120 DI 10.1080/00031305.2015.1035962 PG 13 WC Statistics & Probability SC Mathematics GA CL5TK UT WOS:000357023700009 ER PT J AU Kim, CH Kim, JW Jang, SM An, JH Seo, SB Choi, KH AF Kim, Chul-Hong Kim, Jung-Woong Jang, Sang-Min An, Joo-Hee Seo, Sang-Beom Choi, Kyung-Hee TI The chromodomain-containing histone acetyltransferase TIP60 acts as a code reader, recognizing the epigenetic codes for initiating transcription SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE histone modification; transcriptional regulation; code reader; TIP60; chromodomain ID RETINA DEVELOPMENT; DNA; ACTIVATION; CHROMATIN; H3; ACETYLATION; METHYLATION; PROTEIN; KINASE AB TIP60 can act as a transcriptional activator or a repressor depending on the cellular context. However, little is known about the role of the chromodomain in the functional regulation of TIP60. In this study, we found that TIP60 interacted with H3K4me3 in response to TNF-alpha signaling. TIP60 bound to H3K4me3 at the promoters of the NF-kappa B target genes IL6 and IL8. Unlike the wild-type protein, a TIP60 chromodomain mutant did not localize to chromatin regions. Because TIP60 binds to histones with specific modifications and transcriptional regulators, we used a histone peptide assay to identify histone codes recognized by TIP60. TIP60 preferentially interacted with methylated or acetylated histone H3 and H4 peptides. Phosphorylation near a lysine residue significantly reduced the affinity of TIP60 for the modified histone peptides. Our findings suggest that TIP60 acts as a functional link between the histone code and transcriptional regulators. C1 [Kim, Chul-Hong; Kim, Jung-Woong; Jang, Sang-Min; An, Joo-Hee; Seo, Sang-Beom; Choi, Kyung-Hee] Chung Ang Univ, Coll Nat Sci, Dept Life Sci, Seoul 156756, South Korea. [Kim, Jung-Woong] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. RP Choi, KH (reprint author), Chung Ang Univ, Coll Nat Sci, Dept Life Sci, Seoul 156756, South Korea. EM khchoi@cau.ac.kr FU National Research Foundation of Korea (NRF) - Korea government (MSIP) [2012008662] FX This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) [grant number 2012008662]. NR 24 TC 2 Z9 2 U1 3 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD APR 3 PY 2015 VL 79 IS 4 BP 532 EP 538 DI 10.1080/09168451.2014.993914 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA CG7JK UT WOS:000353479000002 PM 25560918 ER PT J AU Hutchison, M Pei, J Leung, WSW Mackenzie, M Hicks, MD Thurm, AE Han, JC Haqq, AM AF Hutchison, Marnie Pei, Jacqueline Leung, Wing Sze Wence Mackenzie, Michelle Hicks, Melanie D. Thurm, Audrey E. Han, Joan C. Haqq, Andrea M. TI Parental Ratings of Children and Adolescents With Prader-Willi Syndrome on the Behavior Rating Inventory of Executive Function (BRIEF) SO JOURNAL OF MENTAL HEALTH RESEARCH IN INTELLECTUAL DISABILITIES LA English DT Article DE behavioral phenotype; Prader-Willi syndrome; neurocognition; executive function ID AUTISM SPECTRUM DISORDERS; MALADAPTIVE BEHAVIOR; DEVELOPMENTAL DISORDERS; GENETIC SUBTYPES; ABILITIES; INTELLIGENCE; CHILDHOOD; SYMPTOMS; DELETION; ADULTS AB We investigated executive functioning in 25 children and adolescents with Prader-Willi syndrome (PWS) on the Behavior Rating Inventory of Executive Function (BRIEF). Significant deficits emerged, with mean scores on all but two scales reaching levels of clinical significance (T score >= 65). Older children tended to have higher scores than younger children. Children with uniparental disomy demonstrated higher scores than children with deletion and were more likely than children with deletion to have ratings in the clinically significant range on two scales. The PWS BRIEF profile resembles that of children with autism and intellectual disability from previous studies. Results are discussed in the context of intervention development. C1 [Hutchison, Marnie; Pei, Jacqueline; Leung, Wing Sze Wence] Univ Alberta, Dept Educ Psychol, Edmonton, AB T6G 2G5, Canada. [Mackenzie, Michelle; Haqq, Andrea M.] Univ Alberta, Dept Pediat, Edmonton, AB T6G 2G5, Canada. [Hicks, Melanie D.] NICHD, Unit Metab & Neuroendocrinol, NIH, Bethesda, MD USA. [Thurm, Audrey E.] NIMH, Pediat & Dev Neurosci Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Han, Joan C.] NICHD, Sect Growth & Obes, NIH, Bethesda, MD USA. [Han, Joan C.] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. RP Hutchison, M (reprint author), Univ Alberta, 6-102 Educ North, Edmonton, AB T6G 2G5, Canada. EM mhutchis@ualberta.ca FU Foundation for Prader-Willi Research (FPWR); Hyperphagia Conference Best Idea Grant from the Prader-Willi Syndrome Association (US); Canadian Institutes of Health Research; Intramural Research Programs of the National Institute of Child Health and Human Development [12-CH-0051, NCT01517048]; National Institute of Mental Health FX This study was supported by the Foundation for Prader-Willi Research (FPWR), the Hyperphagia Conference Best Idea Grant from the Prader-Willi Syndrome Association (US), the Canadian Institutes of Health Research, and the Intramural Research Programs of the National Institute of Child Health and Human Development (protocol 12-CH-0051; NCT01517048) and the National Institute of Mental Health. NR 42 TC 1 Z9 1 U1 5 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1931-5864 EI 1931-5872 J9 J MENT HEALTH RES IN JI J. Ment. Health Res. Intellect. Disabil. PD APR 3 PY 2015 VL 8 IS 2 BP 55 EP 71 DI 10.1080/19315864.2015.1017893 PG 17 WC Education, Special; Psychiatry; Rehabilitation SC Education & Educational Research; Psychiatry; Rehabilitation GA CG7RQ UT WOS:000353502900001 ER PT J AU Shah, SK Wendler, D Danis, M AF Shah, Seema K. Wendler, David Danis, Marion TI Examining the Ethics of Clinical Use of Unproven Interventions Outside of Clinical Trials During the Ebola Epidemic SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE resource allocation; research ethics; physician-patient relationship; compassionate use; experimental therapy ID VIRUS DISEASE; EXPERIMENTAL DRUGS; COMPASSIONATE USE; WEST-AFRICA; THERAPIES; OUTBREAK; ACCESS AB The recent Ebola outbreak in West Africa began in the spring of 2014 and has since caused the deaths of over 6,000 people. Since there are no approved treatments or prevention modalities specifically targeted at Ebola Virus Disease (EVD), debate has focused on whether unproven interventions should be offered to Ebola patients outside of clinical trials. Those engaged in the debate have responded rapidly to a complex and evolving crisis, however, and this debate has not provided much opportunity for in-depth analysis. Additionally, the existing literature on access to unproven therapies has focused on contexts like HIV/AIDS and oncology, which are very different than the Ebola epidemic. In this paper, we examine the ethical issues surrounding access to unproven therapies in the context of the recent Ebola outbreak to yield new insights about this controversial and unsettled issue. We argue first that, in this context, the interests of patients in obtaining access to unproven therapies are not fully aligned with the interests of their providers and drug developers. Second, we focus on the resource constraints facing providers, funders, and patients and conclude that they often counsel against the use of unproven interventions against EVD. C1 [Shah, Seema K.] NIH, Ctr Clin, Dept Bioeth, Div Aids, Bethesda, MD 20892 USA. [Wendler, David; Danis, Marion] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. RP Shah, SK (reprint author), NIH, Dept Bioeth, Div Aids, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM shahse@mail.nih.gov FU Intramural Research Program of the National Institutes of Health (NIH); Warren G. Magnuson Clinical Center FX The Intramural Research Program of the National Institutes of Health (NIH) and the Warren G. Magnuson Clinical Center supported this research. The authors are U.S. government employees who must comply with the NIH Public Access Policy, and the authors or NIH will deposit in NIH's PubMed Central archive, an electronic version of the final manuscript upon acceptance for publication, to be made publicly available no later than twelve months after the official date of publication. NR 27 TC 5 Z9 5 U1 6 U2 23 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD APR 3 PY 2015 VL 15 IS 4 BP 11 EP 16 DI 10.1080/15265161.2015.1010996 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA CF5RO UT WOS:000352614900003 PM 25856592 ER PT J AU Millum, J AF Millum, Joseph TI Controlling Ebola Trials SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Millum, Joseph] NIH, Bethesda, MD 20892 USA. RP Millum, J (reprint author), NIH, Ctr Clin, Dept Bioeth, Fogarty Int Ctr, Bldg 10,1C118,10 Ctr Dr, Bethesda, MD 20892 USA. EM joseph.millum@nih.gov FU National Institutes of Health Clinical Center; Fogarty International Center FX This work was supported, in part, by intramural funds from the National Institutes of Health Clinical Center and Fogarty International Center. I thank Annette Rid for very helpful comments on an earlier draft. NR 6 TC 1 Z9 1 U1 0 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD APR 3 PY 2015 VL 15 IS 4 BP 36 EP 37 DI 10.1080/15265161.2015.1009568 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA CF5RO UT WOS:000352614900008 PM 25856597 ER PT J AU Dawson, L AF Dawson, Liza TI Not All RCTs Are Created Equal: Lessons From Early AIDS Trials SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID ZIDOVUDINE; INFECTION C1 [Dawson, Liza] NIH, Bethesda, MD USA. RP Dawson, L (reprint author), NIAID, NIH, Div Aids, Res Eth Team, 5601 Fishers Lane, Bethesda, MD 20892 USA. EM dawsonl@niaid.nih.gov NR 10 TC 4 Z9 4 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD APR 3 PY 2015 VL 15 IS 4 BP 45 EP 47 DI 10.1080/15265161.2015.1010019 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA CF5RO UT WOS:000352614900012 PM 25856601 ER PT J AU Yamada, KJ Barker, T Dyer, KD Rice, TA Percopo, CM Garcia-Crespo, KE Cho, S Lee, JJ Druey, KM Rosenberg, HF AF Yamada, Kelsey J. Barker, Tolga Dyer, Kimberly D. Rice, Tyler A. Percopo, Caroline M. Garcia-Crespo, Katia E. Cho, Soochin Lee, James J. Druey, Kirk M. Rosenberg, Helene F. TI Eosinophil-associated Ribonuclease 11 Is a Macrophage Chemoattractant SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LETHAL PNEUMOVIRUS INFECTION; RNASE-A RIBONUCLEASES; INNATE HOST-DEFENSE; TOLL-LIKE RECEPTORS; CATIONIC PROTEIN; GENE FAMILY; IN-VIVO; MOUSE EOSINOPHILS; MOLECULAR-CLONING; RAPID EVOLUTION AB RNase A is the prototype of an extensive family of divergent proteins whose members share a unique disulfide-bonded tertiary structure, conserved catalytic motifs, and the ability to hydrolyze polymeric RNA. Several members of this family maintain independent roles as ribonucleases and modulators of innate immunity. Here we characterize mouse eosinophil-associated RNase (Ear) 11, a divergent member of the eosinophil ribonuclease cluster, and the only known RNase A ribonuclease expressed specifically in response to Th2 cytokine stimulation. Mouse Ear 11 is differentially expressed in somatic tissues at baseline (brain << liver < lung < spleen); systemic stimulation with IL-33 results in 10-5000-fold increased expression in lung and spleen, respectively. Ear 11 is also expressed in response to protective priming of the respiratory mucosa with Lactobacillus plantarum; transcripts are detected both locally in lung as well as systemically in bone marrow and spleen. Mouse Ear 11 is enzymatically active, although substantially less so than mEar 1 and mEar 2; the relative catalytic efficiency (k(cat)/K-m) of mEar 11 is diminished similar to 1000-1500-fold. However, in contrast to RNase 2/EDN and mEar 2, which have been characterized as selective chemoattractants for CD11c(+) dendritic cells, mEar 11 has prominent chemoattractant activity for F4/80(+)CD11c(-) tissue macrophages. Chemoattractant activity is not dependent on full enzymatic activity, and requires no interaction with the pattern recognition receptor, Toll-like receptor 2 (TLR2). Taken together, this work characterizes a divergent RNase A ribonuclease with a unique expression pattern and function, and highlights the versatility of this family in promoting innate immunity. C1 [Yamada, Kelsey J.; Dyer, Kimberly D.; Rice, Tyler A.; Percopo, Caroline M.; Garcia-Crespo, Katia E.; Rosenberg, Helene F.] NIAID, Inflammat Immunobiol, NIH, Bethesda, MD 20892 USA. [Barker, Tolga; Druey, Kirk M.] NIAID, Mol Signal Transduct Sect, NIH, Bethesda, MD 20892 USA. [Cho, Soochin] Creighton Univ, Dept Biol, Omaha, NE 68178 USA. [Lee, James J.] Mayo Clin, Div Pulm Med, Dept Biochem & Mol Biol, Scottsdale, AZ 85259 USA. RP Rosenberg, HF (reprint author), NIAID, IIS, LAD, NIH, Bldg 10,Rm 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov FU National Institutes of Health from the NIAID Division of Intramural Research [AI000942]; National Institutes of Health [AI000746] FX This work was supported, in whole or in part, by National Institutes of Health Grants AI000942 from the NIAID Division of Intramural Research (to H. F. R.) and AI000746 (to K. M. D.). NR 67 TC 4 Z9 4 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 3 PY 2015 VL 290 IS 14 BP 8863 EP 8875 DI 10.1074/jbc.M114.626648 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CF0BI UT WOS:000352207100015 PM 25713137 ER PT J AU Thomas, CC Richards, TB Plescia, M Wong, FL Ballard, R Levin, TR Calonge, BN Brawley, OW Iskander, J AF Thomas, Cheryll C. Richards, Thomas B. Plescia, Marcus Wong, Faye L. Ballard, Rachel Levin, Theodore R. Calonge, Bruce N. Brawley, Otis W. Iskander, John TI CDC Grand Rounds: the Future of Cancer Screening SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT LA English DT Article ID COLORECTAL-CANCER; UNITED-STATES; HEALTH C1 [Thomas, Cheryll C.; Richards, Thomas B.; Plescia, Marcus; Wong, Faye L.] CDC, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Ballard, Rachel] NCI, Bethesda, MD 20892 USA. [Levin, Theodore R.] Permanente Med Grp Inc, Oakland, CA USA. [Levin, Theodore R.] Kaiser Permanente Med Ctr, Walnut Creek, CA USA. [Brawley, Otis W.] Amer Canc Soc, Atlanta, GA USA. [Iskander, John] CDC, Off Associate Director Sci, Atlanta, GA 30333 USA. RP Thomas, CC (reprint author), CDC, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. EM ccthomas@cdc.gov NR 13 TC 0 Z9 0 U1 0 U2 3 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 0149-2195 EI 1545-861X J9 MMWR-MORBID MORTAL W JI MMWR-Morb. Mortal. Wkly. Rep. PD APR 3 PY 2015 VL 64 IS 12 BP 324 EP 327 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CE8MO UT WOS:000352097000004 PM 25837243 ER PT J AU Rosenberg, SA Restifo, NP AF Rosenberg, Steven A. Restifo, Nicholas P. TI Adoptive cell transfer as personalized immunotherapy for human cancer SO SCIENCE LA English DT Review ID TUMOR-INFILTRATING LYMPHOCYTES; CD8(+) T-CELLS; CHIMERIC ANTIGEN RECEPTORS; METASTATIC MELANOMA; IN-VIVO; AUTOLOGOUS TUMOR; GENE-THERAPY; RECOMBINANT INTERLEUKIN-2; ANTITUMOR-ACTIVITY; CD4+T CELLS AB Adoptive cell therapy (ACT) is a highly personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer activity. ACT using naturally occurring tumor-reactive lymphocytes has mediated durable, complete regressions in patients with melanoma, probably by targeting somatic mutations exclusive to each cancer. These results have expanded the reach of ACT to the treatment of common epithelial cancers. In addition, the ability to genetically engineer lymphocytes to express conventional T cell receptors or chimeric antigen receptors has further extended the successful application of ACT for cancer treatment. C1 [Rosenberg, Steven A.; Restifo, Nicholas P.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,CRC Bldg,Room 3W-3940, Bethesda, MD 20892 USA. EM sar@nih.gov; restifo@nih.gov OI Restifo, Nicholas P./0000-0003-4229-4580 FU Center for Cancer Research, NCI, NIH, Bethesda, Maryland; Milstein Family Foundation FX We thank the Center for Cancer Research, NCI, NIH, Bethesda, Maryland, and the Milstein Family Foundation for their generous support. NR 94 TC 241 Z9 256 U1 58 U2 245 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD APR 3 PY 2015 VL 348 IS 6230 BP 62 EP 68 DI 10.1126/science.aaa4967 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE8GJ UT WOS:000352079500027 PM 25838374 ER PT J AU Hoenen, T Safronetz, D Groseth, A Wollenberg, KR Koita, OA Diarra, B Fall, IS Haidara, FC Diallo, F Sanogo, M Sarro, YS Kone, A Togo, ACG Traore, A Kodio, M Dosseh, A Rosenke, K de Wit, E Feldmann, F Ebihara, H Munster, VJ Zoon, KC Feldmann, H Sow, S AF Hoenen, T. Safronetz, D. Groseth, A. Wollenberg, K. R. Koita, O. A. Diarra, B. Fall, I. S. Haidara, F. C. Diallo, F. Sanogo, M. Sarro, Y. S. Kone, A. Togo, A. C. G. Traore, A. Kodio, M. Dosseh, A. Rosenke, K. de Wit, E. Feldmann, F. Ebihara, H. Munster, V. J. Zoon, K. C. Feldmann, H. Sow, S. TI Mutation rate and genotype variation of Ebola virus from Mali case sequences SO SCIENCE LA English DT Article ID OUTBREAK; TRANSMISSION; CONGO AB The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 x 10(-4) substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns. C1 [Hoenen, T.; Safronetz, D.; Groseth, A.; Rosenke, K.; de Wit, E.; Ebihara, H.; Munster, V. J.; Feldmann, H.] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA. [Wollenberg, K. R.] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA. [Koita, O. A.; Diarra, B.; Sanogo, M.; Sarro, Y. S.; Kone, A.; Togo, A. C. G.] Univ Sci Tech & Technol Bamako, Ctr Res & Training HIV & TB, Bamako, Mali. [Fall, I. S.] World Hlth Org Off, Bamako, Mali. [Haidara, F. C.; Diallo, F.; Traore, A.; Kodio, M.; Sow, S.] Minist Sante & Hyg Publ, Ctr Natl Appui Lutte Maladie, Ctr Dev Vaccins CVD Mali, Ctr Operat Urgence, Bamako, Mali. [Dosseh, A.] WHO, Inter Country Support Team, Ouagadougou, Burkina Faso. [Feldmann, F.] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH, Hamilton, MT 59840 USA. [Zoon, K. C.] NIAID, Off Sci Director, NIH, Bethesda, MD 20895 USA. RP Feldmann, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA. EM feldmannh@niaid.nih.gov; ssow@medicine.umaryland.edu OI de Wit, Emmie/0000-0002-9763-7758; Munster, Vincent/0000-0002-2288-3196 FU Intramural Research Program of the NIH, NIAID FX We thank S. Nichol and U. Stroher (U. S. Centers for Disease Control and Prevention); T. Schwan, R. Sakai, M. Niang, and M. Pineda (NIH, NIAID); and S. Diop, S. Tounkara, and F. Daou Centre de Recherche et de Formation sur le VIH/TB SEREFO for helpful discussion and help with logistics and sample preparation. We also thank the Research Technology Branch at the Rocky Mountain Laboratories, particularly S. Kramer, K. Barbian, and S. Porcella, for sequencing services. This study made use of the high-performance computational capabilities of the Biowulf Linux cluster at the NIH, Bethesda, MD (http://biowulf.nih.gov), and the Office of Cyber Infrastructure and Computational Biology High-Performance Computing cluster at the NIAID, Bethesda, MD. This work was supported in part by the Intramural Research Program of the NIH, NIAID. The full-length sequences of the Malian EBOVs were deposited at GenBank under the accession numbers KP260799.1, KP260800.1, KP260801.1, and KP260802.1 (Ebola virus/H.sapiens-wt/MLI/2014/Makona-Mali-DPR1 to 4). There are no conflicts of interest, material transfer agreements, patents, or patent applications that apply to reagents, methods, or data in the paper for any of the authors. NR 14 TC 64 Z9 66 U1 3 U2 68 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD APR 3 PY 2015 VL 348 IS 6230 BP 117 EP 119 DI 10.1126/science.aaa5646 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE8GJ UT WOS:000352079500039 PM 25814067 ER PT J AU Fowler, SL Geers, AL AF Fowler, Stephanie L. Geers, Andrew L. TI Dispositional and comparative optimism interact to predict avoidance of a looming health threat SO PSYCHOLOGY & HEALTH LA English DT Article DE coping; dispositional optimism; comparative optimism; construal level theory; information processing ID UNREALISTIC OPTIMISM; PSYCHOLOGICAL DISTANCE; RISK PERCEPTIONS; BIAS; INFORMATION; INTENTIONS; MODERATORS; JUDGMENTS; KNOWLEDGE; BEHAVIOR AB Research indicates that when confronted with a health threat, individuals high in both dispositional and comparative optimism employ a more avoidant style of coping than individuals high in dispositional but low in comparative optimism. We examined the hypothesis that threat distance moderates this interactive optimism association. In two studies, participants were randomly assigned to a looming or distant threat condition. Study 1 revealed that in the looming threat condition, participants high in both forms of optimism were more likely to minimise the threat and less inclined to seek additional health information relative to participants high in dispositional but low in comparative optimism. In Study 2, the same interaction pattern emerged on a measure of psychological abstraction suggesting these variables combine to alter broad information processing strategies. Implications for considering multiple forms of optimism when delivering health status information are discussed. C1 [Fowler, Stephanie L.; Geers, Andrew L.] Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. [Fowler, Stephanie L.] NCI, NIH, Rockville, MD USA. RP Fowler, SL (reprint author), Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. EM stephanie.fowler@nih.gov FU NINDS NIH HHS [R03 NS051687] NR 43 TC 2 Z9 2 U1 5 U2 23 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0887-0446 EI 1476-8321 J9 PSYCHOL HEALTH JI Psychol. Health PD APR 3 PY 2015 VL 30 IS 4 BP 456 EP 474 DI 10.1080/08870446.2014.977282 PG 19 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA AY8EO UT WOS:000347787400005 PM 25320864 ER PT J AU Anderson, TK Campbell, BA Nelson, MI Lewis, NS Janas-Martindale, A Killian, ML Vincent, AL AF Anderson, Tavis K. Campbell, Brian A. Nelson, Martha I. Lewis, Nicola S. Janas-Martindale, Alicia Killian, Mary Lea Vincent, Amy L. TI Characterization of co-circulating swine influenza A viruses in North America and the identification of a novel H1 genetic clade with antigenic significance SO VIRUS RESEARCH LA English DT Article DE Influenza A virus; Antigenic drift; Swine; Zoonotic diseases; Vaccines; Epidemiology ID BINDING SITE DETERMINE; UNITED-STATES; US SWINE; INTERSPECIES TRANSMISSION; RESPIRATORY-DISEASE; AGRICULTURAL FAIRS; MAXIMUM-LIKELIHOOD; 2011-2012 H3N2V; COUNTY FAIR; JULY 2012 AB Multiple genetically and antigenically distinct hemagglutinin genes of the H1 and H3 influenza A virus (IAV) subtypes co-circulate in North American swine. This diversity has evolved by repeated transmission of IAVs from humans to swine and subsequent antigenic drift in swine. To understand the evolutionary dynamics of these diverse HA lineages in North American swine, we undertook a phylogenetic analysis of 1576 H1 and 607 H3 HA gene segments, as well as 834 N1 and 1293 N2 NA gene segments, and 2126 M gene segments. These data revealed yearly co-circulation of H1N1, H1N2, and H3N2 viruses, with three HA clades representing the majority of the HA sequences: of the H1 viruses, 42% were classified as H1 delta 1 and 40.6% were classified as H1 gamma; and of the H3 viruses 53% were classified as cluster IV-A H3N2. We detected a genetically distinct minor clade consisting of 37 H1 viruses isolated between 2003 and 2013, which we classified as H1 gamma-2. We estimated that this clade circulated in swine since approximately 1995, but it was not detected in swine until 2003. Though this clade only represents 1.07% of swine H1 sequences reported over the past 10 years, hemagglutination inhibition (HI) assays demonstrated that representatives of this clade of viruses are antigenically distinct, and, when measured using antigenic cartography, were as many as 7 antigenic units from other H1 gamma viruses. Therefore vaccines against the contemporary H1 gamma viruses are not likely to cross-protect against gamma-2 viruses. The long-term circulation of these gamma-2 viruses suggests that minor populations of viruses may be underreported in the national dataset given the long branch lengths and gaps in detections. The identification of these gamma-2 viruses demonstrates the need for robust surveillance to capture the full diversity IAVs in swine in the USA and the importance of antigenic drift in the diversification and emergence of new antigenic-variants in swine, which complicates vaccine design. Published by Elsevier B.V. C1 [Anderson, Tavis K.] Georgia So Univ, Dept Biol, Statesboro, GA 30460 USA. [Campbell, Brian A.; Vincent, Amy L.] USDA ARS, Virus & Prion Res Unit, Natl Anim Dis Ctr, Ames, IA 50010 USA. [Nelson, Martha I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Nelson, Martha I.] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ USA. [Lewis, Nicola S.] Univ Cambridge, Dept Zool, Cambridge, England. [Janas-Martindale, Alicia; Killian, Mary Lea] USDA APHIS VS STAS, Natl Vet Serv Labs, Ames, IA USA. RP Vincent, AL (reprint author), USDA ARS, Virus & Prion Res Unit, Natl Anim Dis Ctr, 1920 Dayton Ave,POB 70, Ames, IA 50010 USA. EM amy.vincent@ars.usda.gov OI Anderson, Tavis/0000-0002-3138-5535 FU USDA-ARS; USDA-APHIS-VS; USDA-ARS SCA [58-3625-2-103F, 58-3625-4-070]; EC [259949] FX We gratefully acknowledge pork producers, swine veterinarians, and laboratories for participating in the USDA Influenza Virus Surveillance System for swine. We wish to thank Michelle Harland, Gwen Nordholm, and Juan Carlos Mora for laboratory assistance and Jason Huegal, Jason Crabtree and Tyler Standley for animal care and handling assistance. Funding was provided by USDA-ARS and USDA-APHIS-VS by the Supplemental Appropriations Act of 2009. NSL was funded by USDA-ARS SCA agreement number 58-3625-2-103F and the EC FP7 award number 259949. TKA was funded by USDA-ARS SCA agreement number 58-3625-4-070. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture USDA is an equal opportunity provider and employer. NR 54 TC 10 Z9 10 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 EI 1872-7492 J9 VIRUS RES JI Virus Res. PD APR 2 PY 2015 VL 201 BP 24 EP 31 DI 10.1016/j.virusres.2015.02.009 PG 8 WC Virology SC Virology GA CI8MP UT WOS:000355026700004 PM 25701742 ER PT J AU Sironi, F Malnati, M Mongelli, N Cozzi, P Guzzo, C Ghezzi, S Martinez-Romero, C Garcia-Sastre, A Lusso, P Jabes, D Biswas, P AF Sironi, Francesca Malnati, Mauro Mongelli, Nicola Cozzi, Paolo Guzzo, Christina Ghezzi, Silvia Martinez-Romero, Carles Garcia-Sastre, Adolfo Lusso, Paolo Jabes, Daniela Biswas, Priscilla TI Characterization of HIV-1 entry inhibitors with broad activity against R5 and X4 viral strains SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TREATMENT-EXPERIENCED PATIENTS; T-CELLS; GLYCOPROTEIN GP120; CORECEPTOR USE; TYPE-1; CD4; INFECTION; SURAMIN; DISCOVERY AB Background: Combined antiretroviral therapy has drastically reduced mortality and morbidity of HIV-infected individuals. Nevertheless long-term toxicity and appearance of viral resistance hampers the prolonged effectiveness of combination therapy, requiring a continuous input of drugs to replace those utilized in combination regimens. We here investigated the anti-HIV activity of novel derivatives of the suradista chemical class. Methods: Compounds were tested on acute HIV-1 infection of activated peripheral blood mononuclear cells. HIV production was monitored by enzyme-linked immunosorbent assay measuring the protein p24 released in culture supernatants. Fusion assays were carried out to study the mechanism of action of these compounds. A modified version of a previously established recombinant vaccinia virus-based assay was used measuring activation of a reporter gene upon fusion of two distinct cell populations. Flow cytometry was performed in competition assays for the binding of several antibodies targeting different sites of the viral envelope glycoprotein gp120, or the receptor CD4, or the coreceptors CXCR4 and CCR5. Results: Four compounds inhibited replication of a prototypic R5 (BaL) and X4 (IIIB) laboratory-adapted HIV-1 strain at low micromolar concentrations, in the absence of cytotoxicity. Approximately a ten fold greater activity was achieved against the X4 as compared to the R5 strain. The compounds blocked X4 and R5 HIV-1 fusion, a step of viral entry. This activity appeared specific for HIV-1, as entry of human herpesvirus 6 (HHV-6) and influenza virus was not substantially affected. Further investigation of the inhibitory mechanism revealed that these new molecules target the viral envelope, rather than the coreceptors, as previously shown for a congener of the same class characterized by a long plasmatic half-life. Indeed ND-4043, the most active compound, specifically competed with binding of monoclonal antibodies against the CD4-binding site (CD4-BS) and coreceptor-binding site (CoR-BS) of gp120. These compounds displayed broad anti-HIV activity, as they inhibited various primary R5, X4 and, importantly, dualtropic R5X4 HIV-1 isolates. Of the four derivatives tested, the dimeric compounds were consistently more potent than the monomeric ones. Conclusions: Given their unique features, these molecules represent promising candidates for further development and exploitation as anti-HIV therapeutics. C1 [Sironi, Francesca; Malnati, Mauro] Hosp San Raffaele, Div Immunol Transplantat & Infect Dis, Unit Human Virol, I-20132 Milan, Italy. [Ghezzi, Silvia] Hosp San Raffaele, Div Immunol Transplantat & Infect Dis, Unit Viral Pathogens & Biosafety, I-20132 Milan, Italy. [Guzzo, Christina; Lusso, Paolo] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Martinez-Romero, Carles; Garcia-Sastre, Adolfo] Dept Microbiol, New York, NY 10029 USA. [Martinez-Romero, Carles; Garcia-Sastre, Adolfo] Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA. [Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY 10029 USA. [Jabes, Daniela] NeED Pharmaceut Srl, I-20139 Milan, Italy. [Biswas, Priscilla] Hosp San Raffaele, Div Genet & Cell Biol, Unit Mol Immunol, I-20132 Milan, Italy. RP Biswas, P (reprint author), Hosp San Raffaele, Div Genet & Cell Biol, Unit Mol Immunol, Via Olgettina 60, I-20132 Milan, Italy. EM priscilla.biswas@hsr.it OI Garcia-Sastre, Adolfo/0000-0002-6551-1827; Martinez-Romero, Carles/0000-0001-8888-7715 FU National AIDS Program - Istituto Superiore di Sanita, Rome, Italy [40HI2]; NIH CEIRS [HHSN 266200700010C]; Intramural Research Program of NIAID, NIH FX This research work was supported by grant 40HI2 to PB within the National AIDS Program - Istituto Superiore di Sanita, Rome, Italy, by NIH CEIRS contract HHSN 266200700010C and in part by the Intramural Research Program of the NIAID, NIH. NR 54 TC 2 Z9 2 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD APR 2 PY 2015 VL 13 AR 107 DI 10.1186/s12967-015-0461-9 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CI0NV UT WOS:000354434900001 PM 25888743 ER PT J AU Ho, JE Sritara, P Defilippi, CR Wang, TJ AF Ho, Jennifer E. Sritara, Piyamitr deFilippi, Christopher R. Wang, Thomas J. TI Soluble ST2 Testing in the General Population SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; RECEPTOR FAMILY-MEMBER; CARDIOVASCULAR STRESS; MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE; BIOMARKERS; FAILURE; RISK AB ST2 is a member of the interleukin (IL)-1 receptor family biomarker, and circulating soluble ST2 concentrations are believed to reflect cardiovascular stress. Recent studies have demonstrated soluble ST2 to be a strong predictor of cardiovascular outcomes in community-based populations free of cardiovascular disease. This report reviews the role of soluble ST2 in relation to cardiovascular risk factors and clinical outcomes in the general population. Furthermore, the recommendations regarding the role of soluble ST2 in general population-based testing, as formulated by the International ST2 Consensus Panel, are presented. There may be a role for soluble ST2 in improving current risk-stratification strategies for the prediction of cardiovascular outcomes, potentially in combination with other biomarkers in a multimarker strategy. However, the role of soluble ST2 testing in the general population has not yet been conclusively established. Future studies investigating the clinical utility of soluble ST2 screening in the general population are warranted. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ho, Jennifer E.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ho, Jennifer E.; Wang, Thomas J.] Boston Univ, Sch Med, Framingham, MA USA. [Ho, Jennifer E.] Boston Univ, Sch Med, Dept Med, Div Cardiovasc Med, Boston, MA 02118 USA. [Sritara, Piyamitr] Mahidol Univ, Dept Med, Bangkok 10700, Thailand. [deFilippi, Christopher R.] Univ Maryland, Sch Med, Dept Med, Div Cardiovasc Med, Baltimore, MD 21201 USA. [Wang, Thomas J.] Vanderbilt Univ, Dept Med, Div Cardiovasc Med, Nashville, TN USA. RP Ho, JE (reprint author), Boston Univ, Med Ctr, 88 East Newton St,C-818, Boston, MA 02118 USA. EM jenho@bu.edu OI Ho, Jennifer/0000-0002-7987-4768 FU Critical Diagnostics, San Diego, CA FX Publication of this supplement was supported by funding from Critical Diagnostics, San Diego, CA. NR 20 TC 2 Z9 2 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 2 PY 2015 VL 115 IS 7 SU S BP 22B EP 25B DI 10.1016/j.amjcard.2015.01.036 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF0RZ UT WOS:000352253200004 PM 25665763 ER PT J AU Simons, C Griffin, LB Helman, G Golas, G Pizzino, A Bloom, M Murphy, JLP Crawford, J Evans, SH Topper, S Whitehead, MT Schreiber, JM Chapman, KA Tifft, C Lu, KB Gamper, H Shigematsu, M Taft, RJ Antonellis, A Hou, YM Vanderver, A AF Simons, Cas Griffin, Laurie B. Helman, Guy Golas, Gretchen Pizzino, Amy Bloom, Miriam Murphy, Jennifer L. P. Crawford, Joanna Evans, Sarah H. Topper, Scott Whitehead, Matthew T. Schreiber, John M. Chapman, Kimberly A. Tifft, Cyndi Lu, Katrina B. Gamper, Howard Shigematsu, Megumi Taft, Ryan J. Antonellis, Anthony Hou, Ya-Ming Vanderver, Adeline TI Loss-of-Function Alanyl-tRNA Synthetase Mutations Cause an Autosomal-Recessive Early-Onset Epileptic Encephalopathy with Persistent Myelination Defect SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SPINAL-CORD INVOLVEMENT; MARIE-TOOTH DISEASE; BRAIN-STEM; CAUSE HYPOMYELINATION; HOMOZYGOUS MUTATION; PERRAULT SYNDROME; HEARING-LOSS; LEUKOENCEPHALOPATHY; IDENTIFICATION; AMINOACYLATION AB Mutations in genes encoding aminoacyl-tRNA synthetases are known to cause leukodystrophies and genetic leukoencephalopathies-heritable disorders that result in white matter abnormalities in the central nervous system. Here we report three individuals (two siblings and an unrelated individual) with severe infantile epileptic encephalopathy, clubfoot, absent deep tendon reflexes, extrapyramidal symptoms, and persistently deficient myelination on MRI. Analysis by whole exome sequencing identified mutations in the nuclear-encoded alanyl-tRNA synthetase (AARS) in these two unrelated families: the two affected siblings are compound heterozygous for p.Lys81Thr and p.Arg751Gly AARS, and the single affected child is homozygous for p.Arg751Gly AARS. The two identified mutations were found to result in a significant reduction in function. Mutations in AARS were previously associated with an autosomal-dominant inherited form of axonal neuropathy, Charcot-Marie-Tooth disease type 2N (CMT2N). The autosomal-recessive AARS mutations identified in the individuals described here, however, cause a severe infantile epileptic encephalopathy with a central myelin defect and peripheral neuropathy, demonstrating that defects of alanyl-tRNA charging can result in a wide spectrum of disease manifestations. C1 [Simons, Cas; Crawford, Joanna; Taft, Ryan J.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. [Griffin, Laurie B.; Antonellis, Anthony] Univ Michigan, Cellular & Mol Biol Program, Sch Med, Ann Arbor, MI 48109 USA. [Griffin, Laurie B.; Vanderver, Adeline] Univ Michigan, Sch Med, Med Scientist Training Program, Ann Arbor, MI 48109 USA. [Helman, Guy; Pizzino, Amy; Murphy, Jennifer L. P.; Schreiber, John M.] Childrens Natl Hlth Syst, Dept Neurol, Washington, DC 20010 USA. [Golas, Gretchen] NHGRI, Undiagnosed Dis Program, NIH, Bethesda, MD 20894 USA. [Bloom, Miriam] Childrens Natl Hlth Syst, Dept Hospitalist Med, Washington, DC 20010 USA. [Evans, Sarah H.] Childrens Natl Hlth Syst, Dept Phys Med & Rehabil, Washington, DC 20010 USA. [Topper, Scott] Invitae, San Francisco, CA 94107 USA. [Whitehead, Matthew T.] Childrens Natl Hlth Syst, Dept Neuroradiol, Washington, DC 20010 USA. [Chapman, Kimberly A.] Childrens Natl Hlth Syst, Dept Genet, Washington, DC 20010 USA. [Chapman, Kimberly A.; Vanderver, Adeline] Childrens Natl Hlth Syst, Med Genet Res Ctr, Washington, DC 20010 USA. [Lu, Katrina B.; Gamper, Howard; Shigematsu, Megumi; Hou, Ya-Ming] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA. [Taft, Ryan J.] Illumina Inc, San Diego, CA 92122 USA. [Taft, Ryan J.; Vanderver, Adeline] George Washington Univ, Dept Integrated Syst Biol, Washington, DC 20052 USA. [Taft, Ryan J.; Vanderver, Adeline] George Washington Univ, Dept Pediat, Washington, DC 20052 USA. [Antonellis, Anthony] Univ Michigan, Dept Human Genet, Sch Med, Ann Arbor, MI 48109 USA. [Antonellis, Anthony] Univ Michigan, Dept Neurol, Sch Med, Ann Arbor, MI 48109 USA. RP Vanderver, A (reprint author), Univ Michigan, Sch Med, Med Scientist Training Program, Ann Arbor, MI 48109 USA. EM avanderv@childrensnational.org RI Crawford, Joanna /F-9135-2013; Simons, Cas/A-7905-2011; Helman, Guy/C-7935-2017; OI Crawford, Joanna /0000-0003-0786-6889; Simons, Cas/0000-0003-3147-8042; Helman, Guy/0000-0002-4784-7423; Hou, Ya-Ming/0000-0001-6546-2597 FU Myelin Disorders Bioregistry Project; Delman Fund for Pediatric Neurology Education; NIH National Center for Advancing Translational Sciences [UL1TR000075]; National Institute of General Medical Sciences [GM110184]; NIH Cellular and Molecular Biology Training Grant [T32 GM007315]; Tolz Foundation for Research; Keystone Innovation Network; NIH Medical Scientist Training Grant [T32 GM007863]; NIH [F30 NS092238]; Australian Research Council; National Health and Medical Research Council, Australia [APP1068278]; University of Queensland Foundation Research Excellence Award; NIH Undiagnosed Diseases Program [LD_0115.0A, LD_0115.0B] FX We thank the individuals described in this manuscript and their families. The participation of G.H. and A.V. was supported by the Myelin Disorders Bioregistry Project. G.H. is also supported by the Delman Fund for Pediatric Neurology Education. This publication was supported by Award Number UL1TR000075 from the NIH National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Advancing Translational Sciences or the NIH. This work was also supported by the National Institute of General Medical Sciences (GM110184 to A. A.), the NIH Cellular and Molecular Biology Training Grant (T32 GM007315 to L.B.G.), the Tolz Foundation for Research and the Keystone Innovation Network award (to Y.M.H.), the NIH Medical Scientist Training Grant (T32 GM007863 to L.B.G.), and other NIH grants (F30 NS092238 to L.B.G.). The NIH Undiagnosed Diseases Program evaluated LD_0115.0A and LD_0115.0B. We thank the QCMG and IMB sequencing facility teams for their assistance with this project. Computational support was provided by the NeCTAR Genomics Virtual Laboratory and QRIScloud programs. R.J.T. was supported by an Australian Research Council Discovery Early Career Research Award. This work was supported by National Health and Medical Research Council, Australia Grant (APP1068278), and a University of Queensland Foundation Research Excellence Award. We also thank Marjo van der Knaap for her manuscript revision. NR 25 TC 13 Z9 15 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR 2 PY 2015 VL 96 IS 4 BP 675 EP 681 DI 10.1016/j.ajhg.2015.02.012 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA CF0DJ UT WOS:000352212600015 PM 25817015 ER PT J AU Altekruse, SF Petrick, JL Rolin, AI Cuccinelli, JE Zou, ZH Tatalovich, Z McGlynn, KA AF Altekruse, Sean F. Petrick, Jessica L. Rolin, Alicia I. Cuccinelli, James E. Zou, Zhaohui Tatalovich, Zaria McGlynn, Katherine A. TI Geographic Variation of Intrahepatic Cholangiocarcinoma, Extrahepatic Cholangiocarcinoma, and Hepatocellular Carcinoma in the United States SO PLOS ONE LA English DT Article ID LIVER-CANCER; RISK-FACTORS; C VIRUS; HEPATITIS-B; MORTALITY; CLASSIFICATION; EPIDEMIOLOGY; TRENDS AB Background Intrahepatic (ICC) and extrahepatic cholangiocarcinomas (ECC) are tumors that arise from cholangiocytes in the bile duct, but ICCs are coded as primary liver cancers while ECCs are coded as biliary tract cancers. The etiology of these tumors is not well understood. It has been suggested that the etiology of ICC is more similar to that of another type of liver cancer, hepatocellular carcinoma (HCC), than to the etiology of ECC. If this is true, geographic incidence patterns and trends in ICC incidence should be more similar to that of HCC than ECC. Methods To examine this hypothesis, data from the North American Association of Central Cancer Registries Cancer in North America data file were analyzed. Incidence rates and joinpoint trends were calculated by demographic subgroup. County-level incidence rates were mapped. Results Overall incidence rates, racial distribution, male: female ratio, and peak ages were more similar between ICC and ECC than with HCC. During 2000-2009, average annual incidence rates of ECC increased. During 2005-2009, average annual ICC incidence rates also increased. High rates for all three cancer sites were found in the Pacific region, particularly Hawaii and Alaska. Rates of ICC and ECC were also high in the Northeast and the upper Midwest, while rates of HCC were high in the South. Conclusions Demographic patterns and geographical variation were more closely related between ICC and ECC than HCC, suggesting that the etiology of ICC and ECC may be similar. Increasing rates of both tumors suggest that further etiology studies are warranted. C1 [Altekruse, Sean F.; Rolin, Alicia I.; Tatalovich, Zaria] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Petrick, Jessica L.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Cuccinelli, James E.; Zou, Zhaohui] Informat Management Serv Inc, Calverton, MD USA. RP Petrick, JL (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. EM jessica.petrick@nih.gov FU National Cancer Institute's Surveillance, Epidemiology, and End Results Contracts; North American Association of Central Cancer Registries Cancer in North America project; Division of Cancer Control and Population Sciences; Division of Cancer Epidemiology and Genetics, National Cancer Institute; Information Management Services, Inc. FX This work was supported by National Cancer Institute's Surveillance, Epidemiology, and End Results Contracts; North American Association of Central Cancer Registries Cancer in North America project; Division of Cancer Control and Population Sciences; and the Division of Cancer Epidemiology and Genetics, National Cancer Institute. Information Management Services, Inc. provided support in the form of salaries for authors [JEC and ZZ], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section. NR 27 TC 14 Z9 14 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 2 PY 2015 VL 10 IS 4 AR e0120574 DI 10.1371/journal.pone.0120574 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE9BS UT WOS:000352139000025 PM 25837669 ER PT J AU Turner, TN Sharma, K Oh, EC Liu, YFP Collins, RL Sosa, MX Auer, DR Brand, H Sanders, SJ Moreno-De-Luca, D Pihur, V Plona, T Pike, K Soppet, DR Smith, MW Cheung, SW Martin, CL State, MW Talkowski, ME Cook, E Huganir, R Katsanis, N Chakravarti, A AF Turner, Tychele N. Sharma, Kamal Oh, Edwin C. Liu, Yangfan P. Collins, Ryan L. Sosa, Maria X. Auer, Dallas R. Brand, Harrison Sanders, Stephan J. Moreno-De-Luca, Daniel Pihur, Vasyl Plona, Teri Pike, Kristen Soppet, Daniel R. Smith, Michael W. Cheung, Sau Wai Martin, Christa Lese State, Matthew W. Talkowski, Michael E. Cook, Edwin Huganir, Richard Katsanis, Nicholas Chakravarti, Aravinda TI Loss of delta-catenin function in severe autism SO NATURE LA English DT Article ID SPECTRUM DISORDERS; STRUCTURAL VARIATION; MENTAL-RETARDATION; SIGNALING PATHWAY; SEQUENCING DATA; PROTEIN; KAISO; MORPHOGENESIS; EXPRESSION; GENETICS AB Autism is a multifactorial neurodevelopmental disorder affecting more males than females; consequently, under a multifactorial genetic hypothesis, females are affected only when they cross a higher biological threshold. We hypothesize that deleterious variants at conserved residues are enriched in severely affected patients arising from female-enriched multiplex families with severe disease, enhancing the detection of key autism genes in modest numbers of cases. Here we show the use of this strategy by identifying missense and dosage sequence variants in the gene encoding the adhesive junction-associated delta-catenin protein (CTNND2) in female-enriched multiplex families and demonstrating their loss-of-function effect by functional analyses in zebrafish embryos and cultured hippocampal neurons from wild-type and Ctnnd2 null mouse embryos. Finally, through gene expression and network analyses, we highlight a critical role for CTNND2 in neuronal development and an intimate connection to chromatin biology. Our data contribute to the understanding of the genetic architecture of autism and suggest that genetic analyses of phenotypic extremes, such as female-enriched multiplex families, are of innate value in multifactorial disorders. C1 [Turner, Tychele N.; Sosa, Maria X.; Auer, Dallas R.; Pihur, Vasyl; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, Ctr Complex Dis Genom, Baltimore, MD 21205 USA. [Turner, Tychele N.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Predoctoral Training Program Human Genet & Mol Bi, Baltimore, MD 21205 USA. [Turner, Tychele N.; Sosa, Maria X.; Auer, Dallas R.; Sanders, Stephan J.; Moreno-De-Luca, Daniel; Pihur, Vasyl; Martin, Christa Lese; State, Matthew W.; Chakravarti, Aravinda] Univ Calif Los Angeles, NIMH, Autism Ctr Excellence ACE Genet Consortium, Los Angeles, CA 90095 USA. [Sharma, Kamal; Huganir, Richard] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA. [Oh, Edwin C.; Liu, Yangfan P.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Collins, Ryan L.; Brand, Harrison; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Collins, Ryan L.; Brand, Harrison; Talkowski, Michael E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Brand, Harrison; Talkowski, Michael E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sanders, Stephan J.; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA. [Moreno-De-Luca, Daniel] Yale Univ, Dept Psychiat, New Haven, CT 06511 USA. [Plona, Teri; Pike, Kristen; Soppet, Daniel R.] Leidos Biomed Res Inc, Frederick, MD 21702 USA. [Smith, Michael W.] NHGRI, Bethesda, MD 20892 USA. [Cheung, Sau Wai] Baylor Coll Med, Houston, TX 77030 USA. [Martin, Christa Lese] Geisinger Hlth Syst, Autism & Dev Med Inst, Lewisburg, PA 17837 USA. [Cook, Edwin] Univ Illinois, Chicago, IL 60608 USA. RP Chakravarti, A (reprint author), Johns Hopkins Univ, Sch Med, Ctr Complex Dis Genom, Baltimore, MD 21205 USA. EM aravinda@jhmi.edu OI Collins, Rachel/0000-0002-1559-8135 FU National Institute of Mental Health [1U24MH081810]; Simons Foundation; NIMH [MH095867, 5R25MH071584-07, MH19961-14, R01MH081754]; National Institutes of Health [RO1MH074090]; Autism Speaks Dennis Weatherstone pre-doctoral fellowship [7863] FX We acknowledge the participation of all of the families in the AGRE, NIMH and SSC studies that have been amodel of public participatory research. The AGRE is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health. The SSC used here was developed by the following principal investigators: A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, E. Wijsman. We thank the Allen Brain Atlas for use of their publicly available developing human brain expression data. Finally, we thank V. Kustanovich (AGRE) for helping with access to Autism Diagnostic Observation Schedule severity score data, D. Arking for sharing DNA from the SSC for Taqman genotyping, S. Maragh for zebrafish complementary DNA (cDNA) libraries and eef1a1l1 primers, A. Kapoor for discussions, Q. Jiang for the translation of ref. 43, and J. A. Rosenfeld, L. G. Shaffer, Y. Shenand B.-L. Wufor sharing CNV data sets. Sequencing services were provided by the Johns Hopkins University Next Generation Sequencing Center, Sidney Kimmel Comprehensive Cancer Center, Illumina Sequencing Services and the Johns Hopkins University Genetic Resources Core Facility. E. C. O. is a National Alliance for Research on Schizophrenia and Depression young investigator. N.K. is a Distinguished George W. Brumley Professor. This work was funded by grants from the Simons Foundation to A. C. and to N.K., NIMH grant MH095867 to M.E.T., NIMH grants 5R25MH071584-07 and MH19961-14 to D. M. D. L. (Malison), National Institutes of Health grant RO1MH074090 to C. L. M., NIMH grant R01MH081754 to A. C. and an Autism Speaks Dennis Weatherstone pre-doctoral fellowship (number 7863) to T.T. NR 54 TC 34 Z9 37 U1 3 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 2 PY 2015 VL 520 IS 7545 BP 51 EP + DI 10.1038/nature14186 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE7NE UT WOS:000352027700034 PM 25807484 ER PT J AU Zabow, G Dodd, SJ Koretsky, AP AF Zabow, G. Dodd, S. J. Koretsky, A. P. TI Shape-changing magnetic assemblies as high-sensitivity NMR-readable nanoprobes SO NATURE LA English DT Article ID INTRACELLULAR PH; RESPONSIVE HYDROGEL; MULTISPECTRAL MRI; CONTRAST AGENTS; PARACEST AGENTS; RESONANCE; COMPLEXES; BIOLOGY; PROBES AB Fluorescent and plasmonic labels and sensors have revolutionized molecular biology, helping visualize cellular and biomolecular processes(1-3). Increasingly, such probes are now being designed to respond to wavelengths in the near-infrared region, where reduced tissue autofluorescence and photon attenuation enable subsurface in vivo sensing(4). But even in the near-infrared region, optical resolution and sensitivity decrease rapidly with increasing depth. Here we present a sensor design that obviates the need for optical addressability by operating in the nuclear magnetic resonance (NMR) radio-frequency spectrum, where signal attenuation and distortion by tissue and biological media are negligible, where background interferences vanish, and where sensors can be spatially located using standard magnetic resonance imaging(MRI) equipment. The radio-frequency-addressable sensor assemblies presented here comprise pairs of magnetic disks spaced by swellable hydrogel material; they reversibly reconfigure in rapid response to chosen stimuli, to give geometry-dependent, dynamic NMR spectral signatures. The sensors can be made from biocompatible materials, are themselves detectable down to low concentrations, and offer potential responsive NMR spectral shifts that are close to a million times greater than those of traditional magnetic resonance spectroscopies. Inherent adaptability should allow such shape-changing systems to measure numerous different environmental and physiological indicators, thus providing broadly generalizable, MRI-compatible, radio-frequency analogues to optically based probes for use in basic chemical, biological, medical and engineering research. C1 [Zabow, G.; Dodd, S. J.; Koretsky, A. P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Zabow, G.] NIST, Electromagnet Div, Phys Measurements Lab, Boulder, CO 80305 USA. RP Zabow, G (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. EM gary.zabow@nist.gov FU NIH NINDS Intramural Research Program FX This work was supported in part by the NIH NINDS Intramural Research Program. We thank the NIH Mouse Imaging Facility for use of their 14 T MRI, Y. Chen for providing the MDCK cells, and J. Moreland for discussion and NIST Boulder cleanroom access. NR 39 TC 11 Z9 12 U1 19 U2 191 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 2 PY 2015 VL 520 IS 7545 BP 73 EP U157 DI 10.1038/nature14294 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE7NE UT WOS:000352027700039 PM 25778701 ER PT J AU Naik, S Bouladoux, N Linehan, JL Han, SJ Harrison, OJ Wilhelm, C Conlan, S Himmelfarb, S Byrd, AL Deming, C Quinones, M Brenchley, JM Kong, HH Tussiwand, R Murphy, KM Merad, M Segre, JA Belkaid, Y AF Naik, Shruti Bouladoux, Nicolas Linehan, Jonathan L. Han, Seong-Ji Harrison, Oliver J. Wilhelm, Christoph Conlan, Sean Himmelfarb, Sarah Byrd, Allyson L. Deming, Clayton Quinones, Mariam Brenchley, Jason M. Kong, Heidi H. Tussiwand, Roxanne Murphy, Kenneth M. Merad, Miriam Segre, Julia A. Belkaid, Yasmine TI Commensal-dendritic-cell interaction specifies a unique protective skin immune signature SO NATURE LA English DT Article ID T-CELLS; MICROBIOME; MICE; RESIDENT; ANTIGENS; SUBSETS; MACROPHAGES; EXPRESSION; DIVERSITY; INFECTION AB The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity(1-4). Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges(5-7). How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A(+) CD8(+) T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies. C1 [Naik, Shruti; Bouladoux, Nicolas; Linehan, Jonathan L.; Han, Seong-Ji; Harrison, Oliver J.; Wilhelm, Christoph; Himmelfarb, Sarah; Byrd, Allyson L.; Brenchley, Jason M.; Belkaid, Yasmine] NIAID, Immun Barrier Sites Initiat, NIH, Bethesda, MD 20892 USA. [Naik, Shruti; Bouladoux, Nicolas; Linehan, Jonathan L.; Han, Seong-Ji; Harrison, Oliver J.; Wilhelm, Christoph; Himmelfarb, Sarah; Byrd, Allyson L.; Belkaid, Yasmine] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Conlan, Sean; Byrd, Allyson L.; Deming, Clayton; Segre, Julia A.] NHGRI, Translat & Funct Genom Branch, Bethesda, MD 20892 USA. [Quinones, Mariam] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA. [Brenchley, Jason M.] NIAID, Immunopathogenesis Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Kong, Heidi H.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Tussiwand, Roxanne; Murphy, Kenneth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, Howard Hughes Med Inst, St Louis, MO 63110 USA. [Merad, Miriam] Icahn Sch Med Mt Sinai, Dept Oncol Sci, Tisch Canc Inst, New York, NY 10029 USA. [Merad, Miriam] Icahn Sch Med Mt Sinai, Inst Immunol, New York, NY 10029 USA. RP Belkaid, Y (reprint author), NIAID, Immun Barrier Sites Initiat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov OI Kong, Heidi/0000-0003-4424-064X FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases (NIAID); Human Frontier Science Program FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases (NIAID) and by the Human Frontier Science Program (C.W.). We thank the NIAID animal facility staff, in particular A. Gozalo (isolation of S. xylosus); D. Trageser-Cesler and C. Acevedo (NIAID gnotobiotic facility); K. Holmes, C. Eigsti and E. Stregevsky (NIAID sorting facility); K. Frank and F. Stock (MALDI-TOF analysis); B. Malissen (Langerin-GFP reporter mice); H. C. Morse (Irf8-/- mice); D. Kaplan (Langerin-DTA mice); R. Bosselut (B2m-/- mice); S. B. Hopping (collection of human skin tissue samples); J. Oh, K. Lore, and the Brenchley laboratory (technical advice and reagents); and K. Beacht and L. Martins dos Santos for technical assistance. We also thank the Belkaid laboratory for critical reading of the manuscript. NR 38 TC 61 Z9 61 U1 7 U2 44 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 2 PY 2015 VL 520 IS 7545 BP 104 EP U244 DI 10.1038/nature14052 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE7NE UT WOS:000352027700046 PM 25539086 ER PT J AU van der Lee, SJ Holstege, H Wong, TH Jakobsdottir, J Bis, JC Chouraki, V van Rooij, JGJ Grove, ML Smith, AV Amin, N Choi, SH Beiser, AS Garcia, ME van IJcken, WFJ Pijnenburg, YAL Louwersheimer, E Brouwer, RWW van den Hout, MCGN Oole, E Eirkisdottir, G Levy, D Rotter, JI Emilsson, V O'Donnell, CJ Aspelund, T Uitterlinden, AG Launer, LJ Hofman, A Boerwinkle, E Psaty, BM DeStefano, AL Scheltens, P Seshadri, S van Swieten, JC Gudnason, V van der Flier, WM Ikram, MA van Duijn, CM AF van der Lee, Sven J. Holstege, Henne Wong, Tsz Hang Jakobsdottir, Johanna Bis, Joshua C. Chouraki, Vincent van Rooij, Jeroen G. J. Grove, Megan L. Smith, Albert V. Amin, Najaf Choi, Seung-Hoan Beiser, Alexa S. Garcia, Melissa E. van IJcken, Wilfred F. J. Pijnenburg, Yolande A. L. Louwersheimer, Eva Brouwer, Rutger W. W. van den Hout, Mirjam C. G. N. Oole, Edwin Eirkisdottir, Gudny Levy, Daniel Rotter, Jerome I. Emilsson, Valur O'Donnell, Christopher J. Aspelund, Thor Uitterlinden, Andre G. Launer, Lenore J. Hofman, Albert Boerwinkle, Eric Psaty, Bruce M. DeStefano, Anita L. Scheltens, Philip Seshadri, Sudha van Swieten, John C. Gudnason, Vilmundur van der Flier, Wiesje M. Ikram, M. Arfan van Duijn, Cornelia M. TI PLD3 variants in population studies SO NATURE LA English DT Letter ID DUTCH POPULATION; DISEASE; COHORT; DESIGN C1 [van der Lee, Sven J.; Amin, Najaf; Uitterlinden, Andre G.; Hofman, Albert; Ikram, M. Arfan; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Holstege, Henne; Pijnenburg, Yolande A. L.; Louwersheimer, Eva; Scheltens, Philip; van Swieten, John C.; van der Flier, Wiesje M.] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Alzheimer Ctr, NL-1081 HZ Amsterdam, Netherlands. [Holstege, Henne] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, NL-1081 HZ Amsterdam, Netherlands. [Wong, Tsz Hang; van Swieten, John C.; Ikram, M. Arfan] Erasmus MC, Dept Neurol, NL-3000 CA Rotterdam, Netherlands. [Jakobsdottir, Johanna; Smith, Albert V.; Eirkisdottir, Gudny; Emilsson, Valur; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland. [Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Chouraki, Vincent; Choi, Seung-Hoan; Beiser, Alexa S.; Levy, Daniel; O'Donnell, Christopher J.; DeStefano, Anita L.; Seshadri, Sudha] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Chouraki, Vincent; Levy, Daniel; Seshadri, Sudha] Boston Univ, Sch Med, Boston, MA 02118 USA. [van Rooij, Jeroen G. J.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Grove, Megan L.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA. [Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Choi, Seung-Hoan; Beiser, Alexa S.; DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Garcia, Melissa E.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [van IJcken, Wilfred F. J.; Brouwer, Rutger W. W.; van den Hout, Mirjam C. G. N.; Oole, Edwin] Erasmus MC, Ctr Biom, NL-3000 CA Rotterdam, Netherlands. [Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles BioMed Res Inst, Torrance, CA 90502 USA. [Emilsson, Valur] Univ Iceland, Fac Pharmaceut Sci, IS-101 Reykjavik, Iceland. [Aspelund, Thor] Univ Iceland, Ctr Publ Hlth, IS-101 Reykjavik, Iceland. [Uitterlinden, Andre G.] Netherlands Consortium Hlth Aging & Natl Genom In, NL-2300 RC Leiden, Netherlands. [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [van der Flier, Wiesje M.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1081 HZ Amsterdam, Netherlands. [Ikram, M. Arfan] Erasmus MC, Dept Radiol, NL-3000 CA Rotterdam, Netherlands. RP van der Lee, SJ (reprint author), Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. EM c.vanduijn@erasmusmc.nl RI Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; Smith, Albert/K-5150-2015; OI Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433; Smith, Albert/0000-0003-1942-5845; Beiser, Alexa/0000-0001-8551-7778; Seshadri, Sudha/0000-0001-6135-2622; van IJcken, Wilfred/0000-0002-0421-8301; van Swieten, John /0000-0001-6278-6844 FU NCATS NIH HHS [UL1 TR000124]; NHLBI NIH HHS [R01 HL105756]; NIA NIH HHS [R01 AG033193, U01 AG049505] NR 13 TC 14 Z9 14 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 2 PY 2015 VL 520 IS 7545 BP E2 EP E3 DI 10.1038/nature14038 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CE7NE UT WOS:000352027700002 PM 25832410 ER PT J AU Douglas, PS Hoffmann, U Patel, MR Mark, DB Al-Khalidi, HR Cavanaugh, B Cole, J Dolor, RJ Fordyce, CB Huang, MG Khan, MA Kosinski, AS Krucoff, MW Malhotra, V Picard, MH Udelson, JE Velazquez, EJ Yow, E Cooper, LS Lee, KL AF Douglas, Pamela S. Hoffmann, Udo Patel, Manesh R. Mark, Daniel B. Al-Khalidi, Hussein R. Cavanaugh, Brendan Cole, Jason Dolor, Rowena J. Fordyce, Christopher B. Huang, Megan Khan, Muhammad Akram Kosinski, Andrzej S. Krucoff, Mitchell W. Malhotra, Vinay Picard, Michael H. Udelson, James E. Velazquez, Eric J. Yow, Eric Cooper, Lawton S. Lee, Kerry L. CA PROMISE Investigators TI Outcomes of Anatomical versus Functional Testing for Coronary Artery Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DIAGNOSTIC PERFORMANCE; IONIZING-RADIATION; BLOOD-INSTITUTE; CT ANGIOGRAPHY; UNITED-STATES; CHEST-PAIN; HEART; MANAGEMENT; RADIOLOGY; MORTALITY AB BACKGROUND Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care. METHODS We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure. RESULTS The mean age of the patients was 60.8 +/- 8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3 +/- 21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P = 0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P = 0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001). CONCLUSIONS In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the National Heart, Lung, and Blood Institute; PROMISE ClinicalTrials.gov number, NCT01174550.) C1 [Douglas, Pamela S.; Patel, Manesh R.; Mark, Daniel B.; Al-Khalidi, Hussein R.; Dolor, Rowena J.; Fordyce, Christopher B.; Huang, Megan; Kosinski, Andrzej S.; Krucoff, Mitchell W.; Velazquez, Eric J.; Yow, Eric; Lee, Kerry L.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC 27715 USA. [Hoffmann, Udo; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Udelson, James E.] Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA. [Cavanaugh, Brendan] New Mexico Heart Inst, Albuquerque, NM USA. [Cole, Jason] Cardiol Associates, Mobile, AL USA. [Khan, Muhammad Akram] North Dallas Res Associates, Dallas, TX USA. [Malhotra, Vinay] Cardiac Study Grp, Puyallup, WA USA. [Cooper, Lawton S.] NHLBI, Bethesda, MD 20892 USA. RP Douglas, PS (reprint author), Duke Univ, Sch Med, Med Ctr, 7022 North Pavil,POB 17969, Durham, NC 27715 USA. EM pamela.douglas@duke.edu OI Picard, Michael/0000-0002-9264-3243 FU National Heart, Lung, and Blood Institute FX Funded by the National Heart, Lung, and Blood Institute; PROMISE ClinicalTrials.gov number, NCT01174550. NR 32 TC 189 Z9 192 U1 5 U2 25 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 2 PY 2015 VL 372 IS 14 BP 1291 EP 1300 DI 10.1056/NEJMoa1415516 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CE7NL UT WOS:000352028500004 PM 25773919 ER PT J AU Roth, GA Forouzanfar, MH Moran, AE Barber, R Nguyen, G Feigin, VL Naghavi, M Mensah, GA Murray, CJL AF Roth, Gregory A. Forouzanfar, Mohammad H. Moran, Andrew E. Barber, Ryan Nguyen, Grant Feigin, Valery L. Naghavi, Mohsen Mensah, George A. Murray, Christopher J. L. TI Demographic and Epidemiologic Drivers of Global Cardiovascular Mortality SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DISEASE; COUNTRIES; DEATH; BURDEN AB BACKGROUND Global deaths from cardiovascular disease are increasing as a result of population growth, the aging of populations, and epidemiologic changes in disease. Disentangling the effects of these three drivers on trends in mortality is important for planning the future of the health care system and benchmarking progress toward the reduction of cardiovascular disease. METHODS We used mortality data from the Global Burden of Disease Study 2013, which includes data on 188 countries grouped into 21 world regions. We developed three counterfactual scenarios to represent the principal drivers of change in cardiovascular deaths (population growth alone, population growth and aging, and epidemiologic changes in disease) from 1990 to 2013. Secular trends and correlations with changes in national income were examined. RESULTS Global deaths from cardiovascular disease increased by 41% between 1990 and 2013 despite a 39% decrease in age-specific death rates; this increase was driven by a 55% increase in mortality due to the aging of populations and a 25% increase due to population growth. The relative contributions of these drivers varied by region; only in Central Europe and Western Europe did the annual number of deaths from cardiovascular disease actually decline. Change in gross domestic product per capita was correlated with change in age-specific death rates only among upper-middle income countries, and this correlation was weak; there was no significant correlation elsewhere. CONCLUSIONS The aging and growth of the population resulted in an increase in global cardiovascular deaths between 1990 and 2013, despite a decrease in age-specific death rates in most regions. Only Central and Western Europe had gains in cardiovascular health that were sufficient to offset these demographic forces. C1 [Roth, Gregory A.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA 98121 USA. [Roth, Gregory A.; Forouzanfar, Mohammad H.; Barber, Ryan; Nguyen, Grant; Naghavi, Mohsen; Murray, Christopher J. L.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA. [Moran, Andrew E.] Columbia Univ, Dept Med, Div Gen Med, New York, NY USA. [Feigin, Valery L.] Auckland Univ Technol, Natl Inst Stroke & Appl Neurosci, Fac Hlth & Environm Sci, Auckland, New Zealand. [Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA. RP Roth, GA (reprint author), Univ Washington, Dept Med, Div Cardiol, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA. EM rothg@uw.edu FU Bill and Melinda Gates Foundation FX Funded by the Bill and Melinda Gates Foundation and others. NR 13 TC 88 Z9 94 U1 5 U2 20 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 2 PY 2015 VL 372 IS 14 BP 1333 EP 1341 DI 10.1056/NEJMoa1406656 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CE7NL UT WOS:000352028500008 PM 25830423 ER PT J AU Knepper, MA Kwon, TH Nielsen, S AF Knepper, Mark A. Kwon, Tae-Hwan Nielsen, Soren TI Molecular Physiology of Water Balance SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID RENAL COLLECTING DUCT; THICK ASCENDING LIMB; VASOPRESSIN-INDUCED ANTIDIURESIS; URINARY CONCENTRATING MECHANISM; RAT-KIDNEY; AQUAPORIN-2 TRAFFICKING; DIABETES-INSIPIDUS; HENLES LOOP; TRANSCRIPTIONAL REGULATION; PHOSPHORYLATION SITES AB THE HYPOTHALAMIC-NEUROHYPOPHYSEAL-RENAL AXIS NORMALLY MAINtains water balance during variations in water intake and nonrenal losses of water. Failure of this mechanism is common in hospitalized patients, and it results in a variety of water-balance disorders. In this article, we begin by reviewing the classic, integrative principles of water balance in mammals and then use this classic model as a framework to discuss the genes and gene products (proteins) involved in water balance. In so doing, our goal is to provide clinicians with a mechanistic basis for decisions regarding the diagnosis and treatment of water-balance disorders. The regulation of water balance is governed by a high-gain feedback mechanism involving the hypothalamus, the neurohypophysis, and the kidneys (Fig. 1). Osmoreceptors in the hypothalamus, which originally were described by Verney,(1) sense plasma osmolality. The molecular mechanism of "osmosensing" has recently been described by Danziger and Zeidel.(2) It is, in part, dependent on activation of nonselective calcium-permeable cation channels in osmosensing neurons that can serve as stretch receptors. When plasma osmolality increases to levels above a physiologic threshold (290 to 295 mOsm per kilogram of water in most persons), there is increased secretion of the peptide hormone vasopressin from vasopressinergic nerve endings in the neurohypophysis. High osmolality also triggers thirst. Vasopressin binds to receptors in the kidney that decrease excretion of water (Fig. 2), and a greater fraction of filtered water is returned to the blood. The rate of water excretion can vary over a broad range in response to changes in plasma vasopressin levels without substantial changes in net solute excretion (osmolar clearance). This independent control of water and solute excretion is the result of specialized urinary concentrating and diluting mechanisms; these mechanisms are reviewed elsewhere.(3) Increased renal reabsorption of water in response to vasopressin lowers plasma osmolality, thereby reducing the stimulus for vasopressin secretion and thirst and completing the feedback loop (Fig. 1). Table 1 provides a list of the major proteins that are responsible for components of the integrative model shown in Figure 1. These proteins are the focus of this review. C1 [Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. [Kwon, Tae-Hwan] Kyungpook Natl Univ, Dept Biochem & Cell Biol, Sch Med, Taegu 702701, South Korea. [Nielsen, Soren] Aalborg Univ, Inst Med & Hlth Technol, Aalborg, Denmark. RP Knepper, MA (reprint author), NIH, 10 Ctr Dr,Bldg 10,Rm 6N307, Bethesda, MD 20892 USA. EM knep@helix.nih.gov NR 75 TC 25 Z9 26 U1 3 U2 37 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 2 PY 2015 VL 372 IS 14 BP 1349 EP 1358 DI 10.1056/NEJMra1404726 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CE7NL UT WOS:000352028500010 PM 25830425 ER PT J AU Gahl, RF Tekle, E Zhu, GA Taraska, JW Tjandra, N AF Gahl, Robert F. Tekle, Ephrem Zhu, Gefei Alex Taraska, Justin W. Tjandra, Nico TI Acquiring snapshots of the orientation of trans-membrane protein domains using a hybrid FRET pair SO FEBS LETTERS LA English DT Article DE Fluorescence; Forster resonance energy transfer (FRET); Confocal microscopy; Membrane proteins; Live cells; Giant unilamellar vesicles (GUV) ID RESONANCE ENERGY-TRANSFER; ELECTRIC-FIELDS; TOPOLOGY; CELLS; BAX; INSERTION; APOPTOSIS; FM1-43 AB One challenge in studying the function of membrane-embedded proteins is determining the orientation of key domains in the context of the changing and dynamic membrane environment. We describe a confocal microscopy setup that utilizes external electric field pulses to direct dipicrylamine (DPA) to a membrane leaflet. The detection of FRET between DPA and a fluorescent probe attributes it to the inner or outer leaflet of a membrane. By utilizing short acquisition times and confocal imaging, this attribution could be made even in changing membrane environments. Our setup adds versatility to the study of the biological activity of membrane-embedded proteins. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 [Gahl, Robert F.; Tekle, Ephrem; Zhu, Gefei Alex; Taraska, Justin W.; Tjandra, Nico] NHLBI, Biochem & Biophys Ctr, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Biochem & Biophys Ctr, Lab Mol Biophys, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM tjandran@nhlbi.nih.gov RI Taraska, Justin/H-8876-2016; OI Taraska, Justin/0000-0001-5355-9535; Zhu, Gefei/0000-0002-0255-2664 FU Intramural Research Program of the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) FX We thank Dr. Yu Wang for providing the tBid and Dr. Greg Piszczek of the Biophysics Core Facility, Biochemistry and Biophysics Center, NHLBI, for helpful discussions. The Intramural Research Program of the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) supported this work. NR 25 TC 1 Z9 1 U1 1 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD APR 2 PY 2015 VL 589 IS 8 BP 885 EP 889 DI 10.1016/j.febslet.2015.02.030 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CD7JE UT WOS:000351265800003 PM 25747388 ER PT J AU Barclay, G Huh, J Nilsen, W Spruijt-Metz, D AF Barclay, Gillian Huh, Jimi Nilsen, Wendy Spruijt-Metz, Donna TI REDUCING HEALTH DISPARTIES USING MHEALTH TOOLS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Barclay, Gillian] Aetna Fdn, Hartford, CT USA. [Huh, Jimi] Univ So Calif, Los Angeles, CA 90032 USA. [Nilsen, Wendy] NIH, Bethesda, MD 20892 USA. [Spruijt-Metz, Donna] Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA 90004 USA. EM jimihuh@usc.edu; nilsenwj@od.nih.gov; dmetz@usc.edU NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 24 BP S73 EP S73 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001285 ER PT J AU Beckjord, E Ahern, D van Londen, G Cardy, A Muse, C Novich, C Hesse, B AF Beckjord, Ellen Ahern, David van Londen, G. Cardy, Alexandra Muse, Chantal Novich, Cheyanne Hesse, Bradford TI CANCER SURVIVORS' USE AND EXPECTATIONS OF HEALTH INFORMATION TECHNOLOGY (HIT): A QUALITATIVE STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Beckjord, Ellen] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA. [Ahern, David] Brigham & Womens Hosp, Boston, MA 02115 USA. [van Londen, G.; Cardy, Alexandra] Univ Pittsburgh, Pittsburgh, PA 15232 USA. [Muse, Chantal] Duquesne Univ, Pittsburgh, PA 15219 USA. [Novich, Cheyanne] Carlow Univ, Pittsburgh, PA USA. [Hesse, Bradford] NCI, Rockville, MD USA. EM beckjorde@upmc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA A021 BP S9 EP S9 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001032 ER PT J AU Bowen, D Quintiliani, LM Rosenberg, D Baskin, ML Taplin, S AF Bowen, Deborah Quintiliani, Lisa M. Rosenberg, Dori Baskin, Monica L. Taplin, Stephen TI MULTI-LEVEL RESEARCH CHANGING DIET AND PHYSICAL ACTIVITY AMONG UNDERSERVED POPULATIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bowen, Deborah] Univ Washington, Seattle, WA 98195 USA. [Quintiliani, Lisa M.] Boston Univ, Boston, MA 02215 USA. [Rosenberg, Dori] Grp Hlth Res Inst, Seattle, WA USA. [Baskin, Monica L.] Univ Alabama Birmingham, Birmingham, AL USA. [Taplin, Stephen] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 49 BP S158 EP S158 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002110 ER PT J AU Boynton, MH Portnoy, DB Noar, SM Flaherty, B Grana, R AF Boynton, Marcella H. Portnoy, David B. Noar, Seth M. Flaherty, Brian Grana, Rachel TI MIND THE GAPS: USING THEORY-BASED TOBACCO PREVENTION AND CONTROL RESEARCH TO INFORM REGULATORY SCIENCE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Boynton, Marcella H.] Univ N Carolina, Chapel Hill, NC USA. [Portnoy, David B.] US FDA, Silver Spring, MD USA. [Noar, Seth M.] Univ N Carolina, Chapel Hill, NC USA. [Flaherty, Brian] Univ Washington, Seattle, WA 98195 USA. [Grana, Rachel] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 48 BP S157 EP S157 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002106 ER PT J AU Cole-Lewis, H Perotte, A Galica, K Dreyer, L Schwarz, M Augustson, E Patrick, H AF Cole-Lewis, Heather Perotte, Adler Galica, Kasia Dreyer, Lindy Schwarz, Mary Augustson, Erik Patrick, Heather TI USING COMPUTATIONAL METHODS TO ASSESS INTERPERSONAL INTERACTIONS IN A SMOKING CESSATION FACEBOOK COMMUNITY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cole-Lewis, Heather; Galica, Kasia] ICF Int, Rockville, MD 20850 USA. [Perotte, Adler] Columbia Univ, Dept Biomed Informat, New York, NY USA. [Dreyer, Lindy] ICF Int, Fairifax, VA USA. [Schwarz, Mary] ICF Int, Fairfax, VA USA. [Augustson, Erik; Patrick, Heather] NCI, Rockville, MD USA. EM heather.cole-lewis@icfi.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 BP S212 EP S212 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002324 ER PT J AU Dietz, S Tennant, B Keefe, B Freeman, C Schwarz, M Augustson, E Patrick, H AF Dietz, Sondra Tennant, Bethany Keefe, Brian Freeman, Carol Schwarz, Mary Augustson, Erik Patrick, Heather TI EVALUATION OF A SMOKING CESSATION TEXT MESSAGE PROGRAM WITH FORMER AND CURRENT USERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Dietz, Sondra; Tennant, Bethany; Schwarz, Mary] ICF Int, Fairfax, VA USA. [Keefe, Brian; Freeman, Carol] ICF Int, Rockville, MD 20850 USA. [Augustson, Erik; Patrick, Heather] NCI, Rockville, MD USA. EM brian.keefe@icfi.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 BP S213 EP S213 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002325 ER PT J AU Dwyer, L Oh, A Hennessy, E Yaroch, A Nebeling, L AF Dwyer, Laura Oh, April Hennessy, Erin Yaroch, Amy Nebeling, Linda TI CORRELATES OF SUN PROTECTION BEHAVIORS AMONG LATINO PARENTS AND ADOLESCENTS IN THE UNITED STATES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Dwyer, Laura] NCI, Rockville, MD 20850 USA. [Oh, April] NCI, Bethesda, MD 20892 USA. [Hennessy, Erin] Leidos Biomed Res Inc, Frederick, MD USA. [Yaroch, Amy] Gretchen Swanson Ctr Nutr, Omaha, NE USA. [Nebeling, Linda] NCI, Behav Res Program, Bethesda, MD 20892 USA. EM laura.dwyer@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 BP S77 EP S77 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001300 ER PT J AU Eisenberg, MH Thompson, K Quinn, MC Abrams, J Renninger, S Moore, P Phillips, LA AF Eisenberg, Miriam H. Thompson, Katherine Quinn, Margot C. Abrams, Jessica Renninger, Steffi Moore, Philip Phillips, Leigh Alison TI POSITIVE BODY IMAGE PREDICTS MORE EXERCISE LONGITUDINALLY FOR EXERCISE MAINTAINERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Eisenberg, Miriam H.] NICHD, NIH, Washington, DC 20009 USA. [Thompson, Katherine] George Washington Univ, Bethesda, MD USA. [Quinn, Margot C.; Renninger, Steffi; Moore, Philip] George Washington Univ, Washington, DC USA. [Abrams, Jessica] George Washington Univ, Somerville, MA USA. [Phillips, Leigh Alison] Iowa State Univ, Ames, IA USA. EM miriam.h.eisenb@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA B114 BP S120 EP S120 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001468 ER PT J AU Eisenberg, MH Quinn, MC Thompson, K Abrams, J Fowler, LA Moore, P Phillips, LA AF Eisenberg, Miriam H. Quinn, Margot C. Thompson, Katherine Abrams, Jessica Fowler, Lauren A. Moore, Philip Phillips, Leigh Alison TI USING GOOGLE DOCS TO MEASURE DAILY PHYSICAL ACTIVITY AMONG COLLEGE STUDENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Eisenberg, Miriam H.] NICHD, NIH, Washington, DC 20009 USA. [Quinn, Margot C.; Fowler, Lauren A.; Moore, Philip] George Washington Univ, Washington, DC USA. [Thompson, Katherine] George Washington Univ, Bethesda, MD USA. [Abrams, Jessica] George Washington Univ, Somerville, MA USA. [Phillips, Leigh Alison] Iowa State Univ, Ames, IA USA. EM miriam.h.eisenb@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA A093 BP S27 EP S27 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001104 ER PT J AU Fellows, JL Rigotti, NA Leo, MC Richter, K Harrington, KF Sherman, SE Tindle, HA Duffy, SA Stoney, C AF Fellows, Jeffrey L. Rigotti, Nancy A. Leo, Michael C. Richter, Kimber Harrington, Kathleen F. Sherman, Scott E. Tindle, Hilary A. Duffy, Sonia A. Stoney, Catherine TI POPULATION DISPARITIES AMONG HOSPITALIZED SMOKERS ENROLLED IN ONE OF SIX CHART STUDIES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Fellows, Jeffrey L.; Leo, Michael C.] Kaiser Permanente Ctr Hlth Res, Portland, OR 97227 USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. [Richter, Kimber] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Harrington, Kathleen F.] Univ Alabama Birmingham, Birmingham, AL USA. [Sherman, Scott E.] NYU, New York, NY USA. [Tindle, Hilary A.] Vanderbilt Univ, Nashville, TN USA. [Duffy, Sonia A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Stoney, Catherine] NHLBI, Bethesda, MD 20892 USA. EM jeffrey.fellows@kpchr.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA C118 BP S203 EP S203 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002289 ER PT J AU Gee, B Nansel, TR Liu, AY AF Gee, Benjamin Nansel, Tonja R. Liu, Aiyi TI A CLINIC-INTEGRATED BEHAVIORAL INTERVENTION REDUCES HYPOGLYCEMIA IN YOUTH WITH TYPE 1 DIABETES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gee, Benjamin] NICHD, Hlth Behav Branch, NIH, Bethesda, MD 20892 USA. [Nansel, Tonja R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Liu, Aiyi] NIH, Rockville, MD USA. EM benjamin.gee@nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 BP S57 EP S57 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001223 ER PT J AU Gee, B Li, KG Haynie, D Iannotti, RJ Simons-Morton, B AF Gee, Benjamin Li, Kaigang Haynie, Denise Iannotti, Ronald J. Simons-Morton, Bruce TI PROSPECTIVE ASSOCIATIONS BETWEEN PHYSICIAN ADVICE AND SUBSTANCE USE IN A YOUTH COHORT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Gee, Benjamin] NICHD, Hlth Behav Branch, NIH, Bethesda, MD USA. [Li, Kaigang; Haynie, Denise; Simons-Morton, Bruce] NICHHD, Bethesda, MD 20892 USA. [Iannotti, Ronald J.] Univ Massachusetts, Boston, MA 02125 USA. EM haynied@exchange.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 BP S81 EP S81 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001317 ER PT J AU Ginexi, E Hornik, R Ling, P Noar, SM AF Ginexi, Elizabeth Hornik, Robert Ling, Pamela Noar, Seth M. TI TOBACCO CENTERS FOR REGULATORY SCIENCE: A SEISMIC SHIFT IN TOBACCO PREVENTION AND CONTROL SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ginexi, Elizabeth] NCI, Bethesda, MD 20892 USA. [Hornik, Robert] Univ Penn, Philadelphia, PA 19104 USA. [Ling, Pamela] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Noar, Seth M.] Univ N Carolina, Chapel Hill, NC USA. EM lginexi@mail.nih.gov; rhornik@asc.upenn.edu; pling@medicine.ucsf.edu; noar@email.unc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 35 BP S136 EP S136 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002027 ER PT J AU Graves, KD Tucker-Seeley, R Gonzalez, BD Deshpande, A Lowenstein, LM Rowland, JH AF Graves, Kristi D. Tucker-Seeley, Reginald Gonzalez, Brian D. Deshpande, Anjali Lowenstein, Lisa M. Rowland, Julia H. TI AGING AND CANCER: IMPLICATIONS FOR COGNITIVE OUTCOMES AND CLINICAL ENCOUNTERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Graves, Kristi D.] Georgetown Univ, Washington, DC USA. [Tucker-Seeley, Reginald] Harvard Univ, Sch Publ Hlth, DFCI, Boston, MA 02115 USA. [Gonzalez, Brian D.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Deshpande, Anjali] Washington Univ, St Louis, MO USA. [Lowenstein, Lisa M.] Univ Rochester, Rochester, NY USA. [Rowland, Julia H.] NCI, Bethesda, MD 20892 USA. EM brian.gonzalez@moffitt.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 29 BP S130 EP S130 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002001 ER PT J AU Hekler, EB Riley, WT Collins, LM Patrick, K AF Hekler, Eric B. Riley, William T. Collins, Linda M. Patrick, Kevin TI WHAT IS THE NEXT-GENERATION PIPELINE FOR DEVELOPING AND EVALUATING HEALTH BEHAVIOR INTERVENTIONS? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hekler, Eric B.] Arizona State Univ, Phoenix, AZ USA. [Riley, William T.] NIH, Bethesda, MD 20892 USA. [Collins, Linda M.] Penn State Univ, State Coll, PA USA. [Patrick, Kevin] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 50 BP S159 EP S159 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002114 ER PT J AU Hekler, EB Moser, RP Michie, S Riley, WT Bickmore, TW AF Hekler, Eric B. Moser, Richard P. Michie, Susan Riley, William T. Bickmore, Timothy W. TI ORGANIZING WITH ONTOLOGIES! A PANEL DISCUSSION ON HOW ONTOLOGIES CAN SUPPORT BEHAVIORAL SCIENCE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hekler, Eric B.] Arizona State Univ, Phoenix, AZ 85003 USA. [Moser, Richard P.] NCI, Bethesda, MD 20892 USA. [Michie, Susan] UCL, London WC1E 7HB, England. [Riley, William T.] NIH, Bethesda, MD 20892 USA. [Bickmore, Timothy W.] Northeastern Univ, Boston, MA 02115 USA. EM ehekler@asu.edu; moserr@mail.nih.gov; s.michie@ucl.ac.uk; wiriley@mail.nih.gov; bickmore@ccs.neu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 11 BP S54 EP S54 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001213 ER PT J AU Hekler, EB Fletcher, R Rivera, DE Kumar, S Nilsen, W AF Hekler, Eric B. Fletcher, Rich Rivera, Daniel E. Kumar, Santosh Nilsen, Wendy TI ENGINEERING BEHAVIOR: ENGINEERING & COMPUTER SCIENCE WORK THAT FACILITATE BETTER MHEALTH RESEARCH SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hekler, Eric B.] Arizona State Univ, Phoenix, AZ USA. [Fletcher, Rich] MIT, Cambridge, MA 02142 USA. [Rivera, Daniel E.] Arizona State Univ, Tempe, AZ 85287 USA. [Kumar, Santosh] Univ Memphis, Memphis, TN 38152 USA. [Nilsen, Wendy] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 01 BP S39 EP S39 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001151 ER PT J AU Hunt, YM Sanders, A Cole-Lewis, H Schwarz, M Augustson, E AF Hunt, Yvonne M. Sanders, Amy Cole-Lewis, Heather Schwarz, Mary Augustson, Erik TI REAL-WORLD ENGAGEMENT WITH A TEXT-MESSAGE DELIVERED SMOKING CESSATION INTERVENTION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hunt, Yvonne M.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD 20850 USA. [Sanders, Amy] ICF Interact, Rockville, MD USA. [Cole-Lewis, Heather] ICF Int, Rockville, MD USA. [Schwarz, Mary] ICF Int, Fairfax, VA USA. [Augustson, Erik] NCI, Rockville, MD USA. EM huntym@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 BP S213 EP S213 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002327 ER PT J AU Kaplan, R Morgan, G AF Kaplan, Robert Morgan, Glen TI PROVIDERS ADVICE CONCERNING SMOKING CESSATION: EVIDENCE FROM THE MEDICAL EXPENDITURES PANEL SURVEY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kaplan, Robert] AHRQ, Rockville, MD 20850 USA. [Morgan, Glen] NCI, Rockville, MD USA. EM rmkaplan@ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA B133 BP S124 EP S124 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001486 ER PT J AU Kaufman, PG Powell, LH Freedland, KE AF Kaufman, Peter G. Powell, Lynda H. Freedland, Kenneth E. TI ISSUES IN DESIGN AND CONDUCT OF RANDOMIZED BEHAVIORAL CLINICAL TRIALS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kaufman, Peter G.] NHLBI, Bethesda, MD 20892 USA. [Powell, Lynda H.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Freedland, Kenneth E.] Washington Univ, Sch Med, St Louis, MO 63108 USA. EM kaufmannp@nhlbi.nih.gov; lpowell@rush.edu; freedlak@bmc.wustl.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 09 BP S2 EP S2 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001008 ER PT J AU Kiviniemi, MT Ellis, EM Orom, H Waters, EA Hay, J AF Kiviniemi, Marc T. Ellis, Erin M. Orom, Heather Waters, Erika A. Hay, Jennifer TI PROVIDING A "DON'T KNOW" RESPONSE OPTION CHANGES POPULATION PERCEIVED RISK ESTIMATES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kiviniemi, Marc T.; Orom, Heather] SUNY Buffalo, Buffalo, NY 14214 USA. [Ellis, Erin M.] NCI, Silver Spring, MD USA. [Waters, Erika A.] Washington Univ, Sch Med, St Louis, MO USA. [Hay, Jennifer] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. EM mtk8@buffalo.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA C120 BP S204 EP S204 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002291 ER PT J AU Lechner, SC Park, C Siembida, E Wettergren, L Smith, AW AF Lechner, Suzanne C. Park, Crystal Siembida, Elizabeth Wettergren, Lena Smith, Ashley W. TI ADOLESCENTS AND YOUNG ADULTS WITH CANCER: AN UNDER-RECOGNIZED CANCER DISPARITIES POPULATION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Lechner, Suzanne C.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Park, Crystal; Siembida, Elizabeth] Univ Connecticut, Storrs, CT USA. [Wettergren, Lena; Smith, Ashley W.] NCI, Bethesda, MD 20850 USA. EM crysdara@aol.com; elizabeth.siembida@uconn.edu; lena.wettergren@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 28 BP S129 EP S129 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001504 ER PT J AU Li, KG Haynie, D Palla, H Lipsky, L Simons-Morton, B AF Li, Kaigang Haynie, Denise Palla, Hira Lipsky, Leah Simons-Morton, Bruce TI CLASSIFYING WEIGHT STATUS IN ADOLESCENTS: A COMPARISON OF CDC BMI PERCENTILE AND IOTF CUT POINTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Li, Kaigang; Haynie, Denise; Palla, Hira; Lipsky, Leah; Simons-Morton, Bruce] NICHHD, Bethesda, MD 20852 USA. EM haynied@exchange.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA A074 BP S22 EP S22 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001085 ER PT J AU Michie, S West, R Sheals, KE Carey, RN Connell, L Larsen, K Gershuny, V An, L Riley, WT AF Michie, Susan West, Robert Sheals, Kate E. Carey, Rachel N. Connell, Lauren Larsen, Kai Gershuny, Victoria An, Larry Riley, William T. TI TOWARDS AN ONTOLOGY OF BEHAVIOR CHANGE: AN INNOVATIVE APPROACH TO INTERVENTION DEVELOPMENT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Michie, Susan; West, Robert; Sheals, Kate E.; Carey, Rachel N.; Connell, Lauren] UCL, London, England. [Larsen, Kai] Univ Colorado, Boulder, CO 80309 USA. [Gershuny, Victoria] Univ Arizona, Tucson, AZ USA. [An, Larry] Univ Michigan, Ann Arbor, MI 48109 USA. [Riley, William T.] NIH, Bethesda, MD 20892 USA. EM s.michie@ucl.ac.uk; kai.larsen@colorado.edu; lcan@umich.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 37 BP S138 EP S138 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002036 ER PT J AU Moser, RP Cole-Lewis, H Buman, M Ayzenberg, Y AF Moser, Richard P. Cole-Lewis, Heather Buman, Matthew Ayzenberg, Yadid TI ACCESSING AND ANALYZING NON-TRADITIONAL DATA: CHALLENGES, CONSIDERATIONS, AND FUNDING OPPORTUNITIES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Moser, Richard P.] NCI, Bethesda, MD 20892 USA. [Cole-Lewis, Heather] ICF Int, Rockville, MD 20850 USA. [Buman, Matthew] Arizona State Univ, Phoenix, AZ 85004 USA. [Ayzenberg, Yadid] MIT, Cambridge, MA 02139 USA. EM heather.cole-lewis@icfi.com; matthew.buman@asu.edu; yadid@media.mit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 18 BP S142 EP S142 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002046 ER PT J AU Nebeling, L Oh, A Hennessy, E Yaroch, A AF Nebeling, Linda Oh, April Hennessy, Erin Yaroch, Amy TI ASSESSING CANCER PREVENTIVE BEHAVIORS AMONG PARENT-ADOLESCENT DYADS: OPPORTUNITIES AND CHALLENGES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nebeling, Linda] NCI, Behav Res Program, Bethesda, MD 20892 USA. [Oh, April] NCI, Bethesda, MD 20892 USA. [Hennessy, Erin] Leidos Biomed Res Inc, Frederick, MD USA. [Yaroch, Amy] Gretchen Swanson Ctr Nutr, Omaha, NE USA. EM linda.nebeling@nih.gov; april.oh@nih.gov; erin.hennessy@fnlcr.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 01 BP S52 EP S52 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001203 ER PT J AU Nilsen, W Stirrat, M AF Nilsen, Wendy Stirrat, Michael TI NIH ADHERENCE RESEARCH NETWORK PANEL SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nilsen, Wendy; Stirrat, Michael] NIH, Bethesda, MD 20892 USA. EM nilsenwj@od.nih.gov; stirrattm@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 06 BP S53 EP S53 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001208 ER PT J AU Nilsen, W Spruijt-Metz, D Klasnja, P Kumar, S Riley, WT AF Nilsen, Wendy Spruijt-Metz, Donna Klasnja, Predrag Kumar, Santosh Riley, William T. TI NIH MHEALTH TRAINING INSTITUTE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nilsen, Wendy; Riley, William T.] NIH, Bethesda, MD 20892 USA. [Spruijt-Metz, Donna] Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA 90004 USA. [Klasnja, Predrag] Univ Michigan, Ann Arbor, MI 48109 USA. EM nilsenwj@od.nih.gov; dmetz@usc.edu; klasnja@umich.edu; santosh.kumar@memphis.edu; wiriley@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 01 BP S1 EP S1 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001001 ER PT J AU Nilsen, W Stirrat, M Atienza, AA Elwood, W Fitzsimmons, S Davidson, KW Keefe, FJ Spruijt-Metz, D AF Nilsen, Wendy Stirrat, Michael Atienza, Audie A. Elwood, William Fitzsimmons, Stacey Davidson, Karina W. Keefe, Francis J. Spruijt-Metz, Donna TI NIH GRANTWRITING WORKSHOP SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nilsen, Wendy; Stirrat, Michael] NIH, Bethesda, MD 20582 USA. [Atienza, Audie A.] NCI, Sci Res & Technol Branch, Bethesda, MD 20892 USA. [Davidson, Karina W.] Columbia Univ, New York, NY 10027 USA. [Keefe, Francis J.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Spruijt-Metz, Donna] Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA 90004 USA. EM stirrattm@mail.nih.gov; atienzaa@mailnih.gov; Fitzsimmons@nih.gov; kd2124@columbia.edu; francis.keefe@duke.edu; dmetz@usc.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 02 BP S1 EP S1 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001002 ER PT J AU Pellegrini, C Roberts, S Tomlinson, AN Rodriguez, L AF Pellegrini, Christine Roberts, Scott Tomlinson, Ashley N. Rodriguez, Laura TI GIVING PATIENTS INCIDENTAL INFORMATION FROM GENOMIC SEQUENCING: INSIGHTS FROM THE CSER CONSORTIUM SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Pellegrini, Christine] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Roberts, Scott] Univ Michigan, Ann Arbor, MI 48109 USA. [Tomlinson, Ashley N.] Univ Penn, Philadelphia, PA 19104 USA. [Rodriguez, Laura] NHGRI, Bethesda, MD 20892 USA. EM c-pellegrini@northwestern.edu; jscottr@umich.edu; ashley.tomlinson@uphs.upenn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 21 BP S70 EP S70 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001272 ER PT J AU Pellegrini, C Gibson, B Lewis, M Balgrosky, J Hesse, B AF Pellegrini, Christine Gibson, Bryan Lewis, Megan Balgrosky, Jean Hesse, Bradford TI USING TECHNOLOGY TO ADDRESS CHALLENGES IN HEALTH DECISION MAKING: CASE STUDIES AND RECOMMENDATIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Pellegrini, Christine] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gibson, Bryan] Univ Utah, Salt Lake City, UT USA. [Lewis, Megan] RTI Int, Res Triangle Pk, NC USA. [Balgrosky, Jean] MD Revolut Inc, San Diego, CA USA. [Hesse, Bradford] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 06 BP S44 EP S44 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001173 ER PT J AU Persky, S Ferrer, RA Klein, WM AF Persky, Susan Ferrer, Rebecca A. Klein, William M. TI GENOMIC INFORMATION MAY INHIBIT BEHAVIOR CHANGE INCLINATIONS AMONG INDIVIDUALS IN A FEAR STATE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Persky, Susan] NHGRI, NIH, Bethesda, MD 20892 USA. [Ferrer, Rebecca A.; Klein, William M.] NCI, Bethesda, MD 20892 USA. EM perskys@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 BP S211 EP S211 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002317 ER PT J AU Phillips, SM Dodd, KW Steeves, J McClain, J Alfano, C McAuley, E AF Phillips, Siobhan M. Dodd, Kevin W. Steeves, Jeremy McClain, James Alfano, Catherine McAuley, Edward TI OBJECTIVELY MEASURED ACTIVITY PATTERNS IN BREAST CANCER SURVIVORS COMPARED TO CONTROLS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Phillips, Siobhan M.] Northwestern Univ, Chicago, IL 60610 USA. [Dodd, Kevin W.; McClain, James; Alfano, Catherine] NCI, Rockville, MD USA. [Steeves, Jeremy] Univ Wisconsin, Milwaukee, WI 53201 USA. [McAuley, Edward] Univ Illinois, Urbana, IL USA. EM smphillips@northwestern.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 BP S91 EP S91 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001354 ER PT J AU Posluszny, DM Jim, H Syrjala, KL Bevans, M AF Posluszny, Donna M. Jim, Heather Syrjala, Karen L. Bevans, Margaret TI THE TRAJECTORY OF RECOVERY IN HEMATOPOIETIC CELL TRANSPLANT: FROM GENETIC TO COMMUNITY INFLUENCES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Posluszny, Donna M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Jim, Heather] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Syrjala, Karen L.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Bevans, Margaret] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 45 BP S154 EP S154 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002094 ER PT J AU Rahim-Williams, B Erlen, JA Tamres, LK Fourie, NH Henderson, WA AF Rahim-Williams, Bridgett Erlen, Judith A. Tamres, Lisa K. Fourie, Nicholas H. Henderson, Wendy A. TI HEALTH DISPARITIES IN GASTROINTESTINAL SYMPTOMS AND CHRONIC ABDOMINAL PAIN IN INDIVIDUALS WITH HIV SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Rahim-Williams, Bridgett; Fourie, Nicholas H.] NIH, Bethesda, MD 20892 USA. [Erlen, Judith A.; Tamres, Lisa K.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [Henderson, Wendy A.] NINR, NIH, DHHS, Bethesda, MD 20892 USA. EM bridgett.rahim-williams@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA A045 BP S15 EP S15 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001056 ER PT J AU Serrano, KJ Atienza, AA AF Serrano, Katrina J. Atienza, Audie A. TI WILLINGNESS TO EXCHANGE HEALTH INFORMATION USING MOBILE PHONES: A QUANTITATIVE ANALYSIS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Serrano, Katrina J.; Atienza, Audie A.] NCI, Sci Res & Technol Branch, Bethesda, MD 20892 USA. EM katrina.serrano@nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 BP S214 EP S214 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002331 ER PT J AU Spruijt-Metz, D Nilsen, W Kumar, S Pirolli, P Youngblood, M AF Spruijt-Metz, Donna Nilsen, Wendy Kumar, Santosh Pirolli, Peter Youngblood, Michael TI MONITORING, MEASURING, MODELING AND CHANGING BEHAVIOR IN REAL TIME SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Spruijt-Metz, Donna] Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA USA. [Nilsen, Wendy] NIH, Bethesda, MD 20892 USA. [Kumar, Santosh] Univ Memphis, Memphis, TN 38152 USA. [Pirolli, Peter] Xerox Corp, Palo Alto Res Ctr, Palo Alto, CA 94304 USA. [Youngblood, Michael] PARC, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA 42 BP S151 EP S151 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002082 ER PT J AU Taber, JM Klein, WM Ferrer, RA Kent, EE Harris, PR AF Taber, Jennifer M. Klein, William M. Ferrer, Rebecca A. Kent, Erin E. Harris, Peter R. TI ASSOCIATIONS OF SPONTANEOUS SELF-AFFIRMATION AND OPTIMISM WITH HEALTH AMONG CANCER SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Taber, Jennifer M.; Klein, William M.; Ferrer, Rebecca A.; Kent, Erin E.] NCI, Bethesda, MD 20892 USA. [Harris, Peter R.] Univ Sussex, Brighton, E Sussex, England. EM jennifer.taber@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA A014 BP S7 EP S7 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825001025 ER PT J AU Taylor, A Agurs-Collins, T Persoskie, A Perna, F AF Taylor, Antione Agurs-Collins, Tanya Persoskie, Alexander Perna, Frank TI MORE THAN JUST SKIN-DEEP: IMPACTS OF LIFETIME DISCRIMINATION ON BMI, PHYSICAL ACTIVITY AND CRP LEVEL SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Taylor, Antione] Univ Maryland Baltimore Cty, Windsor Mill, MD 21244 USA. [Agurs-Collins, Tanya; Perna, Frank] NCI, Bethesda, MD 20892 USA. [Persoskie, Alexander] NCI, NIH, Bethesda, MD 20892 USA. EM antione1@umbc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2015 VL 49 SU 1 MA C009 BP S176 EP S176 PG 1 WC Psychology, Multidisciplinary SC Psychology GA DA5EH UT WOS:000367825002181 ER PT J AU Logan, JK Rais-Bahrami, S Merino, MJ Pinto, PA AF Logan, Jennifer K. Rais-Bahrami, Soroush Merino, Maria J. Pinto, Peter A. TI Upgrading prostate cancer following proton beam therapy SO UROLOGY ANNALS LA English DT Article DE Biopsy; proton beam; prostate adenocarcinoma; radiation-induced changes ID ULTRASOUND; CARCINOMA AB Pre- and post-radiation therapy (RT) effects on prostate histology have not been rigorously studied, but there appears to be a correlation between escalating radiation dosage and increasing post-RT histologic changes. Despite this dose-response relationship, radiation-induced changes may be heterogenous among different patients and even within a single tumor. When assessing residual tumor it is important to understand biopsy evaluation in the post-RT setting. We present the case of a poorly differentiated prostate adenocarcinoma following proton beam RT in a 45-year-old man with pre-RT Gleason 4 3 = 7 disease diagnosed in the setting of an elevated serum prostate-specific antigen level. C1 [Rais-Bahrami, Soroush; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210,Bldg 10,CRC Room 2W-5940, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Pinto, Peter A.] NCI, Ctr Intervent Oncol, 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 Rais-Bahrami, Soroush/0000-0001-9466-9925 NR 6 TC 0 Z9 0 U1 0 U2 1 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0974-7796 EI 0974-7834 J9 UROL ANNALS JI Urol. Annals PD APR-JUN PY 2015 VL 7 IS 2 BP 262 EP 264 DI 10.4103/0974-7796.152944 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA DE2DF UT WOS:000370436100026 PM 25837674 ER PT J AU Hickman, AB Dyda, F AF Hickman, Alison B. Dyda, Fred TI Mechanisms of DNA Transposition SO MICROBIOLOGY SPECTRUM LA English DT Article ID SINGLE-STRANDED-DNA; SITE-SPECIFIC RECOMBINATION; ROLLING-CIRCLE TRANSPOSONS; CUT-AND-PASTE; REPETITIVE EXTRAGENIC PALINDROMES; SLEEPING-BEAUTY TRANSPOSITION; BACTERIOPHAGE-MU TRANSPOSASE; GAMMA-DELTA RESOLVASE; P-ELEMENT TRANSPOSASE; V(D)J RECOMBINATION AB DNA transposases use a limited repertoire of structurally and mechanistically distinct nuclease domains to catalyze the DNA strand breaking and rejoining reactions that comprise DNA transposition. Here, we review the mechanisms of the four known types of transposition reactions catalyzed by (1) RNase H-like transposases (also known as DD(E/D) enzymes); (2) HUH single-stranded DNA transposases; (3) serine transposases; and (4) tyrosine transposases. The large body of accumulated biochemical and structural data, particularly for the RNase H-like transposases, has revealed not only the distinguishing features of each transposon family, but also some emerging themes that appear conserved across all families. The more-recently characterized single-stranded DNA transposases provide insight into how an ancient HUH domain fold has been adapted for transposition to accomplish excision and then site-specific integration. The serine and tyrosine transposases are structurally and mechanistically related to their cousins, the serine and tyrosine site-specific recombinases, but have to date been less intensively studied. These types of enzymes are particularly intriguing as in the context of site-specific recombination they require strict homology between recombining sites, yet for transposition can catalyze the joining of transposon ends to forman excised circle and then integration into a genomic site with much relaxed sequence specificity. C1 [Hickman, Alison B.; Dyda, Fred] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dyda, F (reprint author), NIDDK, Mol Biol Lab, NIH, 5 Ctr Dr, Bethesda, MD 20892 USA. EM dyda@helix.nih.gov FU Intramural NIH HHS NR 182 TC 5 Z9 5 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA EI 2165-0497 J9 MICROBIOL SPECTR JI Microbiol. Spectr. PD APR PY 2015 VL 3 IS 2 AR MDNA3-0034-2014 DI 10.1128/microbiolspec.MDNA3-0034-2014 PG 22 WC Microbiology SC Microbiology GA DA1EQ UT WOS:000367539500018 PM 26104718 ER PT J AU Hughes, SH AF Hughes, Stephen H. TI Reverse Transcription of Retroviruses and LTR Retrotransposons SO MICROBIOLOGY SPECTRUM LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; AVIAN-SARCOMA VIRUS; CENTRAL POLYPURINE TRACT; MURINE LEUKEMIA-VIRUS; DEPENDENT DNA-POLYMERASE; AMINO-ACID SUBSTITUTIONS; VIVO MUTATION-RATE; HIV-1 INTERSUBTYPE RECOMBINATION; INFECTIOUS MOLECULAR CLONES; RIBONUCLEASE-H ACTIVITY AB The enzyme reverse transcriptase (RT) was discovered in retroviruses almost 50 years ago. The demonstration that other types of viruses, and what are now called retrotransposons, also replicated using an enzyme that could copy RNA into DNA came a few years later. The intensity of the research in both the process of reverse transcription and the enzyme RT was greatly stimulated by the recognition, in the mid-1980s, that human immunodeficiency virus (HIV) was a retrovirus and by the fact that the first successful anti-HIV drug, azidothymidine (AZT), is a substrate for RT. Although AZT monotherapy is a thing of the past, the most commonly prescribed, and most successful, combination therapies still involve one or both of the two major classes of anti-RT drugs. Although the basic mechanics of reverse transcription were worked out many years ago, and the first high-resolution structures of HIV RT are now more than 20 years old, we still have much to learn, particularly about the roles played by the host and viral factors that make the process of reverse transcription much more efficient in the cell than in the test tube. Moreover, we are only now beginning to understand how various host factors that are part of the innate immunity system interact with the process of reverse transcription to protect the host-cell genome, the host cell, and the whole host, from retroviral infection, and from unwanted retrotransposition. C1 [Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, Ctr Canc Res, 1050 Boyles St,Bldg 539,Rm 130A, Frederick, MD 21702 USA. EM hughesst@mail.nih.gov NR 239 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA EI 2165-0497 J9 MICROBIOL SPECTR JI Microbiol. Spectr. PD APR PY 2015 VL 3 IS 2 AR MDNA3-0027-2014 DI 10.1128/microbiolspec.MDNA3-0027-2014 PG 25 WC Microbiology SC Microbiology GA DA1EQ UT WOS:000367539500013 PM 26104704 ER PT J AU Ginwala, R Sagar, D Akkina, R Jacobson, S AF Ginwala, R. Sagar, D. Akkina, R. Jacobson, S. TI HTLV-1 infection and T-cell exhaustion in Ragl(-/-)gamma c(-/-) (RAG1) mouse model SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Meeting Abstract C1 [Ginwala, R.; Sagar, D.] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19129 USA. [Ginwala, R.; Sagar, D.] Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Philadelphia, PA 19129 USA. [Akkina, R.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80045 USA. [Jacobson, S.] NIH, Neuroimmunol Branch, Viral Immunol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 EI 1557-1904 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD APR PY 2015 VL 10 SU 2 BP S72 EP S72 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA DA1KG UT WOS:000367554100042 ER PT J AU Sagar, D Masih, S Schell, T Jacobson, S Comber, JD Philip, R Wigdahl, B Jain, P Khan, ZK AF Sagar, D. Masih, Shet Schell, T. Jacobson, S. Comber, J. D. Philip, R. Wigdahl, B. Jain, P. Khan, Z. K. TI In vivo immunogenicity of Tax (11-19) epitope in HLA-A2/DTR transgenic mice: Implication for dendritic cell-based anti-HTLV-1 vaccine SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Meeting Abstract C1 [Sagar, D.; Masih, Shet; Wigdahl, B.; Jain, P.; Khan, Z. K.] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19129 USA. [Sagar, D.; Masih, Shet; Wigdahl, B.; Jain, P.; Khan, Z. K.] Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Philadelphia, PA 19129 USA. [Schell, T.] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. [Jacobson, S.] NIH, Neuroimmunol Branch, Viral Immunol Sect, Bethesda, MD 20892 USA. [Comber, J. D.; Philip, R.] Immunotope Inc, Penn Biotechnol Ctr, Doylestown, PA 18902 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 EI 1557-1904 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD APR PY 2015 VL 10 SU 2 BP S99 EP S99 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA DA1KG UT WOS:000367554100112 ER PT J AU Ramos, NR Mo, CC Karp, JE Hourigan, CS AF Ramos, Nestor R. Mo, Clifton C. Karp, Judith E. Hourigan, Christopher S. TI Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia SO JOURNAL OF CLINICAL MEDICINE LA English DT Review DE salvage therapy; leukemia; neoplasm metastasis; AML; relapse ID STEM-CELL TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; MINIMAL RESIDUAL DISEASE; HIGH-DOSE CYTARABINE; SINGLE-CENTER EXPERIENCE; LIPOSOME-ENCAPSULATED DAUNORUBICIN; CHIMERIC ANTIGEN RECEPTORS; PRIMARY INDUCTION FAILURE; MODIFIED T-CELLS AB The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for "complete" remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial. C1 [Ramos, Nestor R.; Hourigan, Christopher S.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Ramos, Nestor R.; Mo, Clifton C.] Walter Reed Natl Mil Med Ctr, Dept Hematol Oncol, John P Murtha Canc Ctr, Bethesda, MD 20889 USA. [Karp, Judith E.] Johns Hopkins Sch Med, Div Hematol Malignancies, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. RP Hourigan, CS (reprint author), NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM nestor.r.ramos.mil@mail.mil; clifton.c.mo.mil@mail.mil; jkarp2@jhmi.edu; hourigan@nih.gov RI Hourigan, Christopher/S-2476-2016 OI Hourigan, Christopher/0000-0002-6189-8067 FU Intramural NIH HHS [ZIA HL006163-02] NR 150 TC 12 Z9 13 U1 3 U2 4 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2077-0383 J9 J CLIN MED JI J. Clin. Med. PD APR PY 2015 VL 4 IS 4 BP 665 EP 695 DI 10.3390/jcm4040665 PG 31 WC Medicine, General & Internal SC General & Internal Medicine GA CT9LQ UT WOS:000363138900009 PM 25932335 ER PT J AU Armato, SG Hadjiiski, L Tourassi, GD Drukker, K Giger, ML Li, F Redmond, G Farahani, K Kirby, JS Clarke, LP AF Armato, Samuel G., III Hadjiiski, Lubomir Tourassi, Georgia D. Drukker, Karen Giger, Maryellen L. Li, Feng Redmond, George Farahani, Keyvan Kirby, Justin S. Clarke, Laurence P. TI LUNGx Challenge for computerized lung nodule classification: reflections and lessons learned SO JOURNAL OF MEDICAL IMAGING LA English DT Editorial Material ID TOMOGRAPHY SCANS; AIDED DETECTION; PERFORMANCE; ALGORITHMS; SCHEMES C1 [Armato, Samuel G., III; Drukker, Karen; Giger, Maryellen L.; Li, Feng] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Hadjiiski, Lubomir] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Tourassi, Georgia D.] Oak Ridge Natl Lab, Hlth Data Sci Inst, Biomed Sci & Engn Ctr, Oak Ridge, TN 37831 USA. [Redmond, George; Farahani, Keyvan; Clarke, Laurence P.] NCI, Div Canc Treatment & Diag, Canc Imaging Program, Bethesda, MD 20892 USA. [Kirby, Justin S.] Leidos Biomed Res Inc, Canc Imaging Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Armato, SG (reprint author), Univ Chicago, Dept Radiol, MC 2026 5841 S Maryland Ave, Chicago, IL 60637 USA. EM s-armato@uchicago.edu FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E] NR 12 TC 7 Z9 7 U1 1 U2 5 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 2329-4302 EI 2329-4310 J9 J MED IMAGING JI J. Med. Imaging PD APR-JUN PY 2015 VL 2 IS 2 AR 020103 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CZ1ES UT WOS:000366849300002 PM 26158094 ER PT J AU Mammen, AL Sartorelli, V AF Mammen, Andrew L. Sartorelli, Vittorio TI IL-6 Blockade as a Therapeutic Approach for Duchenne Muscular Dystrophy SO EBIOMEDICINE LA English DT Editorial Material C1 [Mammen, Andrew L.; Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Express, NIH, Bethesda, MD 20892 USA. RP Mammen, AL (reprint author), NIAMSD, Muscle Dis Unit, Lab Muscle Stem Cells & Gene Express, NIH, 50 South Dr,Room 1146,Bldg 50,MSC 8024, Bethesda, MD 20892 USA. EM andrew.mammen@nih.gov NR 7 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD APR PY 2015 VL 2 IS 4 BP 274 EP 275 DI 10.1016/j.ebiom.2015.03.018 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CX8KL UT WOS:000365952100002 PM 26137566 ER PT J AU Jabbari, A Dai, ZP Xing, LZ Cerise, JE Ramot, Y Berkun, Y Sanchez, GAM Goldbach-Mansky, R Christiano, AM Clynes, R Zlotogorski, A AF Jabbari, Ali Dai, Zhenpeng Xing, Luzhou Cerise, Jane E. Ramot, Yuval Berkun, Yackov Sanchez, Gina A. Montealegre Goldbach-Mansky, Raphaela Christiano, Angela M. Clynes, Raphael Zlotogorski, Abraham TI Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib SO EBIOMEDICINE LA English DT Article DE Alopecia areata; Interferon gamma; JAK inhibitor; CANDLE syndrome; Autoimmune disease; Baricitinib; Gene expression profiling; Autoinflammatory ID ATYPICAL NEUTROPHILIC DERMATOSIS; PROTEASOME SUBUNIT; PLAQUE PSORIASIS; LIPODYSTROPHY; TOFACITINIB; UNIVERSALIS; EFFICACY; PATIENT; SAFETY; TRIAL AB Background: Alopecia areata (AA) is an autoimmune disease resulting in hair loss with devastating psychosocial consequences. Despite its high prevalence, there are no FDA-approved treatments for AA. Prior studies have identified a prominent interferon signature in AA, which signals through JAK molecules. Methods: A patient with AA was enrolled in a clinical trial to examine the efficacy of baricitinib, a JAK1/2 inhibitor, to treat concomitant CANDLE syndrome. In vivo, preclinical studieswere conducted using the C3H/HeJ AA mouse model to assess the mechanism of clinical improvement by baricitinib. Findings: The patient exhibited a striking improvement of his AA on baricitinib over several months. In vivo studies using the C3H/HeJ mouse model demonstrated a strong correlation between resolution of the interferon signature and clinical improvement during baricitinib treatment. Interpretation: Baricitinib may be an effective treatment for AA and warrants further investigation in clinical trials. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Jabbari, Ali; Dai, Zhenpeng; Cerise, Jane E.; Christiano, Angela M.; Clynes, Raphael] Columbia Univ, Dept Dermatol, New York, NY 10032 USA. [Xing, Luzhou; Clynes, Raphael] Columbia Univ, Dept Pathol, New York, NY 10032 USA. [Ramot, Yuval; Zlotogorski, Abraham] Hadassah Hebrew Univ, Med Ctr, Dept Dermatol, Jerusalem, Israel. [Berkun, Yackov] Hadassah Hebrew Univ, Med Ctr, Dept Pediat, Jerusalem, Israel. [Sanchez, Gina A. Montealegre; Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA. [Christiano, Angela M.] Columbia Univ, Dept Genet & Dev, New York, NY USA. [Clynes, Raphael] Columbia Univ, Dept Med, New York, NY 10032 USA. RP Christiano, AM (reprint author), Columbia Univ, Coll Phys & Surg, Dept Dermatol, 1150 St Nicholas Ave,3rd Floor, New York, NY 10032 USA. EM amc65@columbia.edu; zloto@cc.huji.ac.il OI Jabbari, Ali/0000-0002-8559-7314 FU NCRR NIH HHS [S10 RR027050]; NIAMS NIH HHS [P30 AR044535, R01 AR056016, R01AR056016, R21 AR061881, R21AR061881] NR 18 TC 24 Z9 24 U1 5 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD APR PY 2015 VL 2 IS 4 BP 351 EP 355 DI 10.1016/j.ebiom.2015.02.015 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CX8KL UT WOS:000365952100015 PM 26137574 ER PT J AU Rothwell, S Cooper, RG Lundberg, I Miller, FW Gregersen, PK Vencovsky, J Danko, K Wedderburn, LR Limaye, V Selva-O'Callaghan, A Hanna, MG Pachman, LM Reed, AM Molberg, O Benveniste, O Mathiesen, P Radstake, T Doria, A De Bleecker, J Ollier, WE O'Hanlon, TP Lee, AT Chinoy, H Lamb, J AF Rothwell, Simon Cooper, Robert G. Lundberg, Ingrid Miller, Frederick W. Gregersen, Peter K. Vencovsky, Jiri Danko, Katalin Wedderburn, Lucy R. Limaye, Vidya Selva-O'Callaghan, Albert Hanna, Michael G. Pachman, Lauren M. Reed, Ann M. Molberg, Oyvind Benveniste, Olivier Mathiesen, Pernille Radstake, Timothy Doria, Andrea De Bleecker, Jan Ollier, William E. O'Hanlon, Terrance P. Lee, Annette T. Chinoy, Hector Lamb, Janine TI INTERNATIONAL IMMUNOCHIP STUDY IN THE IDIOPATHIC INFLAMMATORY MYOPATHIES IDENTIFIES GENETIC DIFFERENCES BETWEEN CLINICAL SUBGROUPS, AND CONFIRMS HLA ALLELES AS STRONGEST GENETIC RISK FACTOR SO RHEUMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the British-Society-for-Rheumatology and British-Health-Professionals-in-Rheumatology CY APR 28-30, 2015 CL Manchester, ENGLAND SP British Soc Rheumatol, British Hlth Profess Rheumatol C1 [Rothwell, Simon; Chinoy, Hector] Univ Manchester, Ctr Musculoskeletal Res, Manchester, Lancs, England. [Cooper, Robert G.] Univ Liverpool, Dept Musculoskeletal Biol, Liverpool L69 3BX, Merseyside, England. [Lundberg, Ingrid] Karolinska Inst, Dept Med, Stockholm, Sweden. [Miller, Frederick W.; O'Hanlon, Terrance P.] NIH, Environm Autoimmun Grp, Bethesda, MD 20892 USA. [Gregersen, Peter K.; Lee, Annette T.] Ctr Genom & Human Genet, Feinstein Inst, Manhasset, NY USA. [Vencovsky, Jiri] Charles Univ Prague, Inst Rheumatol, Prague, Czech Republic. [Danko, Katalin] Univ Debrecen, Dept Internal Med, Debrecen, Hungary. [Wedderburn, Lucy R.] UCL, Arthrit Res UK Ctr Adolescent Rheumatol, London, England. [Limaye, Vidya] Royal Adelaide Hosp, Rheumatol Unit, Adelaide, SA 5000, Australia. [Selva-O'Callaghan, Albert] Vall Hebron Gen Hosp, Dept Internal Med, Barcelona, Spain. [Hanna, Michael G.] UCL, Natl Hosp Neurol & Neurosurg, London, England. [Pachman, Lauren M.] Northwestern Univ Feinberg, Ann & Robert H Lurie Childrens Hosp Chicago, Sch Med, Chicago, IL USA. [Reed, Ann M.] Mayo Clin, Div Rheumatol, Rochester, MN USA. [Molberg, Oyvind] Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway. [Benveniste, Olivier] Hop La Pitie Salpetriere, AP HP, Paris, France. [Mathiesen, Pernille] Copenhagen Univ Hosp, Paediat Clin, Copenhagen, Denmark. [Radstake, Timothy] Univ Med Ctr Utrecht, Dept Rheumatol & Clin Immunol, Utrecht, Netherlands. [Doria, Andrea] Univ Padua, Div Rheumatol, Padua, Italy. [De Bleecker, Jan] Univ Ghent, Dept Neurol, B-9000 Ghent, Belgium. [Ollier, William E.; Lamb, Janine] Univ Manchester, Ctr Integrated Genom Med Res, Manchester, Lancs, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD APR PY 2015 VL 54 SU 1 MA O50 BP 47 EP 48 PG 2 WC Rheumatology SC Rheumatology GA CV8ER UT WOS:000364513700116 ER PT J AU Seeliger, B Judge, A Sznajd, J Merkel, PA Watts, RA Suppiah, R Robson, JC Grayson, PC Craven, A Luqmani, RA AF Seeliger, Benjamin Judge, Andrew Sznajd, Jan Merkel, Peter A. Watts, Richard A. Suppiah, Ravi Robson, Joanna C. Grayson, Peter C. Craven, Anthea Luqmani, Raashid A. TI RE-APPRAISAL OF THE 1990 AMERICAN COLLEGE OF RHEUMATOLOGY CLASSIFICATION CRITERIA FOR SYSTEMIC VASCULITIS: ANALYSIS OF DATA FROM THE DIAGNOSTIC AND CLASSIFICATION CRITERIA IN VASCULITIS STUDY SO RHEUMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the British-Society-for-Rheumatology and British-Health-Professionals-in-Rheumatology CY APR 28-30, 2015 CL Manchester, ENGLAND SP British Soc Rheumatol, British Hlth Profess Rheumatol C1 [Seeliger, Benjamin; Judge, Andrew; Sznajd, Jan; Robson, Joanna C.; Craven, Anthea; Luqmani, Raashid A.] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England. [Seeliger, Benjamin] Univ Jena, Dept Internal Med 1, Jena, Germany. [Judge, Andrew] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England. [Sznajd, Jan] Jagiellonian Univ, Sch Med, Dept Internal Med, Krakow, Poland. [Merkel, Peter A.] Univ Penn, Penn Inst Immunol, Philadelphia, PA 19104 USA. [Watts, Richard A.] Univ E Anglia, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England. [Suppiah, Ravi] Auckland Dist Hlth Board, Dept Rheumatol, Auckland, New Zealand. [Grayson, Peter C.] NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD APR PY 2015 VL 54 SU 1 MA 317 BP 173 EP 173 PG 1 WC Rheumatology SC Rheumatology GA CV8ER UT WOS:000364513700436 ER PT J AU Canini, L Koh, C Cotler, SJ Zhao, X Uprichard, SL Haynes-Williams, V Winters, MA Subramanya, G Cooper, SL Pinto, P Wolff, E Bishop, R Han, MAT Kleiner, DE Keskin, O Idilman, R Yurdaydin, C Glenn, JS Heller, T Dahari, H AF Canini, L. Koh, C. Cotler, S. J. Zhao, X. Uprichard, S. L. Haynes-Williams, V. Winters, M. A. Subramanya, G. Cooper, S. L. Pinto, P. Wolff, E. Bishop, R. Han, M. A. Than Kleiner, D. E. Keskin, O. Idilman, R. Yurdaydin, C. Glenn, J. S. Heller, T. Dahari, H. TI UNDERSTANDING HEPATITIS DELTA VIRUS AND HBsAg KINETICS DURING TREATMENT WITH PRENYLATION INHIBITOR LONAFARNIB VIA MATHEMATICAL MODELING SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Canini, L.; Cotler, S. J.; Uprichard, S. L.; Subramanya, G.; Dahari, H.] Loyola Univ, Med Ctr, Div Hepatol, Program Expt & Theoret Modeling, Maywood, IL 60153 USA. [Canini, L.] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland. [Koh, C.; Haynes-Williams, V.; Han, M. A. Than; Heller, T.] NIDDK, Translat Hepatol Unit, Liver Dis Branch, Bethesda, MD 20892 USA. [Zhao, X.] NIDDK, Off Director, NIH, Bethesda, MD 20892 USA. [Winters, M. A.; Glenn, J. S.] Stanford Sch Med, Dept Med, Div Gastroenterol & Hepatol, Stanford, CA USA. [Winters, M. A.; Glenn, J. S.] Stanford Sch Med, Dept Microbiol & Immunol, Stanford, CA USA. [Cooper, S. L.] Calif Pacific Med Ctr, Div Hepatol, San Francisco, CA USA. [Pinto, P.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Wolff, E.] NICHHD, Unit Reprod & Regenerat Med, Bethesda, MD 20892 USA. [Bishop, R.] NEI, Consult Serv Sect, Bethesda, MD 20892 USA. [Kleiner, D. E.] NCI, Lab Pathol, NIH, Bethesda, MD 20892 USA. [Keskin, O.; Idilman, R.; Yurdaydin, C.] Ankara Univ, Dept Gastroenterol, TR-06100 Ankara, Turkey. [Dahari, H.] Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM USA. EM harel.dahari@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA LP36 BP S281 EP S282 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3IZ UT WOS:000361967600190 ER PT J AU Castven, D Fischer, M Heinrich, S Andersen, JB Sprinzl, MF Gockel, I Heilmann, S Worns, MA Thorgeirsson, SS Galle, PR Lang, H Marquardt, JU AF Castven, D. Fischer, M. Heinrich, S. Andersen, J. B. Sprinzl, M. F. Gockel, I. Heilmann, S. Woerns, M. A. Thorgeirsson, S. S. Galle, P. R. Lang, H. Marquardt, J. U. TI THE HEPATIC MICROENVIRONMENT INDUCES A CSC PHENOTYPE AND DETERMINES THE PROGNOSIS OF HCC PATIENTS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Castven, D.; Fischer, M.; Sprinzl, M. F.; Woerns, M. A.; Galle, P. R.; Marquardt, J. U.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-55122 Mainz, Germany. [Heinrich, S.; Lang, H.] Johannes Gutenberg Univ Mainz, Dept Surg, D-55122 Mainz, Germany. [Andersen, J. B.] Univ Copenhagen, Res & Innovat Ctr BRIC 5Biotech, Copenhagen, Denmark. [Gockel, I.] Univ Leipzig, Dept Visceral Transplant Vasc & Thorac Surg, D-04109 Leipzig, Germany. [Heilmann, S.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Thorgeirsson, S. S.] NCI, CCR, NIH, Bethesda, MD 20892 USA. EM marquarj@uni-mainz.de NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA O100 BP S244 EP S244 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3IZ UT WOS:000361967600119 ER PT J AU Pereira, TD Borthwick, L Xie, G Vidigal, P Machado, M Voieta, I Resende, V Cheever, A Andrade, Z Lambertucci, J Wynn, T Diehl, AM AF De Almeida Pereira, T. Borthwick, L. Xie, G. Vidigal, P. Machado, M. Voieta, I. Resende, V. Cheever, A. Andrade, Z. Lambertucci, J. Wynn, T. Diehl, A. M. TI CROSS-TALK BETWEEN IL13 AND HEDGEHOG PATHWAYS CONTRIBUTES TO SCHISTOSOMIASIS MANSONI FIBROSIS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [De Almeida Pereira, T.; Andrade, Z.] UFBA FIOCRUZ, Lab Patol Expt, Salvador, BA, Brazil. [De Almeida Pereira, T.; Xie, G.; Machado, M.; Diehl, A. M.] Duke Univ, Med GI, Durham, NC 27706 USA. [Borthwick, L.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Vidigal, P.] Univ Fed Minas Gerais, Anat Patol & Med Legal, Belo Horizonte, MG, Brazil. [Voieta, I.; Lambertucci, J.] Univ Fed Minas Gerais, Lab Doencas Infecciosas & Parasitarias, Belo Horizonte, MG, Brazil. [Resende, V.] Univ Fed Minas Gerais, Fac Med, Cirurgia, Belo Horizonte, MG, Brazil. [Cheever, A.; Wynn, T.] NIAID, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA. EM dealmeida.thiago@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA O028 BP S204 EP S204 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3IZ UT WOS:000361967600036 ER PT J AU Hameed, B Terrault, N Gill, R Loomba, R Chalasani, N Hoofnagle, JH Van Natta, ML AF Hameed, B. Terrault, N. Gill, R. Loomba, R. Chalasani, N. Hoofnagle, J. H. Van Natta, M. L. CA Nonalcoholic Steatohepatitis Clini TI SEPARATE AND COMBINED EFFECTS OF OBETICHOLIC ACID AND WEIGHT LOSS IN NONALCOHOLIC STEATOHEPATITIS (NASH) SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Hameed, B.; Terrault, N.; Gill, R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Loomba, R.] Univ Calif San Diego, San Diego, CA 92103 USA. [Chalasani, N.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Hoofnagle, J. H.] NIDDK, Bethesda, MD 20892 USA. [Van Natta, M. L.] Johns Hopkins Univ, Baltimore, MD USA. EM lwilson9@jhu.edu NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA LP15 BP S271 EP S271 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3IZ UT WOS:000361967600169 ER PT J AU Wilson, EMP Kattakuzhy, S Sims, Z Tang, L McLaughlin, M Price, A Silk, R Gross, C Akoth, E Osinusi, A Masur, H Kohli, A Kottilil, S AF Wilson, E. M. P. Kattakuzhy, S. Sims, Z. Tang, L. McLaughlin, M. Price, A. Silk, R. Gross, C. Akoth, E. Osinusi, A. Masur, H. Kohli, A. Kottilil, S. TI HIGH EFFICACY OF RETREATMENT WITH LEDIPASVIR AND SOFOSBUVIR IN HCV PATIENTS WHO FAILED INITIAL SHORT COURSE THERAPY WITH COMBINATION DAA REGIMENS (NIH SYNERGY TRIAL) SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Wilson, E. M. P.; Sims, Z.; Masur, H.; Kohli, A.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Wilson, E. M. P.] Leidos Biomed Res Inc, Clin Monitoring Res Program, Frederick, MD USA. [Kattakuzhy, S.; Tang, L.; Price, A.; Silk, R.; Gross, C.; Akoth, E.; Kottilil, S.] Univ Maryland, Inst Human Virol, Dept Infect Dis, Baltimore, MD 21201 USA. [McLaughlin, M.] NIAID, NIH, Bethesda, MD 20892 USA. [Osinusi, A.] Gilead Sci Inc, Foster City, CA 94404 USA. EM eleanor.wilson@nih.gov NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA LP09 BP S267 EP S268 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CS3IZ UT WOS:000361967600163 ER PT J AU Ahluwalia, N Dalmasso, P Rasmussen, M Lipsky, L Currie, C Haug, E Kelly, C Damsgaard, MT Due, P Tabak, I Ercan, O Maes, L Aasvee, K Cavallo, F AF Ahluwalia, Namanjeet Dalmasso, Paola Rasmussen, Mette Lipsky, Leah Currie, Candace Haug, Ellen Kelly, Colette Damsgaard, Mogens Trab Due, Pernille Tabak, Izabela Ercan, Oya Maes, Lea Aasvee, Katrin Cavallo, Franco TI Trends in overweight prevalence among 11-, 13-and 15-year-olds in 25 countries in Europe, Canada and USA from 2002 to 2010 SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID OBESITY; CHILDREN; ADOLESCENTS; HEALTH; VALIDITY; BMI AB Background: The purpose of this study was to assess recent changes in the prevalence of overweight (including obesity) among 11-, 13 and 15-year-olds in 33 countries from 2002 to 2010. Methods: Data from 25 countries from three consecutive survey cycles (2002, 2006 and 2010) that had at least 80% response rate for self-reported height, weight and age were analysed using logistic regression analysis. Results: Overweight prevalence increased among boys in 13 countries and among girls in 12 countries; in 10 countries, predominantly in Eastern Europe, an increase was observed for both boys and girls. Stabilization in overweight rates was noted in the remaining countries; none of the countries exhibited a decrease over the 8-year period examined. In the majority of countries (20/25) there were no age differences in trends in overweight prevalence. Conclusion: In over half of the countries examined overweight prevalence did not change during 2002-2010. However, increasing overweight prevalence was noted in many Eastern European countries over this time period. Overweight prevalence remained high in several countries in Europe and North America. These patterns call for continued research in youth overweight and highlight the need to understand cross-national differences by examining macro-level indicators. Such research should feed into developing sound translations and practices to prevent and reduce overweight in youth. C1 [Ahluwalia, Namanjeet] Univ Paris 13, Fac Med, Bobigny, France. [Dalmasso, Paola; Cavallo, Franco] Univ Turin, Dept Publ Hlth & Paediat, Sch Med, Turin, Italy. [Rasmussen, Mette; Damsgaard, Mogens Trab; Due, Pernille] Univ Southern Denmark, Natl Inst Publ Hlth, Copenhagen, Denmark. [Lipsky, Leah] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Publ Hlth Res, Bethesda, MD USA. [Currie, Candace] Univ St Andrews, Sch Med, Child & Adolescent Hlth Res Unit, St Andrews, Fife, Scotland. [Haug, Ellen] Univ Bergen, Bergen, Norway. [Kelly, Colette] Natl Univ Ireland, Hlth Promot Res Ctr, Galway, Ireland. [Tabak, Izabela] Inst Mother & Child Hlth, Dept Child & Adolescent Hlth, Warsaw, Poland. [Ercan, Oya] Istanbul Univ, Cerrahpasa Med Fac, Pediat Endocrinol Div, Istanbul, Turkey. [Ercan, Oya] Istanbul Univ, Cerrahpasa Med Fac, Adolescent Div, Istanbul, Turkey. [Maes, Lea] Acad Hosp, Ghent, Belgium. [Aasvee, Katrin] Natl Inst Hlth Dev, Chron Dis Dept, Tallinn, Estonia. RP Ahluwalia, N (reprint author), Univ Paris 13, Fac Med, Bobigny, France. EM naman123@sfr.fr OI Kelly, Colette/0000-0001-7598-0160; Dalmasso, Paola/0000-0001-6081-6966; Lipsky, Leah/0000-0003-2645-4388 FU HBSC survey; Nordea Foundation [02-2011-0122]; Flemish Government; Department of Health, Government of Ireland; National Centre for Disease Prevention and Control, Ministry of Health, Italy; Ministry of Science and Higher Education, Poland; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Health Plan of Estonia FX The data collection for each HBSC survey is funded at the national level. The Danish HBSC Trend Data File was financed by the Nordea Foundation (Grant number 02-2011-0122). The Flemish HBSC study was financed by the Flemish Government. HBSC Ireland was funded by the Department of Health, Government of Ireland. HBSC in Italy was part of the Project 'Sistema di indagini sui rischi comportamentali in eta 6-17 anni' promoted and financed by the National Centre for Disease Prevention and Control, Ministry of Health, Italy. The Polish team acknowledges the Ministry of Science and Higher Education, Poland for funding HBSC study in Poland. The research for the USA HBSC study was funded in part by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The Estonian HBSC study was funded through the National Health Plan 2009-2020 of Estonia. Some of the findings from this research were presented at the Annual Meeting in the International Society of Behavioural Nutrition and Physical Activity, San Diego, USA, May 21-24 2014. NR 20 TC 17 Z9 17 U1 4 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 EI 1464-360X J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD APR PY 2015 VL 25 SU 2 BP 28 EP 32 DI 10.1093/eurpub/ckv016 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CT7CR UT WOS:000362971500008 PM 25805783 ER PT J AU de Looze, M Raaijmakers, Q Ter Bogt, T Bendtsen, P Farhat, T Ferreira, M Godeau, E Kuntsche, E Molcho, M Pfortner, TK Simons-Morton, B Vieno, A Vollebergh, W Pickett, W AF de Looze, Margaretha Raaijmakers, Quinten Ter Bogt, Tom Bendtsen, Pernille Farhat, Tilda Ferreira, Mafalda Godeau, Emmanuelle Kuntsche, Emmanuel Molcho, Michal Pfoertner, Timo-Kolja Simons-Morton, Bruce Vieno, Alessio Vollebergh, Wilma Pickett, William TI Decreases in adolescent weekly alcohol use in Europe and North America: evidence from 28 countries from 2002 to 2010 SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID DRINKING; TRENDS; PATTERNS AB Background: This study examined trends in adolescent weekly alcohol use between 2002 and 2010 in 28 European and North American countries. Methods: Analyses were based on data from 11-, 13- and 15-year-old adolescents who participated in the Health Behaviour in School-Aged Children (HBSC) study in 2002, 2006 and 2010. Results: Weekly alcohol use declined in 20 of 28 countries and in all geographic regions, from 12.1 to 6.1% in Anglo-Saxon countries, 11.4 to 7.8% in Western Europe, 9.3 to 4.1% in Northern Europe and 16.3 to 9.9% in Southern Europe. Even in Eastern Europe, where a stable trend was observed between 2002 and 2006, weekly alcohol use declined between 2006 and 2010 from 12.3 to 10.1%. The decline was evident in all gender and age subgroups. Conclusions: These consistent trends may be attributable to increased awareness of the harmful effects of alcohol for adolescent development and the implementation of associated prevention efforts, or changes in social norms and conditions. Although the declining trend was remarkably similar across countries, prevalence rates still differed considerably across countries. C1 [de Looze, Margaretha; Ter Bogt, Tom; Vollebergh, Wilma] Univ Utrecht, Fac Social & Behav Sci, Dept Interdisciplinary Social Sci, NL-3508 TC Utrecht, Netherlands. [Raaijmakers, Quinten] Univ Utrecht, Fac Social & Behav Sci, Dept Pedag Sci, NL-3508 TC Utrecht, Netherlands. [Bendtsen, Pernille] Syddansk Univ, Statens Inst Folkesundhed, Copenhagen, Denmark. [Farhat, Tilda; Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD USA. [Ferreira, Mafalda] Univ Tecn Lisboa, Fac Human Kinet, Lisbon, Portugal. [Godeau, Emmanuelle] Univ Toulouse 3, UMR Inserm U1027, Serv Med Rectorat Toulouse, F-31062 Toulouse, France. [Kuntsche, Emmanuel] Res Inst, Addict Switzerland, Lausanne, Switzerland. [Kuntsche, Emmanuel] Radboud Univ Nijmegen, Inst Behav Sci, NL-6525 ED Nijmegen, Netherlands. [Molcho, Michal] Natl Univ Ireland, Ctr Hlth Promot, Galway, Ireland. [Pfoertner, Timo-Kolja] Univ Halle Wittenberg, Fac Med, IMS, Halle, Germany. [Vieno, Alessio] Univ Padua, Dept Dev & Social Psychol, Padua, Italy. [Pickett, William] Queens Univ, Dept Publ Hlth Sci, Kingston, ON, Canada. RP de Looze, M (reprint author), Univ Utrecht, Fac Social & Behav Sci, Dept Interdisciplinary Social Sci, POB 80-140, NL-3508 TC Utrecht, Netherlands. EM M.E.deLooze@uu.nl RI Vollebergh, Wilma/C-2323-2012; OI VIENO, ALESSIO/0000-0003-4417-4822; Simons-Morton, Bruce/0000-0003-1099-6617 FU HBSC survey FX The data collection for each HBSC survey is funded at the national level. NR 17 TC 10 Z9 10 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 EI 1464-360X J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD APR PY 2015 VL 25 SU 2 BP 69 EP 72 DI 10.1093/eurpub/ckv031 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CT7CR UT WOS:000362971500017 ER PT J AU Holstein, BE Andersen, A Fotiou, A Gobina, I Godeau, E Hansen, EH Iannotti, R Levin, K Gabhainn, SN Ravens-Sieberer, U Valimaa, R AF Holstein, Bjorn E. Andersen, Anette Fotiou, Anastasios Gobina, Inese Godeau, Emmanuelle Hansen, Ebba Holme Iannotti, Ron Levin, Kate Gabhainn, Saoirse Nic Ravens-Sieberer, Ulrike Valimaa, Raili CA Med Use Writing Grp TI Adolescents' medicine use for headache: secular trends in 20 countries from 1986 to 2010 SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MEDICATION USE; CHILDREN; PERCEPTIONS; TIME AB Background: This study reports secular trends in medicine use for headache among adolescents in 20 countries from 1986 to 2010. Methods: The international Health Behaviour in School-aged Children (HBSC) survey includes self-reported data about medicine use for headaches among nationally representative samples of 11-, 13- and 15-year-olds. We included 20 countries with data from at least three data collection waves, with a total of 380 129 participants. Results: The prevalence of medicine use for headaches varied from 16.5% among Hungarian boys in 1994 to 62.9% among girls in Wales in 1998. The prevalence was higher among girls than boys in every country and data collection year. The prevalence of medicine use for headaches increased in 12 of 20 countries, most notably in the Czech Republic, Poland, Russia, Sweden and Wales. Conclusion: The prevalence of medicine use for headaches among adolescents is high and increasing in many countries. As some medicines are toxic this may constitute a public health problem. C1 [Holstein, Bjorn E.; Andersen, Anette] Univ Southern Denmark, Natl Inst Publ Hlth, DK-1353 Copenhagen, Denmark. [Fotiou, Anastasios] Univ Mental Hlth, Res Inst, Athens, Greece. [Gobina, Inese] Riga Stradins Univ, Dept Publ Hlth & Epidemiol, Riga, Latvia. [Godeau, Emmanuelle] French Inst Hlth & Med Res, Paris, France. [Hansen, Ebba Holme] Univ Copenhagen, Dept Pharm, Copenhagen, Denmark. [Iannotti, Ron] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD USA. [Levin, Kate] Univ St Andrews, Sch Med Med & Biol Sci, St Andrews, Fife, Scotland. [Gabhainn, Saoirse Nic] Natl Univ Ireland, Hlth Promot Res Ctr, Sch Hlth Sci, Galway, Ireland. [Ravens-Sieberer, Ulrike] Univ Med Ctr Hamburg Eppendorf, Dept Child & Adolescent Psychiat Psychotherapy &, Hamburg, Germany. [Valimaa, Raili] Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla, Finland. RP Holstein, BE (reprint author), Univ Southern Denmark, Natl Inst Publ Hlth, Oster Farimagsgade 5A, DK-1353 Copenhagen, Denmark. EM bho@niph.dk OI Fotiou, Anastasios/0000-0001-7905-3241; Holstein, Bjorn/0000-0002-4348-280X FU Nordea Foundation [02-2011-0122] FX The authors thank the Nordea Foundation (02-2011-0122) for financial support. NR 20 TC 1 Z9 1 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 EI 1464-360X J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD APR PY 2015 VL 25 SU 2 BP 76 EP 79 DI 10.1093/eurpub/ckv035 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CT7CR UT WOS:000362971500019 PM 25805794 ER PT J AU de Boer, YS Kosinski, AS Urban, TJ Zhao, Z Long, N Chalasani, N Hoofnagle, JH AF de Boer, Y. S. Kosinski, A. S. Urban, T. J. Zhao, Z. Long, N. Chalasani, N. Hoofnagle, J. H. CA Drug-Induced Liver Injury Network TI AUTOIMMUNE HEPATITIS-LIKE DRUG INDUCED LIVER INJURY SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [de Boer, Y. S.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Kosinski, A. S.] Duke Clin Res Inst, Durham, NC USA. [Urban, T. J.; Long, N.] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA. [Zhao, Z.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Chalasani, N.] Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. [Hoofnagle, J. H.] NIDDK, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM y.deboer@vumc.nl NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA P1131 BP S775 EP S775 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5EL UT WOS:000362830900323 ER PT J AU Kattakuzhy, S Sidharthan, S Wilson, E Price, A Silk, R Gross, C Akoth, E Meissner, E Teferi, G Jenkins, V Pang, P Mo, H Osinusi, A Masur, H Kottilil, S Kohli, A AF Kattakuzhy, S. Sidharthan, S. Wilson, E. Price, A. Silk, R. Gross, C. Akoth, E. Meissner, E. Teferi, G. Jenkins, V. Pang, P. Mo, H. Osinusi, A. Masur, H. Kottilil, S. Kohli, A. TI PREDICTORS OF SUSTAINED VIRAL RESPONSE TO 4-6 WEEK DURATION THERAPY WITH LEDIPASVIR plus SOFOSBUVIR + GS-9451+/- GS-9669 IN EARLY AND ADVANCED FIBROSIS (NIH/UMD SYNERGY TRIAL) SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Kattakuzhy, S.; Sidharthan, S.; Price, A.; Silk, R.; Gross, C.; Akoth, E.; Kottilil, S.] Univ Maryland, Inst Human Virol, Dept Infect Dis, Baltimore, MD 21201 USA. [Wilson, E.; Kohli, A.] Leidos Biomed Res Inc, Clin Monitoring Res Program, Clin Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA. [Meissner, E.] Med Univ S Carolina, Div Infect Dis, Charleston, SC 29425 USA. [Teferi, G.] Unity Healthcare Inc, Infect Dis, Washington, DC USA. [Jenkins, V.] Family Med Counseling Serv Inc, Dept Med, Washington, DC USA. [Pang, P.; Mo, H.; Osinusi, A.] Gilead Sci Inc, Foster City, CA 94404 USA. [Masur, H.] NIH, Crit Care Dept, Bethesda, MD 20892 USA. EM sarah.kattakuzhy@nih.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA P0875 BP S669 EP S669 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5EL UT WOS:000362830900070 ER PT J AU Khalili, M Lombardero, M Feld, J Shuhart, M Chung, R Terrault, N Kowdley, K Lisker-Melman, M Ghany, M Kim, WR Sanyal, A Lok, A AF Khalili, M. Lombardero, M. Feld, J. Shuhart, M. Chung, R. Terrault, N. Kowdley, K. Lisker-Melman, M. Ghany, M. Kim, W. R. Sanyal, A. Lok, A. CA HBRN TI THE IMPACT OF METABOLIC SYNDROME ON ALT LEVELS AMONG THE LARGE MULTIETHNIC COHORT OF NORTH AMERICAN PATIENTS WITH CHRONIC HEPATITIS B INFECTION ENROLLED IN THE HEPATITIS B RESEARCH NETWORK (HBRN) SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Khalili, M.; Terrault, N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lombardero, M.] Univ Pittsburgh, Pittsburgh, PA USA. [Feld, J.] Univ Toronto, Toronto, ON, Canada. [Shuhart, M.] Univ Washington, Seattle, WA 98195 USA. [Chung, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kowdley, K.] Swedish Med Ctr, Seattle, WA USA. [Lisker-Melman, M.] Washington Univ, St Louis, MO USA. [Ghany, M.] NIH, Bethesda, MD 20892 USA. [Kim, W. R.] Stanford Univ, Palo Alto, CA 94304 USA. [Sanyal, A.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Lok, A.] Univ Michigan, Ann Arbor, MI 48109 USA. EM mandana.khalili@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA P1019 BP S729 EP S730 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5EL UT WOS:000362830900212 ER PT J AU Ouaguia, L Morales, O Wychowski, C Carpentier, A Aoudjehane, L Dubuisson, J Calmus, Y deLaunoit, Y Conti, F Delhem, N AF Ouaguia, L. Morales, O. Wychowski, C. Carpentier, A. Aoudjehane, L. Dubuisson, J. Calmus, Y. deLaunoit, Y. Conti, F. Delhem, N. TI THE HEPATITIS C VIRUS CONTRIBUTES TO THE AGGRAVATION OF THE IMMUNOSUPPRESSIVE ENVIRONMENT BY INCREASING THE SUPPRESSIVE ACTIVITY OF NATURAL REGULATORY T CELLS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Ouaguia, L.; Morales, O.; deLaunoit, Y.; Delhem, N.] Biol Inst Lille, CNRS, UMR 8161, Lille, France. [Wychowski, C.; Dubuisson, J.] Ctr Infect & Immun Lille, CNRS, UMR8204, InsermU1019, Lille, France. [Carpentier, A.] NIH, Bethesda, MD 20892 USA. [Aoudjehane, L.; Calmus, Y.; Conti, F.] Univ Paris 06, F-75012 Paris, France. [Aoudjehane, L.; Calmus, Y.; Conti, F.] CdR St Antoine, INSERM, UMR S 938, F-75012 Paris, France. EM laurissa.ouaguia@ibl.cnrs.fr NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA P0689 BP S580 EP S581 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5EJ UT WOS:000362830600406 ER PT J AU Ruhl, CE Unalp-Arida, A AF Ruhl, C. E. Unalp-Arida, A. TI RACIAL-ETHNIC DISPARITIES IN LIVER DISEASE MORTALITY IN THE UNITED STATES SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Ruhl, C. E.] Social & Sci Syst Inc, Silver Spring, MD USA. [Unalp-Arida, A.] NIDDK, Bethesda, MD 20892 USA. EM cruhl@s-3.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA P1029 BP S733 EP S734 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5EL UT WOS:000362830900222 ER PT J AU Shen, Z Liu, Y Hu, J Park, O Feng, T Dewidar, B Xu, C Yu, C Li, H Augustin, HG ten Dijke, P Gao, B Ebert, MPA Dooley, S Li, Y Weng, H AF Shen, Z. Liu, Y. Hu, J. Park, O. Feng, T. Dewidar, B. Xu, C. Yu, C. Li, H. Augustin, H. G. ten Dijke, P. Gao, B. Ebert, M. P. A. Dooley, S. Li, Y. Weng, H. TI DELTA LIKE LIGAND 4 DRIVES LIVER DAMAGE THROUGH REGULATING CHEMOKINES SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Shen, Z.; Xu, C.; Yu, C.; Li, Y.] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Gastroenterol, Hangzhou 310003, Zhejiang, Peoples R China. [Liu, Y.; Feng, T.; Dewidar, B.; Ebert, M. P. A.; Dooley, S.; Weng, H.] Heidelberg Univ, Dept Med 2, Med Fac Mannheim, Mannheim, Germany. [Hu, J.; Augustin, H. G.] DKFZ Ctr Mol Biol Alliance, Div Vasc Oncol & Metastasis, German Canc Res Ctr DKFZ, Heidelberg, Germany. [Park, O.; Gao, B.] NIAAA, Lab Liver Dis, NIH, Rockville, MD USA. [Li, H.] Shanghai Jiao Tong Univ, Dept Gastroenterol, Renji Hosp, Sch Med, Shanghai 200030, Peoples R China. [ten Dijke, P.] Leiden Univ, Med Ctr, Dept Mol Cell Biol, Leiden, Netherlands. [ten Dijke, P.] Leiden Univ, Ctr Biomed Genet, Med Ctr, Leiden, Netherlands. EM honglei.weng@medma.uni-heidelberg.de NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA P0430 BP S474 EP S474 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5EJ UT WOS:000362830600148 ER PT J AU Thi, VLD Emerson, SU Ahola, T Moradpour, D Gouttenoire, J AF Thi, V. Loan Dao Emerson, S. U. Ahola, T. Moradpour, D. Gouttenoire, J. TI HEPATITIS E VIRUS RNA REPLICATION IS ENSURED BY UNPROCESSED ORF1 PROTEIN SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2015 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [Thi, V. Loan Dao; Moradpour, D.; Gouttenoire, J.] Univ Lausanne, Ctr Hosp Univ Vaudois, Div Gastroenterol & Hepatol, Lausanne, Switzerland. [Emerson, S. U.] NIAID, Hepatitis & Hepatitis Viruses Sect 2Mol, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Ahola, T.] Univ Helsinki, Inst Biotechnol, Helsinki, Finland. EM Jerome.Gouttenoire@chuv.ch NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD APR PY 2015 VL 62 SU 2 MA P0534 BP S515 EP S515 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT5EJ UT WOS:000362830600251 ER PT J AU Adams, E Kuczmarski, MF Mason, M Allegro, D Zonderman, A Evans, M AF Adams, Erica Kuczmarski, Marie Fanelli Mason, Marc Allegro, Deanne Zonderman, Alan Evans, Michele TI Snacks Consumed by an Urban African American and White Population SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Adams, Erica; Kuczmarski, Marie Fanelli; Allegro, Deanne] Univ Delaware, Behav Hlth & Nutr, Newark, DE USA. [Mason, Marc; Zonderman, Alan; Evans, Michele] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 736.38 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702082 ER PT J AU Ahmad, F Shen, WX Vandeput, F Szabo-Fresnais, N Krall, J Degerman, E Goetz, F Klussmann, E Movsesian, M Manganiello, V AF Ahmad, Faiyaz Shen, Weixing Vandeput, Fabrice Szabo-Fresnais, Nicolas Krall, Judith Degerman, Eva Goetz, Frank Klussmann, Enno Movsesian, Matthew Manganiello, Vincent TI Phosphorylation-dependent Association of PDE3A1 with SERCA2 and its Regulation of SERCA2 Activity in Human Myocardium SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Ahmad, Faiyaz; Shen, Weixing; Manganiello, Vincent] NHLBI, CPB, Bethesda, MD 20892 USA. [Vandeput, Fabrice; Szabo-Fresnais, Nicolas; Krall, Judith; Movsesian, Matthew] Univ Utah, Cardiol Sect, Salt Lake City, UT USA. [Degerman, Eva] Lund Univ, Div Diabet, Lund, Sweden. [Goetz, Frank; Klussmann, Enno] DZHK GCCR, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 728.24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701420 ER PT J AU Ashour, F Addo, Y Sullivan, K Suchdev, P Mei, ZG Temple, V Raiten, D Flores-Ayala, R AF Ashour, Fayrouz Addo, Yaw Sullivan, Kevin Suchdev, Parmi Mei, Zuguo Temple, Victor Raiten, Daniel Flores-Ayala, Rafael TI Associations Between Markers of Inflammation and Hemoglobin Concentration: Implications for Diagnosis of Anemia in Women of Reproductive Age SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Ashour, Fayrouz; Addo, Yaw; Raiten, Daniel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Growth & Nutr, NIH, Bethesda, MD USA. [Addo, Yaw; Sullivan, Kevin; Suchdev, Parmi] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Sullivan, Kevin; Suchdev, Parmi; Mei, Zuguo; Flores-Ayala, Rafael] Ctr Dis Control & Prevent, Div Nutr, Atlanta, GA USA. [Temple, Victor] Univ Papua New Guinea, Sch Med & Hlth Sci, Port Moresby, Papua N Guinea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 913.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706013 ER PT J AU Beck, J Miller, M Frank, C DuSold, D Ramos-Vara, J AF Beck, Jessica Miller, Margaret Frank, Chad DuSold, Deidre Ramos-Vara, Jose TI Napsin A and Thyroid Transcription Factor-1 Immunohistochemistry in the Diagnosis of Canine Pulmonary Carcinomas SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Beck, Jessica; Miller, Margaret; DuSold, Deidre; Ramos-Vara, Jose] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. [Beck, Jessica] NCI, CBSTP, Bethesda, MD 20892 USA. [Frank, Chad] Colorado State Univ, Dept Microbiol, Immunol, Pathol, Ft Collins, CO 80523 USA. RI Frank, Chad/E-6197-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 762.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702385 ER PT J AU Byun, J Gardner, K AF Byun, Jung Gardner, Kevin TI CTBP-BRCA1 modulates Epithelial Cell Fate in Breast Cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Byun, Jung; Gardner, Kevin] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 926.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706195 ER PT J AU Canter, J Sheckells, S Saylor, C Patterson, A Carlson, B Gladyshev, V Yu, YK Cao, L May, M Davis, C Hatfield, D Tsuji, P AF Canter, Jessica Sheckells, Sarah Saylor, Charlotte Patterson, Angelica Carlson, Bradley Gladyshev, Vadim Yu, Yunkai Cao, Liang May, Meghan Davis, Cindy Hatfield, Dolph Tsuji, Petra TI Modulation of Intestinal Microbiota by Dietary Selenium and 15kDa Selenoprotein Expression in Inflammatory Colon Cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Canter, Jessica; Sheckells, Sarah; Saylor, Charlotte; Patterson, Angelica; Tsuji, Petra] Towson Univ, Biol Sci, Towson, MD USA. [Carlson, Bradley; Hatfield, Dolph] NIH, Mol Biol Selenium Sect, Bethesda, MD 20892 USA. [Gladyshev, Vadim] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Yu, Yunkai; Cao, Liang] NIH, Mol Targets Core, Bethesda, MD 20892 USA. [May, Meghan] Univ New England, Biomed Sci, Biddeford, ME USA. [Davis, Cindy] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 759.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702361 ER PT J AU Chandyo, R Maciel, B Ambikapathi, R Patil, C Bose, A Amour, C Islam, M Turab, A Bessong, P Caulfield, L AF Chandyo, Ram Maciel, Bruna Ambikapathi, Ramya Patil, Crystal Bose, Anuradha Amour, Caroline Islam, Munirul Turab, Ali Bessong, Pascal Caulfield, Laura TI Quality of the Early Infant Diet across the Eight Low and Middle Income Countries from the Malnutrition and Enteric Disease (MAL-ED) Study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Chandyo, Ram] UiB, Ctr Int Hlth, Bergen, Norway. [Maciel, Bruna] Univ Estadual Ceara, Dept Nutr, Fortaleza, Ceara, Brazil. [Ambikapathi, Ramya] NIH, Fogarty Int Ctr, Bethesda, MD USA. [Patil, Crystal] UIC, Dept Women Children & Family Hlth Sci, Chicago, IL USA. [Bose, Anuradha] CMC, Vellore, Tamil Nadu, India. [Amour, Caroline] HLH, Moshi, Tanzania. [Islam, Munirul] ICDDR B, Dhaka, Bangladesh. [Turab, Ali] AKU, Dept Pediat, Karachi, Pakistan. [Bessong, Pascal] Univ Venda, Dept Nutr, Thohoyandou, South Africa. [Caulfield, Laura] JHSPH, Ctr Human Nutr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 901.28 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722705352 ER PT J AU Cho, HY Miller-DeGraff, L Park, S Lao, HC Langenbach, R Kleeberger, S AF Cho, Hye-Youn Miller-DeGraff, Laura Park, Soojung Lao, Huei-Chen Langenbach, Robert Kleeberger, Steven TI Role of Mucin 5ac in Murine Airways SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Cho, Hye-Youn; Miller-DeGraff, Laura; Park, Soojung; Lao, Huei-Chen; Langenbach, Robert; Kleeberger, Steven] NIEHS, Immun Inflammat & Dis Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 1014.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722707392 ER PT J AU Choi, BE Abeykoon, A Chao, CC Wang, G Gucek, M Ching, WM Chock, PB Buchanan, S Yang, DCH AF Choi, Bok-Eum Abeykoon, A. Chao, C. C. Wang, G. Gucek, M. Ching, W. M. Chock, P. B. Buchanan, S. Yang, D. C. H. TI Expression and Purification of Rickettsial Outer Membrane Protein B SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Choi, Bok-Eum; Yang, D. C. H.] Georgetown Univ, Dept Chem, Washington, DC 20057 USA. [Abeykoon, A.; Buchanan, S.] NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. [Chao, C. C.; Ching, W. M.] NMRC, Viral & Rickettsial Dis Dept, Silver Spring, MD USA. [Wang, G.; Gucek, M.] NHLBI, Prote Core Facil, Bethesda, MD 20892 USA. [Chock, P. B.] NHLBI, Biochem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 714.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701076 ER PT J AU Cruz-Topete, D Myers, P Foley, J Willis, M Cidlowski, J AF Cruz-Topete, Diana Myers, Page Foley, Julie Willis, Monte Cidlowski, John TI Stress Hormones are Critical in Maintaining Cardiac Gene Expression and Function in Mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Cruz-Topete, Diana; Myers, Page; Foley, Julie; Cidlowski, John] NIEHS, LST, CMB, CMPB,NIH, Res Triangle Pk, NC USA. [Willis, Monte] UNC, McAllister Heart Inst, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 1037.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722708006 ER PT J AU Dasso, M Arnaoutov, A AF Dasso, Mary Arnaoutov, Alexei TI IRBIT is a Novel Regulator of Ribonucleotide Reductase in Higher Eukaryotes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Dasso, Mary; Arnaoutov, Alexei] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 884.60 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722704473 ER PT J AU Diaz-Moreno, I Garcia-Maurino, S Del Conte, R Angulo, J Karlsson, B Gorospe, M Wilce, J Cruz-Gallardo, I AF Diaz-Moreno, Irene Garcia-Maurino, Sofia Del Conte, Rebecca Angulo, Jesus Karlsson, B. Gorospe, Myriam Wilce, Jacqueline Cruz-Gallardo, Isabel TI The Regulation of TIA-1 Binding to RNA by pH Conditions SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Diaz-Moreno, Irene; Garcia-Maurino, Sofia; Cruz-Gallardo, Isabel] Univ Seville, CSIC, CicCartuja, Inst Plant Biochem & Photosynth, Seville, Spain. [Del Conte, Rebecca] Univ Florence, CERM, Florence, Italy. [Angulo, Jesus] Univ E Anglia, Sch Pharm, Norwich NR4 7TJ, Norfolk, England. [Karlsson, B.] Univ Gothenburg, Swedish NMR Ctr, Gothenburg, Sweden. [Gorospe, Myriam] NIA, Lab Genet, Intramural Res Program, Baltimore, MD 21224 USA. [Wilce, Jacqueline] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia. RI Diaz-Moreno, Irene/E-7181-2010 OI Diaz-Moreno, Irene/0000-0002-5318-7644 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 711.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701017 ER PT J AU Edwards, J Gehret, A O'Handley, S AF Edwards, Jasmine Gehret, Austin O'Handley, Suzanne TI A Phosphoglycolate Phosphatase Virulence Factor from Staphylococcus aureus SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Edwards, Jasmine; O'Handley, Suzanne] Rochester Inst Technol, Dept Chem & Mat Sci, Rochester, NY 14623 USA. [Gehret, Austin] Natl Inst Deaf, Sci & Math, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 721.11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701241 ER PT J AU Galinn, S Rosso, L Carlson, B Tobe, R Naranjo-Suarez, S Tsuji, P AF Galinn, Sarah Rosso, Lauren Carlson, Bradley Tobe, Ryuta Naranjo-Suarez, Salvador Tsuji, Petra TI The 15kDa Selenoprotein Expression May Be Regulated Through The AhR Pathway SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Galinn, Sarah; Rosso, Lauren] Towson Univ, Biol Sci, Towson, MD USA. [Carlson, Bradley; Tobe, Ryuta] NIH, Mol Biol Selenium Sect, Bethesda, MD 20892 USA. [Naranjo-Suarez, Salvador] Johns Hopkins Univ, Pathol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 759.9 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702363 ER PT J AU Guertin, K Freedman, N Loftfield, E Graubard, B Caporaso, N Sinha, R AF Guertin, Kristin Freedman, Neal Loftfield, Erikka Graubard, Barry Caporaso, Neil Sinha, Rashmi TI Coffee Consumption and Risk of Lung Cancer in the NIH-AARP Diet and Health Study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Guertin, Kristin; Freedman, Neal; Loftfield, Erikka; Graubard, Barry; Caporaso, Neil; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 906.28 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722705451 ER PT J AU Hao, SJ DelliPizzi, A Jiang, HL Quiroz-Munoz, M Cespedes, C Knepper, M Vio, C Ferreri, N AF Hao, Shoujin DelliPizzi, AnnMarie Jiang, Houli Quiroz-Munoz, Mariana Cespedes, Carlos Knepper, Mark Vio, Carlos Ferreri, Nicholas TI Activation of EP3 receptors suppresses COX-2 in thick ascending limb (TAL) and inhibits water excretion SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Hao, Shoujin; DelliPizzi, AnnMarie; Jiang, Houli; Ferreri, Nicholas] New York Med Coll, Pharmacol, Valhalla, NY 10595 USA. [Quiroz-Munoz, Mariana; Cespedes, Carlos; Vio, Carlos] Catholic Univ, Physiol, Santiago, Chile. [Knepper, Mark] NIH, Epithelial Syst Biol Lab, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 809.21 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722703150 ER PT J AU Hao, SJ DelliPizzi, A Hao, M Knepper, M Ferreri, N AF Hao, Shoujin DelliPizzi, AnnMarie Hao, Mary Knepper, Mark Ferreri, Nicholas TI Tumor necrosis factor-alpha (TNF) regulates NKCC2 and AQP2 expression and adaptation to high NaCl intake SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Hao, Shoujin; DelliPizzi, AnnMarie; Hao, Mary; Ferreri, Nicholas] New York Med Coll, Pharmacol, Valhalla, NY 10595 USA. [Knepper, Mark] NIH, Epithelial Syst Biol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 666.20 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722700061 ER PT J AU Jang, S Sun, JH Chen, P Lakshman, S Molokin, A Harnly, J Urban, J Davis, C Solano-Aguilar, G AF Jang, Saebyeol Sun, Jianghao Chen, Pei Lakshman, Sukla Molokin, Aleksey Harnly, James Urban, Joseph, Jr. Davis, Cindy Solano-Aguilar, Gloria TI Changes in the Intestinal Microbiota and Host Inflammatory Gene Expression in Pigs Fed a Flavanol-Enriched Cocoa Powder SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Jang, Saebyeol; Lakshman, Sukla; Molokin, Aleksey; Urban, Joseph, Jr.; Solano-Aguilar, Gloria] ARS, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, USDA, Beltsville, MD USA. [Sun, Jianghao; Chen, Pei; Harnly, James] ARS, Beltsville Human Nutr Res Ctr, Food Composit & Methods Dev Lab, USDA, Beltsville, MD USA. [Davis, Cindy] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 914.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706029 ER PT J AU Kaur, S Singh, S Elkahloun, A Wu, WW Song, T Arora, A Roberts, D AF Kaur, Sukhbir Singh, Satya Elkahloun, Abdel Wu, Weiwei Song, Tim Arora, Ashi Roberts, David TI Role of CD47 in triple negative breast cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Kaur, Sukhbir; Song, Tim; Arora, Ashi; Roberts, David] CCR NCI, Lab Pathol, NIH, Bethesda, MD USA. [Singh, Satya] NIAID, Inflammat Biol Sect, NIH, Bethesda, MD 20892 USA. [Elkahloun, Abdel; Wu, Weiwei] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 890.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722705104 ER PT J AU Kemper, M Pawlosky, R King, MT Wainwright, C Clarke, K Veech, R AF Kemper, Martin Pawlosky, Robert King, M. Todd Wainwright, Camilla Clarke, Kieran Veech, Richard TI Oral administration of a Ketone Ester regulates blood cholesterol in rats and humans SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Kemper, Martin; Pawlosky, Robert; King, M. Todd; Veech, Richard] NIAAA, Lab Metab Control, NIH, Rockville, MD 20852 USA. [Clarke, Kieran] Univ Oxford, Physiol Anat & Genet, Oxford, England. [Wainwright, Camilla] St Vincents Clin, Cardiol, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 715.17 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701106 ER PT J AU Krebs-Smith, SM Kirkpatrick, SI Subar, AF Rodgers, AB Schap, TE Reedy, J Wilson, MM De Aguiar, CK Thompson, FE AF Krebs-Smith, S. M. Kirkpatrick, S. I. Subar, A. F. Rodgers, A. B. Schap, T. E. Reedy, J. Wilson, M. M. De Aguiar, C. K. Thompson, F. E. TI The National Cancer Institute's Dietary Assessment Primer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Krebs-Smith, S. M.; Subar, A. F.; Rodgers, A. B.; Schap, T. E.; Reedy, J.; Wilson, M. M.; De Aguiar, C. K.; Thompson, F. E.] NCI, DCCPS, Rockville, MD USA. [Kirkpatrick, S. I.] Univ Waterloo, Publ Hlth, Waterloo, ON N2L 3G1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 905.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722705416 ER PT J AU Lee, J Lam, T Consonni, D Pesatori, A Bertazzi, P Landi, M AF Lee, Jennifer Lam, Tram Consonni, Dario Pesatori, Agnela Bertazzi, Pier Landi, Maria TI Association of Nut Consumption and Lung Cancer Risk in a Large Population-based Case-control Study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Lee, Jennifer; Lam, Tram] NCI, Epidemiol & Genom Res, DCCPS, NIH, Rockville, MD USA. [Consonni, Dario; Pesatori, Agnela; Bertazzi, Pier] Univ Milan, Epidemiol Res Ctr, EPOCA, Milan, Italy. [Landi, Maria] NCI, Genet Epidemiol Branch, DCEG, NIH, Bethesda, MD 20892 USA. RI Consonni, Dario/K-7943-2016 OI Consonni, Dario/0000-0002-8935-3843 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 736.11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702055 ER PT J AU Li, K Wu, SP Playford, M Sun, J AF Li, Kendy Wu, Shaopig Playford, Martin Sun, Jun TI Deletion of Sorting Nexin 27 Reverses Epithelial-Mesenchymal-Transition in Highly Aggressive Breast Cancer Cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Li, Kendy; Wu, Shaopig; Sun, Jun] Rush Univ, Biochem, Chicago, IL 60612 USA. [Li, Kendy] Langley High Sch, Sci, Mclean, VA USA. [Playford, Martin] NHLBI, Sect Inflammat & Cardiometabol Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 926.20 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706209 ER PT J AU Li, SS Ladhani, F Gao, B Zang, MW AF Li, Shan-Shan Ladhani, Farhan Gao, Bin Zang, Mengwei TI mTORC1 Inhibition Reduces ER Stress and Ameliorates Alcoholic Liver Injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Li, Shan-Shan; Ladhani, Farhan; Zang, Mengwei] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gao, Bin] NIH, Alcohol Abuse & Alcoholism, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 846.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722704027 ER PT J AU Li, YW Liu, L Rao, J Zou, TT Xiao, L Chang, HK Gorospe, M Wang, JY AF Li, Yanwu Liu, Lan Rao, Jaladankj Zou, Tongtong Xiao, Lan Chang, Hee Kyoung Gorospe, Myriam Wang, Jian-Ying TI miR-29b Regulates Intestinal Epithelium Homeostasis by Modulating Wnt Co-receptor LRP6 Translation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Li, Yanwu; Liu, Lan; Rao, Jaladankj; Zou, Tongtong; Xiao, Lan; Chang, Hee Kyoung; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. [Li, Yanwu; Liu, Lan; Rao, Jaladankj; Zou, Tongtong; Xiao, Lan; Chang, Hee Kyoung; Wang, Jian-Ying] VA Med Ctr, Baltimore, MD USA. [Gorospe, Myriam] NIA, NIH, Baltimore, MD 21224 USA. [Wang, Jian-Ying] Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 851.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722704050 ER PT J AU Luo, ZP Dauter, Z AF Luo, Zhipu Dauter, Zbigniew TI Flexibility of Terminal Cytidines in Ca2+ Form B-DNA SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET ID IONS C1 [Luo, Zhipu; Dauter, Zbigniew] NCI, Macromol Crystallog Lab, NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 710.15 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701004 ER PT J AU Nelson, S Weinstein, S Albanes, D AF Nelson, Shakira Weinstein, Stephanie Albanes, Demetrius TI Coffee Consumption and Risk of Prostate Cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Nelson, Shakira; Weinstein, Stephanie; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 906.23 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722705446 ER PT J AU Paramasivam, M Muniandy, P Wang, WD Seidman, M AF Paramasivam, Manikandan Muniandy, Parameswary Wang, Weidong Seidman, Michael TI Proximal and Distal interactions of Fanconi Anemia (FA) protein FANCD2 with Genomic Interstrand Crosslinks (ICLs) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Paramasivam, Manikandan; Seidman, Michael] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. [Muniandy, Parameswary] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Muniandy, Parameswary] NIA, Lab Genet, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 879.19 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722704331 ER PT J AU Park, SS Yi, DI Liang, GQ Yan, TF Ambs, S Byun, JS Gardner, K AF Park, Sam Sangil Yi, Dae Ik Liang, Genqing Yan, Tingfen Ambs, Stefan Byun, Jung S. Gardner, Kevin TI Exploring Molecular and Morphological Relationships between Obesity and CtBP in Breast Cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Park, Sam Sangil; Yi, Dae Ik; Liang, Genqing; Yan, Tingfen; Ambs, Stefan; Byun, Jung S.; Gardner, Kevin] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 926.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706194 ER PT J AU Patial, S Blackshear, P AF Patial, Sonika Blackshear, Perry TI Genetic deletion of an instability motif in the Tristetraprolin (TTP) transcript increases TTP mRNA stability and protein expression and provides protection against inflammatory diseases SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Patial, Sonika; Blackshear, Perry] NIEHS, LST, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 711.15 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701027 ER PT J AU Pratt, C Sundaresan, S AF Pratt, Charlotte Sundaresan, Shyamala TI Are Adolescents Meeting the 2020 Goals of the American Heart Association (AHA) for Ideal Cardiovascular Health? (906.1) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Pratt, Charlotte; Sundaresan, Shyamala] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 906.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722705426 ER PT J AU Procino, G Milano, S Dal Monte, M Nicoletti, M Mastrodonato, M Li, J Wess, J Carmosino, M Bagnoli, P Svelto, M AF Procino, Giuseppe Milano, Serena Dal Monte, Massimo Nicoletti, Maria Mastrodonato, Maria Li, Jian Wess, Jurgen Carmosino, Monica Bagnoli, Paola Svelto, Maria TI Sympathetic Stimulation In The Kidney: A Possible Antidiuretic Effect Of BAR3? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Procino, Giuseppe; Milano, Serena; Nicoletti, Maria; Carmosino, Monica; Svelto, Maria] Univ Bari, Biosci Biotechnol & Biopharmaceut, Bari, Italy. [Dal Monte, Massimo; Bagnoli, Paola] Univ Pisa, Biol, Pisa, Italy. [Mastrodonato, Maria] Univ Bari, Biol, Bari, Italy. [Li, Jian; Wess, Jurgen] NIDDKD, Bethesda, MD USA. RI mastrodonato, Maria/P-4513-2016 OI mastrodonato, Maria/0000-0002-0799-8032 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 809.13 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722703143 ER PT J AU Quinn, M Cidlowski, J AF Quinn, Matthew Cidlowski, John TI Endogenous Glucocorticoids Regulate Hepatic Inflammation and Apoptosis in a Sexually Dimorphic Manner SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Quinn, Matthew; Cidlowski, John] NIEHS, Lab Signal Transduct Mol Endocrinol, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 1008.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722707351 ER PT J AU Raghavan, R Wang, GY Chen, Z Wang, XB AF Raghavan, Ramkripa Wang, Guoying Chen, Zhu Wang, Xiaobin TI Vitamin B12, Folate and Homocysteine Levels in the US Urban Minority Mothers Post Delivery SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Raghavan, Ramkripa; Wang, Guoying; Chen, Zhu; Wang, Xiaobin] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA. [Raghavan, Ramkripa] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 919.11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706065 ER PT J AU Rosso, L Galinn, S Carlson, B Tobe, R Naranjo-Suarez, S Tsuji, P AF Rosso, Lauren Galinn, Sarah Carlson, Bradley Tobe, Ryuta Naranjo-Suarez, Salvador Tsuji, Petra TI Effect of Dietary Bioactive Compounds on Thioredoxin Reductase 1 and 15kDa Selenoprotein Expression in Colon Cancer Cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Rosso, Lauren; Galinn, Sarah; Tsuji, Petra] Towson Univ, Biol Sci, Towson, MD USA. [Carlson, Bradley; Tobe, Ryuta] NIH, Mol Biol Selenium Sect, Bethesda, MD 20892 USA. [Naranjo-Suarez, Salvador] Johns Hopkins Univ, Pathol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 759.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702362 ER PT J AU Shearrer, G O'Reilly, G Belcher, B Daniels, M Goran, M Spruijt-Metz, D Davis, J AF Shearrer, Grace O'Reilly, Gillian Belcher, Britini Daniels, Michael Goran, Michael Spruijt-Metz, Donna Davis, Jaimie TI The Impact of Sugar Sweetened Beverage (SSB) Intake on Hunger and Satiety in Minority Adolescents SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Shearrer, Grace; Davis, Jaimie] Univ Texas Austin, Dept Nutr, Austin, TX 78712 USA. [O'Reilly, Gillian; Goran, Michael] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Belcher, Britini] NCI, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. [Daniels, Michael] Univ Texas Austin, Dept Stat & Computat, Austin, TX 78712 USA. [Spruijt-Metz, Donna] Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 747.20 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702201 ER PT J AU Stowe, S Cavalier, M Godoy-Ruiz, R Varney, K Wilder, P Gartenhaus, R Weber, D AF Stowe, Sean Cavalier, Michael Godoy-Ruiz, Raquel Varney, Kristen Wilder, Paul Gartenhaus, Ronald Weber, David TI Understanding the Formation of the MCT-1:DenR Complex, a Translational Enhancer for Lymphoma Survival SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Stowe, Sean; Cavalier, Michael; Godoy-Ruiz, Raquel; Varney, Kristen; Wilder, Paul; Weber, David] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Wilder, Paul; Gartenhaus, Ronald; Weber, David] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum NCI Canc Ctr, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 883.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722704407 ER PT J AU Stull, A Cash, K Champagne, C Gupta, A Boston, R Beyl, R Johnson, W Cefalu, W AF Stull, April Cash, Katherine Champagne, Catherine Gupta, Alok Boston, Raymond Beyl, Robbie Johnson, William Cefalu, William TI Blueberry Bioactives Improve Endothelial Function in Adults with Metabolic Syndrome SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Stull, April; Cash, Katherine; Champagne, Catherine; Beyl, Robbie; Johnson, William; Cefalu, William] LSU Syst, PBRC, Baton Rouge, LA USA. [Stull, April; Johnson, William; Cefalu, William] NIH, Ctr Study Botanicals & Metab Syndrome, PBRC, Baton Rouge, LA USA. [Gupta, Alok] Hosp Med Grp, Baton Rouge, LA USA. [Boston, Raymond] Univ Penn, Dept Clin Studies, NBC, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 923.17 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706144 ER PT J AU Sullivan, K Suchdev, P Raiten, D Flores, R Namaste, S Temple, V Serdula, M Mei, ZG Jefferds, M Whitehead, R AF Sullivan, Kevin Suchdev, Parmi Raiten, Daniel Flores, Rafael Namaste, Sorrel Temple, Victor Serdula, Mary Mei, Zugou Jefferds, Maria Whitehead, Ralph TI Association between Two Acute Phase Proteins with Hemoglobin in Preschool Children SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Sullivan, Kevin; Suchdev, Parmi; Flores, Rafael; Serdula, Mary; Mei, Zugou; Jefferds, Maria; Whitehead, Ralph] CDC, CCDPHP, Atl, GA USA. [Raiten, Daniel] NICHD, NIH, Bethesda, MD USA. [Namaste, Sorrel; Temple, Victor] UPNG, SMHS, Port Moresby, Papua N Guinea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 757.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702336 ER PT J AU Toth, J Gulyas, G Toth, D Hunyady, L Balla, T Varnai, P AF Toth, Jozsef Gulyas, Gergo Toth, Daniel Hunyady, Laszlo Balla, Tamas Varnai, Peter TI Monitoring the Dynamic Change of Inositol Lipid Pools upon EGFR and M3R Activation in Live Cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Toth, Jozsef; Hunyady, Laszlo] HAS, HAS SE Lab Mol Physiol, Budapest, Hungary. [Gulyas, Gergo; Toth, Daniel; Varnai, Peter] Semmelweis Univ, Dept Physiol, H-1085 Budapest, Hungary. [Balla, Tamas] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 715.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701090 ER PT J AU Tsuji, P Carlson, B Canter, J Onyewu, C Saylor, C Tobe, R Seifried, H Yu, YK Cao, L Gladyshev, V Davis, C Hatfield, D AF Tsuji, Petra Carlson, Bradley Canter, Jessica Onyewu, Chukwuka Saylor, Charlotte Tobe, Ryuta Seifried, Harold Yu, Yunkai Cao, Liang Gladyshev, Vadim Davis, Cindy Hatfield, Dolph TI Potential Role of the 15kDA Selenoprotein in Colorectal Inflammation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Tsuji, Petra; Canter, Jessica; Onyewu, Chukwuka; Saylor, Charlotte] Towson Univ, Biol Sci, Towson, MD USA. [Carlson, Bradley; Tobe, Ryuta; Hatfield, Dolph] NIH, Mol Biol Selenium Sect, Bethesda, MD 20892 USA. [Seifried, Harold] NIH, Nutr Sci Res Grp, Bethesda, MD 20892 USA. [Yu, Yunkai; Cao, Liang] NIH, Mol Targets Core, Bethesda, MD 20892 USA. [Gladyshev, Vadim] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Davis, Cindy] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 759.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722702355 ER PT J AU Umejiego, E Chou, CL Knepper, MA AF Umejiego, E. Chou, C-L Knepper, M. A. TI FDA-Approved PDE4 Inhibitor Roflumilast Enhances Vasopressin-Induced Aquaporin-2 Phosphorylation Changes in Renal Collecting Duct SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Umejiego, E.; Chou, C-L; Knepper, M. A.] NHLBI, Epithelial Syst Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 809.20 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722703149 ER PT J AU Wang, LD Scott, I Han, K Sack, M AF Wang, Lingdi Scott, Iain Han, Kim Sack, Michael TI Gcn5-like Protein 1 (Gcn5L1) Regulates Unfolded Protein Response and Hepatic Glucose Production SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Wang, Lingdi; Han, Kim; Sack, Michael] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD USA. [Scott, Iain] Univ Pittsburgh, Div Med, Cardiol Vasc Med Inst, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 884.26 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722704439 ER PT J AU Xiao, TJ Wongtrakoongate, P Trainor, C Felsenfeld, G AF Xiao, Tiaojiang Wongtrakoongate, Patompon Trainor, Cecelia Felsenfeld, Gary TI CTCF protein recruits centromeric protein CENP-E to the centromeric regions through unusual CTCF binding sites SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Xiao, Tiaojiang; Wongtrakoongate, Patompon; Trainor, Cecelia; Felsenfeld, Gary] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 709.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722700477 ER PT J AU Yi, DI Park, S Liang, GQ Yan, TF Byun, J Gardner, K AF Yi, Dae Ik Park, Sam Liang, Genqing Yan, Tingfen Byun, Jung Gardner, Kevin TI Functional Studies of CtBP in Breast Cancer Using the Lentiviral pINDUCER System SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Yi, Dae Ik; Park, Sam; Liang, Genqing; Yan, Tingfen; Byun, Jung; Gardner, Kevin] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 926.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722706191 ER PT J AU Yin, Y Garcia, M Novak, A Fisher, L AF Yin, Ying Garcia, Mekka Novak, Alex Fisher, Larry TI Cargo Receptor Traffics Many Matrix Proteins Out of the Endoplasmic Reticulum (ER) by Binding to N-Terminal IleProVal (IPV)-Like Motif SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY MAR 28-APR 01, 2015 CL Boston, MA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, ASIP, ASN, ASPET C1 [Yin, Ying; Garcia, Mekka; Novak, Alex; Fisher, Larry] NIDCR, Matrix Biochem Sect, CSDB, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 719.12 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CS0BT UT WOS:000361722701213 ER PT J AU Mcintyre, S Badawi, N Blair, E Nelson, KB AF Mcintyre, Sarah Badawi, Nadia Blair, Eve Nelson, Karin B. TI Does aetiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy influence the outcome of treatment? SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID LOW APGAR SCORES; WHOLE-BODY HYPOTHERMIA; CEREBRAL-PALSY; TERM INFANTS; NEWBORN ENCEPHALOPATHY; BIRTH ASPHYXIA; PRETERM BIRTH; RISK-FACTORS; ASSOCIATION; POPULATION AB Neonatal encephalopathy, a clinical syndrome affecting term-born and late preterm newborn infants, increases the risk of perinatal death and long-term neurological morbidity, especially cerebral palsy. With the advent of therapeutic hypothermia, a treatment designed for hypoxic or ischaemic injury, associated mortality and morbidity rates have decreased. Unfortunately, only about one in eight neonates (95% confidence interval) who meet eligibility criteria for therapeutic cooling apparently benefit from the treatment. Studies of infants in representative populations indicate that neonatal encephalopathy is a potential result of a variety of antecedents and that asphyxial complications at birth account for only a small percentage of neonatal encephalopathy. In contrast, clinical case series suggest that a large proportion of neonatal encephalopathy is hypoxic or ischaemic, and trials of therapeutic hypothermia are specifically designed to include only infants exposed to hypoxia or ischaemia. This review addresses the differences, definitional and methodological, between infants studied and investigations undertaken, in population studies compared with cooling trials. It raises the question if there may be subgroups of infants with a clinical diagnosis of hypoxic-ischaemic encephalopathy (HIE) in whom the pathobiology of neonatal neurological depression is not fundamentally hypoxic or ischaemic and, therefore, for whom cooling may not be beneficial. In addition, it suggests approaches to future trials of cooling plus adjuvant therapy that may contribute to further improvement of care for these vulnerable neonates. C1 [Mcintyre, Sarah; Badawi, Nadia] Univ Notre Dame, Cerebral Palsy Alliance, Darlinghurst, NSW, Australia. [Badawi, Nadia] Univ Sydney, Childrens Hosp Westmead, Grace Ctr Newborn Care, Sydney, NSW 2006, Australia. [Blair, Eve] Univ Western Australia, Telethon Inst Child Hlth Res, Perth, WA 6009, Australia. [Nelson, Karin B.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Nelson, Karin B.] NINDS, NIH, Bethesda, MD 20892 USA. RP Nelson, KB (reprint author), 5524 Charles St, Bethesda, MD 20814 USA. EM nelsonk@ninds.nih.gov RI Badawi, Nadia/A-3179-2014 FU Castang Foundation; Cerebral Palsy Research Foundation; Macquarie Group Foundation; NHMRC program [353514] FX Funding sources: the Castang Foundation supported SM to travel to the meeting; the Cerebral Palsy Research Foundation supported SM; Macquarie Group Foundation and Cerebral Palsy Research Foundation supported NB; NHMRC program grant No 353514 supported EB. The authors have stated that they had no interests that might be perceived as posing a conflict or bias. NR 36 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1622 EI 1469-8749 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD APR PY 2015 VL 57 SU 3 SI SI BP 2 EP 7 DI 10.1111/dmcn.12725 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA CS7RM UT WOS:000362282900002 PM 25800486 ER PT J AU Addo, OY Ashour, F Namaste, S Sullivan, K Suchdev, P Mei, ZG Rohner, F Northrop-Clewes, C Flores-Ayala, R Raiten, D AF Addo, O. Yaw Ashour, Fayrouz Namaste, Sorrel Sullivan, Kevin Suchdev, Parminder Mei, Zuguo Rohner, Fabian Northrop-Clewes, Christine Flores-Ayala, Rafael Raiten, Daniel TI Relationship between Transferrin Receptor and Two Acute Phase Proteins in Women of Reproductive Age SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Addo, O. Yaw; Sullivan, Kevin; Suchdev, Parminder; Flores-Ayala, Rafael] Emory Univ, RSPH, Atlanta, GA 30322 USA. [Addo, O. Yaw; Ashour, Fayrouz; Namaste, Sorrel; Raiten, Daniel] NICHD, PGNB, Bethesda, MD USA. [Sullivan, Kevin; Suchdev, Parminder; Mei, Zuguo; Flores-Ayala, Rafael] CDC, Nutr Branch, Atlanta, GA 30333 USA. [Namaste, Sorrel] HKI, SPRING, Washington, DC USA. [Rohner, Fabian] GroundWork, Crans Pres Celigny, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 393.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503029 ER PT J AU Akabas, S Paxson, E Bailey, R Saklani, S Tucker, K AF Akabas, Sharon Paxson, Erin Bailey, Regan Saklani, Shilpa Tucker, Katherine TI Use of NHANES 2007-2010 Data to Identify Groups Vulnerable for Inadequate Micronutrient Intake SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Akabas, Sharon; Paxson, Erin] Columbia Univ, Inst Human Nutr, Med Ctr, New York, NY 10032 USA. [Bailey, Regan] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Saklani, Shilpa; Tucker, Katherine] Univ Massachusetts, Ctr Populat Hlth & Hlth Dispar, Lowell, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 587.16 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504477 ER PT J AU Albanes, D Moore, S Weinstein, S Mondul, A AF Albanes, Demetrius Moore, Steven Weinstein, Stephanie Mondul, Alison TI Serum Metabolomic Response to Vitamin E Supplementation in a Controlled Cancer Prevention Trial SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Albanes, Demetrius; Moore, Steven; Weinstein, Stephanie; Mondul, Alison] NIH, Nutr Epidemiol Branch, DCEG, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 389.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502498 ER PT J AU Bagh, M Chandra, G Peng, SY Zhang, ZJ Mukherjee, A AF Bagh, Maria Chandra, Goutam Peng, Shiyong Zhang, Zhongjian Mukherjee, Anil TI A lysosomal targeting defect of V0a1 suppresses V-ATPase activity elevating lysosomal pH in Ppt1(-/-) mice: amelioration by NtBuHA SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bagh, Maria; Chandra, Goutam; Peng, Shiyong; Zhang, Zhongjian; Mukherjee, Anil] NICHD, SDG, PEDGN, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 570.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504138 ER PT J AU Bortner, C Scoltock, A Cidlowski, J AF Bortner, Carl Scoltock, Alyson Cidlowski, John TI Development of Resistance to Intrinsic Apoptotic Stimuli in Lymphocytes without Alterations in Bcl-2 Family Member Gene Expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bortner, Carl; Scoltock, Alyson; Cidlowski, John] NIEHS, Traitement Signal Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 569.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504119 ER PT J AU Calvo, E Chagas, A Ramirez, J Ribeiro, J AF Calvo, Eric Chagas, Andrezza Ramirez, Jose Ribeiro, Jose TI Molecular Mechanism of FXa Inhibition by Cufaxapin, the Main Salivary Anticoagulant of the West Nile Virus Vector Culex quinquesfaciatus SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Calvo, Eric; Chagas, Andrezza; Ramirez, Jose; Ribeiro, Jose] NIAID, Lab Malaria & Vector Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 609.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470505288 ER PT J AU Carpenter, K Pereira, M Odegaard, A Jacobs, D Sternfeld, B Reis, J Gabriel, K AF Carpenter, Katie Pereira, Mark Odegaard, Andrew Jacobs, David Sternfeld, Barbara Reis, Jacob Gabriel, Kelley TI Sedentary Behavior and CVD Risk Factors in Year 25 of the CARDIA Study SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Carpenter, Katie; Pereira, Mark; Jacobs, David] Univ Minnesota, Epidemiol & Community Hlth, Minneapolis, MN USA. [Odegaard, Andrew] Univ Calif Irvine, Epidemiol, Irvine, CA USA. [Sternfeld, Barbara] Kaiser Permanente, Div Res, Oakland, CA USA. [Reis, Jacob] NHLBI, NIH, Bethesda, MD 20892 USA. [Gabriel, Kelley] UT Sch Publ Hlth, Epidemiol Human Genet & Environm Sci, Austin, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA LB275 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470500273 ER PT J AU Chen-Edinboro, L Murray-Kolb, L Simonsick, E Ferrucci, L Allen, R Payne, M Spira, A AF Chen-Edinboro, Lenis Murray-Kolb, Laura Simonsick, Eleanor Ferrucci, Luigi Allen, Richard Payne, Martha Spira, Adam TI Association Between Anemia Subtypes and Insomnia Symptoms in Community-Dwelling Older Adults SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Chen-Edinboro, Lenis; Spira, Adam] Johns Hopkins Bloomberg Sch Publ Hlth, Mental Hlth, Baltimore, MD USA. [Murray-Kolb, Laura] Penn State Univ, Nutr Sci, University Pk, PA 16802 USA. [Simonsick, Eleanor; Ferrucci, Luigi] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Allen, Richard] Johns Hopkins Sch Med, Neurol, Baltimore, MD USA. [Payne, Martha] Duke Univ, Psychiat & Behav Sci, Durham, NC USA. [Spira, Adam] Johns Hopkins Sch Med, Psychiat & Behav Sci, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 392.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503025 ER PT J AU Davis, A Chertow, D Qi, L Taubenberger, J AF Davis, A. Chertow, Daniel Qi, Li Taubenberger, Jeffery TI Binding and Entry of 1918 Pandemic Influenza Receptor Binding Domain Variants in Normal Human Bronchial Epithelial Cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Davis, A.; Qi, Li; Taubenberger, Jeffery] NIAID, LID, NIH, Bethesda, MD 20892 USA. [Davis, A.] CVM, DMP, KSU, Manhattan, KS USA. [Chertow, Daniel] NIH, CCMD, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 507.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503178 ER PT J AU Emamian, MS Yang, CR Tongyoo, P Sandoval, PC Raghuram, V Knepper, MA AF Emamian, M. S. Yang, C-R Tongyoo, P. Sandoval, P. C. Raghuram, V. Knepper, M. A. TI Comprehensive Proteomics in Vasopressin-Sensitive mpkCCD Cells: Virtual Western Blotting SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Emamian, M. S.; Yang, C-R; Tongyoo, P.; Sandoval, P. C.; Raghuram, V.; Knepper, M. A.] NHLBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA LB734 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501155 ER PT J AU Emenaker, N Pantoja, DS Snipes, M Morris, N Roberts, D AF Emenaker, Nancy Pantoja, David Soto Snipes, Michael Morris, Niccole Roberts, David TI Thrombospondin-1 Regulates Hepatic Lipid and Energy Metabolism to Increase Carcinogenesis in an In Vivo Model of Colorectal Cancer SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Emenaker, Nancy] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Pantoja, David Soto; Snipes, Michael; Roberts, David] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Morris, Niccole] Leidos Biomed Res Inc, Chem Biol Lab, Natl Lab Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 394.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503034 ER PT J AU Ganta, C Pawar, H Garcia, A Lu, N Becker, K Kenney, M AF Ganta, Chanran Pawar, Hitesh Garcia, Anthony Lu, Nanyan Becker, Kevin Kenney, Michael TI Analysis of RVLM Gene Expression in Young, Middle-Aged and Aged F344 Rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Ganta, Chanran; Pawar, Hitesh; Garcia, Anthony; Kenney, Michael] Kansas State Univ, Anat & Physiol, Manhattan, KS 66506 USA. [Lu, Nanyan] Kansas State Univ, Biol, Manhattan, KS 66506 USA. [Becker, Kevin] NIA, Genet Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA LB718 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501139 ER PT J AU Goodman, M Erdem, A Jaszczur, M Bertram, J Woodgate, R Cox, M AF Goodman, Myron Erdem, Aysen Jaszczur, Malgorzata Bertram, Jeffrey Woodgate, Roger Cox, Michael TI Mutations for Worse or Better: Low Fidelity DNA Synthesis by SOS DNA Polymerase V is a Tightly-Regulated Double-Edged Sword SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Goodman, Myron; Erdem, Aysen; Jaszczur, Malgorzata; Bertram, Jeffrey] Univ So Calif, Biol Sci & Chem, Los Angeles, CA USA. [Woodgate, Roger; Cox, Michael] Univ So Calif, Biol Sci, Los Angeles, CA USA. NIH, Lab Genom Integr, Bethesda, MD 20892 USA. Univ Wisconsin, Biochem, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 108.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501366 ER PT J AU Gusev, P Andrews, K Palachuvattil, J Dang, P Savarala, S Han, F Pehrsson, P Douglass, L Dwyer, J Betz, J Saldanha, L Costello, R Bailey, R AF Gusev, P. Andrews, K. Palachuvattil, J. Dang, P. Savarala, S. Han, F. Pehrsson, P. Douglass, L. Dwyer, J. Betz, J. Saldanha, L. Costello, R. Bailey, R. TI Analytical Content of Multivitamin/Mineral (MVM) Products Manufactured for Different Consumer Categories SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Gusev, P.; Andrews, K.; Palachuvattil, J.; Dang, P.; Savarala, S.; Han, F.; Pehrsson, P.] ARS, Nutrient Data Lab BHNRC, USDA, Beltsville, MD USA. [Douglass, L.] Statistician Consultant, Longmont, CO USA. [Dwyer, J.; Betz, J.; Saldanha, L.; Costello, R.; Bailey, R.] NIH, Off Dietary Supplements, DHHS, Bethesda, MD 20892 USA. RI Han, Fei/O-1980-2015 OI Han, Fei/0000-0003-2454-4187 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 586.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504458 ER PT J AU Guterres, H Ma, BY Nussinov, R Mattos, C AF Guterres, Hugo Ma, Buyong Nussinov, Ruth Mattos, Carla TI Ras Isoforms Conformational Clustering and Community Networks Studies: Simulating Ras with Accelerated Molecular Dynamics SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Guterres, Hugo; Mattos, Carla] Northeastern Univ, Chem & Chem Biol, Boston, MA 02115 USA. [Ma, Buyong; Nussinov, Ruth] NCI, Basic Sci Program, Leidos Biomed Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA LB203 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470500201 ER PT J AU Hammond, G Balla, T AF Hammond, Gerald Balla, Tamas TI Does PtdIns(4,5)P-2 concentrate so it can multitask? SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hammond, Gerald; Balla, Tamas] Natl Inst Child Hlth & Human Dev NICHD, Sect Mol Signal Transduct, NIH, Bethesda, MD USA. [Hammond, Gerald] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 568.22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504101 ER PT J AU Hanif, A Zeldin, D Nayeem, M AF Hanif, Ahmad Zeldin, Darryl Nayeem, Mohammed TI Increased Endothelial Expression of Human Soluble Epoxide Hydrolase Negatively Modulates Coronary Reactive Hyperemia in Isolated Mouse Heart SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hanif, Ahmad; Nayeem, Mohammed] W Virginia Univ, Physiol & Pharmacol, Morgantown, WV 26506 USA. [Zeldin, Darryl] NIEHS, Div Pulm, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 644.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470505452 ER PT J AU Hewitt, S Chung, JY Perry, C Ylaya, K AF Hewitt, Stephen Chung, Joon-Yong Perry, Candice Ylaya, Kris TI A Metric of RNA Quality for RNA Isolated from Formalin Fixed, Paraffin Embedded Tissue SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hewitt, Stephen; Chung, Joon-Yong; Perry, Candice; Ylaya, Kris] NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 417.12 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503125 ER PT J AU Hibbeln, J Champagne, C Montain, S Hawes, M Berry, K Marriott, B AF Hibbeln, Joseph Champagne, Catherine Montain, Scott Hawes, Michael Berry, Kevin Marriott, Bernadette TI Raising omega-3 and lowering omega-6 in military diet recipes: effects on blood fatty acids SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hibbeln, Joseph] NIAAA, NIH, Bethesda, MD USA. [Champagne, Catherine] LSU, PBRC, Baton Rouge, LA USA. [Montain, Scott] USARIEM, Mil Nutr, Natick, MA USA. [Hawes, Michael] BELOVO, Principal, Pinehurst, NC USA. [Berry, Kevin] Samueli Inst, Mil Med, Alexandria, VA USA. [Marriott, Bernadette] MUSC, Med, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 401.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503051 ER PT J AU Huang, J Bellani, M Xue, YT Wang, WD Meetei, AR Seidman, M AF Huang, Jing Bellani, Marina Xue, Yutong Wang, Weidong Meetei, Amom Ruhikanta Seidman, Michael TI ATR Promotes the Replication Traverse of DNA Interstrand Crosslinks SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Huang, Jing; Bellani, Marina; Seidman, Michael] NIA, LMG, NIH, Baltimore, MD 21224 USA. [Xue, Yutong; Wang, Weidong] NIA, LG, NIH, Baltimore, MD 21224 USA. [Meetei, Amom Ruhikanta] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc, Cincinnati, OH 45229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 560.9 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503440 ER PT J AU Jahns, L Scheett, A Johnson, L Hoverson, B Krebs-Smith, S Payne, C Whigham, L Kranz, S AF Jahns, Lisa Scheett, Angela Johnson, LuAnn Hoverson, Bonita Krebs-Smith, Susan Payne, Collin Whigham, Leah Kranz, Sibylle TI Diet Quality of Supermarket Sales Circulars measured by the Healthy Eating Index-2010 SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Jahns, Lisa; Scheett, Angela; Johnson, LuAnn; Hoverson, Bonita] GFHNRC USDA ARS, Grand Forks, ND 58203 USA. [Krebs-Smith, Susan] NCI, DCCPS, Bethesda, MD 20892 USA. [Payne, Collin] New Mexico State Univ, Dept Mkt, Las Cruces, NM 88003 USA. [Whigham, Leah] UTEP, Inst Hlth Living, El Paso, TX USA. [Kranz, Sibylle] Univ Bristol, Exercise Nutr & Hlth Sci, Bristol BS8 1TH, Avon, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 132.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501465 ER PT J AU Karlsen, M Troy, L Rogers, G Dwyer, J McKeown, N Jacques, P AF Karlsen, Micaela Troy, Lisa Rogers, Gail Dwyer, Johanna McKeown, Nicola Jacques, Paul TI Protein sources, nutrient adequacy and diet quality SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Karlsen, Micaela; Troy, Lisa; Rogers, Gail; Dwyer, Johanna; McKeown, Nicola; Jacques, Paul] USDA, HNRCA, Washington, DC USA. [Karlsen, Micaela; Troy, Lisa; Dwyer, Johanna; McKeown, Nicola; Jacques, Paul] Tufts Univ, Friedman Sch Nutr, Medford, MA USA. [Troy, Lisa] UMass, Amherst, MA USA. [Dwyer, Johanna] Tufts Med Ctr, Frances Stern Nutr Ctr, Boston, MA USA. [Dwyer, Johanna] NIH, ODS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 599.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470505149 ER PT J AU Khan, R Gebreab, S Crespo, P Xu, RH Sims, M Davis, S AF Khan, Rumana Gebreab, Samson Crespo, Pia Xu, Ruihua Sims, Mario Davis, Sharon TI Correlates and the Heritability Estimates of Metabolic Syndrome among African American: The Jackson Heart Study SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Khan, Rumana; Gebreab, Samson; Crespo, Pia; Xu, Ruihua; Davis, Sharon] NHGRI, NIH, Bethesda, MD USA. [Sims, Mario] Univ Mississippi, Med Ctr, Dept Med, University, MS 38677 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA LB377 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470500375 ER PT J AU Kim, YJ Guzman-Hernandez, M Wisniewski, E Balla, T AF Kim, Yeun Ju Guzman-Hernandez, Maria Wisniewski, Eva Balla, Tamas TI Nir2 Plays a Central Role in ER-PM Junctions Maintaining Phosphoinositide Signaling Competence SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kim, Yeun Ju; Guzman-Hernandez, Maria; Wisniewski, Eva; Balla, Tamas] NICHD, Program Dev Neurosci, NIH, Bethesda, MD USA. RI Wisniewski, Eva/O-9233-2015 OI Wisniewski, Eva/0000-0001-8698-6867 NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA LB177 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470500176 ER PT J AU Kim, Y Wang, T AF Kim, Young Wang, Thomas TI The Suppressive Effects of Indole-3-carbinol (I3C)/3,3 ' Diindolylmethane (DIM) on LPS-induced IL1 Release May Be Associated with Changes in CD84 in THP-1 Monocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kim, Young] NCI, NSRG, Rockville, MD USA. [Wang, Thomas] USDA, Genom & Immunol Lab, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 593.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470505037 ER PT J AU Krebs-Smith, S Wilson, M Reedy, J AF Krebs-Smith, Susan Wilson, Magdalena Reedy, Jill TI Visualization of Dietary Patterns SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Krebs-Smith, Susan; Wilson, Magdalena; Reedy, Jill] NCI, DCCPS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 131.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501454 ER PT J AU Kwong, P AF Kwong, Peter TI Penetrating the Glycan Shield on HIV-1 SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kwong, Peter] NIAID, Struct Biol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 106.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501360 ER PT J AU Levin, R Hammond, G Balla, T Fairn, G Grinstein, S AF Levin, Roni Hammond, Gerald Balla, Tamas Fairn, Gregory Grinstein, Sergio TI Phosphatidylinositol 4-phosphate dynamics during phagocytosis SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Levin, Roni; Grinstein, Sergio] Hosp Sick Children, Div Cell Biol, Toronto, ON M5G 1X8, Canada. [Hammond, Gerald; Balla, Tamas] NIH, Program Dev Neurosci, Bethesda, MD 20892 USA. [Fairn, Gregory; Grinstein, Sergio] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 568.17 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504096 ER PT J AU Li, Y McGreal, S Zhao, J Huang, RL Xia, MH Ding, WX AF Li, Yuan McGreal, Steven Zhao, Jean Huang, Ruili Xia, Menghang Ding, Wen-Xing TI A High Throughput Image-based Screening Reveals Novel Autophagy Inducers For Treating Drug-Induced Liver Injury SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Li, Yuan; McGreal, Steven; Ding, Wen-Xing] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. [Zhao, Jean; Huang, Ruili; Xia, Menghang] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 148.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502031 ER PT J AU Mayer, M Meyerson, J Chittori, S Subramaniam, S AF Mayer, Mark Meyerson, Joel Chittori, Sagar Subramaniam, Sriram TI Structural Studies on Glutamate Receptor Gating SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Mayer, Mark; Chittori, Sagar] NICHD, NIH, Bethesda, MD USA. [Meyerson, Joel; Subramaniam, Sriram] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 95.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501341 ER PT J AU McGlinchey, R Lee, J AF McGlinchey, Ryan Lee, Jennifer TI Effect of Glucocerebrosidase and Its Substrate, Glucosylceramide on alpha-Synuclein Aggregation and Degradation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [McGlinchey, Ryan; Lee, Jennifer] NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 564.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504011 ER PT J AU McGlinchey, R Lee, J AF McGlinchey, Ryan Lee, Jennifer TI Cysteine Cathepsins Are Essential in Lysosomal Degradation of alpha-Synuclein SO FASEB JOURNAL LA English DT Meeting Abstract C1 [McGlinchey, Ryan; Lee, Jennifer] NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 564.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504012 ER PT J AU Merrill, R Sullivan, K Northrop-Clewes, C Flores-Ayala, R Namaste, S Serdula, M Suchdev, P AF Merrill, Rebecca Sullivan, K. Northrop-Clewes, C. Flores-Ayala, R. Namaste, S. Serdula, M. Suchdev, P. TI Prevalence of Inflammation Varies among Preschool Aged Children across 12 Countries SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Merrill, Rebecca; Sullivan, K.; Flores-Ayala, R.; Serdula, M.; Suchdev, P.] CDC, IMMPaCt, Atlanta, GA 30333 USA. [Sullivan, K.; Suchdev, P.] Emory Univ, Atlanta, GA 30322 USA. [Namaste, S.] NIH, Bethesda, MD 20892 USA. [Namaste, S.] SPRING, Washington, DC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 403.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503071 ER PT J AU Montain, S Johannsen, N Champagne, C Marriott, B Hibbeln, J Hawes, M Berry, K AF Montain, Scott Johannsen, Neil Champagne, Catherine Marriott, Bernadette Hibbeln, Joseph Hawes, Michael Berry, Kevin TI Influence of Omega-6 HUFA Status on Recovery of Muscle Performance After Fatiguing Exercise SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Montain, Scott] US Army, Inst Environm Med, Mil Nutr, Natick, MA 01760 USA. [Johannsen, Neil; Champagne, Catherine] Pennington Biomed Res Ctr, Dept Nutr, Baton Rouge, LA 70808 USA. [Marriott, Bernadette] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Hibbeln, Joseph] NIAAA, Nutr Neurosci, NIH, Silver Spring, MD USA. [Hawes, Michael] Owner Belovo Inc, Pinehurst, NC USA. [Berry, Kevin] Samueli Inst, Mil Med Res, Alexandria, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 598.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470505127 ER PT J AU Nash, S Till, C Song, XL Platz, E Schenk, J AF Nash, Sarah Till, Cathee Song, Xiaoling Platz, Elizabeth Schenk, Jeannette TI Serum Carotenoid Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Nash, Sarah] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Till, Cathee; Song, Xiaoling; Schenk, Jeannette] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Platz, Elizabeth] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 406.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503090 ER PT J AU O'Brien, D Votruba, S Krakoff, J AF O'Brien, Diane Votruba, Susanne Krakoff, Jonathan TI Validation of Stable Isotope Ratios as Biomarkers of Meat, Fish, and Soda Intake SO FASEB JOURNAL LA English DT Meeting Abstract C1 [O'Brien, Diane] Univ Alaska Fairbanks, Inst Arctic Biol, Fairbanks, AK USA. [Votruba, Susanne; Krakoff, Jonathan] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 131.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501456 ER PT J AU Oubrahim, H Bacsik, D Chock, P AF Oubrahim, Hammou Bacsik, David Chock, P. TI Role of mTOR and ERK in PMT-induced Cell Proliferation and Survivin Upregulation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Oubrahim, Hammou; Bacsik, David; Chock, P.] NHLBI, Biochem Lab, BBC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 570.16 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504148 ER PT J AU Pommier, Y Huang, SY Williams, J Kunkel, T AF Pommier, Yves Huang, Shar-Yin Williams, Jessica Kunkel, Thomas TI Topoisomerase-Induced DNA Cleavage at Ribonucleotide Misincorporation Sites SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Pommier, Yves; Huang, Shar-Yin] NCI, Lab Mol Pharmacol, Dev Therapeut Branch, Ctr Canc Res,NIH,DHHS, Bethesda, MD 20892 USA. [Williams, Jessica; Kunkel, Thomas] NIEHS, Lab Mol Genet, NIH, Res Triangle Pk, NC USA. [Williams, Jessica; Kunkel, Thomas] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 371.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502434 ER PT J AU Rajani, V Sheikhbahaei, S Zhang, Y Chu, N Zwicker, J de Chaves, EP Pagliardini, S Smith, J Kasparov, S Gourine, A Funk, G AF Rajani, Vishaal Sheikhbahaei, Shahriar Zhang, Yong Chu, Nathan Zwicker, Jennifer de Chaves, Elena Posse Pagliardini, Silvia Smith, Jeffrey Kasparov, Sergey Gourine, Alexander Funk, Gregory TI Exocytotic Release of ATP from preBotzinger Complex Astrocytes Contributes to the Hypoxic Ventilatory Response via a P2Y(1) Receptor, PLC, PKC-Dependent Mechanism SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Rajani, Vishaal; Pagliardini, Silvia; Funk, Gregory] Univ Alberta, NMHI, Edmonton, AB T6G 2M7, Canada. [Zhang, Yong; Chu, Nathan; Zwicker, Jennifer; Pagliardini, Silvia; Funk, Gregory] Univ Alberta, Physiol, Edmonton, AB T6G 2M7, Canada. [Sheikhbahaei, Shahriar; Gourine, Alexander] UCL, Neurosci Physiol & Pharmacol, London, England. [Sheikhbahaei, Shahriar; Smith, Jeffrey] NINDS, Cellular & Syst Neurobiol, NIH, Bethesda, MD 20892 USA. [de Chaves, Elena Posse] Univ Alberta, Pharmacol, Edmonton, AB T6G 2M7, Canada. [Kasparov, Sergey] Univ Bristol, Physiol & Pharmacol, Bristol BS8 1TH, Avon, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA LB748 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501169 ER PT J AU Rawal, S Huedo-Medina, T Hoffman, H Duffy, V AF Rawal, Shristi Huedo-Medina, Tania Hoffman, Howard Duffy, Valerie TI Statistical Modeling Approaches with Taste Functioning and Central Adiposity in Women: Implications for Mining the New National Health and Nutrition Examination Survey (NHANES) Taste and Smell Protocol SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Rawal, Shristi; Huedo-Medina, Tania; Duffy, Valerie] Univ Connecticut, Allied Hlth Sci, Storrs, CT USA. [Hoffman, Howard] NIDCD, Epidemiol & Stat Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 602.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470505165 ER PT J AU Restifo, N AF Restifo, Nicholas TI Update on the Development of Curative Cancer Immunotherapies SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Restifo, Nicholas] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 486.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503140 ER PT J AU Sahni, S Mangano, K Tucker, K Fox, C Kiel, D Dufour, A Zhang, XC Hannan, M AF Sahni, Shivani Mangano, Kelsey Tucker, Katherine Fox, Caroline Kiel, Douglas Dufour, Alyssa Zhang, Xiaochun Hannan, Marian TI Protective Association of Serum Uric Acid on Hip Fracture Risk among Older Men But Not Women SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Sahni, Shivani; Mangano, Kelsey; Kiel, Douglas; Dufour, Alyssa; Zhang, Xiaochun; Hannan, Marian] Harvard Univ, Sch Med, BIDMC, IFAR HSL, Boston, MA USA. [Tucker, Katherine] Univ Massachusetts, Lowell, MA USA. [Fox, Caroline] Harvard Univ, Sch Med, Framingham Heart Study NHLBI, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 383.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502476 ER PT J AU Schap, T Subar, A Anic, G George, S Krebs-Smith, S Park, Y Reedy, J AF Schap, T. Subar, A. Anic, G. George, S. Krebs-Smith, S. Park, Y. Reedy, Jill TI Index-based Dietary Patterns and All-cause and Cause-specific Mortality Stratified by Body Mass Index and Race/Ethnicity: NIH-AARP Diet and Health Study SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Schap, T.; Subar, A.; Anic, G.; George, S.; Krebs-Smith, S.; Reedy, Jill] NCI, NIH, Rockville, MD USA. [Park, Y.] Washington Univ, Div Publ Hlth Sci, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 119.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501390 ER PT J AU Stave, E Kuczmarski, MF Beydoun, M Zonderman, A Evans, M AF Stave, Emily Kuczmarski, Marie Fanelli Beydoun, May Zonderman, Alan Evans, Michele TI Nutritional Supplement Use of an Urban African American and White Population SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Stave, Emily; Kuczmarski, Marie Fanelli] Univ Delaware, Behav Hlth & Nutr, Newark, DE USA. [Beydoun, May; Zonderman, Alan; Evans, Michele] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 586.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470504456 ER PT J AU Subar, A Mittl, B Zimmerman, T Kirkpatrick, S Schap, T Wilson, M Potischman, N AF Subar, Amy Mittl, Beth Zimmerman, Thea Kirkpatrick, Sharon Schap, TusaRebecca Wilson, Maggie Potischman, Nancy TI Use of the Automated Self-administered 24-hour Recall (ASA24) in the Real World SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Subar, Amy; Schap, TusaRebecca; Wilson, Maggie; Potischman, Nancy] NCI, NIH, Bethesda, MD 20892 USA. [Mittl, Beth; Zimmerman, Thea] WESTAT Corp, Hlth Studies, Rockville, MD USA. [Kirkpatrick, Sharon] Univ Waterloo, Sch Publ Hlth, Waterloo, ON N2L 3G1, Canada. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 131.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501458 ER PT J AU Subramanian, P Mendez, E Becerra, SP AF Subramanian, Preeti Mendez, Emily Becerra, S. Patricia TI Identification of A Novel Inhibitor of 5-Lipoxygenase SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Subramanian, Preeti; Mendez, Emily; Becerra, S. Patricia] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA LB107 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470500107 ER PT J AU Tomasi, ML Ryoo, MJ Gao, B AF Tomasi, Maria Lauda Ryoo, Minjung Gao, Bin TI Sumoylation regulates Cytochrome P450 2E1 (CYP2E1) expression in alcoholic liver disease SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Tomasi, Maria Lauda; Ryoo, Minjung] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Gao, Bin] NIAAA, Lab Liver Dis, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 148.9 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502034 ER PT J AU Vargas, A Quackenbush, J Glass, K AF Vargas, Ashley Quackenbush, John Glass, Kimberly TI Diet-induced Weight Loss Changes in Gene Regulatory Networks in the Rectum: Network Analysis as a Compliment to Traditional Gene Expression Analysis SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Vargas, Ashley; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Biostat, Boston, MA 02115 USA. [Vargas, Ashley] NCI, Div Canc Prevent, Bethesda, MD 20892 USA. [Glass, Kimberly] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 275.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502296 ER PT J AU Wilson, M Reedy, J Krebs-Smith, S AF Wilson, Magdalena Reedy, Jill Krebs-Smith, Susan TI Effect of Meeting the Healthy People 2020 Objectives on Diet Quality Relative to Current Trends SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wilson, Magdalena; Reedy, Jill; Krebs-Smith, Susan] NCI, DCCPS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 384.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470502478 ER PT J AU Yang, W Lee, YS Gao, Y Gregory, M AF Yang, Wei Lee, Young-Sam Gao, Yang Gregory, Mark TI Mechanisms for Translesion DNA Synthesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Yang, Wei; Lee, Young-Sam; Gao, Yang; Gregory, Mark] NIH, Mol Biol Lab, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 108.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470501364 ER PT J AU Zhang, Y Tripathi, V Sixt, K Heller, M AF Zhang, Ying Tripathi, Veenu Sixt, Katherine Heller, Mary TI TGF-beta Regulates Alternative Splicing of CD44 by Inducing Smad3 Binding to CD44 pre-mRNA SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Zhang, Ying; Tripathi, Veenu; Sixt, Katherine; Heller, Mary] NCI, LCMB, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 SU 1 MA 562.15 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CR6PV UT WOS:000361470503473 ER PT J AU Lopera-Mesa, TM Doumbia, S Konate, D Anderson, JM Doumbouya, M Keita, AS Diakite, SAS Traore, K Krause, MA Diouf, A Moretz, SE Tullo, GS Miura, K Gu, WJ Fay, MP Taylor, SM Long, CA Diakite, M Fairhurst, RM AF Lopera-Mesa, Tatiana M. Doumbia, Saibou Konate, Drissa Anderson, Jennifer M. Doumbouya, Mory Keita, Abdoul S. Diakite, Seidina A. S. Traore, Karim Krause, Michael A. Diouf, Ababacar Moretz, Samuel E. Tullo, Gregory S. Miura, Kazutoyo Gu, Wenjuan Fay, Michael P. Taylor, Steve M. Long, Carole A. Diakite, Mahamadou Fairhurst, Rick M. TI Effect of red blood cell variants on childhood malaria in Mali: a prospective cohort study SO LANCET HAEMATOLOGY LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; SYMPATRIC ETHNIC-GROUPS; HEMOGLOBIN-C; SICKLE HEMOGLOBIN; G6PD DEFICIENCY; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE DEFICIENCY; RESISTANCE; SUSCEPTIBILITY; CHILDREN; TRAIT AB Background Red blood cell variants protect African children from severe falciparum malaria. However, their individual and interactive effects on mild disease and parasite density, and their modification by age-dependent immunity, are poorly understood. In this study, we address these knowledge gaps in a prospective cohort study of malaria risk and Plasmodium falciparum densities in Malian children. Methods The Kenieroba Innate Defense Study for Malaria (KIDS-Malaria) was a 4-year prospective cohort study of children aged 6 months to 17 years undertaken in Mali between 2008 and 2011. Red blood cell variants were haemoglobin S (HbS), haemoglobin C (HbC), alpha thalassaemia, ABO blood groups, and glucose-6-phosphate dehydrogenase (G6PD) deficiency encoded by the X-linked A-allele. The primary outcome was malaria incidence, measured as the number of uncomplicated or severe malaria episodes over time. The secondary outcome was parasite density at the time of a malaria episode. We modelled incidence rate ratios with quasi-Poisson regression and we analysed parasite densities using generalised estimating equations. This study is registered with ClinicalTrials.gov, number NCT00669084. Findings Between May 1, 2008, and Dec 29, 2011, we enrolled 1586 children into the study. We successfully typed all five red blood cell variants for 1543 of these children, who therefore constituted the evaluable population and in whom we diagnosed 4091 malaria episodes over 2656 child-years of follow-up. In these 1543 children, red blood cell variants were common, and occurred at the following frequencies: sickle cell trait (HbAS) 220 (14%), HbC heterozygosity (HbAC) 103 (7%), a thalassaemia 438 (28%), type O blood group 621 (40%), and G6PD deficiency 72 (9%) in 767 boys and 158 (20%) in 776 girls. The overall incidence of malaria was 1.54 episodes per child-year of follow-up, ranging from 2.78 episodes per child-year at age 3 years to 0.40 episodes per child-year at age 17 years. The malaria incidence was lower in HbAS children than in HbAA children with normal haemoglobin (adjusted incidence rate ratio [aIRR] 0.66 [95% CI 0.59-0.75], p<0.0001) and lower in G6PD A-/A- homozygous girls than in G6PD A+/A+ girls (0.51 [0.29-0.90], p=0.020), but was higher in HbAC children than in HbAA children (1.15 [1.01-1.32], p=0.039). Parasite density was lower in HbAS children (median 10 550 parasites per mu L [IQR 1350-26250]) than in HbAA children (15150 parasites per mu L [4250-31050]; p=0.0004). The HbAS-associated reductions in malaria risk and parasite density were greatest in early childhood. Interpretation The individual and interactive effects of HbAS, HbAC, and G6PD A-/A- genotypes on malaria risk and parasite density define clinical and cellular correlates of protection. Further identification of the molecular mechanisms of these protective effects might uncover new targets for intervention. C1 [Lopera-Mesa, Tatiana M.; Anderson, Jennifer M.; Krause, Michael A.; Diouf, Ababacar; Moretz, Samuel E.; Tullo, Gregory S.; Miura, Kazutoyo; Long, Carole A.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Doumbia, Saibou; Konate, Drissa; Doumbouya, Mory; Keita, Abdoul S.; Diakite, Seidina A. S.; Traore, Karim; Diakite, Mahamadou] Univ Bamako, Malaria Res & Training Ctr, Bamako, Mali. [Gu, Wenjuan] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Rockville, MD USA. [Taylor, Steve M.] Duke Univ, Med Ctr, Div Infect Dis & Int Hlth, Durham, NC USA. [Taylor, Steve M.] Duke Univ, Med Ctr, Duke Global Hlth Inst, Durham, NC USA. [Taylor, Steve M.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Diouf, Ababacar; Moretz, Samuel E.; Tullo, Gregory S.; Miura, Kazutoyo] Kelly Sci Resources, Rockville, MD USA. RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10A, Rockville, MD 20852 USA. EM rfairhurst@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes of Health (NIH); NIAID [K08AI100924]; National Cancer Institute, NIH [HHSN261200800001E] FX This research was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes of Health (NIH). JMA, MAK, MPF, CAL, and RMF are currently employees of the NIH, and SMT was supported by the NIAID under award number K08AI100924. This project was also supported in part by federal funds from the National Cancer Institute, NIH (contract number HHSN261200800001E). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government. We thank Jaymin Patel and Steven Meshnick (University of North Carolina, Chapel Hill, NC, USA) for helpful discussions; Robert Gwadz, Dick Sakai, and Thomas Wellems (NIAID/NIH, Rockville, MD, USA) for supporting this work; the children and parents in Kenieroba, Fourda, and Bozokin for their participation; and the village communities and health district authorities of Bancoumana and Kati for their long-term commitment to this study. NR 41 TC 8 Z9 8 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2352-3026 J9 LANCET HAEMATOL JI Lancet Haematol. PD APR PY 2015 VL 2 IS 4 BP E140 EP E149 DI 10.1016/S2352-3026(15)00043-5 PG 10 WC Hematology SC Hematology GA CS4US UT WOS:000362072100008 PM 26687956 ER PT J AU Subramaniam, M St Jean, B Taylor, NG Kodama, C Follman, R Casciotti, D AF Subramaniam, Mega St Jean, Beth Taylor, Natalie Greene Kodama, Christie Follman, Rebecca Casciotti, Dana TI Bit by Bit: Using Design-Based Research to Improve the Health Literacy of Adolescents SO JMIR RESEARCH PROTOCOLS LA English DT Article DE health literacy; information literacy; computing literacy; consumer health; health informatics; K-12 education; adolescents; informal education; vulnerable populations; literacy programs ID EHEALTH LITERACY; INFORMATION; FRAMEWORK; SKILLS; VALIDATION; CHILDREN; WORLD; WANT AB Background: Although a low health literacy level has been found to be among the most powerful predictors of poor health outcomes, there is very little research focused on assessing and improving the health literacy skills of adolescents, particularly those from socioeconomically disadvantaged backgrounds. The vast majority of existing research focuses solely on reading comprehension, despite the fact that health literacy is actually a multifaceted concept, which entails many different types of skills. Objective: The aim of this paper is to first mine existing literature to identify the many different skills that have been posited to constitute health literacy, and then, using this collection of skills as an overarching structure, to highlight the challenges that disadvantaged youth participating in our HackHealth after-school program encounter as they identify and articulate their health-related information needs, search for health-related information online, assess the relevance and credibility of this information, and manage and make use of it. Methods: We utilized the design-based research method to design, implement, and revise our HackHealth program. To collect data regarding HackHealth participants' health literacy skills and associated challenges, we used a variety of methods, including participant observation, surveys, interviews, focus groups, and logging of Web browser activities. We also collected data through specialized instructional activities and data collection forms that we developed for this purpose. Quantitative and qualitative techniques were used to analyze this data, as well as all of the artifacts that each student produced, including their final projects. Results: We identified the various challenges that the 30 HackHealth participants faced in completing various health-related information activities during the course of the program. Based on these findings, we describe important implications for working with youth from socioeconomically disadvantaged backgrounds, how to assess and improve their health literacy skills, and offer specific recommendations for health literacy instruction aimed at this population. Conclusions: With an increased societal focus on health and a shift from viewing patients as passive recipients of medical care to viewing them as active arbiters of their own health, today's youth need to possess an array of health literacy skills to ensure that they can live long and healthy lives. Working with adolescents to help them develop and practice these skills will also help to break the cycle between poor health literacy and poor health outcomes, thereby reducing health disparities and improving the long-term outlook for the health of our nation. C1 [Subramaniam, Mega; St Jean, Beth; Taylor, Natalie Greene; Kodama, Christie; Follman, Rebecca] Univ Maryland, Coll Informat Studies, College Pk, MD 20742 USA. [Casciotti, Dana] Natl Lib Med, NIH, Bethesda, MD USA. RP Subramaniam, M (reprint author), Univ Maryland, Coll Informat Studies, 4105 Hornbake Bldg South Wing, College Pk, MD 20742 USA. EM mmsubram@umd.edu NR 65 TC 6 Z9 6 U1 3 U2 13 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1929-0748 J9 JMIR RES PROTOC JI JMIR RES. Protoc. PD APR-JUN PY 2015 VL 4 IS 2 AR e62 DI 10.2196/resprot.4058 PG 15 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CQ8SB UT WOS:000360877600028 PM 26025101 ER PT J AU Gan, C Jenkins, MA Win, AK Macrae, FA AF Gan, Chun Jenkins, Mark A. Win, Aung Ko Macrae, Finlay A. CA Colon Canc Family Registry TI Spectrum of Cancer Phenotypes in Asian Lynch Syndrome Families SO GASTROENTEROLOGY LA English DT Meeting Abstract CT 46th Annual Digestive Disease Week (DDW) CY MAY 16-19, 2015 CL Washington, DC C1 [Gan, Chun; Jenkins, Mark A.; Win, Aung Ko] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia. [Gan, Chun; Macrae, Finlay A.] Royal Melbourne Hosp, Familial Canc Ctr, Dept Colorectal Med & Genet, Melbourne, Vic, Australia. [Colon Canc Family Registry] NIH, Washington, DC USA. RI Jenkins, Mark/P-7803-2015 OI Jenkins, Mark/0000-0002-8964-6160 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2015 VL 148 IS 4 SU 1 MA Su1083 BP S403 EP S403 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP8BW UT WOS:000360117100009 ER PT J AU Boushey, CJ Harray, AJ Kerr, DA Schap, TE Paterson, S Aflague, T Ruiz, MB Ahmad, Z Delp, EJ AF Boushey, Carol Jo Harray, Amelia J. Kerr, Deborah Anne Schap, TusaRebecca E. Paterson, Stacey Aflague, Tanisha Ruiz, Marc Bosch Ahmad, Ziad Delp, Edward J. TI How Willing Are Adolescents to Record Their Dietary Intake? The Mobile Food Record SO JMIR MHEALTH AND UHEALTH LA English DT Article DE adolescents; children; dietary assessment; mobile food record; novel technology ID DOUBLY LABELED WATER; ENERGY-INTAKE; BEHAVIOR-CHANGE; MIXED-METHODS; CHILDREN; TECHNOLOGY; VALIDITY; DEVICES; HEALTH; ADULTS AB Background: Accurately assessing the diets of children and adolescents can be problematic. Use of technologies, such as mobile apps designed to capture food and beverages consumed at eating occasions with images taken using device-embedded cameras, may address many of the barriers to gathering accurate dietary intake data from adolescents. Objective: The objectives of this study were to assess the willingness of adolescents to take images of food and beverages at their eating occasions using a novel mobile food record (mFR) and to evaluate the usability of the user confirmation component of the mFR app, referred to as the "review process." Methods: Mixed methods combining quantitative and qualitative protocols were used in this study. Adolescents (11-15-year olds) attending a summer camp were recruited to participate in the study. First, the participants were asked to take images of foods and beverages consumed as meals and snacks for 2 consecutive days using the mFR app running on an iPhone and the number of images taken was noted. This was followed by focus group sessions to evaluate usability, which was analyzed by content and themes. After using the mFR, a think-aloud method was used to evaluate the usability of the mFR method for reviewing system-identified foods (ie, the review process). A usability questionnaire was administered at the end of all activities. Results: The mFR was accepted by the majority of the 24 boys and 17 girls (n=41) but varied according to gender and eating occasion. Girls were significantly more likely than boys to capture images of their eating occasions (Fisher exact test, P=.03). Participants were more likely to take images of their breakfasts (90%, 36/40) and lunches (90%, 72/80) and least likely to capture afternoon and evening snacks, 54% (43/80) and 40% (32/80), respectively. The major themes from the focus groups with regard to using the mFR were games, rewards, and the need to know more about why they were using the app. Results of the usability questionnaire indicated that including a game component would be important to increase willingness to use the mFR, and a high majority of the participants indicated a willingness to use the mFR for 7 days or more. The image review process was found to be easy to use except for some confusion with overlapping markers on the screen. Conclusions: The adolescents' experiences with and feedback about the mFR highlighted the importance of increased training, reminders, entertainment (eg, games), and training with practice in using the device to capture complete dietary intake as part of their active lifestyles. C1 [Boushey, Carol Jo; Aflague, Tanisha] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA. [Harray, Amelia J.; Kerr, Deborah Anne] Curtin Univ, Sch Publ Hlth, Perth, WA 6845, Australia. [Schap, TusaRebecca E.] NCI, NIH, Canc Prevent Fellowship Program, Div Canc Prevent,Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Paterson, Stacey] Univ Kentucky, Dept Dietet & Human Nutr, Lexington, KY USA. [Ruiz, Marc Bosch] Qualcomm Inc, San Diego, CA USA. [Ahmad, Ziad; Delp, Edward J.] Purdue Univ, Dept Elect & Comp Engn, W Lafayette, IN 47907 USA. RP Boushey, CJ (reprint author), Univ Hawaii, Ctr Canc, 701 Ilalo St,Room 525, Honolulu, HI 96813 USA. EM cjboushey@cc.hawaii.edu FU NCI NIH HHS [U01 CA130784]; NIDDK NIH HHS [R01 DK073711, R56 DK073711] NR 31 TC 13 Z9 13 U1 1 U2 5 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 2291-5222 J9 JMIR MHEALTH UHEALTH JI JMIR mHealth uHealth PD APR-JUN PY 2015 VL 3 IS 2 AR e47 DI 10.2196/mhealth.4087 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CP3PE UT WOS:000359791800018 PM 26024996 ER PT J AU Kim, DH Saver, JL Starkman, S Liebeskind, DS Ali, LK Restrepo, L Valdes-Suerias, M Eckstein, M Pratt, F Stratton, S Hamilton, S Conwit, R Sanossian, N AF Kim, D. H. Saver, J. L. Starkman, S. Liebeskind, D. S. Ali, L. K. Restrepo, L. Valdes-Suerias, M. Eckstein, M. Pratt, F. Stratton, S. Hamilton, S. Conwit, R. Sanossian, N. TI Enrollment yield and reasons for screen failure in a large, phase 3 prehospital trial of paramedic delivery of a potential neuroprotective agent SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Kim, D. H.] Dong A Univ Hosp, Dept Neurol, Busan, South Korea. [Saver, J. L.; Starkman, S.; Liebeskind, D. S.; Ali, L. K.; Restrepo, L.; Valdes-Suerias, M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Starkman, S.; Pratt, F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Emergency Med, Los Angeles, CA 90095 USA. [Eckstein, M.] Univ So Calif, Keck Sch Med, Dept Emergency Med, Los Angeles, CA 90033 USA. [Pratt, F.] Univ Calif Los Angeles, Los Angeles Cty Fire EMS Agcy, Los Angeles, CA USA. [Stratton, S.] Harbor UCLA Med Ctr, Dept Emergency Med, Orange Cty EMS Agcy, Los Angeles EMS Agcy, Los Angeles, CA USA. [Hamilton, S.] Stanford Univ, Palo Alto, CA 94304 USA. [Conwit, R.] NINDS, Bethesda, MD 20892 USA. [Sanossian, N.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-0475 BP 83 EP 83 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304000191 ER PT J AU Dias, C Hsia, AW Nadareishvili, Z Benson, RT Lynch, JK Latour, LL Leigh, R AF Dias, C. Hsia, A. W. Nadareishvili, Z. Benson, R. T. Lynch, J. K. Latour, L. L. Leigh, R. TI Earlier serial MR imaging is associated with a greater rate of T2 signal change in acute stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Dias, C.; Lynch, J. K.; Latour, L. L.; Leigh, R.] Natl Inst Neurol Disorders & Stroke, Intramural Stroke Branch, Bethesda, MD USA. [Hsia, A. W.; Benson, R. T.] Medstar Washington Hosp Ctr, Neurol, Washington, DC USA. [Nadareishvili, Z.] Johns Hopkins Community Phys, Neurol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-1230 BP 317 EP 317 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304002105 ER PT J AU Leigh, R Dias, C Nadareishvili, Z Hsia, AW Lynch, JK Benson, RT Latour, LL AF Leigh, R. Dias, C. Nadareishvili, Z. Hsia, A. W. Lynch, J. K. Benson, R. T. Latour, L. L. TI Early reversible and late inflammatory blood-brain barrier disruption in human acute ischemic stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Leigh, R.; Dias, C.; Lynch, J. K.; Latour, L. L.] Natl Inst Neurol Disorders & Stroke, Intramural Stroke Branch, Bethesda, MD USA. [Nadareishvili, Z.] Johns Hopkins Community Phys, Neurol, Bethesda, MD USA. [Hsia, A. W.; Benson, R. T.] Medstar Washington Hosp Ctr, Neurol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-1218 BP 317 EP 317 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304002104 ER PT J AU Schroeder, J Cheng, B Ebinger, M Kohrmann, M Wu, O Kang, D Liebeskind, D Tourdias, T Singer, O Christensen, S Campbell, B Luby, M Warach, S Fiehler, J Fiebach, J Gerloff, C Thomalla, G AF Schroeder, J. Cheng, B. Ebinger, M. Koehrmann, M. Wu, O. Kang, D. Liebeskind, D. Tourdias, T. Singer, O. Christensen, S. Campbell, B. Luby, M. Warach, S. Fiehler, J. Fiebach, J. Gerloff, C. Thomalla, G. TI Validity of acute stroke lesion volume estimation by DWI-ASPECTS depends on lesion location in 496 MCA stroke patients SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Schroeder, J.; Cheng, B.] Univ Med Ctr Hamburg Eppendorf, Neurol, Hamburg, Germany. [Ebinger, M.; Fiebach, J.] Charite, Neurol, Berlin, Germany. [Koehrmann, M.] Univ Erlangen Nurnberg, Neurol, D-91054 Erlangen, Germany. [Wu, O.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. [Kang, D.] Asan Med Ctr, Neurol, Seoul, South Korea. [Liebeskind, D.] Univ Calif Los Angeles, Neurol, Los Angeles, CA USA. [Tourdias, T.] CHU Bordeaux, Neurol, Bordeaux, France. [Singer, O.] Univ Frankfurt Klinikum, Neurol, Frankfurt, Germany. [Christensen, S.; Campbell, B.] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Neurol, Melbourne, Vic 3050, Australia. [Luby, M.] NINDS, Neurol, Bethesda, MD 20892 USA. [Warach, S.] UT SW Med Ctr, Neurol, Austin, TX USA. [Fiehler, J.; Gerloff, C.; Thomalla, G.] Univ Med Ctr Hamburg Eppendorf, Neurol, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2015 VL 10 SU 2 SI SI MA ESOC-0623 BP 336 EP 336 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO6YP UT WOS:000359304002153 ER PT J AU Arduc, A Saricam, O Dogan, BA Tuna, MM Tutuncu, YA Isik, S Berker, D Sennaroglu, E Guler, S AF Arduc, Ayse Saricam, Orkun Dogan, Bercem Aycicek Tuna, Mazhar Muslum Tutuncu, Yasemin Ates Isik, Serhat Berker, Dilek Sennaroglu, Engin Guler, Serdar TI Should insulin resistance be screened in lean hirsute women? SO GYNECOLOGICAL ENDOCRINOLOGY LA English DT Article DE Insulin resistance; idiopathic hirsutism; lean women; polycystic ovary syndrome ID POLYCYSTIC-OVARY-SYNDROME; 2 DISTINCT POPULATIONS; BETA-CELL FUNCTION; IDIOPATHIC HIRSUTISM; ANDROGEN EXCESS; SENSITIVITY; PREVALENCE; INDEXES; WEIGHT; WHITE AB The role of insulin resistance (IR) is well-documented in obese women with polycystic ovary syndrome (PCOS). Controversies exist concerning the presence of IR in idiopathic hirsutism (IH) or if it is a manifestation of high body mass index (BMI). We aimed to investigate the presence/absence of IR in lean hirsute women. One-hundred fifty-one lean women with hirsutism [96 PCOS (group 1) and 55 IH (group 2)] and 58 age-and BMI-matched healthy controls (group 3) were recruited in the study (mean age 25.21 +/- 6.1 versus 26.26 +/- 4.6years; BMI 21.79 +/- 1.7 versus 22.02 +/- 2.2 kg/m(2), respectively). Significantly higher insulin and HOMA-IR, and significantly lower fasting glucose insulin ratio (FGIR), quantitative insulin sensitivity check index (QUICKI), reciprocal insulin, and Raynaud index were detected in groups 1 and 2 than in group 3 (p<0.05). These IR indices were similar between groups 1 and 2. The number of patients with IR (HOMA-IR>2, FGIR<7.2, or QUICKI<0.357) was significantly higher in groups 1 and 2 than in group 3, but was similar between groups 1 and 2. A higher frequency of IR occurs in lean hirsute women regardless of they having PCOS or IH. IR may contribute to aetiopathogenesis of IH, or may cause some metabolic abnormalities in these patients. C1 [Arduc, Ayse] NIDDK, Diabet Endocrine & Obes Branch, NIH, Bethesda, MD USA. [Saricam, Orkun; Sennaroglu, Engin] Ankara Numune Training & Res Hosp, Dept Internal Med, Minist Hlth, Ankara, Turkey. [Dogan, Bercem Aycicek; Tuna, Mazhar Muslum; Tutuncu, Yasemin Ates; Isik, Serhat; Berker, Dilek] Ankara Numune Training & Res Hosp, Dept Endocrinol & Metab, Minist Hlth, Ankara, Turkey. [Guler, Serdar] Hitit Univ, Dept Endocrinol & Metab, Fac Med, Corum, Turkey. RP Arduc, A (reprint author), 1778 Dawson St, Vienna, VA 22182 USA. EM ayse_arduc@yahoo.com NR 39 TC 2 Z9 2 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0951-3590 EI 1473-0766 J9 GYNECOL ENDOCRINOL JI Gynecol. Endocrinol. PD APR PY 2015 VL 31 IS 4 BP 291 EP 295 DI 10.3109/09513590.2014.994598 PG 5 WC Endocrinology & Metabolism; Obstetrics & Gynecology SC Endocrinology & Metabolism; Obstetrics & Gynecology GA CN5JW UT WOS:000358466600010 PM 25561024 ER PT J AU Edelman, EJ Tate, JP Gordon, KS Becker, W Bryant, K Crothers, K Gaither, JR Gibert, C Gordon, A Marshall, BD Rodriguez-Barradas, M Samet, JH Skanderson, M Justice, AC Fiellin, DA AF Edelman, E. J. Tate, Janet P. Gordon, Kirsha S. Becker, William Bryant, Kendall Crothers, Kristina Gaither, J. R. Gibert, Cynthia Gordon, Adam Marshall, Brandon D. Rodriguez-Barradas, Maria Samet, Jeffrey H. Skanderson, Melissa Justice, Amy C. Fiellin, David A. TI DO PRESCRIBED OPIOIDS IMPACT CD4 COUNT RESTORATION AMONG HIV plus PATIENTS INITIATING ANTIRETROVIRAL THERAPY? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Edelman, E. J.; Tate, Janet P.; Gordon, Kirsha S.; Becker, William; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, New Haven, CT USA. [Becker, William; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Bryant, Kendall] NIH, Bethesda, MD 20892 USA. [Crothers, Kristina] Univ Washington, Seattle, WA 98195 USA. [Gaither, J. R.] Yale Univ, New Haven, CT USA. [Gibert, Cynthia] DC VAMC, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Washington, DC USA. [Gordon, Adam; Skanderson, Melissa] Univ Pittsburgh, Pittsburgh, PA USA. [Gordon, Adam; Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Marshall, Brandon D.] Brown Univ, Providence, RI 02912 USA. [Rodriguez-Barradas, Maria] Michael E DeBakey VAMC, Houston, TX USA. [Rodriguez-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Samet, Jeffrey H.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2199293 BP S142 EP S142 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386900221 ER PT J AU Phillips, KA Louie, D Furnari, M Kowalczyk, W Epstein, DH Preston, KL AF Phillips, Karran A. Louie, Dexter Furnari, Melody Kowalczyk, William Epstein, David H. Preston, Kenzie L. TI TRAIT, STATE, AND PLACE: THE ROLE OF PERSONALITY AND ENVIRONMENT IN DRUG USE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-of-General-Internal-Medicine (SGIM) CY APR 22-25, 2015 CL Toronto, CANADA SP Soc Gen Internal Med C1 [Phillips, Karran A.; Furnari, Melody; Kowalczyk, William; Epstein, David H.; Preston, Kenzie L.] NIDA, NIH, Baltimore, MD USA. [Louie, Dexter] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2015 VL 30 SU 2 MA 2199122 BP S284 EP S285 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN4FV UT WOS:000358386901147 ER PT J AU Taylor, N Choi, K Forster, J AF Taylor, Naomi Choi, Kelvin Forster, Jean TI Snus Use and Smoking Behaviors: Preliminary Findings From a Prospective Cohort Study Among US Midwest Young Adults SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CESSATION; TOBACCO; INITIATION AB The effect of snus use on smoking behaviors among US young adults is largely unknown. Data from the Minnesota Adolescent Community Cohort Study collected in 2010 to 2011 and 2011 to 2012 (participants aged 20-28 years) showed that young adult nonsmokers who had tried snus were subsequently more likely than those who had not tried snus to become current smokers (n = 1696; adjusted odds ratio = 1.79; 95% confidence interval = 1.01, 3.14). Snus use was not associated with subsequent smoking cessation or reduction among young adult current smokers C1 [Taylor, Naomi; Choi, Kelvin; Forster, Jean] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Choi, Kelvin] Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, Bethesda, MD 20892 USA. RP Choi, K (reprint author), Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kelvin.choi@nih.gov RI Choi, Kelvin/H-1544-2015 FU National Cancer Institute [R01 CA86191]; Division of Intramural Research, National Institute on Minority Health and Health Disparities, National Institutes of Health FX The study is funded by the National Cancer Institute (grant R01 CA86191; Principal Investigator: J. Forster). K. Choi's effort is supported by the Division of Intramural Research, National Institute on Minority Health and Health Disparities, National Institutes of Health. NR 12 TC 3 Z9 3 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2015 VL 105 IS 4 BP 683 EP 685 DI 10.2105/AJPH.2014.302536 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CM0SE UT WOS:000357387800036 PM 25713948 ER PT J AU Sopher, CJ Adamson, BJS Andrasik, MP Flood, DM Wakefield, SF Stoff, DM Cook, RS Kublin, JG Fuchs, JD AF Sopher, Carrie J. Adamson, Blythe Jane S. Andrasik, Michele P. Flood, Danna M. Wakefield, Steven F. Stoff, David M. Cook, Ryan S. Kublin, James G. Fuchs, Jonathan D. TI Enhancing Diversity in the Public Health Research Workforce: The Research and Mentorship Program for Future HIV Vaccine Scientists SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID AFRICAN-AMERICAN; RACIAL/ETHNIC MINORITIES; CLINICAL-RESEARCH; MENTAL-HEALTH; INVESTIGATORS; DISPARITIES; TRIALS; CAREER; COMMUNITIES; PREVENTION AB Objectives. We developed and evaluated a novel National Institutes of Health-sponsored Research and Mentorship Program for African American and Hispanic medical students embedded within the international, multisite HIV Vaccine Trials Network, and explored its impact on scientific knowledge, acquired skills, and future career plans. Methods. Scholars conducted social, behavioral, clinical, or laboratory-based research projects with HIV Vaccine Trials Network investigators over 8 to 16 weeks (track 1) or 9 to 12 months (track 2). We conducted an in-depth, mixed-methods evaluation of the first 2 cohorts (2011-2013) to identify program strengths, areas for improvement, and influence on professional development. Results. A pre-post program assessment demonstrated increases in self-reported knowledge, professional skills, and interest in future HIV vaccine research. During in-depth interviews, scholars reported that a supportive, centrally administered program; available funding; and highly involved mentors and staff were keys to the program's early success. Conclusions. A multicomponent, mentored research experience that engages medical students from underrepresented communities and is organized within a clinical trials network may expand the pool of diverse public health scientists. Efforts to sustain scholar interest over time and track career trajectories are warranted. C1 [Sopher, Carrie J.; Adamson, Blythe Jane S.; Andrasik, Michele P.; Flood, Danna M.; Wakefield, Steven F.; Cook, Ryan S.; Kublin, James G.] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98104 USA. [Stoff, David M.] NIMH, Neuropsychiat HIV AIDS, AIDS Res Training, HIV AIDS Hlth Dispar,Div AIDS Res, Bethesda, MD 20892 USA. [Fuchs, Jonathan D.] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Fuchs, Jonathan D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Sopher, CJ (reprint author), 1100 Fairview Ave N E3-300, Seattle, WA 98109 USA. EM csopher@fhcrc.org FU HIV Vaccine Trials Network through National Institute of Allergy and Infectious Diseases [UM1 AI068614]; National Institutes of Mental Health FX The Research and Mentorship Program is supported by the HIV Vaccine Trials Network through its cooperative agreement with the National Institute of Allergy and Infectious Diseases (UM1 AI068614) and through an administrative supplement from the National Institutes of Mental Health linked to this grant. NR 34 TC 8 Z9 8 U1 3 U2 8 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2015 VL 105 IS 4 BP 823 EP 830 DI 10.2105/AJPH.2014.302076 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CM0SE UT WOS:000357387800056 PM 25122028 ER PT J AU Carpenter, CR Neta, G Glasgow, RE Rabin, BA Brownson, RC AF Carpenter, Christopher R. Neta, Gila Glasgow, Russell E. Rabin, Borsika A. Brownson, Ross C. TI STORYTELLING TO ENHANCE THE VALUE OF RESEARCH RESPONSE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID CANCER PREVENTION; NARRATIVES C1 [Carpenter, Christopher R.] Washington Univ, Sch Med, Div Emergency Med, St Louis, MO 63110 USA. [Neta, Gila] NCI, Implementat Sci, Div Canc Control & Populat Sci, NIH, Rockville, MD USA. [Glasgow, Russell E.] Univ Colorado, Dept Family Med, Denver, CO 80202 USA. [Glasgow, Russell E.] Univ Colorado, Colorado Hlth Outcomes Res Program, Denver, CO 80202 USA. [Rabin, Borsika A.] Univ Colorado, Sch Med, Dept Family Med, Denver, CO USA. [Rabin, Borsika A.] Kaiser Permanente Colorado, CRN Canc Commun Res Ctr, Inst Hlth Res, Denver, CO USA. [Brownson, Ross C.] Prevent Res Ctr, St Louis, MO USA. [Brownson, Ross C.] Washington Univ, Brown Sch, St Louis, MO 63110 USA. [Brownson, Ross C.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO 63110 USA. [Brownson, Ross C.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. RP Carpenter, CR (reprint author), Washington Univ, Sch Med, Campus Box 8072,660 S Euclid Ave, St Louis, MO 63110 USA. EM carpenterc@wusm.wustl.edu RI Carpenter, Christopher/E-3720-2013 OI Carpenter, Christopher/0000-0002-2603-7157 FU NCATS NIH HHS [UL1 TR000448] NR 8 TC 1 Z9 1 U1 4 U2 10 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2015 VL 105 IS 4 BP E1 EP E2 DI 10.2105/AJPH.2015.302606 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CM0SE UT WOS:000357387800002 PM 25713956 ER PT J AU Noinaj, N Rollauer, SE Buchanan, SK AF Noinaj, Nicholas Rollauer, Sarah E. Buchanan, Susan K. TI The beta-barrel membrane protein insertase machinery from Gram-negative bacteria SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID OUTER-MEMBRANE; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; ASSEMBLY MACHINERY; ESSENTIAL COMPONENT; STRUCTURAL BASIS; BAM COMPLEX; IN-VITRO; TRANSPORTER; BIOGENESIS AB The outer membranes (OM) of Gram-negative bacteria contain a host of beta-barrel outer membrane proteins (OMPs) which serve many functions for cell survival and virulence. The biogenesis of these OMPs is mediated by the p-barrel assembly machinery (BAM) complex which is composed of five components including the essential core component called BamA that mediates the insertase function within the OM. The crystal structure of BamA has recently been reported from three different species, including a full-length structure from Neisseria gonorrhoeae. Mutagenesis and functional studies identified several conformational changes within BamA that are required for function, providing a significant advancement towards unraveling exactly how BamA and the BAM complex are able to fold and insert new OMPs in the OM. C1 [Noinaj, Nicholas] Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA. [Rollauer, Sarah E.; Buchanan, Susan K.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Buchanan, SK (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM skbuchan@helix.nih.gov RI Rollauer, Sarah/L-4576-2016 OI Rollauer, Sarah/0000-0002-2116-3170 FU Department of Biological Sciences at Purdue University; National Institute of Allergy and Infectious Diseases [1K22AI113078-01]; Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; Sir Henry Wellcome Post-Doctoral Fellowship [103040/Z/13/Z] FX We would like to acknowledge JC Gumbart for help preparing additional representations of the molecular dynamic simulations. NN is supported by the Department of Biological Sciences at Purdue University and by the National Institute of Allergy and Infectious Diseases (1K22AI113078-01). SER and SKB are supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. SER is also supported by a Sir Henry Wellcome Post-Doctoral Fellowship (103040/Z/13/Z). All figures were prepared using PyMOL (Schrodinger), Adobe Photoshop, and Adobe Illustrator. NR 33 TC 31 Z9 31 U1 1 U2 14 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X EI 1879-033X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD APR PY 2015 VL 31 BP 35 EP 42 DI 10.1016/j.sbi.2015.02.012 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CM5DC UT WOS:000357706000007 PM 25796031 ER PT J AU Hawkins, M Newman, AB Madero, M Patel, KV Shlipak, MG Cooper, J Johansen, KL Navaneethan, SD Shorr, RI Simonsick, EM Fried, LF AF Hawkins, Marquis Newman, Anne B. Madero, Magdalena Patel, Kushang V. Shlipak, Michael G. Cooper, Jennifer Johansen, Kirsten L. Navaneethan, Sankar D. Shorr, Ronald I. Simonsick, Eleanor M. Fried, Linda F. TI TV Watching, but Not Physical Activity, Is Associated With Change in Kidney Function in Older Adults SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE sedentary lifestyle; chronic disease; aged; renal health ID SERUM CYSTATIN-C; BODY-COMPOSITION; ESTIMATING GFR; SITTING TIME; HEALTH ABC; DISEASE; RISK; CKD; OBESITY; LIFE AB Background: Physical activity (PA) may play a role in preserving kidney health. The purpose of this study was to determine if PA and sedentary behavior are associated with incident chronic kidney disease (CKD) and change in kidney function in older adults. Methods: The Health, Aging, and Body Composition study is a prospective cohort of 3075 well-functioning older adults. PA and television watching was measured by self-report, and serum cystatin C was used to estimate glomerular filtration rate (eGFR). CKD was defined as an eGFR <60 ml/min/1.73m(2). Rapid kidney function decline was defined as an annual loss in eGFR of >3ml/min/1.73m(2). Discrete survival analysis was used to determine if baseline PA and television watching were related to 10-year cumulative incidence of CKD and rapid decline in kidney function. Results: Individuals who reported watching television >3 hours/day had a higher risk of incident CKD (HR 1.34; 95% CI, 1.09-1.65) and experiencing a rapid decline in kidney function (HR 1.26; 95% CI, 1.05-1.52) compared with individuals who watched television <2 hours/day. PA was not related to either outcome. Conclusions: High levels of television watching are associated with declining kidney function; the mechanisms that underlie this association need further study. C1 [Hawkins, Marquis; Fried, Linda F.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Newman, Anne B.; Cooper, Jennifer] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Madero, Magdalena] Inst Nacl Cardiol Ignacio Chavez, Mexico City, DF, Mexico. [Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Shlipak, Michael G.; Johansen, Kirsten L.] San Francisco VA, San Francisco, CA USA. [Shlipak, Michael G.; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Navaneethan, Sankar D.] Cleveland Clin, Dept Hypertens & Nephrol, Cleveland, OH 44106 USA. [Shorr, Ronald I.] Univ Florida, Dept Epidemiol, Gainseville, FL USA. [Simonsick, Eleanor M.] NIA, Baltimore, MD 21224 USA. RP Hawkins, M (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA. EM mshawkins@schoolph.umass.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050, R01-AG029364]; NINR [R01-NR012459]; Intramural Research Program of the National Institutes of Health, National Institute on Aging FX This research was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA Grant R01-AG028050, NIA Grant R01-AG029364, NINR Grant R01-NR012459, and the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 33 TC 0 Z9 0 U1 3 U2 5 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD APR PY 2015 VL 12 IS 4 BP 561 EP 568 DI 10.1123/jpah.2013-0289 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CM7XE UT WOS:000357909000018 PM 24762526 ER PT J AU Wang, S Chen, XA Hu, J Jiang, JK Li, YF Chan-Salis, KY Gu, Y Chen, G Thomas, C Pugh, BF Wang, YM AF Wang, Shu Chen, Xiangyun Amy Hu, Jing Jiang, Jian-kang Li, Yunfei Chan-Salis, Ka Yim Gu, Ying Chen, Gong Thomas, Craig Pugh, B. Franklin Wang, Yanming TI ATF4 Gene Network Mediates Cellular Response to the Anticancer PAD Inhibitor YW3-56 in Triple-Negative Breast Cancer Cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; ACTIVATING TRANSCRIPTION FACTOR-4; ARGININE METHYLATION; OXIDATIVE STRESS; AUTOPHAGY; EXPRESSION; TARGET; RESISTANCE; P53; BORTEZOMIB AB We previously reported that a pan-PAD inhibitor, YW3-56, activates p53 target genes to inhibit cancer growth. However, the p53-independent anticancer activity and molecular mechanisms of YW3-56 remain largely elusive. Here, gene expression analyses found that ATF4 target genes involved in endoplasmic reticulum ( ER) stress response were activated by YW3-56. Depletion of ATF4 greatly attenuated YW3-56-mediated activation of the mTORC1 regulatory genes SESN2 and DDIT4. Using the ChIP-exo method, high-resolution genomic binding sites of ATF4 and CEBPB responsive to YW3-56 treatment were generated. In human breast cancer cells, YW3-56-mediated cell death features mitochondria depletion and autophagy perturbation. Moreover, YW3-56 treatment effectively inhibits the growth of triple-negative breast cancer xenograft tumors in nude mice. Taken together, we unveiled the anticancer mechanisms and therapeutic potentials of the pan-PAD inhibitor YW3-56. (C)2015 AACR. C1 [Wang, Shu; Chen, Xiangyun Amy; Hu, Jing; Li, Yunfei; Chan-Salis, Ka Yim; Gu, Ying; Pugh, B. Franklin; Wang, Yanming] Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, State Coll, PA 16802 USA. [Jiang, Jian-kang; Thomas, Craig] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Chen, Gong] Penn State Univ, Dept Chem, State Coll, PA 16802 USA. RP Wang, YM (reprint author), Penn State Univ, Dept Biochem & Mol Biol, 454 North Frear Bldg, State Coll, PA 16802 USA. EM yuw12@psu.edu RI Chen, Gong/A-8063-2013 OI Chen, Gong/0000-0002-5067-9889 FU NIH/NCI grant [R01 CA136856]; PBCC grant FX This work was supported by a NIH/NCI grant R01 CA136856 and a PBCC grant to Y. Wang. NR 63 TC 7 Z9 7 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD APR PY 2015 VL 14 IS 4 BP 877 EP 888 DI 10.1158/1535-7163.MCT-14-1093-T PG 12 WC Oncology SC Oncology GA CM9TS UT WOS:000358052500004 PM 25612620 ER PT J AU Pacak, K Wimalawansa, SJ AF Pacak, Karel Wimalawansa, Sunil J. TI PHEOCHROMOCYTOMA AND PARAGANGLIOMA SO ENDOCRINE PRACTICE LA English DT Review ID GERMLINE MUTATIONS; DEHYDROGENASE MUTATIONS; B GENE; FAMILY; TUMOR; SDHB; MANAGEMENT; NEUROFIBROMATOSIS; SUSCEPTIBILITY; POLYCYTHEMIA AB Objective: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are neural crest cell tumors associated with catecholamine production and assessed by a metanephrine/methoxytyramine measurement. This review summarizes the genetics of these tumors. Methods: Case presentation, review of the relevant literature, and bullet point conclusions. Results: Genetic research over the past 10 years has led to a better understanding of the pathogenesis of these tumors, currently associated with 20 susceptibility genes (both somatic and germ-line mutations). Although most of these genes can be divided into two clusters (clusters 1 and 2), recent data suggest that all mutations converge on the hypoxia-inducible factor signaling pathway. Most of the susceptibility genes are well characterized and associated with specific clinical presentations, including biochemical phenotype, tumor location and behavior, as well as neoplasms or similar characteristics. Correct and early detection of hereditary PHEO/PGL is paramount, as early diagnosis leads to improved and focused treatment, along with better outcomes. However, missed or delayed diagnosis of hereditary PHEO/PGL forestalls proper treatment and results in multiple, recurrent, or metastatic tumors and avoidable complications in some patients. Conclusion: Early diagnosis allows prompt screening for potentially lethal cancers associated with specific gene mutations and makes genetic testing more readily available to first-degree and other relatives of an index patient. Thus, understanding the genetics of these tumors is an essential part of endocrinology. C1 [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Wimalawansa, Sunil J.] Cardio Metab Inst New Jersey, Somerset, NJ USA. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, NIH, CRC, Bldg 10,1 East,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Development, National Institutes of Health FX We would like to acknowledge the technical assistance of Joan Nambuba in the production of this manuscript. This research was supported, in part, by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Development, National Institutes of Health. NR 38 TC 9 Z9 10 U1 0 U2 8 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD APR PY 2015 VL 21 IS 4 BP 406 EP 412 DI 10.4158/EP14481.RA PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CM5MF UT WOS:000357731300012 PM 25716634 ER PT J AU Bohannon, JK Lackemeyer, MG Kuhn, JH Wada, J Bollinger, L Jahrling, PB Johnson, RF AF Bohannon, J. Kyle Lackemeyer, Matthew G. Kuhn, Jens H. Wada, Jiro Bollinger, Laura Jahrling, Peter B. Johnson, Reed F. TI Generation and characterization of large-particle aerosols using a center flow tangential aerosol generator with a non-human-primate, head-only aerosol chamber SO INHALATION TOXICOLOGY LA English DT Article DE ABSL-4; aerobiology; aerosol; BSL-4; CenTAG; large particle ID AFRICAN-GREEN MONKEYS; CYNOMOLGUS MACAQUES; RHESUS MACAQUES; VIRUS-INFECTION; MACACA-MULATTA; EXPOSURE; FEVER; SIZE; ENCEPHALITIS; DEPOSITION AB Aerosol droplets or particles produced from infected respiratory secretions have the potential to infect another host through inhalation. These respiratory particles can be polydisperse and range from 0.05 to 500 mu m in diameter. Animal models of infection are generally established to facilitate the potential licensure of candidate prophylactics and/or therapeutics. Consequently, aerosol-based animal infection models are needed to properly study and counter airborne infections. Ideally, experimental aerosol exposure should reliably result in animal disease that faithfully reproduces the modeled human disease. Few studies have been performed to explore the relationship between exposure particle size and induced disease course for infectious aerosol particles. The center flow tangential aerosol generator (CenTAG (TM)) produces large-particle aerosols capable of safely delivering a variety of infectious aerosols to non-human primates (NHPs) within a Class III Biological Safety Cabinet (BSC) for establishment or refinement of NHP infectious disease models. Here, we report the adaptation of this technology to the Animal Biosafety Level 4 (ABSL-4) environment for the future study of high-consequence viral pathogens and the characterization of CenTAG (TM)-created sham (no animal, no virus) aerosols using a variety of viral growth media and media supplements. C1 [Bohannon, J. Kyle; Lackemeyer, Matthew G.; Kuhn, Jens H.; Wada, Jiro; Bollinger, Laura; Jahrling, Peter B.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD 21702 USA. [Jahrling, Peter B.; Johnson, Reed F.] NIAID, EVPS, NIH, Frederick, MD 21702 USA. RP Johnson, RF (reprint author), NIAID, EVPS, DIR, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA. EM johnsonreed@mail.nih.gov FU Battelle Memorial Institute; NIAID [HHSN272200700016I]; NIAID Division of Intramural Research FX The work was funded in part through Battelle Memorial Institute's prime contract with NIAID, under Contract No. HHSN272200700016I. J.K.B., J.W. and L.B. performed this work as employees of Battelle Memorial Institute. Subcontractors to Battelle Memorial Institute who performed this work are: J.H.K., an employee of Tunnell Government Services, Inc. and M.G.L., an employee of Lovelace Respiratory Research Institute, Inc. This work was supported in part by NIAID Division of Intramural Research. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, and companies affiliated with the authors. Mention of trade names or commercial products does not constitute endorsement of recommendation for use. NR 39 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0895-8378 EI 1091-7691 J9 INHAL TOXICOL JI Inhal. Toxicol. PD APR PY 2015 VL 27 IS 5 BP 247 EP 253 DI 10.3109/08958378.2015.1033570 PG 7 WC Toxicology SC Toxicology GA CM2MJ UT WOS:000357514200002 PM 25970823 ER PT J AU Thrift, AP Gong, J Peters, U Chang-Claude, J Rudolph, A Slattery, ML Chan, AT Esko, T Wood, AR Yang, J Vedantam, S Gustafsson, S Pers, TH Baron, JA Bezieau, S Kury, S Ogino, S Berndt, SI Casey, G Haile, RW Du, MM Harrison, TA Thornquist, M Duggan, DJ Le Marchand, L Lemire, M Lindor, NM Seminara, D Song, MY Thibodeau, SN Cotterchio, M Win, AK Jenkins, MA Hopper, JL Ulrich, CM Potter, JD Newcomb, PA Schoen, RE Hoffmeister, M Brenner, H White, E Hsu, L Campbell, PT AF Thrift, Aaron P. Gong, Jian Peters, Ulrike Chang-Claude, Jenny Rudolph, Anja Slattery, Martha L. Chan, Andrew T. Esko, Tonu Wood, Andrew R. Yang, Jian Vedantam, Sailaja Gustafsson, Stefan Pers, Tune H. Baron, John A. Bezieau, Stephane Kuery, Sebastien Ogino, Shuji Berndt, Sonja I. Casey, Graham Haile, Robert W. Du, Mengmeng Harrison, Tabitha A. Thornquist, Mark Duggan, David J. Le Marchand, Loic Lemire, Mathieu Lindor, Noralane M. Seminara, Daniela Song, Mingyang Thibodeau, Stephen N. Cotterchio, Michelle Win, Aung Ko Jenkins, Mark A. Hopper, John L. Ulrich, Cornelia M. Potter, John D. Newcomb, Polly A. Schoen, Robert E. Hoffmeister, Michael Brenner, Hermann White, Emily Hsu, Li Campbell, Peter T. CA GIANT Consortium TI Mendelian randomization study of height and risk of colorectal cancer SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Body height; colorectal cancer; epidemiology ID GENOME-WIDE ASSOCIATION; COLON-CANCER; BODY-SIZE; UNITED-STATES; INSTRUMENTAL VARIABLES; GENETIC EPIDEMIOLOGY; SUSCEPTIBILITY LOCI; CIGARETTE-SMOKING; RECTAL-CANCER; WOMEN AB Background: For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk. Methods: To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using 696 genetic variants associated with height) in 10 226 CRC cases and 10 286 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height, genetically predicted height and CRC. Results: Using conventional methods, increased height (per 10-cm increment) was associated with increased CRC risk (OR = 1.08, 95% CI = 1.02-1.15). In sex-specific analyses, height was associated with CRC risk for women (OR = 1.15, 95% CI = 1.05-1.26), but not men (OR = 0.98, 95% CI = 0.92-1.05). Consistent with these results, carrying greater numbers of (weighted) height-increasing alleles (per 1-unit increase) was associated with higher CRC risk for women and men combined (OR = 1.07, 95% CI = 1.01-1.14) and for women (OR = 1.09, 95% CI = 1.01-1.19). There was weaker evidence of an association for men (OR = 1.05, 95% CI = 0.96-1.15). Conclusion: We provide evidence for a causal association between height and CRC for women. The CRC-height association for men remains unclear and warrants further investigation in other large studies. C1 [Thrift, Aaron P.; Gong, Jian; Peters, Ulrike; Du, Mengmeng; Harrison, Tabitha A.; Thornquist, Mark; Potter, John D.; Newcomb, Polly A.; White, Emily; Hsu, Li] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Thrift, Aaron P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Thrift, Aaron P.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Peters, Ulrike; Potter, John D.; Newcomb, Polly A.; White, Emily] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu; Vedantam, Sailaja; Pers, Tune H.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Esko, Tonu; Vedantam, Sailaja; Pers, Tune H.] Boston Childrens Hosp, Div Genet, Boston, MA USA. [Esko, Tonu; Vedantam, Sailaja; Pers, Tune H.] Boston Childrens Hosp, Ctr Basic Translat Obes Res, Boston, MA USA. [Esko, Tonu; Pers, Tune H.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Esko, Tonu; Vedantam, Sailaja; Pers, Tune H.] Broad Inst, Cambridge, MA USA. [Wood, Andrew R.] Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England. [Yang, Jian] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Yang, Jian] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia. [Yang, Jian] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Gustafsson, Stefan] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Bezieau, Stephane; Kuery, Sebastien] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Casey, Graham] Univ So Calif, USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Haile, Robert W.] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Duggan, David J.] Translat Genom Res Inst, Phoenix, AZ USA. [Le Marchand, Loic] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA. [Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Song, Mingyang] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med, Rochester, MN USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Pathol, Rochester, MN USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Genet, Rochester, MN USA. [Cotterchio, Michelle] Canc Care Ontario, Prevent & Canc Control, Toronto, ON, Canada. [Win, Aung Ko; Jenkins, Mark A.; Hopper, John L.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic, Australia. [Ulrich, Cornelia M.] Populat Sci Huntsman Canc Inst, Salt Lake City, UT USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Epidemiol, Pittsburgh, PA USA. [Hoffmeister, Michael; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Hsu, Li] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. RP Thrift, AP (reprint author), Baylor Coll Med, Dan L Duncan Canc Ctr, One Baylor Plaza,MS BCM305, Houston, TX 77030 USA. EM aaron.thrift@bcm.edu RI KURY, Sebastien/G-5971-2015; Hoffmeister, Michael/B-5745-2012; Song, Mingyang/M-6701-2013; Bezieau, stephane/G-5621-2015; Jenkins, Mark/P-7803-2015; Brenner, Hermann/B-4627-2017; OI Win, Aung Ko/0000-0002-2794-5261; KURY, Sebastien/0000-0001-5497-0465; Hoffmeister, Michael/0000-0002-8307-3197; Song, Mingyang/0000-0002-1324-0316; Bezieau, stephane/0000-0003-0095-1319; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Esko, Tonu/0000-0003-1982-6569; Yang, Jian/0000-0003-2001-2474 FU National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045]; National Institutes of Health (RFA) [CA-95-011]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; National Institutes of Health [R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993, P50 CA 127003, R01 CA137178, P01 CA 087969, R01 CA151993, R01 CA042182, U01 CA074783, K05 CA154337]; Ontario Research Fund; Canadian Institutes of Health Research; Ontario Institute for Cancer Research, through Ontario Ministry of Research and Innovation; Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; National Institutes of Health (NIH) [U01 HG004446, GEI U01 HG 004438]; Genes, Environment and Health Initiative (GEI) [Z01 CP 010200]; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN 268201100046C, HHSN268201100001C, HHSN2682011000 02C, HHSN268201100003C, HHSN268201100004C, HHS N271201100004C] FX This work is supported by grants to GECCO and CCFR, as well as by grants to the individual studies (as noted below). The funders of the study had no role in the design, analysis or interpretation of the data, or in writing or publication decisions related to this article.; GECCO: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088; R01 CA059045).; CCFR: National Institutes of Health (RFA # CA-95-011) and through cooperative agreements with members of the Colon Cancer Family Registry and principal investigators. This genome-wide scan was supported by the National Cancer Institute, National Institutes of Health by U01 CA122839. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CFRs, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the CFR. The following Colon CFR centres contributed data to this manuscript and were supported by National Institutes of Health: Australasian Colorectal Cancer Family Registry (U01 CA097735), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783) and the Seattle Colorectal Cancer Family Registry (U01 CA074794).; DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814).; DALS: National Institutes of Health (R01 CA48998 to M.L.S).; H.P.F.S. is supported by the National Institutes of Health (P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993 and P50 CA 127003), N.H.S. by the National Institutes of Health (R01 CA137178, P01 CA 087969, R01 CA151993 and P50 CA 127003,) and P.H.S. by the National Institutes of Health (R01 CA042182).; OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. Additional funding toward genetic analyses of OFCCR includes the Ontario Research Fund, the Canadian Institutes of Health Research and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation.; PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Additionally, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager M et al. Nat Genet 2007;39:645-49), Colon CGEMS pancreatic cancer scan (PanScan) (Amundadottir L et al. Nat Genet 2009;41:986-90 and Petersen GM et al. Nat Genet 2010;42:224-28), and the Lung Cancer and Smoking study. The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping. PMH: National Institutes of Health (R01 CA076366 to P.A.N.). VITAL: National Institutes of Health (K05 CA154337).; VITAL: National Institutes of Health (K05 CA154337). WHI: The WHI programme is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN 268201100046C, HHSN268201100001C, HHSN2682011000 02C, HHSN268201100003C, HHSN268201100004C and HHS N271201100004C. NR 39 TC 10 Z9 10 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2015 VL 44 IS 2 BP 662 EP 672 DI 10.1093/ije/dyv082 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL6VO UT WOS:000357106100028 PM 25997436 ER PT J AU Gaudet, MM Kitahara, CM Newton, CC Bernstein, L Reynolds, P Weiderpass, E Kreimer, AR Yang, G Adami, HO Alavanja, MC Freeman, LEB Boeing, H Buring, J Chaturvedi, A Chen, Y D'Aloisio, AA Freedman, M Gao, YT Gaziano, JM Giles, GG Hakansson, N Huang, WY Lee, IM Linet, MS MacInnis, RJ Park, Y Prizment, A Purdue, MP Riboli, E Robien, K Sandler, DP Schairer, C Sesso, HD Shu, XO White, E Wolk, A Xiang, YB Zelenuich-Jacquotte, A Zheng, W Patel, AV Hartge, P de Gonzalez, AB Gapstur, SM AF Gaudet, Mia M. Kitahara, Cari M. Newton, Christina C. Bernstein, Leslie Reynolds, Peggy Weiderpass, Elisabete Kreimer, Aimee R. Yang, Gong Adami, Hans-Olov Alavanja, Michael C. Freeman, Laura E. Beane Boeing, Heiner Buring, Julie Chaturvedi, Anil Chen, Yu D'Aloisio, Aimee A. Freedman, Michal Gao, Yu-Tang Gaziano, J. Michael Giles, Graham G. Hakansson, Niclas Huang, Wen-Yi Lee, I-Min Linet, Martha S. MacInnis, Robert J. Park, Yikyung Prizment, Anna Purdue, Mark P. Riboli, Elio Robien, Kim Sandler, Dale P. Schairer, Catherine Sesso, Howard D. Shu, Xiao Ou White, Emily Wolk, Alicja Xiang, Yong-Bing Zelenuich-Jacquotte, Anne Zheng, Wei Patel, Alpa V. Hartge, Patricia de Gonzalez, Amy Berrington Gapstur, Susan M. TI Anthropometry and head and neck cancer: a pooled analysis of cohort data SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Head and neck neoplasms; obesity; smoking; waist-hip ratio; waist circumference ID BODY-MASS INDEX; GENERAL-POPULATION SAMPLE; INHANCE CONSORTIUM; RISK; SMOKING; OBESITY; HEIGHT; WEIGHT; FAT; METAANALYSIS AB Background: Associations between anthropometry and head and neck cancer (HNC) risk are inconsistent. We aimed to evaluate these associations while minimizing biases found in previous studies. Methods: We pooled data from 1 941 300 participants, including 3760 cases, in 20 cohort studies and used multivariable-adjusted Cox proportional hazard regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of anthropometric measures with HNC risk overall and stratified by smoking status. Results: Greater waist circumference (per 5cm: HR = 1.04, 95% CI 1.03-1.05, P-value for trend = <0.0001) and waist-to-hip ratio (per 0.1 unit: HR = 1.07, 95% CI 1.05-1.09, P-value for trend = <0.0001), adjusted for body mass index (BMI), were associated with higher risk and did not vary by smoking status (P-value for heterogeneity = 0.85 and 0.44, respectively). Associations with BMI (P-value for interaction = <0.0001) varied by smoking status. Larger BMI was associated with higher HNC risk in never smokers (per 5 kg/m(2): HR = 1.15, 95% CI 1.06-1.24, P-value for trend = 0.0006), but not in former smokers (per 5 kg/m(2): HR = 0.99, 95% CI 0.93-1.06, P-value for trend = 0.79) or current smokers (per 5 kg/m(2): HR = 0.76, 95% CI 0.71-0.82, P-value for trend = <0.0001). Larger hip circumference was not associated with a higher HNC risk. Greater height (per 5cm) was associated with higher risk of HNC in never and former smokers, but not in current smokers. Conclusions: Waist circumference and waist-to-hip ratio were associated positively with HNC risk regardless of smoking status, whereas a positive association with BMI was only found in never smokers. C1 [Gaudet, Mia M.; Newton, Christina C.; Patel, Alpa V.; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30316 USA. [Kitahara, Cari M.; Kreimer, Aimee R.; Alavanja, Michael C.; Freeman, Laura E. Beane; Chaturvedi, Anil; Freedman, Michal; Huang, Wen-Yi; Linet, Martha S.; Park, Yikyung; Purdue, Mark P.; Schairer, Catherine; Hartge, Patricia; de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Reynolds, Peggy] Univ Calif Berkeley, Canc Prevent Inst, Berkeley, CA 94720 USA. [Weiderpass, Elisabete; Adami, Hans-Olov] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Weiderpass, Elisabete] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway. [Weiderpass, Elisabete] Canc Registry Norway, Dept Res, Oslo, Norway. [Weiderpass, Elisabete] Samfundet Folkhalsan, Helsinki, Finland. [Yang, Gong; Shu, Xiao Ou; Zheng, Wei] Vanderbilt Ingram Canc Ctr, Dept Med, Div Epidemiol, Nashville, TN USA. [Adami, Hans-Olov] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Boeing, Heiner] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany. [Buring, Julie; Gaziano, J. Michael; Lee, I-Min; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie; Gaziano, J. Michael; Lee, I-Min; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA USA. [Buring, Julie; Lee, I-Min; Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chen, Yu; Zelenuich-Jacquotte, Anne] NYU Sch Med, Dept Populat Hlth, New York, NY USA. [Chen, Yu; Zelenuich-Jacquotte, Anne] NYU Sch Med, Laura & Isaac Perlmutter Canc Ctr, New York, NY USA. [D'Aloisio, Aimee A.] Social & Sci Syst, Durham, NC USA. [Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Epidemiol,Shanghai Canc Inst, Shanghai 200030, Peoples R China. [Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Giles, Graham G.; MacInnis, Robert J.] Univ Melbourne, Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3010, Australia. [Giles, Graham G.; MacInnis, Robert J.] Univ Melbourne, Ctr Biostat & Epidemiol, Melbourne, Vic 3010, Australia. [Hakansson, Niclas; Wolk, Alicja] Karolinska Inst, Dept Environm Med, Stockholm, Sweden. [Park, Yikyung] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA. [Prizment, Anna] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Purdue, Mark P.] Ontario Inst Canc Res, Toronto, ON, Canada. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Robien, Kim] George Washington Univ, Dept Epidemiol & Biostat, Washington, DC USA. [Sandler, Dale P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [White, Emily] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Gaudet, MM (reprint author), Amer Canc Soc, Epidemiol Res Program, 250 Williams St, Atlanta, GA 30316 USA. EM mia.gaudet@cancer.org RI Purdue, Mark/C-9228-2016; Chaturvedi, Anil/J-2024-2015; Weiderpass, Elisabete/M-4029-2016; Beane Freeman, Laura/C-4468-2015; Kitahara, Cari/R-8267-2016; OI Purdue, Mark/0000-0003-1177-3108; Chaturvedi, Anil/0000-0003-2696-8899; Weiderpass, Elisabete/0000-0003-2237-0128; Beane Freeman, Laura/0000-0003-1294-4124; Robien, Kim/0000-0002-2120-2280; Sandler, Dale/0000-0002-6776-0018; Giles, Graham/0000-0003-4946-9099; Park, Yikyung/0000-0002-6281-489X FU American Cancer Society; Intramural Research Program of the National Cancer Institute, National Institutes of Health; National Institute of Environmental Health Sciences [Z01-ES049030]; National Cancer Institute [Z01-CP010119] FX This work was supported in part by the American Cancer Society and the Intramural Research Program of the National Cancer Institute, National Institutes of Health, the National Institute of Environmental Health Sciences (Z01-ES049030) and National Cancer Institute (Z01-CP010119). Funding and acknowledgement information for each of the individual cohorts is available in the Appendix (available as Supplementary data at IJE online). NR 25 TC 3 Z9 3 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2015 VL 44 IS 2 BP 673 EP 681 DI 10.1093/ije/dyv059 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL6VO UT WOS:000357106100029 PM 26050257 ER PT J AU Kreuzer, M Auvinen, A Cardis, E Hall, J Jourdain, JR Laurier, D Little, MP Peters, A Raj, K Russell, NS Tapio, S Zhang, W Gomolka, M AF Kreuzer, Michaela Auvinen, Anssi Cardis, Elisabeth Hall, Janet Jourdain, Jean-Rene Laurier, Dominique Little, Mark P. Peters, Annette Raj, Ken Russell, Nicola S. Tapio, Soile Zhang, Wei Gomolka, Maria TI Low-dose ionising radiation and cardiovascular diseases - Strategies for molecular epidemiological studies in Europe SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Review DE Epidemiology; Biomarker; Ionising radiation; Cardiovascular diseases; Pathogenesis ID ATOMIC-BOMB SURVIVORS; ISCHEMIC-HEART-DISEASE; CORONARY-ARTERY-DISEASE; IRRADIATED MOUSE KIDNEY; URANIUM MINERS COHORT; C-REACTIVE PROTEIN; BLOOD-PRESSURE; CIRCULATORY DISEASE; SYSTEMATIC ANALYSIS; ENDOTHELIAL-CELLS AB It is well established that high-dose ionising radiation causes cardiovascular diseases. In contrast, the evidence for a causal relationship between long-term risk of cardiovascular diseases after moderate doses (0.5-5 Gy) is suggestive and weak after low doses (<0.5 Gy). However, evidence is emerging that doses under 0.5 Gy may also increase long-term risk of cardiovascular disease. This would have major implications for radiation protection with respect to medical use of radiation for diagnostic purposes and occupational or environmental radiation exposure. Therefore, it is of great importance to gain information about the presence and possible magnitude of radiation-related cardiovascular disease risk at doses of less than 0.5 Gy. The biological mechanisms implicated in any such effects are unclear and results from epidemiological studies are inconsistent. Molecular epidemiological studies can improve the understanding of the pathogenesis and the risk estimation of radiation-induced circulatory disease at low doses. Within the European DoReMi (Low Dose Research towards Multidisciplinary Integration) project, strategies to conduct molecular epidemiological studies in this field have been developed and evaluated. Key potentially useful European cohorts are the Mayak workers, other nuclear workers, uranium miners, Chernobyl liquidators, the Techa river residents and several diagnostic or low-dose radiotherapy patient cohorts. Criteria for informative studies are given and biomarkers to be investigated suggested. A close collaboration between epidemiology, biology and dosimetry is recommended, not only among experts in the radiation field, but also those in cardiovascular diseases. (C) 2015 Elsevier B.V. All rights reserved. C1 [Kreuzer, Michaela; Gomolka, Maria] BfS, Dept Radiat Protect & Hlth, Fed Off Radiat Protect, D-85764 Neuherberg, Germany. [Auvinen, Anssi] Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland. [Auvinen, Anssi] STUK Radiat & Nucl Safety Author, Helsinki, Finland. [Cardis, Elisabeth] Univ Pompeu Fabra, Ctr Res Environm Epidemiol, CREAL, Barcelona, Spain. [Cardis, Elisabeth] CIBER Epidemiol & Salud Publ, Barcelona, Spain. [Hall, Janet] Inst Curie, Inserm U612, F-91405 Orsay, France. [Jourdain, Jean-Rene; Laurier, Dominique] Inst Radiol Protect & Nucl Safety, IRSN, Fontenay Aux Roses, France. [Little, Mark P.] NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. [Peters, Annette] Helmholtz Zentrum Munchen, HMGU, German Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany. [Raj, Ken; Zhang, Wei] Publ Hlth England, Didcot, Oxon, England. [Russell, Nicola S.] Netherlands Canc Inst, NKI, Amsterdam, Netherlands. [Tapio, Soile] Helmholtz Zentrum Munchen, HMGU, German Ctr Environm Hlth, Inst Radiat Biol, Neuherberg, Germany. [Hall, Janet] Ctr Rech Cancerol Lyon, UMR Inserm 1052, CNRS 5286, Lyon, France. RP Kreuzer, M (reprint author), Fed Off Radiat Protect, Dept Radiat Protect & Hlth, Ingolstaedter Landstr 1, D-85764 Neuherberg, Germany. EM mkreuzer@bfs.de RI Peters, Annette/A-6117-2011; Cardis, Elisabeth/C-3904-2017; OI Little, Mark/0000-0003-0980-7567; Peters, Annette/0000-0001-6645-0985 FU EC (EURATOM FP7) [8192]; Dutch Cancer Society [NKI 2009-4480]; Intramural Research Programme of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This work was partially funded by the EC (EURATOM FP7 Grant Number 8192) and the Dutch Cancer Society (Grant NKI 2009-4480). The Intramural Research Programme of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics supported this work. NR 135 TC 10 Z9 11 U1 9 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 EI 1388-2139 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD APR-JUN PY 2015 VL 764 BP 90 EP 100 DI 10.1016/j.mrrev.2015.03.002 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA CM0DX UT WOS:000357349700007 PM 26041268 ER PT J AU Romero, R AF Romero, R. TI The RCOG Singapore lecture: the role of progesterone, cerclage and a pessary to prevent preterm birth SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Meeting Abstract C1 [Romero, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, Perinatol Res Branch, Programme Perinatal Res & Obstet, Detroit, MI USA. [Romero, R.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, R.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Romero, R.] Wayne State Univ, Dept Mol Obstet & Genet, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD APR PY 2015 VL 122 SU 1 SI SI MA P1.02 BP 346 EP 346 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CL1OJ UT WOS:000356713000757 ER PT J AU Romero, R AF Romero, R. TI Infection and inflammation as causes of preterm labour and fetal injury SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Meeting Abstract C1 [Romero, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Programme Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA. [Romero, R.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, R.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Romero, R.] Wayne State Univ, Dept Mol Obstet & Genet, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD APR PY 2015 VL 122 SU 1 SI SI MA C13.02 BP 370 EP 371 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CL1OJ UT WOS:000356713000812 ER PT J AU Treibel, TA Fontana, M Maestrini, V Castelletti, S Rosmini, S Simpson, J Nasis, A Bulluck, H Abdel-Gadir, A White, SK Manisty, C Kellman, P Schelbert, EB Robson, MD Piechnik, SK Moon, JC AF Treibel, T. A. Fontana, M. Maestrini, V. Castelletti, S. Rosmini, S. Simpson, J. Nasis, A. Bulluck, H. Abdel-Gadir, A. White, S. K. Manisty, C. Kellman, P. Schelbert, E. B. Robson, M. D. Piechnik, S. K. Moon, J. C. TI SYNTHETIC ECV - SIMPLIFYING ECV QUANTIFICATION BY DERIVING HAEMATOCRIT FROM T1 BLOOD SO HEART LA English DT Meeting Abstract C1 [Treibel, T. A.; Fontana, M.; Castelletti, S.; Rosmini, S.; Simpson, J.; Nasis, A.; Bulluck, H.; Abdel-Gadir, A.; White, S. K.; Manisty, C.; Moon, J. C.] Univ Coll London Hosp, Heart Hosp, London, England. [Maestrini, V.] Univ Roma La Sapienza, I-00185 Rome, Italy. [Kellman, P.] NHLBI, NIH, Bethesda, MD 20892 USA. [Schelbert, E. B.] Univ Pittsburgh, UPMC Heart & Vasc Inst, Pittsburgh, PA USA. [Robson, M. D.; Piechnik, S. K.] Univ Oxford, John Radcliffe Hosp, Oxford OX3 9DU, England. RI Castelletti, Silvia/J-8926-2016 OI Castelletti, Silvia/0000-0001-9693-4083 NR 0 TC 3 Z9 3 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD APR PY 2015 VL 101 SU 2 MA 29 BP A16 EP A17 DI 10.1136/heartjnl-2015-307845.29 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CL5WP UT WOS:000357033800030 ER PT J AU Calancie, L Leeman, J Pitts, SBJ Khan, LK Fleischhacker, S Evenson, KR Schreiner, M Byker, C Owens, C McGuirt, J Barnidge, E Dean, W Johnson, D Kolodinsky, J Piltch, E Pinard, C Quinn, E Whetstone, L Ammerman, A AF Calancie, Larissa Leeman, Jennifer Pitts, Stephanie B. Jilcott Khan, Laura Kettel Fleischhacker, Sheila Evenson, Kelly R. Schreiner, Michelle Byker, Carmen Owens, Clint McGuirt, Jared Barnidge, Ellen Dean, Wesley Johnson, Donna Kolodinsky, Jane Piltch, Emily Pinard, Courtney Quinn, Emilee Whetstone, Lauren Ammerman, Alice TI Nutrition-Related Policy and Environmental Strategies to Prevent Obesity in Rural Communities: A Systematic Review of the Literature, 2002-2013 SO PREVENTING CHRONIC DISEASE LA English DT Review ID REDUCE CHILDHOOD OBESITY; ARKANSAS ACT 1220; DIABETES PREVENTION; PHYSICAL-ACTIVITY; 1ST NATIONS; PSYCHOSOCIAL FACTORS; DISEASE PREVENTION; UNITED-STATES; HEALTHY FOODS; INTERVENTION AB Introduction Residents of rural communities in the United States are at higher risk for obesity than their urban and suburban counterparts. Policy and environmental-change strategies supporting healthier dietary intake can prevent obesity and promote health equity. Evidence in support of these strategies is based largely on urban and suburban studies; little is known about use of these strategies in rural communities. The purpose of this review was to synthesize available evidence on the adaptation, implementation, and effectiveness of policy and environmental obesity-prevention strategies in rural settings. Methods The review was guided by a list of Centers for Disease Control and Prevention Recommended Community Strategies and Measurements to Prevent Obesity in the United States, commonly known as the "COCOMO" strategies. We searched PubMed, Cumulative Index of Nursing and Allied Health Literature, Public Affairs Information Service, and Cochrane databases for articles published from 2002 through 2013 that reported findings from research on nutrition-related policy and environmental strategies in rural communities in the United States and Canada. Two researchers independently abstracted data from each article, and resolved discrepancies by consensus. Results Of the 663 articles retrieved, 33 met inclusion criteria. The interventions most commonly focused on increasing access to more nutritious foods and beverages or decreasing access to less nutritious options. Rural adaptations included accommodating distance to food sources, tailoring to local food cultures, and building community partnerships. Conclusions Findings from this literature review provide guidance on adapting and implementing policy and environmental strategies in rural communities. C1 [Leeman, Jennifer; Evenson, Kelly R.; Schreiner, Michelle; Owens, Clint; McGuirt, Jared; Ammerman, Alice] Univ N Carolina, Chapel Hill, NC 27599 USA. [Pitts, Stephanie B. Jilcott; Whetstone, Lauren] E Carolina Univ, Elizabeth City, NC USA. [Khan, Laura Kettel] Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Atlanta, GA USA. [Fleischhacker, Sheila] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. [Byker, Carmen] Montana State Univ, Billings, MT USA. [Barnidge, Ellen] St Louis Univ, St Louis, MO 63103 USA. [Dean, Wesley] Food & Nutr Serv, USDA, Washington, DC USA. [Johnson, Donna; Quinn, Emilee] Univ Washington, Seattle, WA 98195 USA. [Kolodinsky, Jane] Univ Vermont, Burlington, VT USA. [Piltch, Emily] Tufts Univ, Boston, MA 02111 USA. [Pinard, Courtney] Univ Nebraska, Lincoln, NE USA. RP Calancie, L (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, CB 7426,1700 MLK Airport Rd,Room 239, Chapel Hill, NC 27599 USA. EM lcalancie@unc.edu OI Byker Shanks, Carmen/0000-0002-9030-9938 FU CDC [5-37850, U48/DP000059]; National Institute of Nursing Research [T32NR007091, 5T32NR008856] FX This study was conducted as a joint project of the CDC-funded NOPREN Rural Food Access Working Group (grant no. 5-37850). This work was also supported by the CDC-funded University of North Carolina at Chapel Hill Prevention Research Center (no. U48/DP000059). Michelle Schreiner's and Clint Owens's work was supported by grants no. T32NR007091 and no. 5T32NR008856 from the National Institute of Nursing Research. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC, the USDA, or the National Institutes of Health. NR 60 TC 4 Z9 4 U1 2 U2 21 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD APR PY 2015 VL 12 AR 140540 DI 10.5888/pcd12.140540 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL0YS UT WOS:000356669600015 ER PT J AU Fleischhacker, S Otten, JJ Dodson, EA Siddiqi, S AF Fleischhacker, Sheila Otten, Jennifer J. Dodson, Elizabeth A. Siddiqi, Sameer TI Elevating the Impact of Nutrition and Obesity Policy Research and Evaluation SO PREVENTING CHRONIC DISEASE LA English DT Article ID HEALTH C1 [Otten, Jennifer J.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Dodson, Elizabeth A.] Brown Sch, St Louis, MO USA. [Dodson, Elizabeth A.] Prevent Res Ctr St Louis, St Louis, MO USA. [Dodson, Elizabeth A.] Washington Univ, St Louis, MO USA. [Siddiqi, Sameer] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Siddiqi, Sameer] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Fleischhacker, S (reprint author), NIH, Div Nutr Res Coordinat, US Dept HHS, 2 Democracy Plaza,Room 635,6707 Democracy Blvd, Bethesda, MD 20892 USA. EM sheila.fleischhacker@nih.gov NR 10 TC 0 Z9 0 U1 1 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD APR PY 2015 VL 12 AR 150142 DI 10.5888/pcd12.150142 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL0YS UT WOS:000356669600017 ER PT J AU Otten, JJ Dodson, EA Fleischhacker, S Siddiqi, S Quinn, EL AF Otten, Jennifer J. Dodson, Elizabeth A. Fleischhacker, Sheila Siddiqi, Sameer Quinn, Emilee L. TI Getting Research to the Policy Table: A Qualitative Study With Public Health Researchers on Engaging With Policy Makers SO PREVENTING CHRONIC DISEASE LA English DT Article AB Introduction Little attention has been given to how researchers can best provide evidence to policy makers so that it informs policy making. The objectives of this study were to increase understanding about the current state of public health nutrition and obesity researcher practices, beliefs, barriers, and facilitators to communicating and engaging with policy makers, and to identify best practices and suggest improvements. Methods Eighteen semistructured interviews were conducted from 2011 to 2013 with public health nutrition and obesity researchers who were highly involved in communicating research to policy makers. Interviews were transcribed verbatim, coded, and analyzed to identify common themes. Results Study participants described wide variation in practices for communicating and engaging with policy makers and had mixed beliefs about whether and when researchers should engage. Besides a lack of formal policy communication training, barriers noted were promotion and tenure processes and a professional culture that does not value communicating and engaging with policy makers. Study participants cited facilitators to engaging with policy makers as ranging from the individual level (eg, desire to make a difference, relationships with collaborators) to the institutional level (eg, training/mentorship support, institutional recognition). Other facilitators identified were research-and funding-driven. Promising strategies suggested to improve policy engagement were more formal training, better use of intermediaries, and learning how to cultivate relationships with policy makers. Conclusion Study findings provide insights into the challenges that will need to be overcome and the strategies that might be tried to improve communication and engagement between public health researchers and policy makers. C1 [Dodson, Elizabeth A.] Washington Univ, Brown Sch, St Louis, MO USA. [Dodson, Elizabeth A.] Washington Univ, Prevent Res Ctr St Louis, St Louis, MO USA. [Fleischhacker, Sheila; Siddiqi, Sameer] NIH, Bethesda, MD 20892 USA. [Siddiqi, Sameer] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Quinn, Emilee L.] Univ Washington, Ctr Publ Hlth Nutr, Seattle, WA 98115 USA. RP Otten, JJ (reprint author), Univ Washington, Sch Publ Hlth, Nutr Sci Program, Box 353410, Seattle, WA 98115 USA. EM jotten@uw.edu FU Centers for Disease Control and Prevention (CDC); CDC, the Prevention Research Centers Program [U48/DP001903]; National Cancer Institute at the National Institutes of Health (NIH) [1R01CA124404-01] FX We thank the interviewees who offered their time and energy to the project and appreciate the invaluable feedback from the members of the NOPREN PRIWG. NOPREN is funded by the Centers for Disease Control and Prevention (CDC). This work was supported by cooperative agreement no. U48/DP001903 from CDC, the Prevention Research Centers Program and the National Cancer Institute at the National Institutes of Health (NIH grant no. 1R01CA124404-01). The content is solely the responsibility of the authors and does not represent the official views of CDC or NIH. NR 19 TC 0 Z9 0 U1 0 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD APR PY 2015 VL 12 AR 140546 DI 10.5888/pcd12.140546 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL0YS UT WOS:000356669600014 ER PT J AU Swanson, PA McGavern, DB AF Swanson, Phillip A., II McGavern, Dorian B. TI Viral diseases of the central nervous system SO CURRENT OPINION IN VIROLOGY LA English DT Article ID WEST-NILE-VIRUS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HERPES-SIMPLEX ENCEPHALITIS; TICK-BORNE ENCEPHALITIS; TUMOR-NECROSIS-FACTOR; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; SCLEROSING PANENCEPHALITIS SSPE; POLYMERASE CHAIN-REACTION; ACUTE FLACCID PARALYSIS; TOLL-LIKE RECEPTOR-3 AB Virus-induced diseases of the central nervous system (CNS) represent a significant burden to human health worldwide. The complexity of these diseases is influenced by the sheer number of different neurotropic viruses, the diverse routes of CNS entry, viral tropism, and the immune system. Using a combination of human pathological data and experimental animal models, we have begun to uncover many of the mechanisms that viruses use to enter the CNS and cause disease. This review highlights a selection of neurotropic viruses that infect the CNS and explores the means by which they induce neurological diseases such as meningitis, encephalitis, and myelitis. C1 [Swanson, Phillip A., II; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA. RP Swanson, PA (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. OI McGavern, Dorian/0000-0001-9568-545X FU National Institutes of Health (NIH) FX This work was supported by National Institutes of Health (NIH) intramural program. P.S. is presently supported by a NIH Intramural Competitive Fellowship. We would like to thank Ethan Tyler and Alan Hoofring in the NIH Medical Arts Design Section for their help with the illustrations. NR 137 TC 16 Z9 17 U1 5 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1879-6257 J9 CURR OPIN VIROL JI Curr. Opin. Virol. PD APR PY 2015 VL 11 BP 44 EP 54 DI 10.1016/j.coviro.2014.12.009 PG 11 WC Virology SC Virology GA CK9FW UT WOS:000356547000009 PM 25681709 ER PT J AU Doria-Rose, NA Joyce, MG AF Doria-Rose, Nicole A. Joyce, M. Gordon TI Strategies to guide the antibody affinity maturation process SO CURRENT OPINION IN VIROLOGY LA English DT Article ID BROADLY NEUTRALIZING ANTIBODIES; IMMUNODEFICIENCY-VIRUS TYPE-1; RECEPTOR-BINDING SITE; B-CELL RECEPTORS; ENVELOPE GLYCOPROTEIN TRIMERS; RESPIRATORY SYNCYTIAL VIRUS; HUMAN MONOCLONAL-ANTIBODIES; INFLUENZA-VIRUS; HIV-1 ENVELOPE; GERMINAL CENTER AB Antibodies with protective activity are critical for vaccine efficacy. Affinity maturation increases antibody activity through multiple rounds of somatic hypermutation and selection in the germinal center. Identification of HIV-1 specific and influenza-specific antibody developmental pathways, as well as characterization of B cell and virus co-evolution in patients, has informed our understanding of antibody development. In order to counteract HIV-1 and influenza viral diversity, broadly neutralizing antibodies precisely target specific sites of vulnerability and require high levels of affinity maturation. We present immunization strategies that attempt to recapitulate these natural processes and guide the affinity maturation process. C1 [Doria-Rose, Nicole A.; Joyce, M. Gordon] NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Joyce, MG (reprint author), NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. EM joycego@mail.nih.gov FU Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Rebecca M. Lynch and Evan M. Cale for careful reading of the manuscript, and Masaru Kanekiyo, Nancy S. Longo, Penny L. Moore and Tongqing Zhou for helpful discussions. Support for this work was provided by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 115 TC 10 Z9 10 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1879-6257 J9 CURR OPIN VIROL JI Curr. Opin. Virol. PD APR PY 2015 VL 11 BP 137 EP 147 DI 10.1016/j.coviro.2015.04.002 PG 11 WC Virology SC Virology GA CK9FW UT WOS:000356547000021 PM 25913818 ER PT J AU Chiu, CT Scheuing, L Liu, GP Liao, HM Linares, GR Lin, D Chuang, DM AF Chiu, Chi-Tso Scheuing, Lisa Liu, Guangping Liao, Hsiao-Mei Linares, Gabriel R. Lin, Dora Chuang, De-Maw TI The Mood Stabilizer Lithium Potentiates the Antidepressant-Like Effects and Ameliorates Oxidative Stress Induced by Acute Ketamine in a Mouse Model of Stress SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ketamine; lithium; mTOR; GSK-3; BDNF ID MAJOR DEPRESSIVE DISORDER; D-ASPARTATE ANTAGONIST; FORCED SWIMMING TEST; TAIL SUSPENSION TEST; ELONGATION FACTOR-II; PREFRONTAL CORTEX; ACTING ANTIDEPRESSANTS; PHYSICAL-DEPENDENCE; BIPOLAR DISORDER; RAT HIPPOCAMPUS AB Background: Evidence suggests that mammalian target of rapamycin activation mediates ketamine's rapid but transient antidepressant effects and that glycogen synthase kinase-3 beta inhibits this pathway. However, ketamine has associated psychotomimetic effects and a high risk of abuse. The mood stabilizer lithium is a glycogen synthase kinase-3 inhibitor with strong antisuicidal properties. Here, we used a mouse stress model to investigate whether adjunct lithium treatment would potentiate ketamine's antidepressant-like effects. Methods: Mice received chronic restraint stress and long-term pre- or postketamine lithium treatment in drinking water. The effects of lithium on ketamine-induced antidepressant-like effects, activation of the mammalian target of rapamycin/brain-derived neurotrophic factor signaling pathways, oxidative stress, and dendritic spine density in the brain of mice were investigated. Results: Subtherapeutic (600 mg/L) lithium-pretreated mice exhibited an antidepressant-like response to an ineffective ketamine (2.5 mg/kg, intraperitoneally) challenge in the forced swim test. Both the antidepressant-like effects and restoration of dendritic spine density in the medial prefrontal cortex of stressed mice induced by a single ketamine (50 mg/kg) injection were sustained by postketamine treatment with 1200 mg/L of lithium for at least 2 weeks. These benefits of lithium treatments were associated with activation of the mammalian target of rapamycin/brain-derived neurotrophic factor signaling pathways in the prefrontal cortex. Acute ketamine (50 mg/kg) injection also significantly increased lipid peroxidation, catalase activity, and oxidized glutathione levels in stressed mice. Notably, these oxidative stress markers were completely abolished by pretreatment with 1200 mg/L of lithium. Conclusions: Our results suggest a novel therapeutic strategy and justify the use of lithium in patients who benefit from ketamine. C1 [Chiu, Chi-Tso; Scheuing, Lisa; Liu, Guangping; Liao, Hsiao-Mei; Linares, Gabriel R.; Lin, Dora; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, Bldg 10,Room 3D41,10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA. EM chiuc@mail.nih.gov; chuang@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS) FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS). The authors thank Ioline Henter of the NIMH, NIH, for critical review and editorial assistance with this manuscript. NR 53 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD APR PY 2015 VL 18 IS 6 DI 10.1093/ijnp/pyu102 PG 13 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CL1JY UT WOS:000356700000008 ER PT J AU Zanetti, MV Otaduy, MC de Sousa, RT Gattaz, WF Busatto, GF Leite, CC Machado-Vieira, R AF Zanetti, Marcus V. Otaduy, Maria C. de Sousa, Rafael T. Gattaz, Wagner F. Busatto, Geraldo F. Leite, Claudia C. Machado-Vieira, Rodrigo TI Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE bipolar disorder; depression; glutamate; hippocampus; lithium; magnetic resonance spectroscopy ID MAGNETIC-RESONANCE-SPECTROSCOPY; MOOD DISORDERS; RATING-SCALE; HUMAN BRAIN; PATHOPHYSIOLOGY; PLASTICITY; SCHIZOPHRENIA; METAANALYSIS; MONOTHERAPY; EXPRESSION AB Background: The hippocampus has been highly implicated in the pathophysiology of bipolar disorder (BD). Nevertheless, no study has longitudinally evaluated hippocampal metabolite levels in bipolar depression under treatment with lithium. Methods: Nineteen medication-free BD patients (78.9% treatment-naive and 73.7% with BD type II) presenting an acute depressive episode and 17 healthy controls were studied. Patients were treated for 6 weeks with lithium in an open-label trial. N-acetyl aspartate (NAA), creatine, choline, myo-Inositol, and glutamate levels were assessed in the left hippocampus before (week 0) and after (week 6) lithium treatment using 3T proton magnetic resonance spectroscopy (1H-MRS). The metabolite concentrations were estimated using internal water as reference and voxel segmentation for partial volume correction. Results: At baseline, acutely depressed BD patients and healthy controls exhibited similar hippocampal metabolites concentrations, with no changes after 6 weeks of lithium monotherapy. A significant correlation between antidepressant efficacy and increases in NAA concentration over time was observed. Also, there was a significant positive correlation between the changes in glutamate concentrations over follow-up and plasma lithium levels at endpoint. Mixed effects model analysis revealed a bimodal effect of lithium plasma levels in hippocampal glutamate concentrations: levels of 0.2 to 0.49 mmol/L (n=9) were associated with a decrease in glutamate concentrations, whereas the subgroup of BD subjects with "standard" lithium levels (>= 0.50 mmol/L; n = 10) showed an overall increase in glutamate concentrations over time. Conclusions: These preliminary results suggest that lithium has a bimodal action in hippocampal glutamate concentration depending on the plasma levels. C1 [Zanetti, Marcus V.; de Sousa, Rafael T.; Gattaz, Wagner F.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci LIM 27, Mood Disorders Program, BR-05508 Sao Paulo, Brazil. [Zanetti, Marcus V.; Gattaz, Wagner F.; Busatto, Geraldo F.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-05508 Sao Paulo, Brazil. [Zanetti, Marcus V.; Busatto, Geraldo F.] Univ Sao Paulo, Dept & Inst Psychiat, Lab Psychiat Neuroimaging, LIM 21, BR-05508 Sao Paulo, Brazil. [Otaduy, Maria C.; Leite, Claudia C.] Univ Sao Paulo, Dept Radiol, BR-05508 Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] NIMH, ETPB, NIH, Bethesda, MD 20892 USA. RP Zanetti, MV (reprint author), Ctr Med Nucl, 3 Andar,LIM 21,Rua Dr Ovidio Pires Campos, BR-05403010 Sao Paulo, SP, Brazil. EM zanetti.mv@gmail.com RI Busatto, Geraldo/D-4431-2009; Leite, Claudia/B-6036-2013; MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU Sao Paulo Research Foundation (FAPESP, Brazil) [2009/14891-9]; Associacao Beneficente Alzira Denise Hertzog da Silva (ABADHS); FAPESP, Brazil [2013/03905-4] FX This study was sponsored by the Sao Paulo Research Foundation (FAPESP, Brazil, 2009/14891-9, RM-V). The Laboratory of Neuroscience, LIM27, is also supported by the Associacao Beneficente Alzira Denise Hertzog da Silva (ABADHS). Dr Zanetti is funded by FAPESP, Brazil (no. 2013/03905-4). This is clinical trial number NCT01919892. NR 42 TC 4 Z9 4 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD APR PY 2015 VL 18 IS 6 DI 10.1093/ijnp/pyu058 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CL1JY UT WOS:000356700000002 ER PT J AU Gorry, C Mesa, G Ortiz, P AF Gorry, Conner Mesa, Guillermo Ortiz, Paulo TI Approaches to Climate Change & Health in Cuba: Guillermo Mesa MD MPhil, Director, Disasters & Health, National School of Public Health Paulo Ortiz MS PhD, Senior Researcher, Climate Center, Cuban Meteorology Institute SO MEDICC REVIEW LA English DT Editorial Material AB The US National Institutes of Health predict climate change will cause an additional 250,000 deaths between 2030 and 2050, with damages to health costing US$2-$4 billion by 2030. Although much debate still surrounds climate change, island ecosystems-such as Cuba's-in the developing world are arguably among the most vulnerable contexts in which to confront climate variability. Beginning in the 1990s, Cuba launched research to develop the evidence base, set policy priorities, and design mitigation and adaptation actions specifically to address climate change and its effects on health. Two researchers at the forefront of this interdisciplinary, intersectoral effort are epidemiologist Dr Guillermo Mesa, who directed design and implementation of the nationwide strategy for disaster risk reduction in the Cuban public health system as founding director of the Latin American Center for Disaster Medicine (CLAMED) and now heads the Disasters and Health department at the National School of Public Health; and Dr Paulo Ortiz, a biostatistician and economist at the Cuban Meteorology Institute's Climate Center (CEN-CLIM), who leads the research on Cuba's Climate and Health project and is advisor on climate change and health for the UN Economic Commission for Latin America and the Caribbean (ECLAC). C1 [Gorry, Conner] NIH, Bethesda, MD 20892 USA. [Mesa, Guillermo] Natl Sch Publ Hlth, Disasters & Hlth, Bethesda, MD USA. RP Gorry, C (reprint author), NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU MEDICC-MED EDUC COOPERATION CUBA PI DECATUR PA 1902 CLAIRMONT RD, STE 250, DECATUR, GEORGIA 30033-3406 USA SN 1555-7960 J9 MEDICC REV JI MEDICC Rev. PD APR PY 2015 VL 17 IS 2 BP 6 EP 9 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CK0UB UT WOS:000355919400003 ER PT J AU Miszczyk, J Rawojc, K Panek, A Swakon, J Prasanna, PG Rydygier, M AF Miszczyk, Justyna Rawojc, Kamila Panek, Agnieszka Swakon, Jan Prasanna, Pataje G. Rydygier, Marzena TI Response of human lymphocytes to proton radiation of 60 MeV compared to 250 kV X-rays by the cytokinesis-block micronucleus assay SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Proton beam; X-rays; Cytokinesis-block micronucleus assay; Human lymphocytes; Micronuclei frequency; Nuclear division index ID IN-VITRO; IONIZING-RADIATION; CHROMOSOME-ABERRATIONS; CANCER-PATIENTS; CYTOME ASSAY; COMET ASSAY; CELL-DEATH; DOSE-RATE; IRRADIATION; EXPOSURE AB Particle radiotherapy such as protons provides a new promising treatment modality to cancer. However, studies on its efficacy and risks are relatively sparse. Using the cytokinesis-blocked micronucleus assay, we characterized response of human peripheral blood lymphocytes, obtained from health donors irradiated in vitro in the dose range: 0-4. 0 Gy, to therapeutic proton radiation of 60 MeV from AIC-144 isochronous cyclotron, by studying nuclear division index and DNA damage and compared them with Xrays. Peripheral blood lymphocytes show decreased ability to proliferate with increasing radiation doses for both radiation types, however, in contrast to X-rays, irradiation with protons resulted in a higher proliferation index at lower doses of 0.75 and 1.0 Gy. Protons are more effective in producing MN at doses above 1.75 Gy compared to X-rays. Dose-response curves for micronucleus incidence can be best described by a cubic model for protons, while for X-rays the response was linear. The differences in the energy spectrum and intracellular distribution of energy between radiation types are also apparent at the intracellular distribution of cytogenetic damage as seen by the distribution of various numbers of micronuclei in binucleated cells. Our studies, although preliminary, further contribute to the understanding of the mechanistic differences in the response of HPBL in terms of cellular proliferation and cytogenetic damage induced by protons and X-rays as well as intra-cellular distribution of energy and thus radiobiological effectiveness. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Miszczyk, Justyna; Rawojc, Kamila; Panek, Agnieszka] Polish Acad Sci, H Niewodniczanski Inst Nucl Phys, Dept Expt Phys Complex Syst, PL-31342 Krakow, Poland. [Rawojc, Kamila] Jagiellonian Univ, Marian Smoluchowski Inst Phys, Krakow, Poland. [Swakon, Jan; Rydygier, Marzena] Polish Acad Sci, H Niewodniczanski Inst Nucl Phys, Cyclotron Ctr Bronowice, Proton Radiotherapy Grp, PL-31342 Krakow, Poland. [Prasanna, Pataje G.] NCI, NIH, Bethesda, MD 20892 USA. RP Miszczyk, J (reprint author), Polish Acad Sci, H Niewodniczanski Inst Nucl Phys, Dept Expt Phys Complex Syst, Radzikowskiego 152 St, PL-31342 Krakow, Poland. EM justyna.miszczyk@ifl.edu.pl FU National Science Centre, Poland [DEC-2013/09/D/NZ7/00324] FX The authors would like to thank Mrs. Jolanta Adamczyk for her assistance in laboratory procedures. A crucially valuable discussion, comments and suggestions by Mr. Wojciech Zajac are highly appreciated. Authors are also grateful for all scientific support given by Professor Jan Stanek and Professor Boguslaw Kamys from Marian Smoluchowski Institute of Physics Jagiellonian University. These investigations were carried out as part of an extended examination of the 60 MeV proton beam from AIC-144 isochronous cyclotron, at IFJ PAN by cytogenetic and molecular methods and were partially supported by Grant DEC-2013/09/D/NZ7/00324 from the National Science Centre, Poland. U.S. National Cancer Institute's (NCI) Radiation Research Program supported Dr. Prasanna's assistance in the preparation of the manuscript. The views expressed are those of the authors; no endorsement by NCI has been given or inferred. In particular, authors gratefully acknowledge the donors for providing blood samples and technical staff for irradiation and dosimetry. NR 50 TC 1 Z9 1 U1 2 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD APR PY 2015 VL 115 IS 1 BP 128 EP 134 DI 10.1016/j.radonc.2015.03.003 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CL1WT UT WOS:000356736300023 PM 25818831 ER PT J AU Banerjee, T Tucker, K Griswold, M Wyatt, SB Herman, J Taylor, H AF Banerjee, T. Tucker, K. Griswold, M. Wyatt, S. B. Herman, J. Taylor, H. TI ASSOCIATION OF DIETARY ACID LOAD (DAL) AND CKD AMONG PARTICIPANTS IN JACKSON HEART STUDY (JHS) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of National-Kidney-Foundation CY MAR 25-29, 2015 CL Grapevine, TX SP Natl Kidney Fdn C1 [Banerjee, T.] NR Powe, Atlanta, GA USA. [Tucker, K.] UCSF, Atlanta, GA USA. [Griswold, M.] UMASS, Atlanta, GA USA. [Wyatt, S. B.] UMMC, Atlanta, GA USA. [Herman, J.] NHLBI, Atlanta, GA USA. [Taylor, H.] MSM, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2015 VL 65 IS 4 MA 30 BP A22 EP A22 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CJ9BE UT WOS:000355796500033 ER PT J AU Locatis, C Gaines, C Liu, WL Gill, M Ackerman, M AF Locatis, Craig Gaines, Cynthia Liu, Wei-Li Gill, Michael Ackerman, Michael TI Lessons learned from ten years of distance learning outreach SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID REACH USERS; EDUCATION; LIBRARY AB Objective: The study tested the efficacy of providing distance learning with real-time videoconferencing to broaden high school student knowledge of health careers. Methods: A pilot program was tried out and extended over ten years to include other schools in four different time zones and the National Library of Medicine. Survey results, site visits, and continued school participation were used as effectiveness indicators. Student ratings, site visits, and ongoing discussions were used to evaluate critical factors in the program. Results: Nine program factors contributed to success. Conclusions: Synchronous communication can be effective for outreach to special populations given appropriate infrastructure, technology, program design, and implementation. C1 [Locatis, Craig; Gaines, Cynthia; Liu, Wei-Li; Gill, Michael] NIH, Natl Lib Med, Bethesda, MD 20894 USA. [Ackerman, Michael] NIH, Natl Lib Med, High Performance Comp & Commun, Bethesda, MD 20894 USA. RP Locatis, C (reprint author), NIH, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM locatis@nlm.nih.gov; gainesc@mail.nlm.nih.gov; wliu@mail.nih.gov; mgill@mail.nih.gov; ackerman@nlm.nih.gov FU National Library of Medicine; National Institutes of Health FX This work was partially supported by the intramural research program of the National Library of Medicine and the National Institutes of Health. NR 19 TC 0 Z9 0 U1 2 U2 5 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD APR PY 2015 VL 103 IS 2 BP 78 EP 82 DI 10.3163/1536-5050.103.2.004 PG 6 WC Information Science & Library Science SC Information Science & Library Science GA CK1YL UT WOS:000356005600004 PM 25918486 ER PT J AU Keselman, A Ahmed, EA Williamson, DC Kelly, JE Dutcher, GA AF Keselman, Alla Ahmed, Einas A. Williamson, Deborah C. Kelly, Janice E. Dutcher, Gale A. TI Harnessing health information to foster disadvantaged teens' community engagement, leadership skills, and career plans: a qualitative evaluation of the Teen Health Leadership Program SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB This paper describes a qualitative evaluation of a small-scale program aiming to improve health information literacy, leadership skills, and interest in health careers among high school students in a low-income, primarily minority community. Graduates participated in semi-structured interviews, transcripts of which were coded with a combination of objectives-driven and data-driven categories. The program had a positive impact on the participants' health information competency, leadership skills, academic orientation, and interest in health careers. Program enablers included a supportive network of adults, novel experiences, and strong mentorship. The study suggests that health information can provide a powerful context for enabling disadvantaged students' community engagement and academic success. C1 [Keselman, Alla; Dutcher, Gale A.] Natl Lib Med, Div Specialized Informat Serv, Bethesda, MD 20892 USA. [Ahmed, Einas A.] Natl Lib Med, Ctr Publ Serv Commun, Div Specialized Informat Serv, Bethesda, MD 20892 USA. [Williamson, Deborah C.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Kelly, Janice E.] Natl Lib Med, Div Specialized Informat Serv, Outreach & Special Populat Branch, Bethesda, MD 20892 USA. RP Keselman, A (reprint author), Natl Lib Med, Div Specialized Informat Serv, 6707 Democracy Blvd,Suite 510, Bethesda, MD 20892 USA. EM keselmana@mail.nih.gov; einas.ahmed@nih.gov; wilmsnd@musc.edu; janice.kelly@nih.gov; dutcherg@mail.nlm.nih.gov FU National Library of Medicine, National Institutes of Health FX This evaluation was supported by the intramural research program of the National Library of Medicine, National Institutes of Health. NR 7 TC 1 Z9 1 U1 1 U2 2 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD APR PY 2015 VL 103 IS 2 BP 82 EP 86 DI 10.3163/1536-5050.103.2.005 PG 6 WC Information Science & Library Science SC Information Science & Library Science GA CK1YL UT WOS:000356005600005 PM 25918487 ER PT J AU Das, D Maeda, K Hayashi, Y Gavande, N Desai, DV Chang, SB Ghosh, AK Mitsuya, H AF Das, Debananda Maeda, Kenji Hayashi, Yasuhiro Gavande, Navnath Desai, Darshan V. Chang, Simon B. Ghosh, Arun K. Mitsuya, Hiroaki TI Insights into the Mechanism of Inhibition of CXCR4: Identification of Piperidinylethanamine Analogs as Anti-HIV-1 Inhibitors SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BICYCLAM NONPEPTIDE ANTAGONISTS; CHEMOKINE RECEPTOR CXCR4; 2ND EXTRACELLULAR LOOP; X4 HIV-1 REPLICATION; SMALL-MOLECULE; POTENT INHIBITORS; CCR5; DOCKING; BINDING AB The cellular entry of HIV-1 into CD4(+) T cells requires ordered interactions of HIV-1 envelope glycoprotein with C-X-C chemokine receptor type 4 (CXCR4) receptors. However, such interactions, which should be critical for rational structure-based discovery of new CXCR4 inhibitors, remain poorly understood. Here we first determined the effects of amino acid substitutions in CXCR4 on HIV-1(NL4-3) glycoprotein-elicited fusion events using site-directed mutagenesis-based fusion assays and identified 11 potentially key amino acid substitutions, including D97A and E288A, which caused >30% reductions in fusion. We subsequently carried out a computational search of a screening library containing similar to 604,000 compounds, in order to identify potential CXCR4 inhibitors. The computational search used the shape of IT1t, a known CXCR4 inhibitor, as a reference and employed various algorithms, including shape similarity, isomer generation, and docking against a CXCR4 crystal structure. Sixteen small molecules were identified for biological assays based on their high shape similarity to IT1t, and their putative binding modes formed hydrogen bond interactions with the amino acids identified above. Three compounds with piperidinylethanamine cores showed activity and were resynthesized. One molecule, designated CX6, was shown to significantly inhibit fusion elicited by X4 HIV-1(NL4-3) glycoprotein (50% inhibitory concentration [IC50], 1.9 mu M), to inhibit Ca2+ flux elicited by stromal cell-derived factor 1 alpha (SDF-1 alpha) (IC50, 92 nM), and to exert anti-HIV-1 activity (IC50, 1.5 mu M). Structural modeling demonstrated that CX6 bound to CXCR4 through hydrogen bond interactions with Asp97 and Glu288. Our study suggests that targeting CXCR4 residues important for fusion elicited by HIV-1 envelope glycoprotein should be a useful and feasible approach to identifying novel CXCR4 inhibitors, and it provides important insights into the mechanism by which small-molecule CXCR4 inhibitors exert their anti-HIV-1 activities. C1 [Das, Debananda; Maeda, Kenji; Hayashi, Yasuhiro; Desai, Darshan V.; Chang, Simon B.; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. [Gavande, Navnath; Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Gavande, Navnath; Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. [Mitsuya, Hiroaki] Kumamoto Univ, Dept Hematol, Grad Sch Med & Pharmaceut Sci, Kumamoto, Japan. [Mitsuya, Hiroaki] Kumamoto Univ, Dept Infect Dis, Grad Sch Med & Pharmaceut Sci, Kumamoto, Japan. RP Das, D (reprint author), NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. EM dasd@mail.nih.gov FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; Global Education and Research Center Aiming at the Control of AIDS (Monbu-Kagakusho); AIDS research from the Ministry of Health, Welfare, and Labor of Japan; Monbu-Kagakusho; National Institutes of Health [GM53386] FX This work was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, and in part by a grant from the Global Education and Research Center Aiming at the Control of AIDS (Global Center of Excellence supported by Monbu-Kagakusho), a grant for promotion of AIDS research from the Ministry of Health, Welfare, and Labor of Japan, the grant to the Cooperative Research Project on Clinical and Epidemiological Studies of Emerging and Re-emerging Infectious Diseases from Monbu-Kagakusho (H.M.), and a grant from the National Institutes of Health (grant GM53386 [A.K.G.]). The study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health (http://biowulf.nih.gov). NR 38 TC 5 Z9 5 U1 0 U2 12 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 APR PY 2015 VL 59 IS 4 BP 1895 EP 1904 DI 10.1128/AAC.04654-14 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CI8BY UT WOS:000354993700009 PM 25583709 ER PT J AU Luque, AE Cohn, SE Park, JG Cramer, Y Weinberg, A Livingston, E Klingman, KL Aweeka, F Watts, DH AF Luque, Amneris E. Cohn, Susan E. Park, Jeong-Gun Cramer, Yoninah Weinberg, Adriana Livingston, Elizabeth Klingman, Karin L. Aweeka, Francesca Watts, D. Heather TI Depot Medroxyprogesterone Acetate in Combination with a Twice-Daily Lopinavir-Ritonavir-Based Regimen in HIV-Infected Women Showed Effective Contraception and a Lack of Clinically Significant Interactions, with Good Safety and Tolerability: Results of the ACTG 5283 Study SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIRETROVIRAL THERAPY; BOOSTED LOPINAVIR; P-GLYCOPROTEIN; PHARMACOKINETICS; LOPINAVIR/RITONAVIR; INHIBITORS; TRIALS; AIDS; 3A4 AB We conducted an open-label, steady-state pharmacokinetic (PK) study of drug-drug interactions between depot medroxyprogesterone acetate (DMPA) and twice-daily lopinavir (LPV) plus low-dose ritonavir (RTV) (LPV/r) among 24 HIV-infected women and compared the results to those for HIV-infected women receiving DMPA while on no antiretroviral therapy or on nucleosides only (n = 14 subjects from the control arm of AIDS Clinical Trials Group [ACTG] study 5093). The objectives of the study were to address the effect of LPV/r on DMPA and to address the effect of DMPA on LPV/r therapy. PK parameters were estimated using noncompartmental analysis with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of LPV and RTV PKs before and 4 weeks after DMPA dosing. Plasma progesterone concentrations were measured every 2 weeks after DMPA dosing through week 12. Although the MPA area under the concentration-time curve and maximum concentration of drug in plasma were statistically significantly increased in the study women on LPV/r compared to those in the historical controls, these increases were not considered clinically significant. There were no changes in LPV or RTV exposure after DMPA. DMPA was well tolerated, and suppression of ovulation was maintained. (This study has been registered at ClinicalTrials.gov under registration no. NCT01296152.) C1 [Luque, Amneris E.] Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. [Cohn, Susan E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Park, Jeong-Gun; Cramer, Yoninah] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Weinberg, Adriana] Univ Colorado Denver, Aurora, CO USA. [Livingston, Elizabeth] Duke Univ, Med Ctr, Durham, NC USA. [Klingman, Karin L.] NIH, Div Aids, Bethesda, MD 20892 USA. [Aweeka, Francesca] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Watts, D. Heather] US Dept State, Off Global AIDS Coordinator, Washington, DC 20520 USA. RP Luque, AE (reprint author), Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. EM amneris_luque@urmc.rochester.edu FU National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health [UM1 AI068634, UM1 AI068636, UM1 AI106701, UL 1RR02460, UL1TR000150, 1U01AI069513, 1U01AI069481, UM1-AI069423-08, 1U01AI069511, 1UL1TR001111, P30 AI50410]; UCSL PSL under NIH [1U01AI068636]; National Institute of Allergy and Infectious Diseases of the National Institutes of Health [UM1AI068632, UM1AI068616, UM1AI106716]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) FX The research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health under award numbers UM1 AI068634, UM1 AI068636, and UM1 AI106701; grant 1U01AI069511 and CRC grant UL 1RR02460 to the University of Rochester; grant 1U01AI069471 and CRC grant UL1TR000150 to Northwestern University; grant 1U01AI069513 to the Cincinnati, OH, CRS; grant 1U01AI069481 to the University of Washington; grant UM1-AI069423-08, CTSA grant 1UL1TR001111, and CFAR grant P30 AI50410 to the University of North Carolina Global CTU: Chapel Hill CRS; and UCSL PSL under NIH grant 1U01AI068636. Overall support for IMPAACT was provided by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC), and UM1AI106716 (IMPAACT LC) with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). NR 19 TC 3 Z9 3 U1 0 U2 4 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 APR PY 2015 VL 59 IS 4 BP 2094 EP 2101 DI 10.1128/AAC.04701-14 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CI8BY UT WOS:000354993700034 PM 25624326 ER PT J AU Dastgheyb, SS Hammoud, S Ketonis, C Liu, AY Fitzgerald, K Parvizi, J Purtill, J Ciccotti, M Shapiro, IM Otto, M Hickok, NJ AF Dastgheyb, Sana S. Hammoud, Sommer Ketonis, Constantinos Liu, Andrew Yongkun Fitzgerald, Keith Parvizi, Javad Purtill, James Ciccotti, Michael Shapiro, Irving M. Otto, Michael Hickok, Noreen J. TI Staphylococcal Persistence Due to Biofilm Formation in Synovial Fluid Containing Prophylactic Cefazolin SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PERIPROSTHETIC JOINT INFECTION; BACTERICIDAL ACTIVITY; ANTIBIOTIC-PROPHYLAXIS; ORTHOPEDIC-SURGERY; UNITED-STATES; ARTHROPLASTY; VANCOMYCIN; BONE; BURDEN; AUREUS AB Antibiotic prophylaxis is standard for patients undergoing surgical procedures, yet despite the wide use of antibiotics, breakthrough infections still occur. In the setting of total joint arthroplasty, such infections can be devastating. Recent findings have shown that synovial fluid causes marked staphylococcal aggregation, which can confer antibiotic insensitivity. We therefore asked in this study whether clinical samples of synovial fluid that contain preoperative prophylactic antibiotics can successfully eradicate a bacterial challenge by pertinent bacterial species. This study demonstrates that preoperative prophylaxis with cefazolin results in high antibiotic levels. Furthermore, we show that even with antibiotic concentrations that far exceed the expected bactericidal levels, Staphylococcus aureus bacteria added to the synovial fluid samples are not eradicated and are able to colonize model implant surfaces, i.e., titanium pins. Based on these studies, we suggest that current prophylactic antibiotic choices, despite high penetration into the synovial fluid, may need to be reexamined. C1 [Dastgheyb, Sana S.; Ketonis, Constantinos; Liu, Andrew Yongkun; Fitzgerald, Keith; Shapiro, Irving M.; Hickok, Noreen J.] Thomas Jefferson Univ, Dept Orthopaed Surg, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Hammoud, Sommer; Ketonis, Constantinos; Parvizi, Javad; Purtill, James; Ciccotti, Michael] Rothman Inst, Philadelphia, PA USA. [Dastgheyb, Sana S.; Otto, Michael] NIAID, NIH, Bethesda, MD 20892 USA. RP Hickok, NJ (reprint author), Thomas Jefferson Univ, Dept Orthopaed Surg, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. EM noreen.hickok@jefferson.edu OI Dastgheyb, Sana/0000-0001-8275-1614; Otto, Michael/0000-0002-2222-4115 FU NIH [HD06153, DE019901]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH) [ZIA AI000904-13]; T32 NIH training grant [T32-AR-052273] FX This study was supported by NIH grants HD06153 and DE019901 to N.J.H., as well as the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), the National Institutes of Health (NIH) (grant ZIA AI000904-13 to M.O.), and a T32 NIH training grant (T32-AR-052273 to I.M.S.). NR 33 TC 5 Z9 5 U1 2 U2 2 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 APR PY 2015 VL 59 IS 4 BP 2122 EP 2128 DI 10.1128/AAC.04579-14 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CI8BY UT WOS:000354993700037 PM 25624333 ER PT J AU Cashman, KD Hayes, A Galvin, K Merkel, J Jones, G Kaufmann, M Hoofnagle, AN Carter, GD Durazo-Arvizu, RA Sempos, CT AF Cashman, Kevin D. Hayes, Aoife Galvin, Karen Merkel, Joyce Jones, Glenville Kaufmann, Martin Hoofnagle, Andrew N. Carter, Graham D. Durazo-Arvizu, Ramon A. Sempos, Christopher T. TI Significance of Serum 24,25-Dihydroxyvitamin D in the Assessment of Vitamin D Status: A Double-edged Sword? SO CLINICAL CHEMISTRY LA English DT Article ID 25-HYDROXYVITAMIN D; NUTRITION SURVEY; SUPPLEMENTATION; STANDARDIZATION; CATABOLISM; ADULTS; ASSAYS AB BACKGROUND: 24,25-Dihydroxyvitamin D [24,25(OH)(2)D] in serum may be both a nuisance and nutritionally valuable. METHODS: We investigated the impact of 24,25(OH)(2)D-3 on the performance of commercially available immunoassays for serum total 25-hydroxyvitamin D [25(OH) D] using (a) serum from a nationally representative sample of adults, (b) serum from a spiking experiment, and (c) data from the UK Vitamin D External Quality Assurance Scheme (DEQAS). We also investigated the utility of the serum ratio of 24,25(OH)(2) D-3 to 25(OH) D as an index of inactivation and of response to vitamin D supplementation using randomized controlled trial (RCT) data. Measurement of 24,25(OH)(2)D in sera by a LC-MS/MS method allowed for an investigation of its impact on immunoassay-derived serum 25(OH) D values as well as its clinical utility. We report data from a nationally representative sample of adults, a recent vitamin D RCT in older adults, and DEQAS. RESULTS: 24,25(OH)(2)D-3 contributed to the positive bias observed in some immunoassays relative to LC-MS/MSderived estimates for total 25(OH) D. A spiking experiment showed that the degree of cross-reactivity with 24,25(OH)(2)D was high and may underpin this positive bias. Adjustment for 24,25(OH)(2)D-3 concentration brought estimates closer to true values. Data from the vitamin D RCT showed that the ratio of 24,25(OH)(2)D-3 to 25(OH) D was associated with serum 25(OH) D-3 and with response of serum 25(OH) D to vitamin D supplementation. CONCLUSIONS: Our findings highlight that the effect of 24,25(OH)(2)D-3 in serum is a double-edged sword-an interferent for some immunoassays, yet potentially informative of nutritional status. (C) 2015 American Association for Clinical Chemistry C1 [Cashman, Kevin D.; Hayes, Aoife; Galvin, Karen] Natl Univ Ireland Univ Coll Cork, Sch Food & Nutr Sci, Vitamin Res Grp D, Cork, Ireland. [Cashman, Kevin D.] Natl Univ Ireland Univ Coll Cork, Dept Med, Cork, Ireland. [Merkel, Joyce; Sempos, Christopher T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Jones, Glenville; Kaufmann, Martin] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON, Canada. [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Carter, Graham D.] Univ London Imperial Coll Sci Technol & Med, Vitamin External Qual Assurance Scheme DEQAS Coor, London, England. [Durazo-Arvizu, Ramon A.] Loyola Univ, Stritch Sch Med, Dept Publ Hlth Sci, Chicago, IL 60611 USA. RP Cashman, KD (reprint author), Natl Univ Ireland Univ Coll Cork, Sch Food & Nutr Sci, Cork, Ireland. EM k.cashman@ucc.ie FU Higher Education Authority under its Programme for Research in Third Level Institutions (FoodIreland); Departement of Health Policy Research Programme [024/0049]; Irish Department of Agriculture, Food and the Marine under its Food for Health Research Initiative FX LC-MS/MS was funded by the Higher Education Authority under its Programme for Research in Third Level Institutions (FoodIreland). K. D. Cashman, Irish Department of Agriculture, Food and the Marine under its Food for Health Research Initiative (2007-2012), the Departement of Health Policy Research Programme (024/0049). NR 24 TC 16 Z9 16 U1 4 U2 12 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2015 VL 61 IS 4 BP 636 EP 645 DI 10.1373/clinchem.2014.234955 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CJ1SU UT WOS:000355265600013 PM 25710460 ER PT J AU Li, TS AF Li, Tiansen TI Leber Congenital Amaurosis Caused by Mutations in RPGRIP1 SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID CONE-ROD DYSTROPHY; REGULATOR (RPGR)-INTERACTING PROTEIN; GENE-THERAPY; PHOTORECEPTOR DEGENERATION; RETINAL DEGENERATION; MURINE MODEL; DOGS; IDENTIFICATION; MORPHOGENESIS; ASSOCIATION AB Recessive null mutations in retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1) gene are the cause of LCA6 and account for 5% to 6% of the total patient population. RPGRIP1 has an essential role in the photoreceptor connecting cilia, and photoreceptors lacking RPGRIP1 are unable to maintain the light sensing outer segments. As a result, patients lose retinal functions at an early age but retain photoreceptors in the central retina well into adulthood thus holding out the prospect for gene augmentation therapies. Laboratory studies in animal models have demonstrated efficacy of gene therapy in slowing disease progression. With further refinement in the design of the replacement gene construct, clinical trials for Leber congenital amaurosis (LCA) caused by RPGRIP1 mutations could be in the offing in the near future. C1 NEI, Retinal Cell Biol & Degenerat Sect, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. RP Li, TS (reprint author), NEI, Retinal Cell Biol & Degenerat Sect, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. EM tiansen.li@nih.gov NR 35 TC 0 Z9 1 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD APR PY 2015 VL 5 IS 4 AR a017384 DI 10.1101/cshperspect.a017384 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CJ0VX UT WOS:000355198300002 ER PT J AU Onozawa, M Goldberg, L Aplan, PD AF Onozawa, Masahiro Goldberg, Liat Aplan, Peter D. TI Landscape of Insertion Polymorphisms in the Human Genome SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE templated sequence insertion polymorphisms (TSIPs); mitochondria; polymorphism; human migration; DNA repair; LINE-1 retrotransposon ID HUMAN MITOCHONDRIAL PSEUDOGENES; DNA; EVOLUTION; ORIGIN; RETROTRANSPOSITION; VARIANTS; BREAKS AB Nucleotide substitutions, small (< 50 bp) insertions or deletions (indels), and large (> 50 bp) deletions are well-known causes of genetic variation within the human genome. We recently reported a previously unrecognized form of polymorphic insertions, termed templated sequence insertion polymorphism (TSIP), in which the inserted sequence was templated from a distant genomic region, and was inserted in the genome through reverse transcription of an RNA intermediate. TSIPs can be grouped into two classes based on nucleotide sequence features at the insertion junctions; class 1 TSIPs show target site duplication, polyadenylation, and preference for insertion at a 5'-TTTT/A-3' sequence, suggesting a LINE-1 based insertion mechanism, whereas class 2 TSIPs show features consistent with repair of a DNA double strand break by nonhomologous end joining. To gain a more complete picture of TSIPs throughout the human population, we evaluated whole-genome sequence from 52 individuals, and identified 171 TSIPs. Most individuals had 25-30 TSIPs, and common (present in > 20% of individuals) TSIPs were found in individuals throughout the world, whereas rare TSIPs tended to cluster in specific geographic regions. The number of rare TSIPs was greater than the number of common TSIPs, suggesting that TSIP generation is an ongoing process. Intriguingly, mitochondrial sequences were a frequent template for class 2 insertions, used more commonly than any nuclear chromosome. Similar to single nucleotide polymorphisms and indels, we suspect that these TSIPs may be important for the generation of human diversity and genetic diseases, and can be useful in tracking historical migration of populations. C1 [Onozawa, Masahiro; Goldberg, Liat; Aplan, Peter D.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Aplan, PD (reprint author), NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. EM aplanp@mail.nih.gov RI Aplan, Peter/K-9064-2016 FU intramural research program of the NCI, NIH; Japan Society for the Promotion of Science (JSPS), Postdoctoral Fellowships for Research Abroad program FX This work was supported by the intramural research program of the NCI, NIH. M.O. was supported by the Japan Society for the Promotion of Science (JSPS), Postdoctoral Fellowships for Research Abroad program. The authors thank Michael Kuehl, Javed Khan, Joshua Waterfall, and Paul Meltzer for insightful discussions. NR 26 TC 2 Z9 2 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PD APR PY 2015 VL 7 IS 4 BP 960 EP 968 DI 10.1093/gbe/evv043 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA CJ0EV UT WOS:000355148800003 PM 25745018 ER PT J AU Krupovic, M Zhi, N Li, JG Hu, GQ Koonin, EV Wong, S Shevchenko, S Zhao, KJ Young, NS AF Krupovic, Mart Zhi, Ning Li, Jungang Hu, Gangqing Koonin, Eugene V. Wong, Susan Shevchenko, Sofiya Zhao, Keji Young, Neal S. TI Multiple Layers of Chimerism in a Single-Stranded DNA Virus Discovered by Deep Sequencing SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE ssDNA viruses; virus evolution; origin of viruses; genetic recombination; metagenomics ID PHYLOGENETIC EVIDENCE; METAGENOMIC ANALYSIS; GIANT VIRUSES; SSDNA VIRUSES; RNA VIRUSES; RECOMBINATION; EVOLUTION; DIVERSITY; ORIGIN; REPLICATION AB Viruses with single-stranded (ss) DNA genomes infect hosts in all three domains of life and include many medically, ecologically, and economically important pathogens. Recently, a new group of ssDNA viruses with chimeric genomes has been discovered through viral metagenomics. These chimeric viruses combine capsid protein genes and replicative protein genes that, respectively, appear to have been inherited from viruses with positive-strand RNA genomes, such as tombusviruses, and ssDNA genomes, such as circoviruses, nanoviruses or geminiviruses. Here, we describe the genome sequence of a new representative of this virus group and reveal an additional layer of chimerism among ssDNA viruses. We show that not only do these viruses encompass genes for capsid proteins and replicative proteins that have distinct evolutionary histories, but also the replicative genes themselves are chimeras of functional domains inherited from viruses of different families. Our results underscore the importance of horizontal gene transfer in the evolution of ssDNA viruses and the role of genetic recombination in the emergence of novel virus groups. C1 [Krupovic, Mart] Inst Pasteur, Dept Microbiol, Paris, France. [Zhi, Ning; Li, Jungang; Wong, Susan; Shevchenko, Sofiya; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Hu, Gangqing; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Krupovic, M (reprint author), Inst Pasteur, Dept Microbiol, Paris, France. EM krupovic@pasteur.fr RI Krupovic, Mart/I-4209-2012 OI Krupovic, Mart/0000-0001-5486-0098 FU Intramural Research Program of the National Institute of Health, National Heart, Lung, and Blood Institute; National Library of Medicine FX This work was supported in part by the Intramural Research Program of the National Institute of Health, National Heart, Lung, and Blood Institute, and National Library of Medicine. NR 56 TC 9 Z9 9 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PD APR PY 2015 VL 7 IS 4 BP 993 EP 1001 DI 10.1093/gbe/evv034 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA CJ0EV UT WOS:000355148800006 PM 25840414 ER PT J AU Peng, Y Cooper, SK Li, Y Mei, JM Qiu, SW Borchert, GL Donald, SP Kung, HF Phang, JM AF Peng, Ying Cooper, Sandra K. Li, Yi Mei, Jay M. Qiu, Shuwei Borchert, Gregory L. Donald, Steven P. Kung, Hsiang-fu Phang, James M. TI Ornithine-delta-Aminotransferase Inhibits Neurogenesis During Xenopus Embryonic Development SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE Xenopus; embryos; development; neuralization; ventralization ID ENCODING DELTA(1)-PYRROLINE-5-CARBOXYLATE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; L-PROLINE TRANSPORTER; GYRATE ATROPHY; FUNCTIONAL CONSEQUENCES; RETINAL DEGENERATION; MISSENSE MUTATIONS; MOLECULAR-CLONING; NEURAL INDUCTION; HOMEOBOX GENE AB PURPOSE. In humans, deficiency of ornithine-delta-aminotransferase (OAT) results in progressive degeneration of the neural retina (gyrate atrophy) with blindness in the fourth decade. In this study, we used the Xenopus embryonic developmental model to study functions of the OAT gene on embryonic development. METHODS. We cloned and sequenced full-length OAT cDNA from Xenopus oocytes (X-OAT) and determined X-OAT expression in various developmental stages of Xenopus embryos and in a variety of adult tissues. The phenotype, gene expression of neural developmental markers, and enzymatic activity were detected by gain-of-function and loss-of-function manipulations. RESULTS. We showed that X-OAT is essential for Xenopus embryonic development, and overexpression of X-OAT produces a ventralized phenotype characterized by a small head, lack of axial structure, and defective expression of neural developmental markers. Using X-OAT mutants based on mutations identified in humans, we found that substitution of both Arg 180 and Leu 402 abrogated both X-OAT enzymatic activity and ability to modulate the developmental phenotype. Neurogenesis is inhibited by X-OAT during Xenopus embryonic development. CONCLUSIONS. Neurogenesis is inhibited by X-OAT during Xenopus embryonic development, but it is essential for Xenopus embryonic development. The Arg 180 and Leu 402 are crucial for these effects of the OAT molecule in development. C1 [Peng, Ying; Li, Yi; Qiu, Shuwei] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Neurol, Guangzhou 510275, Guangdong, Peoples R China. [Cooper, Sandra K.; Borchert, Gregory L.] NCI, Basic Res Program, Leidos Inc, NIH, Frederick, MD 21701 USA. [Mei, Jay M.; Donald, Steven P.; Phang, James M.] NCI, Metab & Canc Susceptibil Sect, Basic Res Lab, NIH, Frederick, MD 21701 USA. [Kung, Hsiang-fu] Chinese Univ Hong Kong, State Key Lab Oncol Southern China, Shatin, Hong Kong, Peoples R China. [Kung, Hsiang-fu] Chinese Univ Hong Kong, Ctr Emerging Infect Dis, Shatin, Hong Kong, Peoples R China. RP Peng, Y (reprint author), Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Neurol, Guangzhou 510275, Guangdong, Peoples R China. EM 2353352460@qq.com; phangj@mail.nih.gov FU National Natural Science Foundation of China (NSFC) from China [305705890, 31070953]; International Collaboration Program of Universities in Guangdong Province [2012gjhz001]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; Federal funds from the National Cancer Institute, NIH [HHSN27612080001] FX Supported in part by a grant from National Natural Science Foundation of China (NSFC) (305705890, 31070953) from China (YP); the International Collaboration Program of Universities in Guangdong Province (2012gjhz001 to YP); and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and has been funded in part with Federal funds from the National Cancer Institute, NIH under contract no. HHSN27612080001. The authors alone are responsible for the content and writing of the paper. NR 66 TC 1 Z9 1 U1 1 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2015 VL 56 IS 4 BP 2486 EP 2497 DI 10.1167/iovs.15-16509 PG 12 WC Ophthalmology SC Ophthalmology GA CJ1NP UT WOS:000355250700041 PM 25783604 ER PT J AU Anderson, WF Rosenberg, PS Prat, A Perou, CM Sherman, ME AF Anderson, William F. Rosenberg, Philip S. Prat, Aleix Perou, Charles M. Sherman, Mark E. TI RE: How Many Etiological Subtypes of Breast Cancer: Two, Three, Four, or More? Response SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Anderson, William F.; Rosenberg, Philip S.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [Sherman, Mark E.] NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Prat, Aleix] Vall dHebron Inst Oncol, Translat Genom Grp, Barcelona, Spain. [Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet & Pathol & Lab Med, Chapel Hill, NC 27599 USA. RP Anderson, WF (reprint author), NCI, Div Canc Epidemiol & Genet, Biostat Branch, 9609 Med Ctr Dr,Room 7E144, Bethesda, MD 20892 USA. EM wanderso@mail.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2015 VL 107 IS 4 AR djv029 DI 10.1093/jnci/djv029 PG 1 WC Oncology SC Oncology GA CI9IB UT WOS:000355082500019 ER PT J AU Kummar, S Williams, PM Lih, CJ Polley, EC Chen, AP Rubinstein, LV Zhao, YD Simon, RM Conley, BA Doroshow, JH AF Kummar, Shivaani Williams, P. Mickey Lih, Chih-Jian Polley, Eric C. Chen, Alice P. Rubinstein, Larry V. Zhao, Yingdong Simon, Richard M. Conley, Barbara A. Doroshow, James H. TI Application of Molecular Profiling in Clinical Trials for Advanced Metastatic Cancers SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PERSONALIZED MEDICINE; HETEROGENEITY; TUMORS AB There is growing interest in the application of molecular profiling, including sequencing, genotyping, and/or mRNA expression profiling, to the analysis of patient tumors with the objective of applying these data to inform therapeutic choices for patients with advanced cancers. Multiple clinical trials that are attempting to validate this personalized or precision medicine approach are in various stages of development and execution. Although preliminary data from some of these efforts have fueled excitement about the value and utility of these studies, their execution has also provoked many questions about the best way to approach complicating factors such as tumor heterogeneity and the choice of which genetic mutations to target. This commentary highlights some of the challenges confronting the clinical application of molecular tumor profiling and the various trial designs being utilized to address these challenges. Randomized trials that rigorously test patient response to molecularly targeted agents assigned based on the presence of a defined set of mutations in putative cancer-driving pathways are required to address some of the current challenges and to identify patients likely to benefit from this approach. C1 [Kummar, Shivaani; Polley, Eric C.; Chen, Alice P.; Rubinstein, Larry V.; Zhao, Yingdong; Simon, Richard M.; Conley, Barbara A.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Williams, P. Mickey; Lih, Chih-Jian] Leidos Biomedical Res Inc, Appl Dev Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Kummar, S (reprint author), Room 3A44M,31 Ctr Dr, Bethesda, MD 20892 USA. EM kummars@mail.nih.gov NR 19 TC 11 Z9 11 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2015 VL 107 IS 4 AR djv003 DI 10.1093/jnci/djv003 PG 6 WC Oncology SC Oncology GA CI9IB UT WOS:000355082500007 ER PT J AU Marcus, PM Prorok, PC Miller, AB DeVoto, EJ Kramer, BS AF Marcus, Pamela M. Prorok, Philip C. Miller, Anthony B. DeVoto, Emily J. Kramer, Barnett S. TI Conceptualizing Overdiagnosis in Cancer Screening SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PROSTATE-CANCER; RADICAL PROSTATECTOMY; NEUROBLASTOMA; PREVALENCE; AUTOPSY; MORTALITY; INFANTS AB The aim of cancer screening is to detect asymptomatic cancers whose treatment will result in extension of life, relative to length of life absent screening. Unfortunately, cancer screening also results in overdiagnosis, the detection of cancers that, in the absence of screening, would not present symptomatically during one's lifetime. Thus, their detection and subsequent treatment is unnecessary and detrimental. This definition of overdiagnosis, while succinct, does not capture the ways it can occur, and our interactions with patients, advocates, researchers, clinicians, and journalists have led us to believe that the concept of overdiagnosis is difficult to explain and, for some, difficult to accept. We propose a dichotomy, the "tumor-patient" classification, to aid in understanding overdiagnosis. The tumor category includes asymptomatic malignant disease that would regress spontaneously if left alone, as well as asymptomatic malignant disease that stagnates or progresses too slowly to be life threatening in even the longest of lifetimes. The patient category includes asymptomatic malignant disease that would progress quickly enough to be life threatening during a lifetime of typical length, but lacks clinical relevance because death due to another cause intercedes prior to what would have been the date of symptomatic diagnosis had screening not occurred. Cancer screening of most organs is likely to result in overdiagnosis of both types. However, the ratio of tumor-to patient-driven overdiagnosis almost certainly varies, and may vary drastically, by organ, screening modality, patient characteristics, and other factors. C1 [Prorok, Philip C.; Kramer, Barnett S.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. RP Marcus, PM (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E608, Bethesda, MD 20892 USA. EM marcusp@mail.nih.gov NR 18 TC 6 Z9 6 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2015 VL 107 IS 4 AR djv014 DI 10.1093/jnci/djv014 PG 4 WC Oncology SC Oncology GA CI9IB UT WOS:000355082500015 ER PT J AU McGlynn, KA Hagberg, K Chen, J Graubard, BI London, WT Jick, S Sahasrabuddhe, VV AF McGlynn, Katherine A. Hagberg, Katrina Chen, Jie Graubard, Barry I. London, W. Thomas Jick, Susan Sahasrabuddhe, Vikrant V. TI Statin Use and Risk for Primary Liver Cancer in the Clinical Practice Research Datalink SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PRACTICE RESEARCH DATABASE; CORONARY-HEART-DISEASE; C VIRUS-INFECTION; HEPATOCELLULAR-CARCINOMA; COA REDUCTASE; PRAVASTATIN USE; UNITED-STATES; METAANALYSIS; CHOLESTEROL; POPULATION AB Background: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely prescribed to reduce cholesterol levels. Studies have suggested that statins are associated with reduced risk for liver cancer, but much of the evidence is from regions of the world with high liver cancer incidence rates. The current study examined the statins-liver cancer relationship in a low-rate region and examined the effects of preexisting liver disease and diabetes on that association. Methods: A nested case-control study was conducted within the United Kingdom's Clinical Practice Research Datalink (CPRD). Persons diagnosed with primary liver cancer between 1988 and 2011 were matched to controls at a four-to-one ratio. Matches stratified on liver disease and on diabetes were also completed. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations of statins with liver cancer were estimated using conditional logistic regression. Results: In total, 1195 persons with primary liver cancer were matched to 4640 control patients. Statin use was associated with a statistically significantly reduced risk for liver cancer (ORadj = 0.55, 95% CI = 0.45 to 0.69), especially among current users (ORadj = 0.53, 95% CI = 0.42 to 0.66). The reduced risk was statistically significant in the presence (ORadj = 0.32, 95% CI = 0.17 to 0.57) and absence of liver disease (ORadj = 0.65, 95% CI = 0.52 to 0.81) and in the presence (ORadj = 0.30, 95% CI = 0.21 to 0.42) and absence of diabetes (ORadj = 0.66, 95% CI = 0.51 to 0.85). Conclusions: In the current study in a low-rate area, statin use was associated with a statistically significantly reduced risk for liver cancer overall. Risk was particularly reduced among persons with liver disease and persons with diabetes, suggesting that statin use may be especially beneficial in persons at elevated risk for liver cancer. C1 [McGlynn, Katherine A.; Chen, Jie; Graubard, Barry I.; Sahasrabuddhe, Vikrant V.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hagberg, Katrina; Jick, Susan] Boston Collaborat Drug Surveillance Program, Lexington, MA USA. [Hagberg, Katrina; Jick, Susan] Boston Univ, Sch Publ Hlth, Lexington, MA USA. [London, W. Thomas] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [London, W. Thomas] Hepatitis B Fdn, Doylestown, PA USA. [Sahasrabuddhe, Vikrant V.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. RP McGlynn, KA (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM mcglynnk@mail.nih.gov RI CPRD, CPRD/B-9594-2017 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. NR 46 TC 8 Z9 9 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2015 VL 107 IS 4 AR djv009 DI 10.1093/jnci/djv009 PG 10 WC Oncology SC Oncology GA CI9IB UT WOS:000355082500012 ER PT J AU Robbins, HA Pfeiffer, RM Shiels, MS Li, JM Hall, HI Engels, EA AF Robbins, Hilary A. Pfeiffer, Ruth M. Shiels, Meredith S. Li, Jianmin Hall, H. Irene Engels, Eric A. TI Excess Cancers Among HIV-Infected People in the United States SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; LUNG-CANCER; EUROPEAN COUNTRIES; PROSPECTIVE COHORT; ANAL CANCER; AIDS; RISK; BURDEN; LESIONS AB Background: Nearly 900 000 people in the United States are living with diagnosed human immunodeficiency virus (HIV) infection and therefore increased cancer risk. The total number of cancers occurring among HIV-infected people and the excess number above expected background cases are unknown. Methods: We derived cancer incidence rates for the United States HIV-infected and general populations from Poisson models applied to linked HIV and cancer registry data and from Surveillance, Epidemiology, and End Results program data, respectively. We applied these rates to estimates of people living with diagnosed HIV at mid-year 2010 to estimate total and expected cancer counts, respectively. We subtracted expected from total cancers to estimate excess cancers. Results: An estimated 7760 (95% confidence interval [CI] = 7330 to 8320) cancers occurred in 2010 among HIV-infected people, of which 3920 cancers (95% CI = 3480 to 4470) or 50% (95% CI = 48 to 54%) were in excess of expected. The most common excess cancers were non-Hodgkin's lymphoma (NHL; n = 1440 excess cancers, occurring in 88% excess), Kaposi's sarcoma (KS, n = 910, 100% excess), anal cancer (n = 740, 97% excess), and lung cancer (n = 440, 52% excess). The proportion of excess cancers that were AIDS defining (ie, KS, NHL, cervical cancer) declined with age and time since AIDS diagnosis (both P < .001). For anal cancer, 83% of excess cases occurred among men who have sex with men, and 71% among those living five or more years since AIDS onset. Among injection drug users, 22% of excess cancers were lung cancer, and 16% were liver cancer. Conclusions: The excess cancer burden in the US HIV population is substantial, and patterns across groups highlight opportunities for cancer control initiatives targeted to HIV-infected people. C1 [Robbins, Hilary A.; Pfeiffer, Ruth M.; Shiels, Meredith S.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Li, Jianmin; Hall, H. Irene] Ctr Dis Control & Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA. RP Robbins, HA (reprint author), 9609 Med Ctr Dr,6-E228, Bethesda, MD 20892 USA. EM hilary.robbins@jhmi.edu FU Intramural Research Program of the National Cancer Institute at the National Institutes of Health; Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: Connecticut [HHSN261201000024C]; Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: New Jersey [HHSN261201300021I, N01-PC-2013-00021]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Colorado [U58 DP000848-04]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Georgia [5U58DP003875-01]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Michigan [5U58DP000812-03]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: New Jersey [5U58/DP003931-02]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Texas [5U58DP000824-04]; state of New Jersey FX This research was supported by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health. The following cancer registries were supported by the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: Connecticut (HHSN261201000024C) and New Jersey (HHSN261201300021I, N01-PC-2013-00021). The following cancer registries were supported by the National Program of Cancer Registries of the Centers for Disease Control and Prevention: Colorado (U58 DP000848-04), Georgia (5U58DP003875-01), Michigan (5U58DP000812-03), New Jersey (5U58/DP003931-02), and Texas (5U58DP000824-04). The New Jersey Cancer Registry was also supported by the state of New Jersey. NR 40 TC 25 Z9 25 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2015 VL 107 IS 4 AR dju503 DI 10.1093/jnci/dju503 PG 8 WC Oncology SC Oncology GA CI9IB UT WOS:000355082500001 ER PT J AU Schully, SD Carrick, DM Mechanic, LE Srivastava, S Anderson, GL Baron, JA Berg, CD Cullen, J Diamandis, EP Doria-Rose, VP Goddard, KAB Hankinson, SE Kushi, LH Larson, EB McShane, LM Schilsky, RL Shak, S Skates, SJ Urban, N Kramer, BS Khoury, MJ Ransohoff, DF AF Schully, Sheri D. Carrick, Danielle M. Mechanic, Leah E. Srivastava, Sudhir Anderson, Garnet L. Baron, John A. Berg, Christine D. Cullen, Jennifer Diamandis, Eleftherios P. Doria-Rose, V. Paul Goddard, Katrina A. B. Hankinson, Susan E. Kushi, Lawrence H. Larson, Eric B. McShane, Lisa M. Schilsky, Richard L. Shak, Steven Skates, Steven J. Urban, Nicole Kramer, Barnett S. Khoury, Muin J. Ransohoff, David F. TI Leveraging Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID OVARIAN-CANCER; ALGORITHM ROCA; BIOMARKER; RISK; SPECIMENS; ACCURACY; OPINION; DESIGN; MODELS; LUNG AB Validation of early detection cancer biomarkers has proven to be disappointing when initial promising claims have often not been reproducible in diagnostic samples or did not extend to prediagnostic samples. The previously reported lack of rigorous internal validity (systematic differences between compared groups) and external validity (lack of generalizability beyond compared groups) may be effectively addressed by utilizing blood specimens and data collected within well-conducted cohort studies. Cohort studies with prediagnostic specimens (eg, blood specimens collected prior to development of clinical symptoms) and clinical data have recently been used to assess the validity of some early detection biomarkers. With this background, the Division of Cancer Control and Population Sciences (DCCPS) and the Division of Cancer Prevention (DCP) of the National Cancer Institute (NCI) held a joint workshop in August 2013. The goal was to advance early detection cancer research by considering how the infrastructure of cohort studies that already exist or are being developed might be leveraged to include appropriate blood specimens, including prediagnostic specimens, ideally collected at periodic intervals, along with clinical data about symptom status and cancer diagnosis. Three overarching recommendations emerged from the discussions: 1) facilitate sharing of existing specimens and data, 2) encourage collaboration among scientists developing biomarkers and those conducting observational cohort studies or managing healthcare systems with cohorts followed over time, and 3) conduct pilot projects that identify and address key logistic and feasibility issues regarding how appropriate specimens and clinical data might be collected at reasonable effort and cost within existing or future cohorts. C1 [Schully, Sheri D.; Carrick, Danielle M.; Mechanic, Leah E.; Doria-Rose, V. Paul; Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Srivastava, Sudhir; Kramer, Barnett S.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [McShane, Lisa M.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Anderson, Garnet L.; Urban, Nicole] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Baron, John A.; Ransohoff, David F.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Berg, Christine D.] Johns Hopkins Med, Dept Radiat Oncol, Baltimore, MD USA. [Cullen, Jennifer] Ctr Prostate Dis Res, Dept Def, Rockville, MD USA. [Diamandis, Eleftherios P.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Goddard, Katrina A. B.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. [Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Kushi, Lawrence H.] Kaiser Permanente, Div Res, Oakland, CA USA. [Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA. [Schilsky, Richard L.] Amer Soc Clin Oncol, Alexandria, VA USA. [Shak, Steven] Genom Hlth Inc, Redwood City, CA USA. [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Gen, Atlanta, GA USA. RP Schully, SD (reprint author), 9609 Med Ctr Dr 4E106, Rockville, MD 20850 USA. EM schullys@mail.nih.gov OI Doria-Rose, Vincent/0000-0002-8802-5143 NR 31 TC 7 Z9 7 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2015 VL 107 IS 4 AR djv012 DI 10.1093/jnci/djv012 PG 7 WC Oncology SC Oncology GA CI9IB UT WOS:000355082500014 ER PT J AU Song, MY Nishihara, R Wu, KN Qian, ZR Kim, SA Sukawa, Y Mima, K Inamura, K Masuda, A Yang, JH Fuchs, CS Giovannucci, EL Ogino, S Chan, AT AF Song, Mingyang Nishihara, Reiko Wu, Kana Qian, Zhi Rong Kim, Sun A. Sukawa, Yasutaka Mima, Kosuke Inamura, Kentaro Masuda, Atsuhiro Yang, Juhong Fuchs, Charles S. Giovannucci, Edward L. Ogino, Shuji Chan, Andrew T. TI Marine omega-3 Polyunsaturated Fatty Acids and Risk for Colorectal Cancer According to Microsatellite Instability SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DNA MISMATCH REPAIR; FOOD FREQUENCY QUESTIONNAIRE; DIETARY-INTAKE; MOLECULAR-FEATURES; ULCERATIVE-COLITIS; CELL-PROLIFERATION; WOMEN; INFLAMMATION; N-3; MEN AB Background: Chronic inflammation is involved in the development of colorectal cancer (CRC) and microsatellite instability (MSI), a distinct phenotype of CRC. Experimental evidence indicates an anti-inflammatory and antineoplastic effect of marine omega-3 polyunsaturated fatty acids (PUFAs). However, epidemiologic data remain inconclusive. Methods: We investigated whether the association between marine omega-3 PUFAs and CRC varies by MSI-defined subtypes of tumors in the Nurses' Health Study and Health Professionals Follow-up Study. We documented and classified 1125 CRC cases into either MSI-high tumors, in which 30% or more of the 10 microsatellite markers demonstrated instability, or microsatellite-stable (MSS) tumors. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of MSS tumors and MSI-high tumors in relation to marine omega-3 PUFA intake. All statistical tests were two-sided. Results: Marine omega-3 PUFA intake was not associated with overall incidence of CRC. However, a statistically significant difference was detected by MSI status (P-heterogeneity = .02): High marine omega-3 PUFA intake was associated with a lower risk for MSI-high tumors (comparing >= 0.30g/d with <0.10g/d: multivariable HR = 0.54, 95% CI = 0.35 to 0.83, P-linearity = .03) but not MSS tumors (HR = 0.97, 95% CI = 0.78 to 1.20, P-linearity = .28). This differential association appeared to be independent of CpG island methylator phenotype and BRAF mutation status. Conclusions: High marine omega-3 PUFA intake is associated with lower risk for MSI-high CRC but not MSS tumors, suggesting a potential role of omega-3 PUFAs in protection against CRC through DNA mismatch repair. Further research is needed to confirm our findings and elucidate potential underlying mechanisms. C1 [Song, Mingyang; Nishihara, Reiko; Wu, Kana; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. [Song, Mingyang; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Nishihara, Reiko; Qian, Zhi Rong; Kim, Sun A.; Sukawa, Yasutaka; Mima, Kosuke; Masuda, Atsuhiro; Yang, Juhong; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nishihara, Reiko; Qian, Zhi Rong; Kim, Sun A.; Sukawa, Yasutaka; Mima, Kosuke; Masuda, Atsuhiro; Yang, Juhong; Fuchs, Charles S.; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Inamura, Kentaro] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Channing Div Network Med, Dept Med,Brigham & Womens Hosp, Boston, MA 02215 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02215 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, 450 Brookline Ave,Room M422, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu; achan@partners.org RI Song, Mingyang/M-6701-2013 OI Song, Mingyang/0000-0002-1324-0316 FU National Institutes of Health [P01 CA87969, UM1 CA167552, P50 CA127003, R01 CA137178, R01 CA151993, K24 DK 098311, K07 CA190673, 1U54CA155626]; Agrusa Fund for Colorectal Cancer Research FX This work was supported by the National Institutes of Health (P01 CA87969, UM1 CA167552, P50 CA127003, R01 CA137178, R01 CA151993, K24 DK 098311, K07 CA190673, and 1U54CA155626) and by a grant from the Agrusa Fund for Colorectal Cancer Research. NR 56 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2015 VL 107 IS 4 AR djv007 DI 10.1093/jnci/djv007 PG 8 WC Oncology SC Oncology GA CI9IB UT WOS:000355082500010 ER PT J AU Umar, A Richmond, E Kramer, BS AF Umar, Asad Richmond, Ellen Kramer, Barnett S. TI Colorectal Cancer Prevention and Fishful Thinking SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID FATTY-ACIDS; DIETARY-INTAKE; RISK; DEFICIENCY; EXPRESSION; MORTALITY; ASPIRIN; OMEGA-6; ESKIMOS; PATTERN C1 [Umar, Asad; Richmond, Ellen; Kramer, Barnett S.] NCI, Canc Prevent Div, Rockville, MD 20852 USA. RP Umar, A (reprint author), NCI, Canc Prevent Div, 9609 Med Ctr Dr, Rockville, MD 20852 USA. EM Asad.Umar@nih.gov NR 17 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2015 VL 107 IS 4 AR djv052 DI 10.1093/jnci/djv052 PG 2 WC Oncology SC Oncology GA CI9IB UT WOS:000355082500027 ER PT J AU Malone, BJ Scott, BH Semple, MN AF Malone, Brian J. Scott, Brian H. Semple, Malcolm N. TI Diverse cortical codes for scene segmentation in primate auditory cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE scene analysis; encoding; decoding; cortex; primate ID SUPERIOR PARAOLIVARY NUCLEUS; BIG BROWN BAT; SOUND-DURATION SELECTIVITY; AWAKE RHESUS MACAQUES; INFERIOR COLLICULUS; RESPONSE PROPERTIES; CORRELATED VARIABILITY; TEMPORAL COHERENCE; BAYESIAN-INFERENCE; STIMULUS-DURATION AB The temporal coherence of amplitude fluctuations is a critical cue for segmentation of complex auditory scenes. The auditory system must accurately demarcate the onsets and offsets of acoustic signals. We explored how and how well the timing of onsets and offsets of gated tones are encoded by auditory cortical neurons in awake rhesus macaques. Temporal features of this representation were isolated by presenting otherwise identical pure tones of differing durations. Cortical response patterns were diverse, including selective encoding of onset and offset transients, tonic firing, and sustained suppression. Spike train classification methods revealed that many neurons robustly encoded tone duration despite substantial diversity in the encoding process. Excellent discrimination performance was achieved by neurons whose responses were primarily phasic at tone offset and by those that responded robustly while the tone persisted. Although diverse cortical response patterns converged on effective duration discrimination, this diversity significantly constrained the utility of decoding models referenced to a spiking pattern averaged across all responses or averaged within the same response category. Using maximum likelihood-based decoding models, we demonstrated that the spike train recorded in a single trial could support direct estimation of stimulus onset and offset. Comparisons between different decoding models established the substantial contribution of bursts of activity at sound onset and offset to demarcating the temporal boundaries of gated tones. Our results indicate that relatively few neurons suffice to provide temporally precise estimates of such auditory "edges," particularly for models that assume and exploit the heterogeneity of neural responses in awake cortex. C1 [Malone, Brian J.] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA. [Scott, Brian H.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Semple, Malcolm N.] NYU, Ctr Neural Sci, New York, NY 10003 USA. RP Malone, BJ (reprint author), Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA. EM brian.malone@ucsf.edu OI Scott, Brian/0000-0003-3949-9737 FU National Institute of Mental Health Grant [MH-12993-02]; National Institutes of Health/Deafness and Communication Disorders Grant [DC-011843]; National Institute on Deafness and Other Communication Disorders Grant [DC-05287-01]; James Arthur Fellowship from New York University; W. M. Keck Foundation FX B. J. Malone was supported by National Institute of Mental Health Grant MH-12993-02 and National Institutes of Health/Deafness and Communication Disorders Grant DC-011843. B. H. Scott was supported by National Institute on Deafness and Other Communication Disorders Grant DC-05287-01 and a James Arthur Fellowship from New York University. M. N. Semple was supported by the W. M. Keck Foundation. NR 110 TC 3 Z9 3 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR 1 PY 2015 VL 113 IS 7 BP 2934 EP 2952 DI 10.1152/jn.01054.2014 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA CI8EA UT WOS:000355000900087 PM 25695655 ER PT J AU Chauhan, G Adams, HHH Bis, JC Weinstein, G Yu, L Toglhofer, AM Smith, AV van der Lee, SJ Gottesmanm, RF Thomson, R Wang, J Yang, Q Niessen, WJ Lopez, OL Becker, JT Phan, TG Beare, RJ Arfanakis, K Fleischman, D Vernooij, MW Mazoyer, B Schmidt, H Srikanth, V Knopman, DS Jack, CR Amouyel, P Hofman, A DeCarli, C Tzourio, C van Duijnc, CM Bennett, DA Schmidt, R Longstreth, WT Mosley, TH Fornage, M Launer, LJ Seshadri, S Ikramc, MA Debette, S AF Chauhan, Ganesh Adams, Hieab H. H. Bis, Joshua C. Weinstein, Galit Yu, Lei Toglhofer, Anna Maria Smith, Albert Vernon van der Lee, Sven J. Gottesmanm, Rebecca F. Thomson, Russell Wang, Jing Yang, Qiong Niessen, Wiro J. Lopez, Oscar L. Becker, James T. Phan, Thanh G. Beare, Richard J. Arfanakis, Konstantinos Fleischman, Debra Vernooij, Meike W. Mazoyer, Bernard Schmidt, Helena Srikanth, Velandai Knopman, David S. Jack, Clifford R., Jr. Amouyel, Philippe Hofman, Albert DeCarli, Charles Tzourio, Christophe van Duijnc, Cornelia M. Bennett, David A. Schmidt, Reinhold Longstreth, William T., Jr. Mosley, Thomas H. Fornage, Myriam Launer, Lenore J. Seshadri, Sudha Ikramc, M. Arfan Debette, Stephanie TI Association of Alzheimer's disease GWAS loci with MRI markers of brain aging SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer; MRI-Markers; Genetic risk score; GWAS; Hippocampal volume ID GENOME-WIDE ASSOCIATION; APOLIPOPROTEIN-E EPSILON-4; SAMPLE-SIZE REQUIREMENTS; HIPPOCAMPAL VOLUME; COMMON VARIANTS; IDENTIFIES VARIANTS; GENETIC-VARIATION; E GENOTYPES; 4 ALLELE; METAANALYSIS AB Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta +/- SE = -0.047 +/- 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons. (C) 2015 Elsevier Inc. All rights reserved. C1 [Chauhan, Ganesh; Tzourio, Christophe; Debette, Stephanie] Univ Bordeaux, INSERM U897, F-33076 Bordeaux, France. [Chauhan, Ganesh; Debette, Stephanie] Univ Bordeaux, F-33076 Bordeaux, France. [Adams, Hieab H. H.; van der Lee, Sven J.; Vernooij, Meike W.; Hofman, Albert; van Duijnc, Cornelia M.; Ikramc, M. Arfan] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Adams, Hieab H. H.; Niessen, Wiro J.; Vernooij, Meike W.; Ikramc, M. Arfan] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Weinstein, Galit; Seshadri, Sudha; Debette, Stephanie] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02215 USA. [Weinstein, Galit; Wang, Jing; Yang, Qiong; Seshadri, Sudha] Framingham Heart Dis Epidemiol Study, Boston, MA USA. [Yu, Lei; Arfanakis, Konstantinos; Fleischman, Debra; Bennett, David A.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA. [Yu, Lei; Bennett, David A.] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA. [Toglhofer, Anna Maria; Schmidt, Helena] Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria. [Smith, Albert Vernon] Iceland Heart Assoc, Reykjavik, Iceland. [Smith, Albert Vernon] Univ Iceland, Dept Med, Reykjavik, Iceland. [Gottesmanm, Rebecca F.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Gottesmanm, Rebecca F.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Thomson, Russell; Srikanth, Velandai] Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas, Australia. [Wang, Jing; Yang, Qiong] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA. [Lopez, Oscar L.; Becker, James T.] Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh, PA 15260 USA. [Lopez, Oscar L.; Becker, James T.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Becker, James T.] Univ Pittsburgh, Dept Psychol, Sch Med, Pittsburgh, PA 15260 USA. [Phan, Thanh G.; Beare, Richard J.; Srikanth, Velandai] Monash Univ, Dept Med, Southern Clin Sch, Stroke & Ageing Res Ctr, Melbourne, Vic 3004, Australia. [Beare, Richard J.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Dev Imaging Grp, Parkville, Vic 3052, Australia. [Arfanakis, Konstantinos] Illinois Inst Technol, Dept Biomed Engn, Chicago, IL USA. [Mazoyer, Bernard] Univ Bordeaux, Grp Imagerie Neurofonctionnelle, UMR5296, CNRS,CEA, Bordeaux, France. [Knopman, David S.] Mayo Clin, Dept Neurol, Coll Med, Rochester, MN USA. [Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Coll Med, Rochester, MN USA. [Amouyel, Philippe] Inst Pasteur, Dept Epidemiol & Publ Hlth, F-59019 Lille, France. [Amouyel, Philippe] INSERM, U744, F-59045 Lille, France. [Amouyel, Philippe] Univ Lille 2, Lille, France. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [van Duijnc, Cornelia M.; Ikramc, M. Arfan] Netherlands Consortium Hlth Aging, Leiden, Netherlands. [van Duijnc, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands. [Schmidt, Reinhold] Med Univ Graz, Dept Neurol Clin Div Neurogeriatr, Graz, Austria. [Longstreth, William T., Jr.] Univ Washington, Dept Neurol & Epidemiol, Seattle, WA 98195 USA. [Mosley, Thomas H.] Univ Mississippi, Dept Med Geriatr Gerontol, Med Ctr, Jackson, MS 39216 USA. [Fornage, Myriam] Univ Texas Houston, Ctr Human Genet, Hlth Sci Ctr, Houston, TX USA. [Fornage, Myriam] Univ Texas Houston, Inst Mol Med, Hlth Sci Ctr, Houston, TX USA. [Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Natl Inst Hlth, Bethesda, MD 20892 USA. [Debette, Stephanie] Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France. RP Debette, S (reprint author), Univ Bordeaux, Ctr Inserm U897, Serv Neuroepidemiol, Batiment ISPED Case 11,146 Rue Leo Saignat, F-33076 Bordeaux, France. EM sdebette@bu.edu RI Smith, Albert/K-5150-2015; Tzourio, christophe/B-4015-2009; Thomson, Russell/H-5653-2012; Jack, Clifford/F-2508-2010; Vernooij, Meike/E-4061-2016; OI Smith, Albert/0000-0003-1942-5845; Tzourio, christophe/0000-0002-6517-2984; Thomson, Russell/0000-0003-4949-4120; Seshadri, Sudha/0000-0001-6135-2622; Jack, Clifford/0000-0001-7916-622X; Arfanakis, Konstantinos/0000-0001-9705-597X; Adams, Hieab/0000-0003-3687-2508 FU NIA [N01-AG-12100]; NEI; NIDCD; NHLBI; NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694, R01HL7825]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C, R01 AG040039, R21 NS076827, P20 MD006886]; NIH Roadmap for Medical Research; NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC15103, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393]; National Institute of Neurological Disorders and Stroke (NINDS); Austrian Science Fond (FWF) [P20545-P05, P13180]; Medical University of Graz; Framingham Heart Study's National Heart, Lung, and Blood Institute [N01-HC-25195]; Affymetrix, Inc for genotyping services [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; National Institute on Aging [R01 AG08122, AG033193, P30 AG0101029, P30AG10161, R01AG17917, R01AG15819]; National Institute of Neurological Disorders and Stroke [R01 NS17950]; Illinois Department of Public Health; Netherlands Organization of Scientific Research NWO [175.010.2005.011]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]; Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for Scientific Research (NWO); Netherlands Organization for the Health Research and Development (ZonMw) [916.13.054]; Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; Internationale Stichting Alzheimer Onderzoek; National Health and Medical Research Council (NHMRC) [403000, 491109, 606543]; Wicking Dementia Education and Research Centre, Hobart; NHMRC/National Heart Foundation Career Development Fellowship [606544]; Fondation pour la Recherche Medicale; Caisse Nationale Maladie des Travailleurs Salaries; Direction Generale de la Sante; Mutuelle Generale de l'Education Nationale (MGEN); Institut de la Longevite; Conseils Regionaux of Aquitaine and Bourgogne; Fondation de France; Ministry of Research-INSERM Programme "Cohortes et collections de donnees biologiques"; Eisai; National Foundation for Alzheimer's Disease and Related Disorders; Institut Pasteur de Lille; Centre National de Genotypage; Fondation Leducq; Agence Nationale de la Recherche (Chaire d'Excellence); [UL1RR025005]; [HL093029] FX Aging Gene-Environment Susceptibility-Reykjavik Study: The research has been funded by NIA contract N01-AG-12100 with contributions from NEI, NIDCD, and NHLBI, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament).; The Atherosclerosis Risk in Communities Study: The research is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694 and R01HL7825; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health (UL1RR025005) and NIH Roadmap for Medical Research. Funds for these projects were also supported by grant HL093029 to Myriam Fornage.; Cardiovascular Health Study: This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC15103; and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, and R01HL120393 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS).; The Austrian Stroke Prevention Study: The research reported in this article was funded by the Austrian Science Fond (FWF) grant number P20545-P05 and P13180. The Medical University of Graz supports the databank of the ASPS. The authors thank the staff and the participants of the ASPS for their valuable contributions. The authors thank Birgit Reinhart for her long-term administrative commitment and Ing Johann Semmler for the technical assistance at creating the DNA bank.; Erasmus Rucphen Family Study: This study is financially supported by the Netherlands Organization for Scientific Research (NWO), the Internationale Stichting Alzheimer Onderzoek (ISAO), the Hersenstichting Nederland (HSN), and the Centre for Medical Systems Biology (CMSB) in the framework of the Netherlands Genomics Initiative (NGI). The authors thank the participants from the Genetic Research in Isolated Populations, Erasmus Rucphen Family who made this work possible.; Framingham Heart Study: This work was supported by the Framingham Heart Study's National Heart, Lung, and Blood Institute contract (N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. It was also funded by grants from the National Institute on Aging (R01 AG08122, AG033193, P30 AG0101029) and the National Institute of Neurological Disorders and Stroke (R01 NS17950).; The Religious Order Study (ROS) and Rush Memory and Aging Project (R-MAP): The R-MAP and ROS data used in this article was supported by National Institute on Aging grants P30AG10161, R01AG17917, and R01AG15819, National Institutes of Health grants (R01 AG040039, R21 NS076827, P20 MD006886) and the Illinois Department of Public Health.; The Rotterdam Study: The GWA database of the Rotterdam Study was funded through the Netherlands Organization of Scientific Research NWO (nr. 175.010.2005.011). This study was further supported by the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project nr. 050-060-810. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University, Rotterdam; the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for the Health Research and Development (ZonMw; Veni-grant 916.13.054), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), the Municipality of Rotterdam, and the Internationale Stichting Alzheimer Onderzoek.; The Tasmanian Study of Gait and Cognition (TASCOG) is supported by Project Grants from the National Health and Medical Research Council (NHMRC IDs 403000, 491109, 606543), and a grant from the Wicking Dementia Education and Research Centre, Hobart. Velandai Srikanth is supported by an NHMRC/National Heart Foundation Career Development Fellowship (ID 606544).; Three City Study (3C): The authors thank the staff and the participants of the 3C Study for their important contributions. The 3C Study is conducted under a partnership agreement between the Institut National de la Sante et de la Recherche Medicale (INSERM), the Victor Segalen-Bordeaux II University, and Sanofi-Aventis. The Fondation pour la Recherche Medicale funded the preparation and initiation of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, Mutuelle Generale de l'Education Nationale (MGEN), Institut de la Longevite, Conseils Regionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research-INSERM Programme "Cohortes et collections de donnees biologiques." Lille Genopole received an unconditional grant from Eisai. The authors thank A. Boland (Centre National de Genotypage) for her technical help in preparing the DNA samples for analyses. This work was supported by the National Foundation for Alzheimer's Disease and Related Disorders, the Institut Pasteur de Lille and the Centre National de Genotypage. Ganesh Chauhan and Stephanie Debette are supported by a grant from the Fondation Leducq and the Agence Nationale de la Recherche (Chaire d'Excellence). NR 46 TC 9 Z9 10 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2015 VL 36 IS 4 AR 1765.e7 DI 10.1016/j.neurobiolaging.2014.12.028 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA CI9MW UT WOS:000355095300021 PM 25670335 ER PT J AU Chio, A Mora, G Sabatelli, M Caponnetto, C Traynor, BJ Johnson, JO Nalls, MA Calvo, A Moglia, C Borghero, G Monsurro, MR La Bella, V Volanti, P Simone, I Salvi, F Logullo, FO Nilo, R Battistini, S Mandrioli, J Tanel, R Murru, MR Mandich, P Zollino, M Conforti, FL Brunetti, M Barberis, M Restagno, G Penco, S Lunetta, C AF Chio, Adriano Mora, Gabriele Sabatelli, Mario Caponnetto, Claudia Traynor, Bryan J. Johnson, Janel O. Nalls, Mike A. Calvo, Andrea Moglia, Cristina Borghero, Giuseppe Monsurro, Maria Rosaria La Bella, Vincenzo Volanti, Paolo Simone, Isabella Salvi, Fabrizio Logullo, Francesco O. Nilo, Riva Battistini, Stefania Mandrioli, Jessica Tanel, Raffaella Murru, Maria Rita Mandich, Paola Zollino, Marcella Conforti, Francesca L. Brunetti, Maura Barberis, Marco Restagno, Gabriella Penco, Silvana Lunetta, Christian CA ITALSGEN Consortium TI CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients SO NEUROBIOLOGY OF AGING LA English DT Article DE Amyotrophic lateral sclerosis; Familial; Sporadic; CHCHD10 ID CHCHD10; DIAGNOSIS; CRITERIA; GENE AB Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) comorbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n = 64) and apparently sporadic ALS (n = 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in 2 unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHCHD10 mutations account for similar to 1% of Italian ALS patients and are a cause of disease in subjects without dementia or other atypical clinical signs. (C) 2015 Elsevier Inc. All rights reserved. C1 [Chio, Adriano; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Barberis, Marco] Univ Torino, ALS Ctr, Rita Levi Montalcini Dept Neurosci Neurol 2, I-10126 Turin, Italy. [Chio, Adriano; Calvo, Andrea] Univ Citta Salute & Sci, Azienda Osped, Turin, Italy. [Mora, Gabriele] IRCCS, Dept Neurol Rehabil, Fdn Salvatore Maugeri, Ist Sci Milan, Milan, Italy. [Sabatelli, Mario] Catholic Univ, Neurol Inst, Rome, Italy. [Sabatelli, Mario] ICOMM Assoc ALS Res, Rome, Italy. [Caponnetto, Claudia; Mandich, Paola] Univ Genoa, Univ San Martino IST, IRCCS Azienda Osped, Dept Neurosci Ophthalmol Genet Rehabil & Chid Hlt, I-16126 Genoa, Italy. [Traynor, Bryan J.; Johnson, Janel O.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Nalls, Mike A.] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Borghero, Giuseppe] Azienda Univ, Dept Neurol, Osped Cagliari, Cagliari, Italy. [Borghero, Giuseppe] Univ Cagliari, Cagliari, Italy. [Monsurro, Maria Rosaria] Univ Naples 2, Dept Neurol Sci, Naples, Italy. [La Bella, Vincenzo] Bio Ne C Univ Palermo, ALS Clin Res Ctr, Palermo, Italy. [Volanti, Paolo] IRCCS, Salvatore Maugeri Fdn, ALS Ctr, Neurorehabilitat Unit,Sci Inst Mistretta, Mistretta, Italy. [Simone, Isabella; ITALSGEN Consortium] Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy. [Salvi, Fabrizio] IRCCS, Dept Neurol, Ctr Diag & Cure Rare Dis, Inst Neurol Sci, Bologna, Italy. [Logullo, Francesco O.] Marche Polytech Univ, Neurol Clin, Ancona, Italy. [Nilo, Riva] IRCCS, San Raffaele Sci Inst, Dept Neurol, Milan, Italy. [Nilo, Riva] IRCCS, San Raffaele Sci Inst, Inst Expt Neurol INSPE, Milan, Italy. [Battistini, Stefania] Univ Siena, Dept Med Surg & Neurol Sci, I-53100 Siena, Italy. [Mandrioli, Jessica] Univ Modena, S Agostino Estense Hosp, Dept Neurosci, I-41100 Modena, Italy. [Tanel, Raffaella] Santa Chiara Hosp, Dept Neurol, Trento, Italy. [Murru, Maria Rita] Univ Cagliari, ASL Cagliari 8, Multiple Sclerosis Ctr, Cagliari, Italy. [Murru, Maria Rita] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Cagliari, Italy. [Zollino, Marcella] Univ Cattolica Sacro Cuore, Inst Med Genet, Rome, Italy. [Conforti, Francesca L.] CNR, Inst Neurol Sci, Cosenza, Italy. [Brunetti, Maura; Barberis, Marco; Restagno, Gabriella] Univ Citta Salute & Sci, Azienda Osped, Mol Genet Lab, Turin, Italy. [Penco, Silvana] Osped Niguarda Ca Granda, Dept Lab Med Med Genet, Milan, Italy. [Lunetta, Christian] Serena Onlus Fdn, NEuroMuscular Omnicenter, Milan, Italy. RP Chio, A (reprint author), Univ Torino, ALS Ctr, Rita Levi Montalcini Dept Neurosci Neurol 2, Via Cherasco 15, I-10126 Turin, Italy. EM achio@usa.net RI MANDRIOLI, JESSICA/K-7235-2016; Moglia, Cristina/K-4142-2016; Conforti, Francesca Luisa/K-8877-2016; mancardi, giovanni luigi/K-8656-2016; Lunetta, Christian/K-9214-2016; La Bella, Vincenzo/H-4532-2012; Mazzei, Rosalucia/G-3874-2014; Battistini, Stefania/N-2596-2015; Mosca, Lorena/K-4015-2016; Calvo, Andrea/K-4141-2016; LOGROSCINO, GIANCARLO/K-5148-2016; Spataro, Rossella/B-3656-2016 OI MANDRIOLI, JESSICA/0000-0002-9244-9782; Sabatelli, Mario/0000-0001-6635-4985; Moglia, Cristina/0000-0001-7377-7222; Conforti, Francesca Luisa/0000-0001-8364-1783; mancardi, giovanni luigi/0000-0001-8427-118X; Chio, Adriano/0000-0001-9579-5341; Riva, Nilo/0000-0002-0513-9517; Ilardi, Antonio/0000-0002-8305-0518; Marrosu, Maria Giovanna/0000-0003-2334-2081; Lunetta, Christian/0000-0002-4788-1875; Mazzei, Rosalucia/0000-0001-6619-6075; Simone, Isabella Laura/0000-0002-7429-3091; Cammarosano, Stefania/0000-0002-0981-5252; Penco, Silvana/0000-0003-1050-095X; Battistini, Stefania/0000-0003-2887-7624; Mosca, Lorena/0000-0002-6767-2368; Calvo, Andrea/0000-0002-5122-7243; LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Spataro, Rossella/0000-0002-8910-3131 FU Packard Centre for ALS Research at Johns Hopkins; Fondazione Vialli e Mauro Onlus; Compagnia di San Paolo; European Community's Health Seventh Framework Programme [259867]; Joint Programme-Neurodegenerative Disease Research; Italian Health Ministry; Italian Ministry of University and Research; Fondazione Mario e Anna Magnetto; Associazione Piemontese per l'Assistenza alla Sclerosi Laterale Amiotrofica (APASLA); Intramural Research Programs of the National Institute on Aging [Z01-AG000949-02]; US National Institutes of Health (NIH) FX Dr Chio had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors thank the patient and her family for having collaborated to this study. The work was also supported by the Packard Centre for ALS Research at Johns Hopkins, Fondazione Vialli e Mauro Onlus, Compagnia di San Paolo, European Community's Health Seventh Framework Programme (FP7/2007-2013) under grant agreement #259867, the Joint Programme-Neurodegenerative Disease Research (Sophia Project, granted by the Italian Health Ministry, and Strength Project, granted by the Italian Ministry of University and Research), the Fondazione Mario e Anna Magnetto, and the Associazione Piemontese per l'Assistenza alla Sclerosi Laterale Amiotrofica (APASLA). This work was supported in part by the Intramural Research Programs of the National Institute on Aging (Z01-AG000949-02), US National Institutes of Health (NIH). ITALSGEN consortium: Fabio Giannini, Claudia Ricci, Gianluigi Mancardi, Ilaria Bartolomei, Massimo Corbo, Amelia Conte, Marco Luigetti, Serena Lattante, Giuseppe Marangi, Irene Ossola, Giancarlo Logroscino, Gioacchino Tedeschi, Maura Pugliatti, Giuseppe Lauria Pinter, Shannon Glynn, J. Raphael Gibbs, Stefania Cammarosano, Antonio Canosa, Umberto Manera, Davide Bertuzzo, Altonio Ilardi, Kalliopi Marinou, Riccardo Sideri, Fabrizio Pisano, Rossella Spataro, Tiziana Colletti, Gianluca Floris, Antonino Cannas, Valeria Piras, Francesco Marrosu, Maria Giovanna Marrosu, Leslie D. Parish, Anna Ticca, Angelo Pirisi, Enzo Ortu, Tea B. Cau, Daniela Loi, Sebastiano Traccis, Nicola Fini, Eleni Georgoulopoulou, Federico Casale, Giuseppe Marrali, Giuseppe Fuda, Paolina Solamone, Eleonora Maestri, Rosalucia Mazzei, Viviana Cristillo, Roberta Puddu, Emanuela Costantino, Carla Pani, Carla Caredda, Paola Origone, Lorena Mosca, Margherita Capasso, Mara Turri, Antonio Petrucci, Luico Tremolizzo, and Marialaura Santarelli. The study has been approved by the institutional review board of each participating center. All authors have reviewed the contents of the article being submitted, approve of its contents, and validate the accuracy of the data. NR 9 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2015 VL 36 IS 4 AR 1767.e3 DI 10.1016/j.neurobiolaging.2015.01.017 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA CI9MW UT WOS:000355095300025 PM 25726362 ER PT J AU Fujii, T Boudreau, RM Guermazi, A Strotmeyer, ES Brach, J Miljkovic, I Carbone, L Harris, TB Nevitt, M Shiroma, EJ Newman, AB Kwoh, C AF Fujii, T. Boudreau, R. M. Guermazi, A. Strotmeyer, E. S. Brach, J. Miljkovic, I. Carbone, L. Harris, T. B. Nevitt, M. Shiroma, E. J. Newman, A. B. Kwoh, C. TI PHYSICAL ACTIVITY AND MRI ASSESSED STRUCTURAL CHANGES IN KNEES OF COMMUNITY-DWELLING OLDER ADULTS SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the Osteoarthritis-Research-Society-International (OARSI) on Osteoarthritis CY APR 30-MAY 03, 2015 CL Seattle, WA SP Osteoarthritis Res Soc Int C1 [Fujii, T.; Boudreau, R. M.; Strotmeyer, E. S.; Brach, J.; Miljkovic, I.; Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA. [Guermazi, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Carbone, L.] Georgia Regents Univ, Augusta, GA USA. [Harris, T. B.; Shiroma, E. J.] NIA, Bethesda, MD 20892 USA. [Nevitt, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kwoh, C.] Univ Arizona, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2015 VL 23 SU 2 MA 342 BP A213 EP A214 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA CI8VC UT WOS:000355048800371 ER PT J AU Hurley, ST Keadle, SK Stanish, WD Hubley-Kozey, CL AF Hurley, S. T. Keadle, S. Kozey Stanish, W. D. Hubley-Kozey, C. L. TI PHYSICAL ACTIVITY ASSESSMENT BASED ON OBJECTIVE ACCELEROMETER AND SELF-REPORT DATA: COMPARING ASYMPTOMATIC AND KNEE OSTEOARTHRITIS GROUPS SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the Osteoarthritis-Research-Society-International (OARSI) on Osteoarthritis CY APR 30-MAY 03, 2015 CL Seattle, WA SP Osteoarthritis Res Soc Int C1 [Hurley, S. T.; Stanish, W. D.; Hubley-Kozey, C. L.] Dalhousie Univ, Halifax, NS, Canada. [Keadle, S. Kozey] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2015 VL 23 SU 2 MA 531 BP A331 EP A332 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA CI8VC UT WOS:000355048800560 ER PT J AU Jonsson, H Olafsdottir, S Sigurdardottir, S Aspelund, T Eiriksdottir, G Sigurdsson, S Harris, TB Launer, L Gudnason, V AF Jonsson, H. Olafsdottir, S. Sigurdardottir, S. Aspelund, T. Eiriksdottir, G. Sigurdsson, S. Harris, T. B. Launer, L. Gudnason, V. TI INCIDENCE AND PREVALENCE OF TOTAL JOINT REPLACEMENTS DUE TO OSTEOARTHRITIS IN THE ELDERLY: RISK FACTORS AND FACTORS ASSOCIATED WITH LATE LIFE PREVALENCE. THE AGES-REYKJAVIK STUDY SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the Osteoarthritis-Research-Society-International (OARSI) on Osteoarthritis CY APR 30-MAY 03, 2015 CL Seattle, WA SP Osteoarthritis Res Soc Int C1 [Jonsson, H.; Olafsdottir, S.; Sigurdardottir, S.] Landspitalinn Univ Hosp, Reykjavik, Iceland. [Jonsson, H.; Aspelund, T.; Gudnason, V.] Univ Iceland, Reykjavik, Iceland. [Aspelund, T.; Eiriksdottir, G.; Sigurdsson, S.; Harris, T. B.; Launer, L.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. NIA, Bethesda, MD 20892 USA. RI Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008 OI Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2015 VL 23 SU 2 MA 292 BP A189 EP A189 PG 1 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA CI8VC UT WOS:000355048800322 ER PT J AU van den Bosch, MH Blom, AB Maeda, A Kilts, TM Davidson, ENB van den Berg, WB Lafeber, FP van Lent, PL Young, MF van der Kraan, PM AF van den Bosch, M. H. Blom, A. B. Maeda, A. Kilts, T. M. Davidson, E. N. Blaney van den Berg, W. B. Lafeber, F. P. van Lent, P. L. Young, M. F. van der Kraan, P. M. TI WISP1 AGGRAVATES OSTEOARTHRITTS BY MODULATION OF TGF-BETA SIGNALING AND POSITIVE REGULATION OF CANONICAL WNT SIGNALING SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the Osteoarthritis-Research-Society-International (OARSI) on Osteoarthritis CY APR 30-MAY 03, 2015 CL Seattle, WA SP Osteoarthritis Res Soc Int C1 [van den Bosch, M. H.; Blom, A. B.; Davidson, E. N. Blaney; van den Berg, W. B.; van Lent, P. L.; van der Kraan, P. M.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Maeda, A.; Kilts, T. M.; Young, M. F.] NIDCR, NIH, Bethesda, MD USA. [Lafeber, F. P.] Univ Med Ctr Utrecht, Utrecht, Netherlands. RI van Lent, Peter/A-4047-2014; Berg, W.B./H-8010-2014; Blom, A.B./L-4206-2015; van den Bosch, Martijn/D-7933-2016; van der Kraan, Peter/D-9115-2011 OI van den Bosch, Martijn/0000-0001-8074-826X; NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD APR PY 2015 VL 23 SU 2 MA 34 BP A44 EP A45 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA CI8VC UT WOS:000355048800067 ER PT J AU Tobian, AAR Kigozi, G Manucci, J Grabowski, MK Serwadda, D Musoke, R Redd, AD Nalugoda, F Reynolds, SJ Kighoma, N Laeyendecker, O Lessler, J Gray, RH Quinn, TC Wawer, MJ AF Tobian, Aaron A. R. Kigozi, Godfrey Manucci, Jordyn Grabowski, Mary K. Serwadda, David Musoke, Richard Redd, Andrew D. Nalugoda, Fred Reynolds, Steven J. Kighoma, Nehemiah Laeyendecker, Oliver Lessler, Justin Gray, Ronald H. Quinn, Thomas C. Wawer, Maria J. CA Rakai Hlth Sci Program TI HIV Shedding from Male Circumcision Wounds in HIV-Infected Men: A Prospective Cohort Study SO PLOS MEDICINE LA English DT Article ID SEXUALLY-TRANSMITTED INFECTIONS; RANDOMIZED CONTROLLED-TRIAL; RISK HUMAN-PAPILLOMAVIRUS; VIRAL LOAD; COMBINATION THERAPY; FEMALE PARTNERS; NAIVE PATIENTS; NEGATIVE MEN; YOUNG MEN; UGANDA AB Background A randomized trial of voluntary medical male circumcision (MC) of HIV-infected men reported increased HIV transmission to female partners among men who resumed sexual intercourse prior to wound healing. We conducted a prospective observational study to assess penile HIV shedding after MC. Methods and Findings HIV shedding was evaluated among 223 HIV-infected men (183 self-reported not receiving antiretroviral therapy [ART], 11 self-reported receiving ART and had a detectable plasma viral load [VL], and 29 self-reported receiving ART and had an undetectable plasma VL [< 400 copies/ml]) in Rakai, Uganda, between June 2009 and April 2012. Preoperative and weekly penile lavages collected for 6 wk and then at 12 wk were tested for HIV shedding and VL using a real-time quantitative PCR assay. Unadjusted prevalence risk ratios (PRRs) and adjusted PRRs (adjPRRs) of HIV shedding were estimated using modified Poisson regression with robust variance. HIV shedding was detected in 9.3% (17/183) of men not on ART prior to surgery and 39.3% (72/183) of these men during the entire study. Relative to baseline, the proportion shedding was significantly increased after MC at 1 wk (PRR = 1.87, 95% CI = 1.12-3.14, p = 0.012), 2 wk (PRR = 3.16, 95% CI = 1.94-5.13, p < 0.001), and 3 wk (PRR = 1.98, 95% CI = 1.19-3.28, p = 0.008) after MC. However, compared to baseline, HIV shedding was decreased by 6 wk after MC (PRR = 0.27, 95% CI = 0.09-0.83, p = 0.023) and remained suppressed at 12 wk after MC (PRR = 0.19, 95% CI = 0.06-0.64, p = 0.008). Detectable HIV shedding from MC wounds occurred in more study visits among men with an HIV plasma VL > 50,000 copies/ml than among those with an HIV plasma VL < 400 copies/ml (adjPRR = 10.3, 95% CI = 4.25-24.90, p < 0.001). Detectable HIV shedding was less common in visits from men with healed MC wounds compared to visits from men without healed wounds (adjPRR = 0.12, 95% CI = 0.07-0.23, p < 0.001) and in visits from men on ART with undetectable plasma VL compared to men not on ART (PRR = 0.15, 95% CI = 0.05-0.43, p = 0.001). Among men with detectable penile HIV shedding, the median log(10) HIV copies/milliliter of lavage fluid was significantly lower in men with ART-induced undetectable plasma VL (1.93, interquartile range [IQR] = 1.83-2.14) than in men not on ART (2.63, IQR = 2.28-3.22, p < 0.001). Limitations of this observational study include significant differences in baseline covariates, lack of confirmed receipt of ART for individuals who reported ART use, and lack of information on potential ART initiation during follow-up for those who were not on ART at enrollment. Conclusion Penile HIV shedding is significantly reduced after healing of MC wounds. Lower plasma VL is associated with decreased frequency and quantity of HIV shedding from MC wounds. Starting ART prior to MC should be considered to reduce male-to-female HIV transmission risk. Research is needed to assess the time on ART required to decrease shedding, and the acceptability and feasibility of initiating ART at the time of MC. C1 [Tobian, Aaron A. R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Tobian, Aaron A. R.; Kigozi, Godfrey; Serwadda, David; Musoke, Richard; Nalugoda, Fred; Reynolds, Steven J.; Kighoma, Nehemiah; Gray, Ronald H.; Quinn, Thomas C.; Wawer, Maria J.] Rakai Hlth Sci Program, Entebbe, Uganda. [Manucci, Jordyn; Redd, Andrew D.; Reynolds, Steven J.; Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Grabowski, Mary K.; Lessler, Justin; Gray, Ronald H.; Wawer, Maria J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Serwadda, David] Makerere Univ, Inst Publ Hlth, Kampala, Uganda. [Redd, Andrew D.; Reynolds, Steven J.; Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Tobian, AAR (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. EM atobian1@jhmi.edu OI Laeyendecker, Oliver/0000-0002-6429-4760; Lessler, Justin/0000-0002-9741-8109 FU Bill & Melinda Gates Foundation [22006.03]; Doris Duke Charitable Foundation [2011036]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases; Fogarty International Center [1D43TWOO9578-01]; NIH [1K23AI093152-01A1, T32AI102]; Doris Duke Charitable Foundation Clinician Scientist Development Award FX This study was supported by the Bill & Melinda Gates Foundation (22006.03, sample collection), the Doris Duke Charitable Foundation (#2011036, laboratory work), the Division of Intramural Research, National Institute of Allergy and Infectious Diseases and the Fogarty International Center, 1D43TWOO9578-01. AART was supported by the NIH 1K23AI093152-01A1 and the Doris Duke Charitable Foundation Clinician Scientist Development Award. MKG was supported by NIH T32AI102 and the Doris Duke Charitable Foundation Clinician Scientist Development Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 7 Z9 7 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD APR PY 2015 VL 12 IS 4 AR e1001820 DI 10.1371/journal.pmed.1001820 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA CI5UQ UT WOS:000354825700009 PM 25919012 ER PT J AU Carregaro, V Ribeiro, JM Valenzuela, JG Souza, DL Costa, DL Oliveira, CJF Sacramento, LA Nascimento, MSL Milanezi, CM Cunha, FQ Silva, JS AF Carregaro, Vanessa Ribeiro, Jose M. Valenzuela, Jesus G. Souza-Junior, Djalma L. Costa, Diego L. Oliveira, Carlo J. F. Sacramento, Lais A. Nascimento, Manuela S. L. Milanezi, Cristiane M. Cunha, Fernando Q. Silva, Joao S. TI Nucleosides Present on Phlebotomine Saliva Induce Immunossuppression and Promote the Infection Establishment SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID REGULATORY T-CELLS; EXPERIMENTAL CUTANEOUS LEISHMANIASIS; LUTZOMYIA-LONGIPALPIS SALIVA; COLLAGEN-INDUCED ARTHRITIS; PAPATASI SAND FLY; ADENOSINE RECEPTORS; BALB/C MICE; IMMUNE-RESPONSE; DENDRITIC CELLS; GLAND LYSATE AB Background Sand fly saliva plays a crucial role in establishing Leishmania infection. We identified adenosine (ADO) and adenosine monophosphate (AMP) as active pharmacologic compounds present in Phlebotomus papatasi saliva that inhibit dendritic cell (DC) functions through a PGE(2)/IL 10-dependent mechanism. Methodology/Principal Findings Herein, we prepared a mixture of ADO and AMP in equimolar amounts similar to those present in the salivary-gland extract (SGE) form one pair of salivary glands of P. papatasi and co-injected it with Leishmania amazonensis or L. major into mouse ears. ADO+ AMP mimicked exacerbative effects of P. papatasi saliva in leishmaniasis, increasing parasite burden and cutaneous lesions. Enzymatic catabolism of salivary nucleosides reversed the SGE-induced immunosuppressive effect associated with IL-10 enhancement. Immunosuppressive factors COX2 and IL-10 were upregulated and failed to enhance ear lesion and parasite burden in IL 10(-/-) infected mice. Furthermore, nucleosides increased regulatory T cell (Treg) marker expression on CD4(+)CD25(-) cells, suggesting induction of Tregs on effector T cells (T eff). Treg induction (iTreg) was associated with nucleoside-induced tolerogenic dendritic cells (tDCs) expressing higher levels of COX2 and IL-10. In vitro generation of Tregs was more efficient in DCs treated with nucleosides. Suppressive effects of nucleosides during cutaneous leishmaniasis were mediated through an A2(A)R-dependent mechanism. Using BALB/c mice deficient in A2A ADO receptor (A2(A)R(-/-)), we showed that co-inoculated mice controlled infection, displaying lower parasite numbers at infection sites and reduced iTreg generation. Conclusion/Significance We have demonstrated that ADO and AMP in P. papatasi saliva mediate exacerbative effects of Leishmania infection by acting preferentially on DCs promoting a tolerogenic profile in DCs and by generating iTregs in inflammatory foci through an A2(A)R mechanism. C1 [Carregaro, Vanessa; Souza-Junior, Djalma L.; Costa, Diego L.; Sacramento, Lais A.; Nascimento, Manuela S. L.; Milanezi, Cristiane M.; Cunha, Fernando Q.; Silva, Joao S.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049 Ribeirao Preto, Brazil. [Ribeiro, Jose M.; Valenzuela, Jesus G.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Ribeiro, Jose M.; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Oliveira, Carlo J. F.] Univ Fed Triangulo Mineiro, Inst Biol & Nat Sci, Uberaba, Brazil. [Cunha, Fernando Q.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-14049 Ribeirao Preto, Brazil. RP Carregaro, V (reprint author), Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049 Ribeirao Preto, Brazil. EM jsdsilva@fmrp.usp.br RI Carregaro, Vanessa/D-2913-2012; CEPID, CRID/J-2644-2015; Cunha, Fernando/M-3090-2014; Silva, Joao/A-4484-2008 OI Costa, Diego/0000-0002-9440-2814; Cunha, Fernando Queiroz/0000-0003-4755-1670; Ribeiro, Jose/0000-0002-9107-0818; FU CAPES/PRODOC; CNPq; FAEPA; Sao Paulo Research Foundation (FAPESP) [2013/08216-2]; University of Sao Paulo NAP-DIN [11.1.21625.01.0]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by CAPES/PRODOC, CNPq, FAEPA and Sao Paulo Research Foundation (FAPESP) under grant agreements no 2013/08216-2 (Center for Research in Inflammatory Disease) and from University of Sao Paulo NAP-DIN under grant agreement no 11.1.21625.01.0. JGV and JMCR were supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 3 Z9 3 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD APR PY 2015 VL 9 IS 4 AR e0003600 DI 10.1371/journal.pntd.0003600 PG 21 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CI7VF UT WOS:000354972200012 PM 25849562 ER PT J AU Guagliardo, SA Morrison, AC Barboza, JL Requena, E Astete, H Vazquez-Prokopec, G Kitron, U AF Guagliardo, Sarah Anne Morrison, Amy C. Luis Barboza, Jose Requena, Edwin Astete, Helvio Vazquez-Prokopec, Gonzalo Kitron, Uriel TI River Boats Contribute to the Regional Spread of the Dengue Vector Aedes aegypti in the Peruvian Amazon SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID INTERNATIONAL-AIRPORT; CULICIDAE PRODUCTION; GENE FLOW; MOSQUITO; IQUITOS; DIPTERA; DISPERSAL; INTRODUCTIONS; DIVERSITY; DYNAMICS AB Background and Objectives The dramatic range expansion of the dengue vector Aedes aegypti is associated with various anthropogenic transport activities, but little is known about the underlying mechanisms driving this geographic expansion. We longitudinally characterized infestation of different vehicle types (cars, boats, etc.) to estimate the frequency and intensity of mosquito introductions into novel locations (propagule pressure). Methods Exhaustive adult and immature Ae. aegypti collections were performed on six different vehicle types at five ports and two bus/taxi departure points in the Amazonian city of Iquitos, Peru during 2013. Aquatic vehicles included 32 large and 33 medium-sized barges, 53 water taxis, and 41 speed boats. Terrestrial vehicles sampled included 40 buses and 30 taxis traveling on the only highway in the region. Ae. aegypti adult infestation rates and immature indices were analyzed by vehicle type, location within vehicles, and sampling date. Results Large barges (71.9% infested) and medium barges (39.4% infested) accounted for most of the infestations. Notably, buses had an overall infestation rate of 12.5%. On large barges, the greatest number of Ae. aegypti adults were found in October, whereas most immatures were found in February followed by October. The vast majority of larvae (85.9%) and pupae (76.7%) collected in large barges were produced in puddles formed in cargo holds. Conclusions Because larges barges provide suitable mosquito habitats (due to dark, damp cargo storage spaces and ample oviposition sites), we conclude that they likely serve as significant contributors to mosquitoes' propagule pressure across long distances throughout the Peruvian Amazon. This information can help anticipate vector population mixing and future range expansions of dengue and other viruses transmitted by Ae. aegypti. C1 [Guagliardo, Sarah Anne; Vazquez-Prokopec, Gonzalo; Kitron, Uriel] Emory Univ, Dept Environm Sci, Atlanta, GA 30322 USA. [Morrison, Amy C.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Luis Barboza, Jose; Requena, Edwin] Univ Nacl Amazonia Peruana, Iquitos, Peru. [Astete, Helvio] NAMRU 6 Iquitos Lab, US Naval Med Res Unit 6, Iquitos, Peru. [Vazquez-Prokopec, Gonzalo; Kitron, Uriel] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Guagliardo, SA (reprint author), Emory Univ, Dept Environm Sci, Atlanta, GA 30322 USA. EM sarah.guagliardo@gmail.com FU National Institutes of Health [T32 AI55404-10]; Achievement Rewards for College Students (ARCS) Global Health Impact Award; NIH/NIAID [R01 AI069341-01] FX Funding for this study was provided by the National Institutes of Health Training Grant in the Population Biology of Infectious Diseases No. T32 AI55404-10 (L Real, PI) and by the Achievement Rewards for College Students (ARCS) Global Health Impact Award. Logistical support for this study was also provided by NIH/NIAID award No. R01 AI069341-01 (TW Scott, PI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 4 Z9 4 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD APR PY 2015 VL 9 IS 4 AR e0003648 DI 10.1371/journal.pntd.0003648 PG 15 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CI7VF UT WOS:000354972200022 PM 25860352 ER PT J AU Safronetz, D Mire, C Rosenke, K Feldmann, F Haddock, E Geisbert, T Feldmann, H AF Safronetz, David Mire, Chad Rosenke, Kyle Feldmann, Friederike Haddock, Elaine Geisbert, Thomas Feldmann, Heinz TI A Recombinant Vesicular Stomatitis Virus-Based Lassa Fever Vaccine Protects Guinea Pigs and Macaques against Challenge with Geographically and Genetically Distinct Lassa Viruses SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID EBOLA VIRUSES; WEST-AFRICA; DNA; NUCLEOPROTEIN; GLYCOPROTEINS; PROGRESS; DISEASE; LIBERIA AB Background Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a "universal" LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models. Methodologies/principle findings Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection/disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever. Conclusions/significance Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever. C1 [Safronetz, David; Rosenke, Kyle; Haddock, Elaine; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Mire, Chad; Geisbert, Thomas] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Mire, Chad; Geisbert, Thomas] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Feldmann, Friederike] NIAID, Rocky Mt Vet Branch, Div Intramural Res, Rocky Mt Labs,NIH, Hamilton, MT USA. RP Safronetz, D (reprint author), NIAID, Virol Lab, Div Intramural Res, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. EM safronetzd@niaid.nih.gov; feldmannh@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 6 Z9 6 U1 2 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD APR PY 2015 VL 9 IS 4 AR e0003736 DI 10.1371/journal.pntd.0003736 PG 14 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CI7VF UT WOS:000354972200068 PM 25884628 ER PT J AU Finney, CAM Kamhawi, S Wasmuth, JD AF Finney, Constance A. M. Kamhawi, Shaden Wasmuth, James D. TI Does the Arthropod Microbiota Impact the Establishment of Vector-Borne Diseases in Mammalian Hosts? SO PLOS PATHOGENS LA English DT Article ID BACTERIAL COMMUNITIES; SPOROGONIC DEVELOPMENT; ANOPHELES-GAMBIAE; IMMUNE-RESPONSES; MIDGUT BACTERIA; GUT MICROBIOTA; RIBOSOMAL-RNA; DIVERSITY; SYMBIONT; TRANSMISSION AB The impact of the microbiota on the immune status of its host is a source of intense research and publicity. In comparison, the effect of arthropod microbiota on vector-borne infectious diseases has received little attention. A better understanding of the vector microbiota in relation to mammalian host immune responses is vital, as it can lead to strategies that affect transmission and improve vaccine design in a field of research where few vaccines exist and effective treatment is rare. Recent demonstrations of how microbiota decrease pathogen development in arthropods, and thus alter vector permissiveness to vector-borne diseases (VBDs), have led to renewed interest. However, hypotheses on the interactions between the arthropod-derived microbiota and the mammalian hosts have yet to be addressed. Advances in DNA sequencing technology, increased yield and falling costs, mean that these studies are now feasible for many microbiologists and entomologists. Here, we distill current knowledge and put forward key questions and experimental designs to shed light on this burgeoning research topic. C1 [Finney, Constance A. M.] Univ Calgary, Dept Biol Sci, Fac Sci, Calgary, AB T2N 1N4, Canada. [Kamhawi, Shaden] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Wasmuth, James D.] Univ Calgary, Fac Vet Med, Dept Ecosyst & Publ Hlth, Calgary, AB, Canada. RP Finney, CAM (reprint author), Univ Calgary, Dept Biol Sci, Fac Sci, 2500 Univ Dr 1 NW, Calgary, AB T2N 1N4, Canada. EM constance.finney@ucalgary.ca FU Intramural NIH HHS NR 44 TC 4 Z9 4 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2015 VL 11 IS 4 AR e1004646 DI 10.1371/journal.ppat.1004646 PG 8 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CI7XE UT WOS:000354978000002 PM 25856431 ER PT J AU Kamenyeva, O Boularan, C Kabat, J Cheung, GYC Cicala, C Yeh, AJ Chan, JL Periasamy, S Otto, M Kehrl, JH AF Kamenyeva, Olena Boularan, Cedric Kabat, Juraj Cheung, Gordon Y. C. Cicala, Claudia Yeh, Anthony J. Chan, June L. Periasamy, Saravanan Otto, Michael Kehrl, John H. TI Neutrophil Recruitment to Lymph Nodes Limits Local Humoral Response to Staphylococcus aureus SO PLOS PATHOGENS LA English DT Article ID IMMUNE-RESPONSE; BONE-MARROW; DENDRITIC CELLS; HOST-DEFENSE; MIGRATION; INFECTIONS; PROTEIN; MICE; ANTIGEN; INNATE AB Neutrophils form the first line of host defense against bacterial pathogens. They are rapidly mobilized to sites of infection where they help marshal host defenses and remove bacteria by phagocytosis. While splenic neutrophils promote marginal zone B cell antibody production in response to administered T cell independent antigens, whether neutrophils shape humoral immunity in other lymphoid organs is controversial. Here we investigate the neutrophil influx following the local injection of Staphylococcus aureus adjacent to the inguinal lymph node and determine neutrophil impact on the lymph node humoral response. Using intravital microscopy we show that local immunization or infection recruits neutrophils from the blood to lymph nodes in waves. The second wave occurs temporally with neutrophils mobilized from the bone marrow. Within lymph nodes neutrophils infiltrate the medulla and interfollicular areas, but avoid crossing follicle borders. In vivo neutrophils form transient and long-lived interactions with B cells and plasma cells, and their depletion augments production of antigen-specific IgG and IgM in the lymph node. In vitro activated neutrophils establish synapse-and nanotube-like interactions with B cells and reduce B cell IgM production in a TGF-beta 1 dependent manner. Our data reveal that neutrophils mobilized from the bone marrow in response to a local bacterial challenge dampen the early humoral response in the lymph node. C1 [Kamenyeva, Olena; Boularan, Cedric; Kehrl, John H.] NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Kabat, Juraj] NIAID, Biol Imaging Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA. [Cheung, Gordon Y. C.; Yeh, Anthony J.; Chan, June L.; Periasamy, Saravanan; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. [Cicala, Claudia] NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kamenyeva, O (reprint author), NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU National Institutes of Allergy and Infectious Diseases FX Funding: This research was supported by the intramural program of the National Institutes of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 10 Z9 10 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2015 VL 11 IS 4 AR e1004827 DI 10.1371/journal.ppat.1004827 PG 31 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CI7XE UT WOS:000354978000038 PM 25884622 ER PT J AU Losada, L Sugui, JA Eckhaus, MA Chang, YC Mounaud, S Figat, A Joardar, V Pakala, SB Pakala, S Venepally, P Fedorova, N Nierman, WC Kwon-Chung, KJ AF Losada, Liliana Sugui, Janyce A. Eckhaus, Michael A. Chang, Yun C. Mounaud, Stephanie Figat, Abigail Joardar, Vinita Pakala, Suman B. Pakala, Suchitra Venepally, Pratap Fedorova, Natalie Nierman, William C. Kwon-Chung, Kyung J. TI Genetic Analysis Using an Isogenic Mating Pair of Aspergillus fumigatus Identifies Azole Resistance Genes and Lack of MAT Locus's Role in Virulence SO PLOS PATHOGENS LA English DT Article ID CRYPTOCOCCUS-NEOFORMANS; GALLERIA-MELLONELLA; AMPHOTERICIN-B; HISTOPLASMA-CAPSULATUM; CONGENIC STRAINS; IN-VITRO; PROTEIN; PATHOGEN; INVASIVENESS; VORICONAZOLE AB Invasive aspergillosis (IA) due to Aspergillus fumigatus is a major cause of mortality in immunocompromised patients. The discovery of highly fertile strains of A. fumigatus opened the possibility to merge classical and contemporary genetics to address key questions about this pathogen. The merger involves sexual recombination, selection of desired traits, and genomics to identify any associated loci. We constructed a highly fertile isogenic pair of A. fumigatus strains with opposite mating types and used them to investigate whether mating type is associated with virulence and to find the genetic loci involved in azole resistance. The pair was made isogenic by 9 successive backcross cycles of the foundational strain AFB62 (MAT1-1) with a highly fertile (MAT1-2) progeny. Genome sequencing showed that the F-9 MAT1-2 progeny was essentially identical to the AFB62. The survival curves of animals infected with either strain in three different animal models showed no significant difference, suggesting that virulence in A. fumigatus was not associated with mating type. We then employed a relatively inexpensive, yet highly powerful strategy to identify genomic loci associated with azole resistance. We used traditional in vitro drug selection accompanied by classical sexual crosses of azole-sensitive with resistant isogenic strains. The offspring were plated under varying drug concentrations and pools of resulting colonies were analyzed by whole genome sequencing. We found that variants in 5 genes contributed to azole resistance, including mutations in erg11A (cyp51A), as well as multi-drug transporters, erg25, and in HMG-CoA reductase. The results demonstrated that with minimal investment into the sequencing of three pools from a cross of interest, the variation(s) that contribute any phenotype can be identified with nucleotide resolution. This approach can be applied to multiple areas of interest in A. fumigatus or other heterothallic pathogens, especially for virulence associated traits. C1 [Losada, Liliana; Mounaud, Stephanie; Joardar, Vinita; Pakala, Suman B.; Pakala, Suchitra; Venepally, Pratap; Nierman, William C.] J Craig Venter Inst, Rockville, MD USA. [Sugui, Janyce A.; Chang, Yun C.; Figat, Abigail; Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Eckhaus, Michael A.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. [Fedorova, Natalie] NCI, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jkchung@nih.gov RI Abrams, Natalie/F-4845-2011 OI Abrams, Natalie/0000-0001-9698-2819 FU federal fund from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200900007C]; federal fund from the intramural program FX This project was funded with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract number HHSN272200900007C (LL, SBP, SP, VJ, SM, PV, NF, and WCN) and from the intramural program (JAS, MAE, YCC, AF and KJKC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 3 Z9 3 U1 3 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2015 VL 11 IS 4 AR e1004834 DI 10.1371/journal.ppat.1004834 PG 23 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CI7XE UT WOS:000354978000041 PM 25909486 ER PT J AU Tsetsarkin, KA Liu, GP Kenney, H Bustos-Arriaga, J Hanson, CT Whitehead, SS Pletnev, AG AF Tsetsarkin, Konstantin A. Liu, Guangping Kenney, Heather Bustos-Arriaga, Jose Hanson, Christopher T. Whitehead, Stephen S. Pletnev, Alexander G. TI Dual miRNA Targeting Restricts Host Range and Attenuates Neurovirulence of Flaviviruses SO PLOS PATHOGENS LA English DT Article ID DENGUE-VIRUS TYPE-4; AEDES-AEGYPTI MOSQUITOS; VACCINE CANDIDATE; GROWTH-CHARACTERISTICS; WEST-NILE; AIRBORNE TRANSMISSION; VIRAL DISSEMINATION; STRUCTURAL GENES; CHIMERIC VIRUSES; RHESUS-MONKEYS AB Mosquito-borne flaviviruses are among the most significant arboviral pathogens worldwide. Vaccinations and mosquito population control programs remain the most reliable means for flavivirus disease prevention, and live attenuated viruses remain one of the most attractive flavivirus vaccine platforms. Some live attenuated viruses are capable of infecting principle mosquito vectors, as demonstrated in the laboratory, which in combination with their intrinsic genetic instability could potentially lead to a vaccine virus reversion back to wild-type in nature, followed by introduction and dissemination of potentially dangerous viral strains into new geographic locations. To mitigate this risk we developed a microRNA-targeting approach that selectively restricts replication of flavivirus in the mosquito host. Introduction of sequences complementary to a mosquito-specific mir-184 and mir-275 miRNAs individually or in combination into the 3'NCR and/or ORF region resulted in selective restriction of dengue type 4 virus (DEN4) replication in mosquito cell lines and adult Aedes mosquitos. Moreover a combined targeting of DEN4 genome with mosquito-specific and vertebrate CNS-specific mir-124 miRNA can silence viral replication in two evolutionally distant biological systems: mosquitoes and mouse brains. Thus, this approach can reinforce the safety of newly developed or existing vaccines for use in humans and could provide an additional level of biosafety for laboratories using viruses with altered pathogenic or transmissibility characteristics. C1 [Tsetsarkin, Konstantin A.; Liu, Guangping; Kenney, Heather; Bustos-Arriaga, Jose; Hanson, Christopher T.; Whitehead, Stephen S.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Pletnev, AG (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM apletnev@niaid.nih.gov FU Division of Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of 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 70 TC 5 Z9 5 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2015 VL 11 IS 4 AR e1004852 DI 10.1371/journal.ppat.1004852 PG 22 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CI7XE UT WOS:000354978000050 PM 25906260 ER PT J AU Abhyankar, S Goodwin, RM Sontag, M Yusuf, C Ojodu, J McDonald, CJ AF Abhyankar, Swapna Goodwin, Rebecca M. Sontag, Marci Yusuf, Careema Ojodu, Jelili McDonald, Clement J. TI An update on the use of health information technology in newborn screening SO SEMINARS IN PERINATOLOGY LA English DT Review DE Neonatal Screening Health; Information Exchange Medical; Informatics Health Information; Technology Electronic Health; Records C1 [Abhyankar, Swapna; Goodwin, Rebecca M.; McDonald, Clement J.] US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, Bethesda, MD 20894 USA. [Abhyankar, Swapna] Regenstrief Inst Hlth Care, Indianapolis, IN USA. [Sontag, Marci] Univ Colorado, Anschutz Med Ctr, Colorado Sch Publ Hlth, Dept Epidemiol, Denver, CO 80202 USA. [Yusuf, Careema; Ojodu, Jelili] APHL, Silver Spring, MD USA. RP Goodwin, RM (reprint author), US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, 8600 Rockville Pike,38A-07N711,MSC 3828, Bethesda, MD 20894 USA. EM rebecca.goodwin@nih.gov FU National Institutes of Health (NIH)/NLM; NIH National Institute of Child Health and Human Development (NICHD) as part of the Newborn Screening Translational Research Network FX This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH)/NLM. The LSD expert workgroup was organized by the American College of Medical Genetics (ACMG), with funding from NIH National Institute of Child Health and Human Development (NICHD), as part of the Newborn Screening Translational Research Network. NR 13 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0146-0005 EI 1558-075X J9 SEMIN PERINATOL JI Semin. Perinatol. PD APR PY 2015 VL 39 IS 3 BP 188 EP 193 DI 10.1053/j.semperi.2015.03.003 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA CI9AQ UT WOS:000355063200003 PM 25935354 ER PT J AU Novelle, MG Davis, A Price, NL Ali, A Furer-Galvan, S Zhang, YQ Becker, K Bernier, M de Cabo, R AF Novelle, Marta G. Davis, Ashley Price, Nathan L. Ali, Ahmed Fuerer-Galvan, Stefanie Zhang, Yongqing Becker, Kevin Bernier, Michel de Cabo, Rafael TI Caloric restriction induces heat shock response and inhibits B16F10 cell tumorigenesis both in vitro and in vivo SO AGING-US LA English DT Article DE caloric restriction; heat shock; stress response; tumorigenesis; aging ID LONGEVITY REGULATION; STRESS; PROTEIN; CANCER; DISEASES; HUMANS; DELAYS; GROWTH; TRANSCRIPTION; PATHWAY AB Caloric restriction (CR) without malnutrition is one of the most consistent strategies for increasing mean and maximal lifespan and delaying the onset of age-associated diseases. Stress resistance is a common trait of many long-lived mutants and life-extending interventions, including CR. Indeed, better protection against heat shock and other genotoxic insults have helped explain the pro-survival properties of CR. In this study, both in vitro and in vivo responses to heat shock were investigated using two different models of CR. Murine B16F10 melanoma cells treated with serum from CR-fed rats showed lower proliferation, increased tolerance to heat shock and enhanced HSP-70 expression, compared to serum from ad libitum-fed animals. Similar effects were observed in B16F10 cells implanted subcutaneously in male C57BL/6 mice subjected to CR. Microarray analysis identified a number of genes and pathways whose expression profile were similar in both models. These results suggest that the use of an in vitro model could be a good alternative to study the mechanisms by which CR exerts its anti-tumorigenic effects. C1 [Novelle, Marta G.; Davis, Ashley; Price, Nathan L.; Ali, Ahmed; Fuerer-Galvan, Stefanie; Bernier, Michel; de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Zhang, Yongqing; Becker, Kevin] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA. [Novelle, Marta G.] Univ Santiago de Compostela, Inst Invest Sanitaria, CIMUS, Dept Physiol, Santiago De Compostela 15782, Spain. [Novelle, Marta G.] CIBER Fisiopatol Obesidad & Nutr CIBERobn, Santiago De Compostela 15706, Spain. RP de Cabo, R (reprint author), NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. EM decabora@grc.nia.nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU National Institute on Aging, National Institutes of Health; CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), an initiative of ISCIII, Spain FX We would like to thank Dr. Zdzislaw Krawczyk for giving us the plasmid encoding GFP-tagged Hsp70. This work has been supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. MGN was supported by CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), an initiative of ISCIII, Spain. NR 41 TC 1 Z9 1 U1 0 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD APR PY 2015 VL 7 IS 4 BP 233 EP 240 PG 8 WC Cell Biology SC Cell Biology GA CH4XM UT WOS:000354036900004 PM 25948793 ER PT J AU Arduc, A Tutuncu, YA Dogan, BA Ileri, ABA Tuna, MM Ozcan, HN Isik, S Berker, D Guler, S AF Arduc, Ayse Tutuncu, Yasemin Ates Dogan, Bercem Aycicek Ileri, Ayse Burcu Arikan Tuna, Mazhar Muslum Ozcan, Hatice Nursun Isik, Serhat Berker, Dilek Guler, Serdar TI Parathyroid Cysts SO AMERICAN SURGEON LA English DT Article C1 [Arduc, Ayse] NIDDK, NIH, Diabet Endocrine & Obes Branch, Bethesda, MD 20892 USA. [Tutuncu, Yasemin Ates; Dogan, Bercem Aycicek; Tuna, Mazhar Muslum; Isik, Serhat; Berker, Dilek] Ankara Numune Training & Res Hosp, Minist Hlth, Dept Endocrinol & Metab, Ankara, Turkey. [Ileri, Ayse Burcu Arikan] Ankara Numune Training & Res Hosp, Minist Hlth, Dept Pathol, Ankara, Turkey. [Ozcan, Hatice Nursun] Ankara Numune Training & Res Hosp, Minist Hlth, Dept Radiol, Ankara, Turkey. [Guler, Serdar] Hitit Univ, Dept Endocrinol & Metab, Fac Med, Corum, Turkey. RP Arduc, A (reprint author), 1778 Dawson St, Vienna, VA 22182 USA. EM ayse_arduc@yahoo.com NR 4 TC 0 Z9 0 U1 0 U2 1 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD APR PY 2015 VL 81 IS 4 BP E163 EP E165 PG 3 WC Surgery SC Surgery GA CI6TQ UT WOS:000354895500010 PM 25831166 ER PT J AU Robert, J Reinhold, WC AF Robert, Jacques Reinhold, William C. TI Bisphosphonates as new anticancer agents SO BULLETIN DU CANCER LA French DT Editorial Material C1 [Robert, Jacques] Univ Bordeaux, INSERM, Unite 916, Inst Bergonie, Bordeaux, France. [Reinhold, William C.] NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Robert, J (reprint author), Univ Bordeaux, INSERM, Unite 916, Inst Bergonie, Bordeaux, France. EM j.robert@bordeaux.unicancer.fr NR 6 TC 1 Z9 1 U1 0 U2 3 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 0007-4551 EI 1769-6917 J9 B CANCER JI Bull. Cancer PD APR PY 2015 VL 102 IS 4 BP 297 EP 299 DI 10.1016/j.bulcan.2015.02.010 PG 3 WC Oncology SC Oncology GA CI2PK UT WOS:000354589300002 PM 26042254 ER PT J AU Zhang, LJ Xiong, Y Nilubol, N He, M Bommareddi, S Zhu, XG Jia, L Xiao, Z Park, JW Xu, X Patel, D Willingham, MC Cheng, SY Kebebew, E AF Zhang, Lisa J. Xiong, Yin Nilubol, Naris He, Mei Bommareddi, Swaroop Zhu, Xuguang Jia, Li Xiao, Zhen Park, Jeong-Won Xu, Xia Patel, Dhaval Willingham, Mark C. Cheng, Sheue-yann Kebebew, Electron TI Testosterone regulates thyroid cancer progression by modifying tumor suppressor genes and tumor immunity SO CARCINOGENESIS LA English DT Article ID CHRONIC LYMPHOCYTIC THYROIDITIS; PROSTATE-CANCER; GENDER DISPARITY; ADENOVIRAL VECTOR; RISK; CARCINOMA; HORMONE; IMMUNOTHERAPY; MUTATION; MRTVP-1 AB Cancer gender disparity has been observed for a variety of human malignancies. Thyroid cancer is one such cancer with a higher incidence in women, but more aggressive disease in men. There is scant evidence on the role of sex hormones on cancer initiation/progression. Using a transgenic mouse model of follicular thyroid cancer (FTC), we found castration led to lower rates of cancer in females and less advanced cancer in males. Mechanistically, less advanced cancer in castrated males was due to increased expression of tumor suppressor (Glipr1, Sfrp1) and immune-regulatory genes and higher tumor infiltration with M1 macrophages and CD8 cells. Functional study showed that GLIPR1 reduced cell growth and increased chemokine secretion (Ccl5) that activates immune cells. Our data demonstrate that testosterone regulates thyroid cancer progression by reducing tumor suppressor gene expression and tumor immunity. C1 [Zhang, Lisa J.; Xiong, Yin; Nilubol, Naris; He, Mei; Bommareddi, Swaroop; Patel, Dhaval; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20814 USA. [Zhu, Xuguang; Park, Jeong-Won; Willingham, Mark C.; Cheng, Sheue-yann] NCI, Lab Mol Biol, NIH, Bethesda, MD 20814 USA. [Jia, Li] NCI, Bioinformat Core Ctr Canc Res, NIH, Bethesda, MD 20814 USA. [Xiao, Zhen; Xu, Xia] Frederick Natl Lab Canc Res, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20814 USA. EM kebebewe@mail.nih.gov OI Patel, Dhaval/0000-0002-5744-568X FU Center for Cancer Research, National Cancer Institute, National Institutes of Health [ZIA BC011275 05] FX Center for Cancer Research, National Cancer Institute, National Institutes of Health. Grant number: ZIA BC011275 05. NR 29 TC 4 Z9 4 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2015 VL 36 IS 4 BP 420 EP 428 DI 10.1093/carcin/bgv001 PG 9 WC Oncology SC Oncology GA CI3KT UT WOS:000354647300002 PM 25576159 ER PT J AU Freeman, BD Butler, K Bolcic-Jankovic, D Clarridge, BR Kennedy, CR LeBlanc, J Hull, SC AF Freeman, Bradley D. Butler, Kevin Bolcic-Jankovic, Dragana Clarridge, Brian R. Kennedy, Carie R. LeBlanc, Jessica Hull, Sara Chandros TI Surrogate Receptivity to Participation in Critical Illness Genetic Research Aligning Research Oversight and Stakeholder Concerns SO CHEST LA English DT Article ID CRITICAL-CARE RESEARCH; CLINICAL-RESEARCH; INFORMED-CONSENT; ILL PATIENTS; MEDICAL-RESEARCH; UNITED-STATES; TRIALS; ADULTS; RECOMMENDATIONS; CHALLENGES AB BACKGROUND: Collection of genetic biospecimens as part of critical illness investigations is increasingly commonplace. Oversight bodies vary in restrictions imposed on genetic research, introducing inconsistencies in study design, potential for sampling bias, and the possibility of being overly prohibitive of this type of research altogether. We undertook this study to better understand whether restrictions on genetic data collection beyond those governing research on cognitively intact subjects reflect the concerns of surrogates for critically ill patients. METHODS: We analyzed survey data collected from 1,176 patients in nonurgent settings and 437 surrogates representing critically ill adults. Attitudes pertaining to genetic data (familiarity, perceptions, interest in participation, concerns) and demographic information were examined using univariate and multivariate techniques. RESULTS: We explored differences among respondents who were receptive (1,333) and nonreceptive (280) to genetic sample collection. Whereas factors positively associated with receptivity to research participation were "complete trust" in health-care providers (OR, 2.091; 95% CI, 1.544-2.833), upper income strata (OR, 2.319; 95% CI, 1.308-4.114), viewing genetic research "very positively" (OR, 3.524; 95% CI, 2.122-5.852), and expressing "no worry at all" regarding disclosure of results (OR, 2.505; 95% CI, 1.436-4.369), black race was negatively associated with research participation (OR, 0.410; 95% CI, 0.288-0.585). We could detect no difference in receptivity to genetic sample collection comparing ambulatory patients and surrogates (OR, 0.738; 95% CI, 0.511-1.066). CONCLUSIONS: Expressing trust in health-care providers and viewing genetic research favorably were associated with increased willingness for study enrollment, while concern regarding breach of confidentiality and black race had the opposite effect. Study setting had no bearing on willingness to participate. C1 [Freeman, Bradley D.; Butler, Kevin; Kennedy, Carie R.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Bolcic-Jankovic, Dragana; Clarridge, Brian R.; LeBlanc, Jessica] Survey Res Ctr, Boston, MA USA. [Hull, Sara Chandros] NIH, Ctr Clin Bioeth, Bethesda, MD 20892 USA. RP Freeman, BD (reprint author), Washington Univ, Sch Med, Dept Surg, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA. EM freemanb@wustl.edu FU National Institutes of Health [GM080591]; National Human Genome Research Institute FX This study was supported by National Institutes of Health [Grant GM080591] and by the intramural research program of the National Human Genome Research Institute. NR 40 TC 0 Z9 0 U1 1 U2 3 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2015 VL 147 IS 4 BP 979 EP 988 DI 10.1378/chest.14-0797 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CI2VT UT WOS:000354606300027 PM 25340645 ER PT J AU Ferradaa, MA Chang, L AF Ferradaa, Marcela A. Chang, Larry TI A man with skin lesions and ataxia: a case of disseminated varicella zoster SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID HERPES-ZOSTER; VIRUS C1 [Ferradaa, Marcela A.] NIH, Crit Care Med Dept, Bethesda, MD 20892 USA. [Ferradaa, Marcela A.; Chang, Larry] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. RP Ferradaa, MA (reprint author), NIH, Crit Care Med Dept, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 EI 1878-3511 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD APR PY 2015 VL 33 BP 55 EP 55 DI 10.1016/j.ijid.2014.10.021 PG 1 WC Infectious Diseases SC Infectious Diseases GA CI0SQ UT WOS:000354448600013 PM 25461652 ER PT J AU Renton, AE Pliner, HA Provenzano, C Evoli, A Ricciardi, R Nalls, MA Marangi, G Abramzon, Y Arepalli, S Chong, S Hernandez, DG Johnson, JO Bartoccioni, E Scuderi, F Maestri, M Gibbs, JR Errichiello, E Chio, A Restagno, G Sabatelli, M Macek, M Scholz, SW Corse, A Chaudhry, V Benatar, M Barohn, RJ McVey, A Pasnoor, M Dimachkie, MM Rowin, J Kissel, J Freimer, M Kaminski, HJ Sanders, DB Lipscomb, B Massey, JM Chopra, M Howard, JF Koopman, WJ Nicolle, MW Pascuzzi, RM Pestronk, A Wulf, C Florence, J Blackmore, D Soloway, A Siddiqi, Z Muppidi, S Wolfe, G Richman, D Mezei, MM Jiwa, T Oger, J Drachman, DB Traynor, BJ AF Renton, Alan E. Pliner, Hannah A. Provenzano, Carlo Evoli, Amelia Ricciardi, Roberta Nalls, Michael A. Marangi, Giuseppe Abramzon, Yevgeniya Arepalli, Sampath Chong, Sean Hernandez, Dena G. Johnson, Janel O. Bartoccioni, Emanuela Scuderi, Flavia Maestri, Michelangelo Gibbs, J. Raphael Errichiello, Edoardo Chio, Adriano Restagno, Gabriella Sabatelli, Mario Macek, Mark Scholz, Sonja W. Corse, Andrea Chaudhry, Vinay Benatar, Michael Barohn, Richard J. McVey, April Pasnoor, Mamatha Dimachkie, Mazen M. Rowin, Julie Kissel, John Freimer, Miriam Kaminski, Henry J. Sanders, Donald B. Lipscomb, Bernadette Massey, Janice M. Chopra, Manisha Howard, James F., Jr. Koopman, Wilma J. Nicolle, Michael W. Pascuzzi, Robert M. Pestronk, Alan Wulf, Charlie Florence, Julaine Blackmore, Derrick Soloway, Aimee Siddiqi, Zaeem Muppidi, Srikanth Wolfe, Gil Richman, David Mezei, Michelle M. Jiwa, Theresa Oger, Joel Drachman, Daniel B. Traynor, Bryan J. TI A Genome-Wide Association Study of Myasthenia Gravis SO JAMA NEUROLOGY LA English DT Article ID TRANSCRIPTION FACTORS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; PARKINSONS-DISEASE; GENETIC-VARIATION; COMMON VARIANTS; PHASE-III; CTLA-4; RISK; HERITABILITY AB IMPORTANCE Myasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups. Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood. OBJECTIVE To identify genetic variants that alter susceptibility to myasthenia gravis, we performed a genome-wide association study. DESIGN, SETTING, AND PARTICIPANTS DNA was obtained from 1032 white individuals from North America diagnosed as having acetylcholine receptor antibody-positive myasthenia gravis and 1998 race/ethnicity-matched control individuals from January 2010 to January 2011. These samples were genotyped on Illumina OmniExpress single-nucleotide polymorphism arrays. An independent cohort of 423 Italian cases and 467 Italian control individuals were used for replication. MAIN OUTCOMES AND MEASURES We calculated P values for association between 8 114 394 genotyped and imputed variants across the genome and risk for developing myasthenia gravis using logistic regression modeling. A threshold P value of 5.0 x 10(-8) was set for genome-wide significance after Bonferroni correction for multiple testing. RESULTS In the overall case-control cohort, we identified association signals at CTLA4 (rs231770; P = 3.98 x 10(-8); odds ratio, 1.37; 95% CI, 1.25-1.49), HLA-DQA1 (rs9271871; P = 1.08 x 10(-8); odds ratio, 2.31; 95% CI, 2.02 - 2.60), and TNFRSF11A (rs4263037; P = 1.60 x 10(-9); odds ratio, 1.41; 95% CI, 1.29-1.53). These findings replicated for CTLA4 and HLA-DQA1 in an independent cohort of Italian cases and control individuals. Further analysis revealed distinct, but overlapping, disease-associated loci for early- and late-onset forms of myasthenia gravis. In the late-onset cases, we identified 2 association peaks: one was located in TNFRSF11A (rs4263037; P = 1.32 x 10(-12); odds ratio, 1.56; 95% CI, 1.44-1.68) and the other was detected in the major histocompatibility complex on chromosome 6p21 (HLA-DQA1; rs9271871; P = 7.02 x 10(-18); odds ratio, 4.27; 95% CI, 3.92-4.62). Association within the major histocompatibility complex region was also observed in early-onset cases (HLA-DQA1; rs601006; P = 2.52 x 10(-11); odds ratio, 4.0; 95% CI, 3.57-4.43), although the set of single-nucleotide polymorphisms was different from that implicated among late-onset cases. CONCLUSIONS AND RELEVANCE Our genetic data provide insights into aberrant cellular mechanisms responsible for this prototypical autoimmune disorder. They also suggest that clinical trials of immunomodulatory drugs related to CTLA4 and that are already Food and Drug Administration approved as therapies for other autoimmune diseases could be considered for patients with refractory disease. C1 [Renton, Alan E.; Pliner, Hannah A.; Marangi, Giuseppe; Abramzon, Yevgeniya; Johnson, Janel O.; Errichiello, Edoardo; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH,Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Provenzano, Carlo; Bartoccioni, Emanuela; Scuderi, Flavia] Univ Cattolica Sacro Cuore, Inst Gen Pathol, Rome, Italy. [Evoli, Amelia; Sabatelli, Mario] Univ Cattolica Sacro Cuore, Inst Neurol, Rome, Italy. [Ricciardi, Roberta; Maestri, Michelangelo] Univ Pisa, Cisanello Hosp, Dept Neurosci, Pisa, Italy. [Nalls, Michael A.] NIA, Mol Genet Sect, Neurogenet Lab, NIH,Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Marangi, Giuseppe] Univ Cattolica Sacro Cuore, Inst Med Genet, Rome, Italy. [Arepalli, Sampath; Chong, Sean; Hernandez, Dena G.] NIA, Genom Technol Grp, Neurogenet Lab, NIH,Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Gibbs, J. Raphael] NIA, Computat Biol Core, Neurogenet Lab, NIH,Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Errichiello, Edoardo; Chio, Adriano] Univ Turin, Rita Levi Montalcini Dept Neurosci, Turin, Italy. [Restagno, Gabriella] ASO OIRM S Anna, Dept Clin Pathol, Mol Genet Unit, Turin, Italy. [Maestri, Michelangelo; Scholz, Sonja W.; Corse, Andrea; Chaudhry, Vinay; Drachman, Daniel B.; Traynor, Bryan J.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Benatar, Michael] Univ Miami, Dept Neurol, Miami, FL USA. [Barohn, Richard J.; McVey, April; Pasnoor, Mamatha] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS USA. [Rowin, Julie] Univ Illinois, Coll Med, Dept Neurol, Chicago, IL USA. [Kissel, John; Freimer, Miriam] Ohio State Univ, Med Ctr, Dept Neurol, Columbus, OH 43210 USA. [Kaminski, Henry J.] George Washington Univ, Dept Neurol, Washington, DC USA. [Sanders, Donald B.; Lipscomb, Bernadette; Massey, Janice M.] Duke Univ, Med Ctr, Dept Neurol, Durham, NC USA. [Chopra, Manisha; Howard, James F., Jr.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Koopman, Wilma J.; Nicolle, Michael W.] London Hlth Sci Ctr, Dept Clin Neurosci, London, ON, Canada. [Pascuzzi, Robert M.] Indiana Univ Purdue Univ, Dept Neurol, Indianapolis, IN 46202 USA. [Pestronk, Alan; Wulf, Charlie; Florence, Julaine] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Blackmore, Derrick; Soloway, Aimee; Siddiqi, Zaeem] Univ Alberta Hosp, Dept Med, Edmonton, AB T6G 2B7, Canada. [Muppidi, Srikanth; Wolfe, Gil] SUNY Buffalo, SMBS, Dept Neurol, Buffalo, NY 14260 USA. [Richman, David] Univ Calif Davis, Med Ctr, Dept Neurol, Davis, CA USA. [Mezei, Michelle M.; Jiwa, Theresa; Oger, Joel] Univ British Columbia, Div Neurol, Vancouver, BC V5Z 1M9, Canada. RP Traynor, BJ (reprint author), Porter Neurosci Res Ctr, Neuromuscular Dis Res Unit, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA. EM traynorb@mail.nih.gov RI Freimer, Miriam/E-3086-2011; Pliner, Hannah/F-3608-2015; Koopman, Werner/N-3586-2014; OI Pliner, Hannah/0000-0003-1484-6501; Sabatelli, Mario/0000-0001-6635-4985; Chio, Adriano/0000-0001-9579-5341; Scholz, Sonja/0000-0002-6623-0429; Howard, James/0000-0002-7136-8617 FU Myasthenia Gravis Foundation; National Institutes of Health National Institute on Aging [Z01-AG000949-02] FX The work was supported by the Myasthenia Gravis Foundation (Drs Drachman and Traynor), a generous bequest by Geraldine Weinrib, and a gift from Philip Swift. This work was also supported in part by the Intramural Research Programs of the National Institutes of Health National Institute on Aging (Z01-AG000949-02). NR 53 TC 22 Z9 23 U1 1 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD APR PY 2015 VL 72 IS 4 BP 396 EP 404 DI 10.1001/jamaneurol.2014.4103 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CH9KG UT WOS:000354353900007 PM 25643325 ER PT J AU Nagaraja, N Adams, HP Merino, JG AF Nagaraja, Nandakumar Adams, Harold P., Jr. Merino, Jose G. TI Validation of the Association Between Neurologic Improvement With Decline in Blood Pressure and Recanalization in Stroke Reply SO JAMA NEUROLOGY LA English DT Letter C1 [Nagaraja, Nandakumar] NINDS, Stroke Diagnost & Therapeut Sect, Bethesda, MD 20892 USA. [Nagaraja, Nandakumar; Adams, Harold P., Jr.] Univ Iowa, Iowa City, IA 52242 USA. [Merino, Jose G.] Johns Hopkins Community Phys, Bethesda, MD USA. RP Nagaraja, N (reprint author), Univ Iowa, 200 Hawkins Dr,2149 RCP, Iowa City, IA 52242 USA. EM nandakumar-nagaraja@uiowa.edu OI Merino, Jose/0000-0002-6676-0008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD APR PY 2015 VL 72 IS 4 BP 477 EP 478 DI 10.1001/jamaneurol.2014.4690 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CH9KG UT WOS:000354353900022 PM 25867726 ER PT J AU Dewan, R Pemov, A Kim, HJ Morgan, KL Vasquez, RA Chittiboina, P Wang, X Chandrasekharappa, SC Ray-Chaudhury, A Butman, JA Stewart, DR Asthagiri, AR AF Dewan, Ramita Pemov, Alex Kim, H. Jeffrey Morgan, Keaton L. Vasquez, Raul A. Chittiboina, Prashant Wang, Xiang Chandrasekharappa, Settara C. Ray-Chaudhury, Abhik Butman, John A. Stewart, Douglas R. Asthagiri, Ashok R. TI Evidence of polyclonality in neurofibromatosis type 2-associated multilobulated vestibular schwannomas SO NEURO-ONCOLOGY LA English DT Article DE clonality; multilobulated vestibular schwannoma; NF2 gene; Sanger sequencing; single nucleotide polymorphism ID COMPARATIVE GENOMIC HYBRIDIZATION; ACOUSTIC NEUROMAS; HEARING PRESERVATION; FACIAL-NERVE; MANAGEMENT; GENE; RADIOSURGERY; NF2; NEURINOMAS; TUMORS AB Background. Neurofibromatosis type 2 (NF2) is a tumor syndrome that results from mutation of the NF2 tumor suppressor gene. The hallmark of NF2 is the presence of bilateral vestibular schwannoma (VS). Though NF2-associated and sporadic VS share identical histopathologic findings and cytogenetic alterations, NF2-associated VS often appears multilobulated, is less responsive to radiosurgery, and has worse surgical outcomes. Temporal bone autopsy specimens and MRI of the inner ear performed on NF2 patients suggest that multiple discrete tumors may be present within the labyrinth and cerebellopontine angle. Methods. Treatment-naive ears in patients enrolled in a prospective NF2 natural history study (NIH#08-N-0044) were included for MRI analysis. T2-weighted and postcontrast T1-weighted MRIs were evaluated for the presence of multiple discrete tumors or a multilobulated mass. Peripheral blood (germline) and regional samples of tumor tissue were procured from consecutive patients enrolled in this study undergoing resection of a multilobulated VS (MVS). Histopathologic evaluation and genetic analysis (single nucleotide polymorphism array analysis, NF2 sequencing) were performed on each specimen. Results. Over half of NF2 ears harbored either an MVS (60/139 ears) or multiple discrete masses (19/139 ears). For 4 successive MVSs, genetic analysis revealed an admixture of cell populations, each with its own somatic NF2 mutation or deletion. Conclusions. These findings suggest that the majority of NF2-associated VSs are polyclonal, such that the tumor mass represents a collision of multiple, distinct tumor clones. This explains the characteristic lobulated gross appearance of NF2-associated VS, and may also explain the substantially different treatment outcomes compared with sporadic VS. C1 [Dewan, Ramita; Morgan, Keaton L.; Vasquez, Raul A.; Chittiboina, Prashant; Wang, Xiang; Ray-Chaudhury, Abhik; Asthagiri, Ashok R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Pemov, Alex; Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Kim, H. Jeffrey] NIDCD, Off Clin Director, NIH, Bethesda, MD USA. [Butman, John A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Chandrasekharappa, Settara C.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Asthagiri, Ashok R.] Univ Virginia, Dept Neurosurg, CDW, Charlottesville, VA USA. RP Asthagiri, AR (reprint author), Univ Virginia, Dept Neurosurg, Box 800212, Charlottesville, VA 22908 USA. EM asthagiri@virginia.edu FU National Institute of Neurological Disorders and Stroke; National Cancer Institute; National Human Genome Research Institute at the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, the National Cancer Institute, and the National Human Genome Research Institute at the National Institutes of Health. NR 36 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2015 VL 17 IS 4 BP 566 EP 573 DI 10.1093/neuonc/nou317 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CI4KT UT WOS:000354718200010 PM 25452392 ER PT J AU Weiss, B Widemann, BC Wolters, P Dombi, E Vinks, A Cantor, A Perentesis, J Schorry, E Ullrich, N Gutmann, DH Tonsgard, J Viskochil, D Korf, B Packer, RJ Fisher, MJ AF Weiss, Brian Widemann, Brigitte C. Wolters, Pamela Dombi, Eva Vinks, Alexander Cantor, Alan Perentesis, John Schorry, Elizabeth Ullrich, Nicole Gutmann, David H. Tonsgard, James Viskochil, David Korf, Bruce Packer, Roger J. Fisher, Michael J. TI Sirolimus for progressive neurofibromatosis type 1-associated plexiform neurofibromas: a Neurofibromatosis Clinical Trials Consortium phase II study SO NEURO-ONCOLOGY LA English DT Article DE neurofibromatosis; NF1; plexiform neurofibroma; rapamycin; sirolimus; mTOR ID QUALITY-OF-LIFE; NERVE SHEATH TUMORS; MAMMALIAN TARGET; RAPAMYCIN PATHWAY; YOUNG-ADULTS; CHILDREN; MTOR; PAIN AB Background. Plexiform neurofibromas (PNs) are benign peripheral nerve sheath tumors that arise in one-third of individuals with neurofibromatosis type 1 (NF1). They may cause significant disfigurement, compression of vital structures, neurologic dysfunction, and/or pain. Currently, the only effective management strategy is surgical resection. Converging evidence has demonstrated that the NF1 tumor suppressor protein, neurofibromin, negatively regulates activity in the mammalian Target of Rapamycin pathway. Methods. We employed a 2-strata clinical trial design. Stratum 1 included subjects with inoperable, NF1-associated progressive PN and sought to determine whether sirolimus safely and tolerably increases time to progression (TTP). Volumetric MRI analysis conducted at regular intervals was used to determine TTP relative to baseline imaging. Results. The estimated median TTP of subjects receiving sirolimus was 15.4 months (95% CI: 14.3-23.7 mo), which was significantly longer than 11.9 months (P < .001), the median TTP of the placebo arm of a previous PN clinical trial with similar eligibility criteria. Conclusions. This study demonstrated that sirolimus prolongs TTP by almost 4 months in patients with NF1-associated progressive PN. Although the improvement in TTP is modest, given the lack of significant or frequent toxicity and the availability of few other treatment options, the use of sirolimus to slow the growth of progressive PN could be considered in select patients. C1 [Weiss, Brian; Perentesis, John] Cincinnati Childrens Hosp Med Ctr, Div Oncol, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA. [Schorry, Elizabeth] Cincinnati Childrens Hosp Med Ctr, Div Genet, Cincinnati, OH 45229 USA. [Vinks, Alexander] Cincinnati Childrens Hosp Med Ctr, Div Clin Pharmacol, Cincinnati, OH 45229 USA. [Widemann, Brigitte C.; Wolters, Pamela; Dombi, Eva] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Korf, Bruce] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Cantor, Alan] Univ Alabama Birmingham, Dept Prevent Med, Birmingham, AL USA. [Ullrich, Nicole] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Gutmann, David H.] Washington Univ, Dept Neurol, St Louis, MO USA. [Packer, Roger J.] Ctr Neurosci & Behav Med, Childrens Natl Hlth Syst, Washington, DC USA. [Fisher, Michael J.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Viskochil, David] Primary Childrens Med Ctr, Div Genet, Salt Lake City, UT USA. [Tonsgard, James] Univ Chicago Med, Comer Childrens Hosp, Div Neurol, Chicago, IL USA. RP Weiss, B (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Oncol, MLC 7015,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM brian.weiss@cchmc.org FU Neurofibromatosis Clinical Trials award [W81XWH-05-1-0615] FX This work was supported by a Neurofibromatosis Clinical Trials award for FY2007, no. W81XWH-05-1-0615. NR 38 TC 14 Z9 15 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2015 VL 17 IS 4 BP 596 EP 603 DI 10.1093/neuonc/nou235 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CI4KT UT WOS:000354718200014 PM 25314964 ER PT J AU Merikangas, KR Calkins, ME Burstein, M He, JP Chiavacci, R Lateef, T Ruparel, K Gur, RC Lehner, T Hakonarson, H Gur, RE AF Merikangas, Kathleen R. Calkins, Monica E. Burstein, Marcy He, Jian-Ping Chiavacci, Rosetta Lateef, Tarannum Ruparel, Kosha Gur, Ruben C. Lehner, Thomas Hakonarson, Hakon Gur, Raquel E. TI Comorbidity of Physical and Mental Disorders in the Neurodevelopmental Genomics Cohort Study SO PEDIATRICS LA English DT Article ID BLIND CLINICAL-TRIAL; CHRONIC ILLNESS; PSYCHIATRIC-DISORDERS; INDEPENDENT PREDICTORS; PSYCHOSIS SPECTRUM; CONDUCT PROBLEMS; YOUNG-ADULTS; CHILD HEALTH; RISK-FACTORS; FOLLOW-UP AB OBJECTIVES: To examine patterns of associations between a broad range of mental and physical conditions by using a large, systematically obtained pediatric registry. METHODS: The sample included 9014 youth ages 8 to 21 years (4349 males and 4665 females; 3585 aged <13 years, 3678 aged 13 to 18 years, and 1751 aged 19 to 21 years) from the Philadelphia Neurodevelopmental Cohort identified through pediatric clinics at the Children's Hospital of Philadelphia health care network by the Center for Applied Genomics. Measures were as follows: physical condition based on electronic medical records and interview data on 42 physical conditions of 14 organ systems/specialties and mental disorders based on an abbreviated version of the structured Kiddie-Schedule for Affective Disorders and Schizophrenia psychiatric diagnostic interview. RESULTS: There was a direct association between the severity of the physical condition and most classes of mental disorders, as well as with functional impairment. Models adjusted for sociodemographic correlates, other physical and mental disorders, and false discovery and revealed broad patterns of associations between neurodevelopmental disorders with behavior disorders (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.3-1.8; P < .004) and attention-deficit/hyperactivity disorder (OR: 3.1; 95% CI: 2.7-3.6; P < .0001), and neurologic/central nervous system conditions (OR: 1.3; 95% CI: 1.1-1.9; P < .05) with mood disorders and attention-deficit/hyperactivity disorder (OR: 1.3; 95% CI: 1.1-1.5; P < .001), and autoimmune/inflammatory conditions with mood disorders (OR: 1.4; 95% CI: 1.1-1.8, P < .05). CONCLUSIONS: Findings show the strong overlap between physical and mental conditions and their impact on severity and functional impairment in youth. Specific patterns of comorbidity have important implications for etiology. Prospective tracking of cross-disorder morbidity will be important to establish more effective mechanisms for prevention and intervention. C1 [Merikangas, Kathleen R.; Burstein, Marcy; He, Jian-Ping; Lateef, Tarannum] NIMH, Genet Epidemiol Res Branch, Div Intramural Res Program, Bethesda, MD 20892 USA. [Lehner, Thomas] NIMH, Translat Genom Branch, Bethesda, MD 20892 USA. [Calkins, Monica E.; Ruparel, Kosha; Gur, Ruben C.; Gur, Raquel E.] Univ Penn, Neuropsychiat Sect, Perelman Sch Med, Philadelphia, PA 19104 USA. [Calkins, Monica E.; Ruparel, Kosha; Gur, Ruben C.; Gur, Raquel E.] Univ Penn, Brain Behav Lab, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hakonarson, Hakon] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chiavacci, Rosetta; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Lateef, Tarannum] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, 35 Convent Dr,1A-201,MSC 3720, Bethesda, MD 20892 USA. EM merikank@mail.nih.gov FU National Institute of Mental Health [5RC2MH089983, K08MH079364]; Intramural Research Program of the National Institute of Mental Health [Z-01-MH002931]; National Institutes of Health (NIH) FX Supported by National Institute of Mental Health grants 5RC2MH089983 (Drs Gur and Hakonarson, principal investigators) and K08MH079364 (Dr Calkins) and grant Z-01-MH002931 from the Intramural Research Program of the National Institute of Mental Health (Dr Merikangas). Funded by the National Institutes of Health (NIH). NR 75 TC 13 Z9 13 U1 1 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD APR PY 2015 VL 135 IS 4 BP E927 EP E938 DI 10.1542/peds.2014-1444 PG 12 WC Pediatrics SC Pediatrics GA CH0QG UT WOS:000353726700016 PM 25755242 ER PT J AU Kim, S Lewis, AE Singh, V Ma, XF Adelstein, R Bush, JO AF Kim, Seungil Lewis, Ace E. Singh, Vivek Ma, Xuefei Adelstein, Robert Bush, Jeffrey O. TI Convergence and Extrusion Are Required for Normal Fusion of the Mammalian Secondary Palate SO PLOS BIOLOGY LA English DT Article ID NONMUSCLE MYOSIN-II; PROGRAMMED CELL-DEATH; EDGE EPITHELIAL-CELLS; NONSYNDROMIC CLEFT-LIP; NEURAL-TUBE CLOSURE; DORSAL CLOSURE; MESENCHYMAL TRANSFORMATION; HEAVY-CHAIN; MOLECULAR-MECHANISMS; F-ACTIN AB The fusion of two distinct prominences into one continuous structure is common during development and typically requires integration of two epithelia and subsequent removal of that intervening epithelium. Using confocal live imaging, we directly observed the cellular processes underlying tissue fusion, using the secondary palatal shelves as a model. We find that convergence of a multi-layered epithelium into a single-layer epithelium is an essential early step, driven by cell intercalation, and is concurrent to orthogonal cell displacement and epithelial cell extrusion. Functional studies in mice indicate that this process requires an actomyosin contractility pathway involving Rho kinase (ROCK) and myosin light chain kinase (MLCK), culminating in the activation of non-muscle myosin IIA (NMIIA). Together, these data indicate that actomyosin contractility drives cell intercalation and cell extrusion during palate fusion and suggest a general mechanism for tissue fusion in development. C1 [Kim, Seungil; Lewis, Ace E.; Singh, Vivek; Bush, Jeffrey O.] Univ Calif San Francisco, Dept Cell & Tissue Biol, Program Craniofacial Biol, San Francisco, CA 94143 USA. [Kim, Seungil; Lewis, Ace E.; Singh, Vivek; Bush, Jeffrey O.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Ma, Xuefei; Adelstein, Robert] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Kim, S (reprint author), Univ Calif San Francisco, Dept Cell & Tissue Biol, Program Craniofacial Biol, San Francisco, CA 94143 USA. EM Jeffrey.bush@ucsf.edu OI Adelstein, Robert/0000-0002-8683-2144 FU National Institute of Dental and Craniofacial Research [R03DE22818, R01DE023337, R00DE020855] FX This work was supported by grants R03DE22818, R01DE023337 and R00DE020855 from the National Institute of Dental and Craniofacial Research (http://www.nidcr.nih.gov/) to JOB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 6 Z9 6 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD APR PY 2015 VL 13 IS 4 AR e1002122 DI 10.1371/journal.pbio.1002122 PG 24 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA CI5UE UT WOS:000354824500015 PM 25848986 ER PT J AU Kucharski, AJ Edmunds, WJ AF Kucharski, Adam J. Edmunds, W. John TI Characterizing the Transmission Potential of Zoonotic Infections from Minor Outbreaks SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID INFLUENZA-A H7N9; SIZE DISTRIBUTION; SOCIAL CONTACTS; MIXING PATTERNS; HUMAN MONKEYPOX; DISEASES; SPREAD; EMERGENCE; EPIDEMIC; VIRUS AB The transmission potential of a novel infection depends on both the inherent transmissibility of a pathogen, and the level of susceptibility in the host population. However, distinguishing between these pathogen- and population-specific properties typically requires detailed serological studies, which are rarely available in the early stages of an outbreak. Using a simple transmission model that incorporates age-stratified social mixing patterns, we present a novel method for characterizing the transmission potential of subcritical infections, which have effective reproduction number R<1, from readily available data on the size of outbreaks. We show that the model can identify the extent to which outbreaks are driven by inherent pathogen transmissibility and pre-existing population immunity, and can generate unbiased estimates of the effective reproduction number. Applying the method to real-life infections, we obtained accurate estimates for the degree of age-specific immunity against monkeypox, influenza A(H5N1) and A(H7N9), and refined existing estimates of the reproduction number. Our results also suggest minimal pre-existing immunity to MERS-CoV in humans. The approach we describe can therefore provide crucial information about novel infections before serological surveys and other detailed analyses are available. The methods would also be applicable to data stratified by factors such as profession or location, which would make it possible to measure the transmission potential of emerging infections in a wide range of settings. C1 [Kucharski, Adam J.; Edmunds, W. John] Univ London London Sch Hyg & Trop Med, Ctr Math Modelling Infect Dis, London WC1E 7HT, England. [Kucharski, Adam J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Kucharski, AJ (reprint author), Univ London London Sch Hyg & Trop Med, Ctr Math Modelling Infect Dis, Keppel St, London WC1E 7HT, England. EM adam.kucharski@lshtm.ac.uk FU Medical Research Council [MR/K021524/1]; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX AJK was supported by the Medical Research Council (www.mrc.ac.uk, fellowship MR/K021524/1) and the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 2 Z9 2 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2015 VL 11 IS 4 AR e1004154 DI 10.1371/journal.pcbi.1004154 PG 17 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CI1PX UT WOS:000354517600022 PM 25860289 ER PT J AU Lindstrom, T Tildesley, M Webb, C AF Lindstrom, Tom Tildesley, Michael Webb, Colleen TI A Bayesian Ensemble Approach for Epidemiological Projections SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID MOUTH-DISEASE; VACCINATION STRATEGIES; MULTIMODEL ENSEMBLES; INFECTIOUS-DISEASES; SIMULATION-MODEL; CLIMATE-CHANGE; FOOT; SPREAD; FUTURE; UNCERTAINTY AB Mathematical models are powerful tools for epidemiology and can be used to compare control actions. However, different models and model parameterizations may provide different prediction of outcomes. In other fields of research, ensemble modeling has been used to combine multiple projections. We explore the possibility of applying such methods to epidemiology by adapting Bayesian techniques developed for climate forecasting. We exemplify the implementation with single model ensembles based on different parameterizations of the Warwick model run for the 2001 United Kingdom foot and mouth disease outbreak and compare the efficacy of different control actions. This allows us to investigate the effect that discrepancy among projections based on different modeling assumptions has on the ensemble prediction. A sensitivity analysis showed that the choice of prior can have a pronounced effect on the posterior estimates of quantities of interest, in particular for ensembles with large discrepancy among projections. However, by using a hierarchical extension of the method we show that prior sensitivity can be circumvented. We further extend the method to include a priori beliefs about different modeling assumptions and demonstrate that the effect of this can have different consequences depending on the discrepancy among projections. We propose that the method is a promising analytical tool for ensemble modeling of disease outbreaks. C1 [Lindstrom, Tom] Linkoping Univ, Dept Phys Chem & Biol, Linkoping, Sweden. [Lindstrom, Tom; Webb, Colleen] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. [Lindstrom, Tom; Tildesley, Michael; Webb, Colleen] US Natl Inst Hlth, Bethesda, MD USA. [Lindstrom, Tom] Univ Exeter, Exeter, Devon, England. [Tildesley, Michael] Univ Nottingham, Sch Vet Med & Sci, Nottingham, Leics, England. RP Lindstrom, T (reprint author), Linkoping Univ, Dept Phys Chem & Biol, Linkoping, Sweden. EM tomli@ifm.liu.se FU RAPIDD program of the Science & Technology Directorate; Fogarty International Center, National Institutes of Health FX This work was supported by the RAPIDD program of the Science & Technology Directorate and the Fogarty International Center, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 10 Z9 10 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2015 VL 11 IS 4 AR e1004187 DI 10.1371/journal.pcbi.1004187 PG 30 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CI1PX UT WOS:000354517600035 PM 25927892 ER PT J AU Lokanga, RA Senejani, AG Sweasy, JB Usdin, K AF Lokanga, Rachel Adihe Senejani, Alireza Ghodsi Sweasy, Joann Balazs Usdin, Karen TI Heterozygosity for a Hypomorphic Pol beta Mutation Reduces the Expansion Frequency in a Mouse Model of the Fragile X-Related Disorders SO PLOS GENETICS LA English DT Article ID DNA-POLYMERASE-BETA; BASE EXCISION-REPAIR; TRINUCLEOTIDE REPEAT INSTABILITY; MISMATCH REPAIR; TRANSGENIC MICE; TRIPLET-REPEAT; CGG REPEATS; HUMAN-CELLS; GERM-CELLS; MUTS-BETA AB The Fragile X-related disorders (FXDs) are members of the Repeat Expansion Diseases, a group of human genetic conditions resulting from expansion of a specific tandem repeat. The FXDs result from expansion of a CGG/CCG repeat tract in the 5' UTR of the FMR1 gene. While expansion in a FXD mouse model is known to require some mismatch repair (MMR) proteins, our previous work and work in mouse models of another Repeat Expansion Disease show that early events in the base excision repair (BER) pathway play a role in the expansion process. One model for repeat expansion proposes that a non-canonical MMR process makes use of the nicks generated early in BER to load the MMR machinery that then generates expansions. However, we show here that heterozygosity for a Y265C mutation in Pol beta, a key polymerase in the BER pathway, is enough to significantly reduce both the number of expansions seen in paternal gametes and the extent of somatic expansion in some tissues of the FXD mouse. These data suggest that events in the BER pathway downstream of the generation of nicks are also important for repeat expansion. Somewhat surprisingly, while the number of expansions is smaller, the average size of the residual expansions is larger than that seen in WT animals. This may have interesting implications for the mechanism by which BER generates expansions. C1 [Lokanga, Rachel Adihe; Usdin, Karen] NIDDK, Sect Gene Struct & Dis, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. [Lokanga, Rachel Adihe] Univ Cape Town, Sch Med, Dept Biochem, ZA-7925 Cape Town, South Africa. [Senejani, Alireza Ghodsi; Sweasy, Joann Balazs] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. [Senejani, Alireza Ghodsi; Sweasy, Joann Balazs] Yale Univ, Sch Med, Dept Human Genet, New Haven, CT 06510 USA. RP Lokanga, RA (reprint author), NIDDK, Sect Gene Struct & Dis, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. EM ku@helix.nih.gov FU National Institute of Diabetes, Digestive and Kidney Diseases [DK057808-07]; National Institute of Environmental Health Sciences [R01ES019179] FX Funding for this work was made possible by a grant from the Intramural program (IRP) of the National Institute of Diabetes, Digestive and Kidney Diseases to KU (DK057808-07). The research was also supported by R01ES019179 from the National Institute of Environmental Health Sciences to JBS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 8 Z9 8 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2015 VL 11 IS 4 AR e1005181 DI 10.1371/journal.pgen.1005181 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA CI1SH UT WOS:000354524200059 PM 25886163 ER PT J AU Ramos, CI Igiesuorobo, O Wang, Q Serpe, M AF Ramos, Cathy I. Igiesuorobo, Oghomwen Wang, Qi Serpe, Mihaela TI Neto-Mediated Intracellular Interactions Shape Postsynaptic Composition at the Drosophila Neuromuscular Junction SO PLOS GENETICS LA English DT Article ID IONOTROPIC GLUTAMATE RECEPTORS; KAINATE RECEPTORS; STRUCTURAL PLASTICITY; SYNAPTIC PLASTICITY; AUXILIARY SUBUNITS; IN-VIVO; PROTEIN; AMPA; SYNAPSES; LOCALIZATION AB The molecular mechanisms controlling the subunit composition of glutamate receptors are crucial for the formation of neural circuits and for the long-term plasticity underlying learning and memory. Here we use the Drosophila neuromuscular junction (NMJ) to examine how specific receptor subtypes are recruited and stabilized at synaptic locations. In flies, clustering of ionotropic glutamate receptors (iGluRs) requires Neto (Neuropillin and Tolloid-like), a highly conserved auxiliary subunit that is essential for NMJ assembly and development. Drosophila neto encodes two isoforms, Neto-alpha and Neto-beta, with common extracellular parts and distinct cytoplasmic domains. Mutations that specifically eliminate Neto-beta or its intracellular domain were generated. When Neto-beta is missing or is truncated, the larval NMJs show profound changes in the subtype composition of iGluRs due to reduced synaptic accumulation of the GluRIIA subunit. Furthermore, neto-beta mutant NMJs fail to accumulate p21-activated kinase (PAK), a critical postsynaptic component implicated in the synaptic stabilization of GluRIIA. Muscle expression of either Neto-alpha or Neto-beta rescued the synaptic transmission at neto null NMJs, indicating that Neto conserved domains mediate iGluRs clustering. However, only Neto-beta restored PAK synaptic accumulation at neto null NMJs. Thus, Neto engages in intracellular interactions that regulate the iGluR subtype composition by preferentially recruiting and/or stabilizing selective receptor subtypes. C1 [Ramos, Cathy I.; Igiesuorobo, Oghomwen; Wang, Qi; Serpe, Mihaela] NICHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA. RP Ramos, CI (reprint author), NICHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA. EM mihaela.serpe@nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; [ZIA HD008914 03]; [ZIA HD008869 05] FX This work was supported by grants: ZIA HD008914 03 and ZIA HD008869 05, Eunice Kennedy Shriver National Institute of Child Health and Human Development (https://www.nichd.nih.gov/about/org/dir/Pages/index.aspx), Intramural Program of the National Institutes of Health, awarded to MS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 2 Z9 2 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2015 VL 11 IS 4 AR e1005191 DI 10.1371/journal.pgen.1005191 PG 26 WC Genetics & Heredity SC Genetics & Heredity GA CI1SH UT WOS:000354524200066 PM 25905467 ER PT J AU Samad, H Coll, F Preston, MD Ocholla, H Fairhurst, RM Clark, TG AF Samad, Hanif Coll, Francesc Preston, Mark D. Ocholla, Harold Fairhurst, Rick M. Clark, Taane G. TI Imputation-Based Population Genetics Analysis of Plasmodium falciparum Malaria Parasites SO PLOS GENETICS LA English DT Article ID RECENT POSITIVE SELECTION; NATURAL-SELECTION; RECOMBINATION HOTSPOTS; GENOTYPE IMPUTATION; HAPLOTYPE STRUCTURE; DRUG-RESISTANCE; HUMAN GENOME; R PACKAGE; SEQUENCE; SCANS AB Whole-genome sequencing technologies are being increasingly applied to Plasmodium falciparum clinical isolates to identify genetic determinants of malaria pathogenesis. However, genome-wide discovery methods, such as haplotype scans for signatures of natural selection, are hindered by missing genotypes in sequence data. Poor correlation between single nucleotide polymorphisms (SNPs) in the P. falciparum genome complicates efforts to apply established missing-genotype imputation methods that leverage off patterns of linkage disequilibrium (LD). The accuracy of state-of-the-art, LD-based imputation methods (IMPUTE, Beagle) was assessed by measuring allelic r(2) for 459 P. falciparum samples from malaria patients in 4 countries: Thailand, Cambodia, Gambia, and Malawi. In restricting our analysis to 86k high-quality SNPs across the populations, we found that the complete-case analysis was restricted to 21k SNPs (24.5%), despite no single SNP having more than 10% missing genotypes. The accuracy of Beagle in filling in missing genotypes was consistently high across all populations (allelic r(2), 0.87-0.96), but the performance of IMPUTE was mixed (allelic r(2), 0.34-0.99) depending on reference haplotypes and population. Positive selection analysis using Beagle-imputed haplotypes identified loci involved in resistance to chloroquine (crt) in Thailand, Cambodia, and Gambia, sulfadoxine-pyrimethamine (dhfr, dhps) in Cambodia, and artemisinin (kelch13) in Cambodia. Tajima's D-based analysis identified genes under balancing selection that encode well-characterized vaccine candidates: apical merozoite antigen 1 (ama1) and merozoite surface protein 1 (msp1). In contrast, the complete- case analysis failed to identify any well-validated drug resistance or candidate vaccine loci, except kelch13. In a setting of low LD and modest levels of missing genotypes, using Beagle to impute P. falciparum genotypes is a viable strategy for conducting accurate large-scale population genetics and association analyses, and supporting global surveillance for drug resistance markers and candidate vaccine antigens. C1 [Samad, Hanif; Coll, Francesc; Preston, Mark D.; Clark, Taane G.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London WC1, England. [Ocholla, Harold] Malawi Liverpool Wellcome Trust Clin Res Programm, Blantyre, Malawi. [Ocholla, Harold] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. [Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Clark, Taane G.] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England. RP Samad, H (reprint author), London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London WC1, England. EM taane.clark@lshtm.ac.uk RI Preston, Mark/P-1429-2015 OI Preston, Mark/0000-0002-6506-3104 FU Singaporean Ministry of Health Healthcare Scholarship; Malaria Capacity Development Consortium - Wellcome Trust [WT084289MA]; Medical Research Council UK [MR/K000551/1]; Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This work was supported by a Singaporean Ministry of Health Healthcare Scholarship, the Malaria Capacity Development Consortium, which is funded by The Wellcome Trust (grant number WT084289MA), the Medical Research Council UK (MR/K000551/1) and the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 5 Z9 5 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2015 VL 11 IS 4 AR e1005131 DI 10.1371/journal.pgen.1005131 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA CI1SH UT WOS:000354524200029 PM 25928499 ER PT J AU Mallucci, G Peruzzotti-Jametti, L Bernstock, JD Pluchino, S AF Mallucci, Giulia Peruzzotti-Jametti, Luca Bernstock, Joshua D. Pluchino, Stefano TI The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Neuroimmunology; Multiple sclerosis; Inflammation; Demyelination; Regeneration; Immune modulation ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EPSTEIN-BARR-VIRUS; CLINICALLY ISOLATED SYNDROMES; PLACEBO-CONTROLLED TRIAL; CENTRAL-NERVOUS-SYSTEM; MYELIN BASIC-PROTEIN; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CONTROLLED PHASE-3 TRIAL; MESENCHYMAL STEM-CELLS; TUMOR-NECROSIS-FACTOR AB Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in-nature, yet increasing correlative evidence supports a strong association between one's genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Mallucci, Giulia; Peruzzotti-Jametti, Luca; Bernstock, Joshua D.; Pluchino, Stefano] Univ Cambridge, Wellcome Trust MRC Stem Cell Inst, John van Geest Ctr Brain Repair, Dept Clin Neurosci, Cambridge CB2 0PY, England. [Mallucci, Giulia; Peruzzotti-Jametti, Luca; Bernstock, Joshua D.; Pluchino, Stefano] Univ Cambridge, NIHR Biomed Res Ctr, Cambridge CB2 0PY, England. [Mallucci, Giulia] Univ Pavia, Natl Neurol Inst C Mondino, Dept Brain & Behav Sci, I-27100 Pavia, Italy. [Bernstock, Joshua D.] NINDS, NIH, Bethesda, MD 20892 USA. RP Pluchino, S (reprint author), Univ Cambridge, Wellcome Trust MRC Stem Cell Inst, John van Geest Ctr Brain Repair, Dept Clin Neurosci, Cambridge CB2 0PY, England. EM spp24@cam.ac.uk FU National Multiple Sclerosis Society (NMSS) [RG-4001-A1]; Italian Multiple Sclerosis Foundation (FISM) [RG 2010/R/31]; Italian Ministry of Health [GR08/7]; European Research Council (ERC) [RG 260511-SEM_SEM]; European Community (EC) [RG 280772-iONE]; Evelyn Trust [RG 69865]; Bascule Charitable Trust [RG 75149]; Great Britain Sakakawa Foundation; Wellcome Trust [RRZA/057 RG79423]; MRC; European Neurological Society (ENS) Training fellowship; NIH-OxCam fellowship FX Research in the author's laboratory is supported by the National Multiple Sclerosis Society (NMSS; RG-4001-A1), the Italian Multiple Sclerosis Foundation (FISM; RG 2010/R/31), the Italian Ministry of Health (GR08/7) the European Research Council (ERC) 2010-StG (RG 260511-SEM_SEM), the European Community (EC) 7th Framework Program (FP7/2007-2013; RG 280772-iONE), The Evelyn Trust (RG 69865), The Bascule Charitable Trust (RG 75149), The Great Britain Sakakawa Foundation and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute. GM was supported by an European Neurological Society (ENS) Training fellowship. LPJ was supported by the Wellcome Trust [RRZA/057 RG79423]. JDB was supported by a NIH-OxCam fellowship. NR 294 TC 15 Z9 16 U1 7 U2 27 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD APR PY 2015 VL 127 BP 1 EP 22 DI 10.1016/j.pneurobio.2015.02.003 PG 22 WC Neurosciences SC Neurosciences & Neurology GA CI8WA UT WOS:000355051200001 PM 25802011 ER PT J AU Xiao, L Huang, L Schrack, JA Ferrucci, L Zipunnikov, V Crainiceanu, CM AF Xiao, Luo Huang, Lei Schrack, Jennifer A. Ferrucci, Luigi Zipunnikov, Vadim Crainiceanu, Ciprian M. TI Quantifying the lifetime circadian rhythm of physical activity: a covariate-dependent functional approach SO BIOSTATISTICS LA English DT Article DE Accelerometer; Bivariate smoothing; Covariance; Sandwich smoother; Trivariate smoothing ID PRINCIPAL COMPONENT ANALYSIS; MIXED EFFECTS MODELS; REGRESSION; SPLINES; ACCELEROMETERS; MEDICINE AB Objective measurement of physical activity using wearable devices such as accelerometers may provide tantalizing new insights into the association between activity and health outcomes. Accelerometers can record quasi-continuous activity information for many days and for hundreds of individuals. For example, in the Baltimore Longitudinal Study on Aging physical activity was recorded every minute for 773 adults for an average of 7 days per adult. An important scientific problem is to separate and quantify the systematic and random circadian patterns of physical activity as functions of time of day, age, and gender. To capture the systematic circadian pattern, we introduce a practical bivariate smoother and two crucial innovations: (i) estimating the smoothing parameter using leave-one-subject-out cross validation to account for within-subject correlation and (ii) introducing fast computational techniques that overcome problems both with the size of the data and with the cross-validation approach to smoothing. The age-dependent random patterns are analyzed by a new functional principal component analysis that incorporates both covariate dependence and multilevel structure. For the analysis, we propose a practical and very fast trivariate spline smoother to estimate covariate-dependent covariances and their spectra. Results reveal several interesting, previously unknown, circadian patterns associated with human aging and gender. C1 [Xiao, Luo; Huang, Lei; Zipunnikov, Vadim; Crainiceanu, Ciprian M.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Schrack, Jennifer A.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA. [Schrack, Jennifer A.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21225 USA. RP Xiao, L (reprint author), Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. EM lxiao16@jhu.edu FU National Institute of Neurological Disorders and Stroke [R01NS060910] FX This work was supported by Grant Number R01NS060910 from the National Institute of Neurological Disorders and Stroke. This work represents the opinions of the researchers and not necessarily that of the granting organizations. NR 35 TC 5 Z9 5 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 EI 1468-4357 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2015 VL 16 IS 2 BP 352 EP 367 DI 10.1093/biostatistics/kxu045 PG 16 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA CI3JV UT WOS:000354644900011 PM 25361695 ER PT J AU Foster, JC Taylor, JMG Kaciroti, N Nan, B AF Foster, Jared C. Taylor, Jeremy M. G. Kaciroti, Niko Nan, Bin TI Simple subgroup approximations to optimal treatment regimes from randomized clinical trial data SO BIOSTATISTICS LA English DT Article DE Optimal treatment regimes; Personalized medicine; Subgroup analysis; Variable selection ID VARIABLE SELECTION; IDENTIFICATION; VALIDATION; DECISION; MODELS; LASSO AB We consider the use of randomized clinical trial (RCT) data to identify simple treatment regimes based on some subset of the covariate space, A. The optimal subset, (A) over cap, is selected by maximizing the expected outcome under a treat-if-in-A regime, and is restricted to be a simple, as it is desirable that treatment decisions be made with only a limited amount of patient information required. We consider a two-stage procedure. In stage 1, non-parametric regression is used to estimate treatment effects for each subject, and in stage 2 these treatment effect estimates are used to systematically evaluate many subgroups of a simple, prespecified form to identify (A) over cap. The proposed methods were found to perform favorably compared with two existing methods in simulations, and were applied to prehypertension data from an RCT. C1 [Foster, Jared C.; Taylor, Jeremy M. G.; Kaciroti, Niko; Nan, Bin] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Foster, Jared C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA. RP Foster, JC (reprint author), Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. EM jared.foster@nih.gov OI Kaciroti, Niko/0000-0001-8843-8231 FU Eli Lilly; National Science Foundation [DMS-1007590]; National Institutes of Health (NIH) [CA083654, AG036802]; Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was partially supported by a grant from Eli Lilly, grant DMS-1007590 from the National Science Foundation, grants CA083654 and AG036802 from the National Institutes of Health (NIH), and the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 24 TC 2 Z9 2 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 EI 1468-4357 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2015 VL 16 IS 2 BP 368 EP 382 DI 10.1093/biostatistics/kxu049 PG 15 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA CI3JV UT WOS:000354644900012 PM 25398774 ER PT J AU Cheng, SY AF Cheng, Sheue-yann TI My journey to unravel complex actions of thyroid hormone: was it fate or destiny? SO ENDOCRINE-RELATED CANCER LA English DT Editorial Material ID 3,3,5-TRIIODO-L-THYRONINE BINDING-PROTEIN; RECEPTOR COREPRESSOR NCOR1; CARCINOMA CELL-LINE; MOUSE MODEL; BETA-RECEPTOR; TUMOR PROGRESSION; CULTURED FIBROBLASTS; TARGETED MUTATION; NUCLEAR RECEPTORS; IN-VIVO C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov NR 49 TC 0 Z9 0 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD APR PY 2015 VL 22 IS 2 BP P1 EP P10 DI 10.1530/ERC-15-0056 PG 10 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA CI3CC UT WOS:000354624100002 PM 25662575 ER PT J AU Reaves, DK Ginsburg, E Bang, JJ Fleming, JM AF Reaves, Denise K. Ginsburg, Erika Bang, John J. Fleming, Jodie M. TI Persistent organic pollutants and obesity: are they potential mechanisms for breast cancer promotion? SO ENDOCRINE-RELATED CANCER LA English DT Review DE breast cancer; persistent organic pollutants; obesity; metabolism ID FATTY-ACID SYNTHASE; SUBCUTANEOUS ADIPOSE-TISSUE; OCCUPATIONAL SOCIAL-CLASS; LACTATING MAMMARY-GLAND; PERFLUORINATED COMPOUNDS; POLYCHLORINATED-BIPHENYLS; ORGANOCHLORINE PESTICIDES; GENE-EXPRESSION; WEIGHT-GAIN; CELL-LINES AB Dietary ingestion of persistent organic pollutants (POPs) is correlated with the development of obesity. Obesity alters metabolism, induces an inflammatory tissue microenvironment, and is also linked to diabetes and breast cancer risk/promotion of the disease. However, no direct evidence exists with regard to the correlation among all three of these factors ( POPs, obesity, and breast cancer). Herein, we present results from current correlative studies indicating a causal link between POP exposure through diet and their bioaccumulation in adipose tissue that promotes the development of obesity and ultimately influences breast cancer development and/or progression. Furthermore, as endocrine disruptors, POPs could interfere with hormonally responsive tissue functions causing dysregulation of hormone signaling and cell function. This review highlights the critical need for advanced in vitro and in vivo model systems to elucidate the complex relationship among obesity, POPs, and breast cancer, and, more importantly, to delineate their multifaceted molecular, cellular, and biochemical mechanisms. Comprehensive in vitro and in vivo studies directly testing the observed correlations as well as detailing their molecular mechanisms are vital to cancer research and, ultimately, public health. C1 [Reaves, Denise K.; Fleming, Jodie M.] N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA. [Ginsburg, Erika] NCI, NIH, Ctr Canc Training, Bethesda, MD 20892 USA. [Bang, John J.] N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA. RP Fleming, JM (reprint author), N Carolina Cent Univ, Dept Biol, MTSC Room 2247,1801 Fayetteville St, Durham, NC 27707 USA. EM Jodie.fleming@nccu.edu FU National Cancer Institute [U54 CA156735, R21 CA175783]; National Institute of General Medical Sciences [SC2 GM102012]; Intramural Research Program of the NIH, NCI FX This work was supported by funding from the National Cancer Institute (U54 CA156735 and R21 CA175783) and the National Institute of General Medical Sciences (SC2 GM102012). This work was supported in part by the Intramural Research Program of the NIH, NCI. NR 174 TC 6 Z9 6 U1 9 U2 28 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD APR PY 2015 VL 22 IS 2 BP R69 EP R86 DI 10.1530/ERC-14-0411 PG 18 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA CI3CC UT WOS:000354624100003 PM 25624167 ER PT J AU Chertow, DS Uyeki, TM DuPont, HL AF Chertow, Daniel S. Uyeki, Timothy M. DuPont, Herbert L. TI Loperamide Therapy for Voluminous Diarrhea in Ebola Virus Disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material DE Ebola; loperamide; diarrhea; gastrointestinal losses; hypovolemia C1 [Chertow, Daniel S.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Uyeki, Timothy M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [DuPont, Herbert L.] Univ Texas Sch Publ Hlth, Ctr Infect Dis, Houston, TX USA. RP Chertow, DS (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,2C-145, Bethesda, MD 20892 USA. EM chertowd@cc.nih.gov NR 11 TC 7 Z9 7 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2015 VL 211 IS 7 BP 1036 EP 1037 DI 10.1093/infdis/jiv001 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CI4DQ UT WOS:000354697500002 PM 25573887 ER PT J AU Gullingsrud, J Milman, N Saveria, T Chesnokov, O Williamson, K Srivastava, A Gamain, B Duffy, PE Oleinikov, AV AF Gullingsrud, Justin Milman, Neta Saveria, Tracy Chesnokov, Olga Williamson, Kathryn Srivastava, Anand Gamain, Benoit Duffy, Patrick E. Oleinikov, Andrew V. TI High-Throughput Screening Platform Identifies Small Molecules That Prevent Sequestration of Plasmodium falciparum-Infected Erythrocytes SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE malaria; Plasmodium falciparum; sequestration of parasites; antiadhesion therapy; high-throughput screening; PfEMP1 proteins; host receptors; CD36; ICAM-1; CSA; small molecules ID CHONDROITIN SULFATE-A; PLACENTAL MALARIA; BINDING; DOMAINS; VAR2CSA; VARIANT; ANTIBODIES; PARASITES; ANTIGENS; ADHESION AB Background. We developed a 2-step approach to screen molecules that prevent and/or reverse Plasmodium falciparum-infected erythrocyte (IE) binding to host receptors. IE adhesion and sequestration in vasculature causes severe malaria, and therefore antiadhesion therapy might be useful as adjunctive treatment. IE adhesion is mediated by the polymorphic family (approximately 60 members) of P. falciparum EMP1 (PfEMP1) multidomain proteins. Methods. We constructed sets of PfEMP1 domains that bind ICAM-1, CSA, or CD36, receptors that commonly support IE binding. Combinations of domain-coated beads were assayed by Bio-Plex technology as a high-throughput molecular platform to screen antiadhesion molecules (antibodies and small molecules). Molecules identified as so-called hits in the screen (first step) then could be assayed individually for inhibition of binding of live IE to receptors (second step). Results. In proof-of-principle studies, the antiadhesion activity of several antibodies was concordant in Bio-Plex and live IE assays. Using this 2-step approach, we identified several molecules in a small molecule library of 10 000 compounds that could inhibit and reverse binding of IEs to ICAM-1 and CSA receptors. Conclusion. This 2-step screening approach should be efficient for identification of antiadhesion drug candidates for falciparum malaria. C1 [Gullingsrud, Justin; Milman, Neta; Saveria, Tracy; Williamson, Kathryn; Oleinikov, Andrew V.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Chesnokov, Olga; Oleinikov, Andrew V.] Florida Atlantic Univ, Dept Biomed Sci, Charles E Schmidt Coll Med, Boca Raton, FL 33431 USA. [Duffy, Patrick E.] NIH, Lab Malaria Immunol & Vaccinol, Bethesda, MD 20892 USA. [Srivastava, Anand; Gamain, Benoit] INSERM, UMR 1134, Paris, France. [Srivastava, Anand; Gamain, Benoit] Univ Paris Diderot, Sorbonne Paris Cite, UMR S1134, Paris, France. [Srivastava, Anand; Gamain, Benoit] Inst Natl Transfus Sanguine, F-75015 Paris, France. RP Oleinikov, AV (reprint author), Florida Atlantic Univ, Coll Med, 777 Glades Rd,BC-71, Boca Raton, FL 33431 USA. EM aoleinikov@fau.edu RI SRIVASTAVA, ANAND/C-9609-2012; OI SRIVASTAVA, ANAND/0000-0002-2031-4643; Gamain, Benoit/0000-0002-8255-2145 FU Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative - Bill and Melinda Gates Foundation [1364]; National Institutes of Health [1R56AI083668, 5R01HD058005, 5R01AI092120] FX This work was supported by the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative, which is funded by the Bill and Melinda Gates Foundation (grant 1364 to P. E. D.) and by the National Institutes of Health (grants 1R56AI083668, 5R01HD058005, and 5R01AI092120 to A. V. O.). NR 31 TC 2 Z9 2 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2015 VL 211 IS 7 BP 1134 EP 1143 DI 10.1093/infdis/jiu589 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CI4DQ UT WOS:000354697500015 PM 25355939 ER PT J AU Pai, M Schito, M AF Pai, Madhukar Schito, Marco TI Tuberculosis Diagnostics in 2015: Landscape, Priorities, Needs, and Prospects SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE tuberculosis; diagnostics; pipeline; unmet needs; market potential ID CHILDHOOD TUBERCULOSIS; MICROSCOPY CENTERS; XPERT MTB/RIF; COUNTRIES; REGIMENS; AFRICA AB In 2015, tuberculosis remains a major global health problem, and drug-resistant tuberculosis is a growing threat. Although tuberculosis diagnosis in many countries is still reliant on older tools, new diagnostics are changing the landscape. Stimulated, in part, by the success and roll out of Xpert MTB/RIF, there is now considerable interest in new technologies. The landscape looks promising, with a robust pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development. However, new diagnostics are yet to reach scale, and there needs to be greater convergence between diagnostics development and development of shorter-duration tuberculosis drug regimens. Another concern is the relative absence of non-sputum-based diagnostics in the pipeline for children and of biomarker tests for triage, cure, and progression of latent Mycobacterium tuberculosis infection. Several initiatives, described in this supplement, have been launched to further stimulate product development and policy, including assessment of needs and priorities, development of target product profiles, compilation of data on resistance-associated mutations, and assessment of market size and potential for new diagnostics. Advocacy is needed to increase funding for tuberculosis research and development, and governments in high-burden countries must invest more in tuberculosis control to meet post-2015 targets for care, control, and prevention. C1 [Pai, Madhukar] McGill Univ, McGill Int TB Ctr, Montreal, PQ H3A 1A2, Canada. [Pai, Madhukar] McGill Univ, McGill Global Hlth Programs, Montreal, PQ H3A 1A2, Canada. [Schito, Marco] NIH, Div Aids, Henry M Jackson Fdn Adv Mil Med, US Dept HHS, Bethesda, MD 20892 USA. RP Pai, M (reprint author), McGill Univ, Dept Epidemiol & Biostat, McGill Global Hlth Programs, 1020 Pine Ave West, Montreal, PQ H3A 1A2, Canada. EM madhukar.pai@mcgill.ca FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200800014C] FX This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services (contract HHSN272200800014C to M. S.). NR 35 TC 41 Z9 42 U1 2 U2 22 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2015 VL 211 SU 2 BP S21 EP S28 DI 10.1093/infdis/jiu803 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CI4DZ UT WOS:000354698600001 PM 25765103 ER PT J AU Salamon, H Yamaguchi, KD Cirillo, DM Miotto, P Schito, M Posey, J Starks, AM Niemann, S Alland, D Hanna, D Aviles, E Perkins, MD Dolinger, DL AF Salamon, Hugh Yamaguchi, Ken D. Cirillo, Daniela M. Miotto, Paolo Schito, Marco Posey, James Starks, Angela M. Niemann, Stefan Alland, David Hanna, Debra Aviles, Enrique Perkins, Mark D. Dolinger, David L. TI Integration of Published Information Into a Resistance-Associated Mutation Database for Mycobacterium tuberculosis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE tuberculosis; drug resistance; resistance-associated mutations; genomic sequencing; drug susceptibility testing; database ID DRUG; LABORATORIES; PROFICIENCY; GENES AB Tuberculosis remains a major global public health challenge. Although incidence is decreasing, the proportion of drug-resistant cases is increasing. Technical and operational complexities prevent Mycobacterium tuberculosis drug susceptibility phenotyping in the vast majority of new and retreatment cases. The advent of molecular technologies provides an opportunity to obtain results rapidly as compared to phenotypic culture. However, correlations between genetic mutations and resistance to multiple drugs have not been systematically evaluated. Molecular testing of M. tuberculosis sampled from a typical patient continues to provide a partial picture of drug resistance. A database of phenotypic and genotypic testing results, especially where prospectively collected, could document statistically significant associations and may reveal new, predictive molecular patterns. We examine the feasibility of integrating existing molecular and phenotypic drug susceptibility data to identify associations observed across multiple studies and demonstrate potential for well-integrated M. tuberculosis mutation data to reveal actionable findings. C1 [Salamon, Hugh; Yamaguchi, Ken D.] Knowledge Synth Inc, Berkeley, CA 94710 USA. [Cirillo, Daniela M.; Miotto, Paolo] IRCCS San Raffaele Sci Inst, Milan, Italy. [Schito, Marco] NIH, HJF DAIDS, DHHS, Bethesda, MD 20892 USA. [Posey, James; Starks, Angela M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Niemann, Stefan] Forschungszentrum Borstel, Borstel, Germany. [Alland, David] Rutgers State Univ, Piscataway, NJ 08855 USA. [Hanna, Debra; Aviles, Enrique] Crit Path Inst, Tucson, AZ USA. [Perkins, Mark D.; Dolinger, David L.] FIND, Geneva, Switzerland. RP Salamon, H (reprint author), Knowledge Synth Inc, 725 Folger Ave, Berkeley, CA 94710 USA. EM hugh@knowledgesynthesis.com RI Niemann, Stefan/C-9327-2011; Miotto, Paolo/E-3940-2017 OI Miotto, Paolo/0000-0003-4610-2427 FU Bill and Melinda Gates Foundation; Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200800014C] FX This work was supported by the Bill and Melinda Gates Foundation. M. S. is funded with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract HHSN272200800014C. The funders had no role in the analysis of data and decision to publish. NR 17 TC 7 Z9 7 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2015 VL 211 SU 2 BP S50 EP S57 DI 10.1093/infdis/jiu816 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CI4DZ UT WOS:000354698600004 PM 25765106 ER PT J AU Dosani, T Carlsten, M Maric, I Landgren, O AF Dosani, T. Carlsten, M. Maric, I. Landgren, O. TI The cellular immune system in myelomagenesis: NK cells and T cells in the development of MM and their uses in immunotherapies SO BLOOD CANCER JOURNAL LA English DT Review ID NATURAL-KILLER-CELLS; UNDETERMINED SIGNIFICANCE MGUS; PRECEDES MULTIPLE-MYELOMA; MONOCLONAL GAMMOPATHY; BONE-MARROW; PERIPHERAL-BLOOD; DENDRITIC CELLS; FLOW-CYTOMETRY; IN-VITRO; EFFECTOR FUNCTIONS AB As vast strides are being made in the management and treatment of multiple myeloma (MM), recent interests are increasingly focusing on understanding the development of the disease. The knowledge that MM develops exclusively from a protracted phase of monoclonal gammopathy of undetermined significance provides an opportunity to study tumor evolution in this process. Although the immune system has been implicated in the development of MM, the scientific literature on the role and status of various immune components in this process is broad and sometimes contradictory. Accordingly, we present a review of cellular immune subsets in myelomagenesis. We summarize the current literature on the quantitative and functional profiles of natural killer cells and T-cells, including conventional T-cells, natural killer T-cells, gamma delta T-cells and regulatory T-cells, in myelomagenesis. Our goal is to provide an overview of the status and function of these immune cells in both the peripheral blood and the bone marrow during myelomagenesis. This provides a better understanding of the nature of the immune system in tumor evolution, the knowledge of which is especially significant considering that immunotherapies are increasingly being explored in the treatment of both MM and its precursor conditions. C1 [Dosani, T.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Carlsten, M.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Maric, I.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Landgren, O.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Hematol Oncol, Myeloma Serv, New York, NY 10021 USA. RP Dosani, T (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bldg 10 Room 1N248,10 Ctr Dr, Bethesda, MD 20892 USA. EM talib.dosani@gmail.com; landgrec@mskcc.org FU NIH FX This research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc., The Doris Duke Charitable Foundation, The Alexandria Real Estate Equities, Inc. and Mr and Mrs Joel S Marcus and the Howard Hughes Medical Institute, as well as other private donors. For a complete list, please visit the Foundation website at: http://fnih.org/work/education-training-0/medical-research-scholars-prog ram. NR 100 TC 1 Z9 1 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD APR PY 2015 VL 5 DI 10.1038/bcj.2015.32 PG 9 WC Oncology SC Oncology GA CH5VB UT WOS:000354102400007 ER PT J AU Costa, VD Averbeck, BB AF Costa, Vincent D. Averbeck, Bruno B. TI Frontal-Parietal and Limbic-Striatal Activity Underlies Information Sampling in the Best Choice Problem SO CEREBRAL CORTEX LA English DT Article DE Bayesian; decision-making; fMRI ID PERCEPTUAL DECISION-MAKING; CORTEX; COMPUTATIONS; MECHANISMS; MODELS AB Best choice problems have a long mathematical history, but their neural underpinnings remain unknown. Best choice tasks are optimal stopping problem that require subjects to view a list of options one at a time and decide whether to take or decline each option. The goal is to find a high ranking option in the list, under the restriction that declined options cannot be chosen in the future. Conceptually, the decision to take or decline an option is related to threshold crossing in drift diffusion models, when this process is thought of as a value comparison. We studied this task in healthy volunteers using fMRI, and used a Markov decision process to quantify the value of continuing to search versus committing to the current option. Decisions to take versus decline an option engaged parietal and dorsolateral prefrontal cortices, as well ventral striatum, anterior insula, and anterior cingulate. Therefore, brain regions previously implicated in evidence integration and reward representation encode threshold crossings that trigger decisions to commit to a choice. C1 [Costa, Vincent D.; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49 Room 1B80,49 Convent Dr MSC 4415, Bethesda, MD 20892 USA. EM bruno.averbeck@nih.gov OI Costa, Vincent/0000-0002-5412-8945 FU National Institute of Mental Health FX This work was supported by the Intramural Research Program of the National Institute of Mental Health. We are grateful to Jessica Carson for her assistance with data collection. NR 29 TC 3 Z9 3 U1 2 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2015 VL 25 IS 4 BP 972 EP 982 DI 10.1093/cercor/bht286 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CH2EN UT WOS:000353838600013 PM 24142842 ER PT J AU Hammond, CJ Niciu, M Drew, S Arias, AJ AF Hammond, Christopher J. Niciu, Mark J. Drew, Shannon Arias, Albert J. TI Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders SO CNS DRUGS LA English DT Review ID PLACEBO-CONTROLLED-TRIAL; RANDOMIZED CONTROLLED-TRIAL; LOW-DOSE TOPIRAMATE; QUALITY-OF-LIFE; DOUBLE-BLIND; OPEN-LABEL; DEPENDENT PATIENTS; ANTIEPILEPTIC DRUGS; ORAL TOPIRAMATE; HEAVY DRINKING AB Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders. C1 [Hammond, Christopher J.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06520 USA. [Hammond, Christopher J.; Arias, Albert J.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Niciu, Mark J.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Drew, Shannon; Arias, Albert J.] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. RP Arias, AJ (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. EM christopher.hammond@yale.edu; albert.arias@yale.edu RI Arias, Albert/H-1334-2011; Niciu, Mark/J-1766-2014 OI Niciu, Mark/0000-0002-5612-3021 FU Intramural Research Program at the National Institutes of Health/National Institute of Mental Health (IRP-NIMH-NIH) FX Funding source: Dr. Niciu receives salary support from the Intramural Research Program at the National Institutes of Health/National Institute of Mental Health (IRP-NIMH-NIH). NR 123 TC 5 Z9 6 U1 3 U2 16 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1172-7047 EI 1179-1934 J9 CNS DRUGS JI CNS Drugs PD APR PY 2015 VL 29 IS 4 BP 293 EP 311 DI 10.1007/s40263-015-0240-4 PG 19 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CH7HR UT WOS:000354207100003 PM 25895020 ER PT J AU Machado-Vieira, R Zanetti, MV Teixeira, AL Uno, M Valiengo, LL Soeiro-de-Souza, MG Oba-Shinjo, SM de Sousa, RT Zarate, CA Gattaz, WF Marie, SKN AF Machado-Vieira, Rodrigo Zanetti, Marcus V. Teixeira, Antonio L. Uno, Miyuki Valiengo, Leandro L. Soeiro-de-Souza, Marcio G. Oba-Shinjo, Sueli M. de Sousa, Rafael T. Zarate, Carlos. A., Jr. Gattaz, Wagner F. Marie, Suety K. N. TI Decreased AKT1/mTOR pathway mRNA expression in short-term bipolar disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Bipolar disorder; AKT; mTOR; Lithium; Treatment; Depression ID SIGNALING PATHWAY; LITHIUM; SCHIZOPHRENIA; GLUTAMATE; KETAMINE; STRESS; BCL-2; ANTAGONISTS; INHIBITION; GENES AB Strong evidence implicates intracellular signaling cascades dysfunction in the pathophysiology of Bipolar Disorder (BD). Regulation of AKT/mTOR pathway is a critical signaling pathway in synaptic neurotransmission and plasticity, also modulating cell proliferation and migration. Gene expression of the AKT/mTOR pathway was assessed in 25 BD (DSM-IV-TR criteria) unmedicated depressed individuals at baseline and after 6 weeks of lithium therapy and 31 matched healthy controls. Decreases in blood AKT/ and mTOR mRNA expression, as well as in BAD/BCL-2 expression ratio were observed in short-term BD patients during depressive episodes in comparison to healthy controls. There was no significant change in the expression of AKT1, mTOR, BCL-2, BAD and NDUFA6 after lithium therapy in the total group of BD subjects. However, the changes in AKT1 expression after lithium treatment were positively correlated with depression improvement. An integrated activity within this pathway was observed at both baseline and post-treatment. The present results support an integrated AKT/mTOR signaling pathway activity in a similar fashion to the described in previous human postmortem and rodents brain studies. Overall, the results reinforce a role for AKT1 and mTOR in the pathophysiology of BD and support the relevance of blood mRNA expression as a valid surrogate biological source to study brain intracellular signaling cascades changes and convergent molecular pathways in psychiatric disorders. Published by Elsevier B.V. C1 [Machado-Vieira, Rodrigo; Zanetti, Marcus V.; Valiengo, Leandro L.; de Sousa, Rafael T.; Gattaz, Wagner F.] Univ Sao Paulo, Dept & Inst Psychiat, Neurosci Lab, LIM 27, BR-05508 Sao Paulo, Brazil. [Machado-Vieira, Rodrigo; Zanetti, Marcus V.; Gattaz, Wagner F.] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-05508 Sao Paulo, Brazil. [Teixeira, Antonio L.] Univ Fed Minas Gerais, Interdisciplinary Lab Med Invest, Belo Horizonte, MG, Brazil. [Machado-Vieira, Rodrigo; Oba-Shinjo, Sueli M.; Zarate, Carlos. A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Uno, Miyuki; Marie, Suety K. N.] Univ Sao Paulo, Dept Neurol, Mol & Cellular Biol Lab, BR-05508 Sao Paulo, Brazil. [Soeiro-de-Souza, Marcio G.] Univ Sao Paulo, Dept Psychiat, Mood Disorders Program, GRUDA, BR-05508 Sao Paulo, Brazil. RP Machado-Vieira, R (reprint author), Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci LIM27, BR-05508 Sao Paulo, Brazil. EM machadovieirar@gmail.com RI Oba-Shinjo, Sueli /C-4017-2012; Marie, Suely/D-1870-2012; Soeiro-de-Souza, Marcio/J-9430-2012; MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI Soeiro-de-Souza, Marcio/0000-0002-9293-3128; MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU Sao Paulo Research Foundation (Fapesp, Brazil) [2009/14891-9]; Associacao Beneficente Alzira Denise Hertzog da Silva (ABADHS) FX This study was sponsored by Sao Paulo Research Foundation (Fapesp, Brazil, 2009/14891-9, RM-V). The Laboratory of Neuroscience, LIM27 is also supported by the Associacao Beneficente Alzira Denise Hertzog da Silva (ABADHS). NR 27 TC 6 Z9 6 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD APR PY 2015 VL 25 IS 4 BP 468 EP 473 DI 10.1016/j.euroneuro.2015.02.002 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CH6JY UT WOS:000354144100003 PM 25726893 ER PT J AU Heissler, SM Chinthalapudi, K Sellers, JR AF Heissler, Sarah M. Chinthalapudi, Krishna Sellers, James R. TI Kinetic characterization of the sole nonmuscle myosin-2 from the model organism Drosophila melanogaster SO FASEB JOURNAL LA English DT Article DE actin; blebbistatin; cytoskeleton; transient kinetics; rotamer ID BLEBBISTATIN INHIBITION; CYTOPLASMIC MYOSIN; MOTOR DOMAIN; DICTYOSTELIUM-DISCOIDEUM; MUSCLE MYOSIN; ACTIN; MORPHOGENESIS; PROTEIN; OOGENESIS; MECHANISM AB Nonmuscle myosin-2 is the primary enzyme complex powering contractility of the F-actin cytoskeleton in the model organism Drosophila. Despite myosin's essential function in fly development and homeostasis, its kinetic features remain elusive. The purpose of this in vitro study is a detailed steady-state and presteady-state kinetic characterization of the Drosophila nonmuscle myosin-2 motor domain. Kinetic features are a slow steady-state ATPase activity, high affinities for F-actin and ADP, and a low duty ratio. Comparative analysis of the overall enzymatic signatures across the nonmuscle myosin-2 complement from model organisms indicates that the Drosophila protein resembles nonmuscle myosin-2s from metazoa rather than protozoa, though modulatory aspects of myosin motor function are distinct. Drosophila nonmuscle myosin-2 is uniquely insensitive toward blebbistatin, a commonly used myosin-2 inhibitor. An in silico modeling approach together with kinetic studies indicate that the nonconsensus amino acid Met466 in the Drosophila nonmuscle myosin-2 active-site loop switch-2 acts as blebbistatin desensitizer. Introduction of the M466I mutation sensitized the protein for blebbistatin, resulting in a half-maximal inhibitory concentration of 36.3 +/- 4.1 mu M. Together, these data show that Drosophila nonmuscle myosin-2 is a bona fide molecular motor and establish an important link between switch-2 and blebbistatin sensitivity. C1 [Heissler, Sarah M.; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Chinthalapudi, Krishna] Scripps Res Inst, Dept Canc Biol, Cell Adhes Lab, Jupiter, FL USA. RP Sellers, JR (reprint author), NHLBI, Lab Mol Physiol, NIH, 50 South Dr,B50-3523, Bethesda, MD 20892 USA. EM sellersj@nhlbi.nih.gov FU U.S. National Institutes of Health National Heart, Lung, and Blood Institute FX The authors thank Adam C. Martin (Massachusetts Institute of Technology, Cambridge, MA, USA) for the Drosophila nonmuscle myosin-2 cDNA and the polycistronic expression vector encoding for Sqh and Mlc-c. They also thank Fang Zhang for the preparation of F-actin. J.R.S. was funded by the Intramural Research Program of the U.S. National Institutes of Health National Heart, Lung, and Blood Institute. NR 48 TC 4 Z9 4 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2015 VL 29 IS 4 BP 1456 EP 1466 DI 10.1096/fj.14-266742 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CH5ZN UT WOS:000354115000031 PM 25636739 ER PT J AU Cameron, D Kavuluru, R Rindflesch, TC Sheth, AP Thirunarayan, K Bodenreider, O AF Cameron, Delroy Kavuluru, Ramakanth Rindflesch, Thomas C. Sheth, Amit P. Thirunarayan, Krishnaprasad Bodenreider, Olivier TI Context-driven automatic subgraph creation for literature-based discovery SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Literature-based discovery (LBD); Graph mining; Path clustering; Hierarchical agglomerative clustering; Semantic relatedness; Medical Subject Headings (MeSH) ID FISH-OIL; GENERATING HYPOTHESES; SEMANTIC PREDICATIONS; KNOWLEDGE; RAYNAUDS; MEDLINE; DISEASE; PROSTACYCLIN; CONNECTIONS; GREENLAND AB Background: Literature-based discovery (LBD) is characterized by uncovering hidden associations in non-interacting scientific literature. Prior approaches to LBD include use of: (I) domain expertise and structured background knowledge to manually filter and explore the literature, (2) distributional statistics and graph-theoretic measures to rank interesting connections, and (3) heuristics to help eliminate spurious connections. However, manual approaches to LBD are not scalable and purely distributional approaches may not be sufficient to obtain insights into the meaning of poorly understood associations. While several graph-based approaches have the potential to elucidate associations, their effectiveness has not been fully demonstrated. A considerable degree of a priori knowledge, heuristics, and manual filtering is still required. Objectives: In this paper we implement and evaluate a context-driven, automatic subgraph creation method that captures multifaceted complex associations between biomedical concepts to facilitate LBD. Given a pair of concepts, our method automatically generates a ranked list of subgraphs, which provide informative and potentially unknown associations between such concepts. Methods: To generate subgraphs, the set of all MEDLINE articles that contain either of the two specified concepts (A, C) are first collected. Then binary relationships or assertions, which are automatically extracted from the MEDLINE articles, called semantic predications, are used to create a labeled directed predications graph. In this predications graph, a path is represented as a sequence of semantic predications. The hierarchical agglomerative clustering (HAC) algorithm is then applied to cluster paths that are bounded by the two concepts (A, C). HAC relies on implicit semantics captured through Medical Subject Heading (MeSH) descriptors, and explicit semantics from the MeSH hierarchy, for clustering. Paths that exceed a threshold of semantic relatedness are clustered into subgraphs based on their shared context. Finally, the automatically generated clusters are provided as a ranked list of subgraphs. Results: The subgraphs generated using this approach facilitated the rediscovery of 8 out of 9 existing scientific discoveries. In particular, they directly (or indirectly) led to the recovery of several intermediates (or B-concepts) between A- and C-terms, while also providing insights into the meaning of the associations. Such meaning is derived from predicates between the concepts, as well as the provenance of the semantic predications in MEDLINE. Additionally, by generating subgraphs on different thematic dimensions (such as Cellular Activity, Pharmaceutical Treatment and Tissue Function), the approach may enable a broader understanding of the nature of complex associations between concepts. Finally, in a statistical evaluation to determine the interestingness of the subgraphs, it was observed that an arbitrary association is mentioned in only approximately 4 articles in MEDLINE on average. Conclusion: These results suggest that leveraging the implicit and explicit semantics provided by manually assigned MeSH descriptors is an effective representation for capturing the underlying context of complex associations, along multiple thematic dimensions in LBD situations. Published by Elsevier Inc. C1 [Cameron, Delroy; Sheth, Amit P.; Thirunarayan, Krishnaprasad] Wright State Univ, Ohio Ctr Excellence Knowledge Enabled Comp Kno E, Dayton, OH 45435 USA. [Kavuluru, Ramakanth] Univ Kentucky, Div Biomed Informat, Lexington, KY 40506 USA. [Bodenreider, Olivier] Natl Lib Med, Bethesda, MD 20894 USA. RP Cameron, D (reprint author), Wright State Univ, Ohio Ctr Excellence Knowledge Enabled Comp Kno E, Dayton, OH 45435 USA. EM delroy@knoesis.org FU Intramural Research Program of the US National Institutes of Health, National Library of Medicine; National Center for Research Resources; National Center for Advancing Translational Sciences, US National Institutes of Health (NIH) [UL1TR000117] FX This research was supported in part by the Intramural Research Program of the US National Institutes of Health, National Library of Medicine. The second author's effort was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, US National Institutes of Health (NIH), through Grant UL1TR000117. We would especially like to thank Pavan Kapanipathi, Wenbo Wang and Shreyansh Bhatt for their insightful feedback on many aspects of this work. We also thank Swapnil Soni, Nishita Jaykumar, Vishnu Bompally, Gary A. Smith, Drashti Dave, Swapna Abhyankar, Mike Cairelli and Gaurish Anand, who contributed to other aspects of this work. NR 55 TC 2 Z9 2 U1 5 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD APR PY 2015 VL 54 BP 141 EP 157 DI 10.1016/j.jbi.2015.01.014 PG 17 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA CH3LP UT WOS:000353932500014 PM 25661592 ER PT J AU Brown, WV Remaley, AT Ridker, PM AF Brown, W. Virgil Remaley, Alan T. Ridker, Paul M. TI JCL Roundtable: Is inflammation a future target in preventing arteriosclerotic cardiovascular disease SO JOURNAL OF CLINICAL LIPIDOLOGY LA English DT Editorial Material DE Inflammation; ASCVD; Prevention; Atherosclerosis; Apolipoprotein B ID IMMUNITY AB It has been a long developing concept that inflammatory infiltration by white blood cells from the blood plasma is an important part of the atherosclerotic process. However, we have thought of this as a secondary phenomenon resulting from the causative insults of high concentrations of apolipoprotein B (apoB)-containing lipoproteins, toxins such as those from cigarette smoke, high blood pressure, and high blood glucose. Much research has provided evidence as to how the invading cells interact with the basic components of the arterial structure to produce the damage observed throughout the vessel wall. We have focused our preventive efforts on the clinical risk factors with significant but partial success in patients with active disease. It is a relatively new concept that suppressing the inflammation itself, as an adjunct to risk factor modification, could help reduce the clinical manifestations of atherosclerosis. This concept is now being tested in randomized clinical trials. Our discussants in this Roundtable are Dr Alan Remaley, a Senior Investigator in the Lipoprotein Metabolism Section of the National Heart Lung and Blood Institute and Dr Paul Ridker, a cardiologist at the Brigham and Women's Hospital and a Professor at the Harvard Medical School. Both have made very significant contributions to our understanding of the signaling process that drives this inflammatory aspect of the disease. (C) 2015 National Lipid Association. All rights reserved. C1 [Brown, W. Virgil] Emory Univ Sch Med, Atlanta, GA 30307 USA. [Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA. [Ridker, Paul M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Brown, WV (reprint author), Emory Univ Sch Med, Atlanta, GA 30307 USA. EM wbrow925@bellsouth.net FU NHLBI NIH HHS [U01 HL101422] NR 7 TC 1 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-2874 EI 1876-4789 J9 J CLIN LIPIDOL JI J. Clin. Lipidol. PD APR PY 2015 VL 9 IS 2 BP 119 EP 128 DI 10.1016/j.jacl.2015.01.007 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CH3KZ UT WOS:000353930900002 PM 25911071 ER PT J AU Kedei, N Kraft, MB Keck, GE Herald, CL Melody, N Pettit, GR Blumberg, PM AF Kedei, Noemi Kraft, Matthew B. Keck, Gary E. Herald, Cherry L. Melody, Noeleen Pettit, George R. Blumberg, Peter M. TI Neristatin 1 Provides Critical Insight into Bryostatin 1 Structure-Function Relationships SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID PROTEIN-KINASE-C; PHORBOL ESTER; NATURAL-PRODUCTS; ANTINEOPLASTIC AGENTS; ANTITUMOR MACROLIDES; ANTICANCER AGENTS; CRYSTAL-STRUCTURE; DRUG DEVELOPMENT; B-RING; CANCER AB Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain. C1 [Kedei, Noemi; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Kraft, Matthew B.; Keck, Gary E.] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA. [Herald, Cherry L.; Melody, Noeleen; Pettit, George R.] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov FU NIH [GM28961]; Arizona Biomedical Research Commission; Robert B. Dalton Endowment Fund; Outstanding Investigator Grant from the Division of Cancer Treatment and Diagnostics, NCI [CA44344-01-01]; Intramural Research Program, Center for Cancer Research, NCI, NIH [Z1A BC 005270] FX This research was supported by NIH grant GM28961 to G.E.K, by grants from the Arizona Biomedical Research Commission and the Robert B. Dalton Endowment Fund (to G.R.P.), by Outstanding Investigator Grant CA44344-01-01 from the Division of Cancer Treatment and Diagnostics, NCI (to G.R.P.), and in part through the Intramural Research Program, Center for Cancer Research, NCI, NIH (Project Z1A BC 005270). NR 39 TC 4 Z9 4 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 EI 1520-6025 J9 J NAT PROD JI J. Nat. Prod. PD APR PY 2015 VL 78 IS 4 BP 896 EP 900 DI 10.1021/acs.jnatprod.5b00094 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA CG9UH UT WOS:000353665100038 PM 25808573 ER PT J AU Paynter, NP Kiefe, CI Lewis, CE Loria, CM Goff, DC Lloyd-Jones, DM AF Paynter, Nina P. Kiefe, Catarina I. Lewis, Cora E. Loria, Catherine M. Goff, David C., Jr. Lloyd-Jones, Donald M. TI Accumulation of Metabolic Cardiovascular Risk Factors in Black and White Young Adults Over 20 Years SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE atherosclerosis; epidemiology; lipids; obesity; primary prevention; risk factors; type 2 diabetes ID INCIDENT HYPERTENSION; CARDIA; ATHEROSCLEROSIS; DISEASE; CHOLESTEROL; CHILDREN; INSULIN; WOMEN AB Background-Cross-sectional clustering of metabolic risk factors for cardiovascular disease in middle-aged adults is well described, but less is known regarding the order in which risk factors develop through young adulthood and their relation to subclinical atherosclerosis. Method and Results-A total of 3178 black and white women and men in the Coronary Artery Risk Development in Young Adults study were assessed to identify the order in which cardiovascular disease risk factors including diabetes, hypertension, dyslipidemia (low high-density lipoprotein cholesterol or high triglyceride levels), hypercholesterolemia (high total or low-density lipoprotein cholesterol), and obesity develop. Observed patterns of risk factor development were compared with those expected if risk factors accumulated randomly, given their overall distribution in the population. Over the 20 years of follow-up, 80% of participants developed at least 1 risk factor. The first factor to occur was dyslipidemia in 39% of participants, obesity in 20%, hypercholesterolemia in 11%, hypertension in 7%, and diabetes in 1%. Dyslipidemia was the only risk factor both to occur first and to be followed by additional risk factors more often than expected (P<0.001 for both). Order of risk factor accrual did not affect subclinical atherosclerosis at year 20. Results were similar by sex, race, and smoking status. Conclusions-Multiple patterns of cardiovascular risk factor development were observed from young adulthood to middle age. Dyslipidemia, a potentially modifiable condition, often preceded the development of other risk factors and may be a useful target for intervention and monitoring. C1 [Paynter, Nina P.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Paynter, Nina P.] Harvard Univ, Sch Med, Boston, MA USA. [Kiefe, Catarina I.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Lewis, Cora E.] Univ Alabama Birmingham, Sch Med, Div Prevent Med, Birmingham, AL USA. [Loria, Catherine M.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Goff, David C., Jr.] Colorado Sch Publ Hlth, Dept Epidemiol & Prevent, Aurora, CO USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. RP Paynter, NP (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave East, Boston, MA 02115 USA. EM npaynter@partners.org FU National Heart, Lung, and Blood Institute (NHLBI); University of Alabama at Birmingham [N01-HC95095, N01-HC48047]; University of Minnesota [N01-HC48048]; Northwestern University [N01-HC48049]; Kaiser Foundation Research Institute [N01-HC48050] FX The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (N01-HC95095 & N01-HC48047), University of Minnesota (N01-HC48048), Northwestern University (N01-HC48049), and Kaiser Foundation Research Institute (N01-HC48050). NR 20 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD APR PY 2015 VL 4 IS 4 AR e001548 DI 10.1161/JAHA.114.001548 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CH6HN UT WOS:000354137300035 ER PT J AU Horvath, KA Mazilu, D Cai, JF Kindzelski, B Li, M AF Horvath, Keith A. Mazilu, Dumitru Cai, Junfeng Kindzelski, Bogdan Li, Ming TI Transapical sutureless aortic valve implantation under magnetic resonance imaging guidance: Acute and short-term results SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID REPLACEMENT; SURGERY; MULTICENTER; REGISTRY; STENOSIS; PATIENT AB Objectives: Despite the increasing success and applicability of transcatheter aortic valve replacement, 2 critical issues remain: the durability of the valves, and the ideal imaging to aid implantation. This study was designed to investigate the transapical implantation of a device of known durability using real-time magnetic resonance imaging (MRI) guidance. Methods: A sutureless aortic valve was used that employs a self-expanding nitinol stent and is amenable to transapical delivery. MRI (1.5-T) was used to identify the anatomic landmarks in 60-kg Yucatan swine. Prostheses were loaded into an MRI-compatible delivery device with an active guidewire to enhance visualization. A series of acute feasibility experiments were conducted (n = 10). Additional animals (n = 6) were allowed to survive and had follow-up MRI scans and echocardiography at 90 days postoperatively. Postmortem gross examination was performed. Results: The valve was MRI compatible and created no significant MRI artifacts. The 3 commissural struts were visible on short-axis view; therefore, coronary ostia obstruction was easily avoided. The average implantation time was 65 seconds. Final results demonstrated stability of the implants with preservation of myocardial perfusion and function over 90 days: the ejection fraction was 48% +/- 15%; the peak gradient was 17.3 +/- 11.3 mm Hg; the mean gradient was 9.8 +/- 7.2 mm Hg. Mild aortic regurgitation was seen in 4 cases, trace in 1 case, and a severe central jet in 1 case. Prosthesis positioning was evaluated during gross examination. Conclusions: We demonstrated that a sutureless aortic valve can be safely and expeditiously implanted through a transapical approach under real-time MRI guidance. Postimplantation results showed a well-functioning prosthesis, with minimal regurgitation, and stability over time. C1 [Horvath, Keith A.; Mazilu, Dumitru; Cai, Junfeng; Kindzelski, Bogdan; Li, Ming] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA. RP Horvath, KA (reprint author), NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10,Room B1D47,10 Ctr Dr, Bethesda, MD 20892 USA. EM horvathka@mail.nih.gov FU NHLBI Division of Intramural Research FX Funded by the NHLBI Division of Intramural Research. NR 18 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 2015 VL 149 IS 4 BP 1067 EP 1072 DI 10.1016/j.jtcvs.2014.10.101 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CG5QG UT WOS:000353347600039 PM 25466854 ER PT J AU Lopez-Dominguez, JA Khraiwesh, H Gonzalez-Reyes, JA Lopez-Lluch, G Navas, P Ramsey, JJ de Cabo, R Buron, MI Villalba, JM AF Alberto Lopez-Dominguez, Jose Khraiwesh, Husam Antonio Gonzalez-Reyes, Jose Lopez-Lluch, Guillermo Navas, Placido Ramsey, Jon Jay de Cabo, Rafael Isabel Buron, Maria Manuel Villalba, Jose TI Dietary Fat and Aging Modulate Apoptotic Signaling in Liver of Calorie-Restricted Mice SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Apoptosis; Calorie restriction; Dietary fat; Liver ID NF-KAPPA-B; RAT-LIVER; OXIDATIVE STRESS; PEROXIDE PRODUCTION; LIPID COMPOSITION; FOOD RESTRICTION; ACID-COMPOSITION; SKELETAL-MUSCLE; CELL-DEATH; SHORT-TERM AB Imbalance between proliferation and cell death accounts for several age-linked diseases. Aging, calorie restriction (CR), and fat source are all factors that may influence apoptotic signaling in liver, an organ that plays a central metabolic role in the organism. Here, we have studied the combined effect of these factors on a number of apoptosis regulators and effectors. For this purpose, animals were fed diets containing different fat sources (lard, soybean oil, or fish oil) under CR for 6 or 18 months. An age-linked increase in the mitochondrial apoptotic pathway was detected with CR, including a decrease in Bcl-2/Bax ratio, an enhanced release of cytochrome c to the cytosol and higher caspase-9 activity. However, these changes were not fully transmitted to the effectors apoptosis-inducing factor and caspase-3. CR (which abated aging-related inflammatory responses) and dietary fat altered the activities of caspases-8, -9, and -3. Apoptotic index (DNA fragmentation) and mean nuclear area were increased in aged animals with the exception of calorie-restricted mice fed a lard-based fat source. These results suggest possible protective changes in hepatic homeostasis with aging in the calorie-restricted lard group. C1 [Alberto Lopez-Dominguez, Jose; Khraiwesh, Husam; Antonio Gonzalez-Reyes, Jose; Isabel Buron, Maria; Manuel Villalba, Jose] Univ Cordoba, Dept Biol Celular Fisiol & Inmunol, CeiA3, Cordoba, Spain. [Lopez-Lluch, Guillermo; Navas, Placido] Univ Pablo Olavide, CSIC, CABD, Seville, Spain. [Lopez-Lluch, Guillermo; Navas, Placido] Inst Salud Carlos III, CIBERER, Seville, Spain. [Ramsey, Jon Jay] Univ Calif Davis, VM Mol Biosci, Davis, CA 95616 USA. [de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. RP Villalba, JM (reprint author), CeiA3, Dept Biol Celular Fisiol & Inmunol, Campus Rabanales,Edificio Severo Ochoa,3a Planta, Cordoba 14014, Spain. EM jmvillalba@uco.es RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Gonzalez-Reyes, Jose A./0000-0003-1918-5490; , rafael/0000-0003-2830-5693; Lopez-Lluch, Guillermo/0000-0001-9830-8502 FU National Institutes of Health [1R01AG028125-01A1]; Ministerio de Economia y Competitividad [BFU2011-23578]; Junta de Andalucia Proyectos de Excelencia [P09-CVI-4887]; Junta de Andalucia Proyectos Internacionales grant; Junta de Andalucia [BIO-276]; University of Cordoba; Spanish Ministerio de Educacion; Agencia Espanola de Cooperacion Internacional al Desarrollo FX Supported by National Institutes of Health grant 1R01AG028125-01A1 (to J.J.R., P.N., and J.M.V.), Ministerio de Economia y Competitividad BFU2011-23578 (to J.M.V.), Junta de Andalucia Proyectos de Excelencia grant P09-CVI-4887 (to J.M.V.), Junta de Andalucia Proyectos Internacionales grant (to J.M.V.), and BIO-276 (Junta de Andalucia and the University of Cordoba to J.M.V.). J.A.L.-D. was funded by a predoctoral fellowship of the Spanish Ministerio de Educacion and BIO-276. H.K. was funded by a predoctoral fellowship of the Agencia Espanola de Cooperacion Internacional al Desarrollo and BIO-276. NR 62 TC 7 Z9 7 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2015 VL 70 IS 4 BP 399 EP 409 DI 10.1093/gerona/glu045 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CH2ZW UT WOS:000353896100001 PM 24691092 ER PT J AU Cesari, M Rolland, Y Van Kan, GA Bandinelli, S Vellas, B Ferrucci, L AF Cesari, Matteo Rolland, Yves Van Kan, Gabor Abellan Bandinelli, Stefania Vellas, Bruno Ferrucci, Luigi TI Sarcopenia-Related Parameters and Incident Disability in Older Persons: Results From the "Invecchiare in Chianti" Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Skeletal muscle; Sarcopenia; Disability; Body composition; Gait speed ID CLINICALLY RELEVANT WEAKNESS; MUSCLE STRENGTH INDEXES; ALTERNATIVE DEFINITIONS; FUNCTIONAL IMPAIRMENT; SKELETAL-MUSCLE; LEAN MASS; EPIDEMIOLOGY; INCHIANTI; MOBILITY; WOMEN AB Background. Current operational definitions of sarcopenia are based on algorithms' simultaneous considering measures of skeletal muscle mass and muscle-specific as well as global function. We hypothesize that quantitative and qualitative sarcopenia-related parameters may not be equally predictive of incident disability, thus presenting different clinical relevance. Methods. Data are from 922 elder adults (mean age = 73.9 years) with no activities of daily living (ADL) impairment recruited in the "Invecchiare in Chianti" study. Incident disability in = 1 ADL defined the outcome of interest. The specific capacities of following sarcopenia-related parameters at predicting incident ADL disability were compared: residuals of skeletal muscle mass, fat-adjusted residuals of skeletal muscle mass, muscle density, ankle extension strength, ratio ankle extension strength/muscle mass, gait speed, and handgrip strength. Results. During the follow-up (median = 9.1 years), 188 (20.4%) incident ADL disability events were reported. Adjusted models showed that only gait speed was significantly associated with the outcome in both men (per standard deviation [SD] = 0.23 m/s increase, hazard ratio [HR] = 0.46, 95% confidence interval [CI] = 0.33-0.63; p <.001) and women (per SD = 0.24 m/s increase, HR = 0.64, 95% CI = 0.50-0.82; p <.001). In women, the fat-adjusted lean mass residual (per SD = 4.41 increase, HR = 0.79, 95% CI = 0.65-0.96; p =.02) and muscle density (per SD = 3.60 increase, HR = 0.76, 95% CI = 0.61-0.93; p =.01) were the only other parameters that predicted disability. In men, several of the tested variables (except muscle mass measures) reported significant results. Conclusions. Gender strongly influences which sarcopenia-related parameters predict disability. Gait speed was a powerful predictor of disability in both men and women, but its nonmuscle-specific nature should impose caution about its inclusion in definitions of sarcopenia. C1 [Cesari, Matteo; Rolland, Yves; Van Kan, Gabor Abellan; Vellas, Bruno] Ctr Hosp Univ Toulouse, Gerontopole, Toulouse, France. [Cesari, Matteo; Rolland, Yves; Van Kan, Gabor Abellan; Vellas, Bruno] Univ Toulouse 3, INSERM, UMR1027, F-31000 Toulouse, France. [Bandinelli, Stefania] Azienda Sanitaria Firenze, Florence, Italy. [Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA. RP Cesari, M (reprint author), Univ Toulouse 3, Inst Vieillissement, Gerontopole, 37 Allees Jules Guesde, F-31000 Toulouse, France. EM macesari@gmail.com RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 FU Italian Ministry of Health [ICS 110.1/RS97.71]; U.S. National Institute on Aging [N01-AG-916413, N01-AG-5-0002, N01-AG-821336, R01-AG-027012]; National Institute on Aging, National Institutes of Health FX The InCHIANTI study was supported as a "targeted project" (ICS 110.1/RS97.71) by the Italian Ministry of Health and by the U.S. National Institute on Aging (contracts N01-AG-916413, N01-AG-5-0002, N01-AG-821336, grant R01-AG-027012). This research was supported in part by the Intramural Research Program, National Institute on Aging, National Institutes of Health. NR 30 TC 7 Z9 7 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2015 VL 70 IS 4 BP 457 EP 463 DI 10.1093/gerona/glu181 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CH2ZW UT WOS:000353896100007 PM 25320055 ER PT J AU Ward, RE Boudreau, RM Caserotti, P Harris, TB Zivkovic, S Goodpaster, BH Satterfield, S Kritchevsky, S Schwartz, AV Vinik, AI Cauley, JA Newman, AB Strotmeyer, ES AF Ward, Rachel E. Boudreau, Robert M. Caserotti, Paolo Harris, Tamara B. Zivkovic, Sasa Goodpaster, Bret H. Satterfield, Suzanne Kritchevsky, Stephen Schwartz, Ann V. Vinik, Aaron I. Cauley, Jane A. Newman, Anne B. Strotmeyer, Elsa S. CA Hlth ABC Study TI Sensory and Motor Peripheral Nerve Function and Longitudinal Changes in Quadriceps Strength SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Aging; Strength; Muscle weakness; Peripheral nerve function; Sensory function; Motor neurons ID SKELETAL-MUSCLE STRENGTH; OLDER-ADULTS; BODY-COMPOSITION; HEALTH; MASS; MEN; QUALITY; HAND; STIMULATION; PREVALENCE AB Background. Poor peripheral nerve function is common in older adults and may be a risk factor for strength decline, although this has not been assessed longitudinally. Methods. We assessed whether sensorimotor peripheral nerve function predicts strength longitudinally in 1,830 participants (age = 76.3 +/- 2.8, body mass index = 27.2 +/- 4.6 kg/m(2), strength = 96.3 +/- 34.7 Nm, 51.0% female, 34.8% black) from the Health ABC study. Isokinetic quadriceps strength was measured semiannually over 6 years. Peroneal motor nerve conduction amplitude and velocity were recorded. Sensory nerve function was assessed with 10-g and 1.4-g monofilaments and average vibration detection threshold at the toe. Lower-extremity neuropathy symptoms were self-reported. Results. Worse vibration detection threshold predicted 2.4% lower strength in men and worse motor amplitude and two symptoms predicted 2.5% and 8.1% lower strength, respectively, in women. Initial 10-g monofilament insensitivity predicted 14.2% lower strength and faster strength decline in women and 6.6% lower strength in men (all p <.05). Conclusion. Poor nerve function predicted lower strength and faster strength decline. Future work should examine interventions aimed at preventing declines in strength in older adults with impaired nerve function. C1 [Ward, Rachel E.; Boudreau, Robert M.; Cauley, Jane A.; Newman, Anne B.; Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Caserotti, Paolo] Univ Southern Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark. [Harris, Tamara B.] NIA, Lab Epidemiol Biometry & Demog, NIH, Bethesda, MD 20892 USA. [Zivkovic, Sasa] Univ Pittsburgh, VA Pittsburgh HCS, Pittsburgh, PA 15213 USA. [Zivkovic, Sasa] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Goodpaster, Bret H.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. [Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Kritchevsky, Stephen] Wake Forest Sch Med, Dept Internal Med Gerontol & Geriatr Med, Winston Salem, NC USA. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Vinik, Aaron I.] Eastern Virginia Med Sch, Dept Neurobiol, Norfolk, VA 23501 USA. RP Strotmeyer, ES (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 N Bellefield Ave,Room 515, Pittsburgh, PA 15213 USA. EM StrotmeyerE@edc.pitt.edu RI Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015; OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408; Strotmeyer, Elsa/0000-0002-4093-6036; Boudreau, Robert/0000-0003-0162-5187 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, 1-R01-AG 028050]; NINR [R01-NR012459]; National Institutes of Health, National Institute on Aging; University of Pittsburgh, Claude D. Pepper Older Americans Independence Center [P30-AG024827]; American Diabetes Association [1-04-JF-46] FX Research was supported by the National Institute on Aging (contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106) grant 1-R01-AG 028050 (to E.S.S.), and NINR grant R01-NR012459 and supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, the University of Pittsburgh, Claude D. Pepper Older Americans Independence Center (P30-AG024827) Pilot Grant (to E.S.S.), and the American Diabetes Association (1-04-JF-46 to E.S.S.). NR 39 TC 10 Z9 10 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2015 VL 70 IS 4 BP 464 EP 470 DI 10.1093/gerona/glu183 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CH2ZW UT WOS:000353896100008 PM 25320056 ER PT J AU Satin, LS Butler, PC Ha, J Sherman, AS AF Satin, Leslie S. Butler, Peter C. Ha, Joon Sherman, Arthur S. TI Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes SO MOLECULAR ASPECTS OF MEDICINE LA English DT Review DE Islets; Oscillations; Insulin pulsatility; Insulin resistance; Diabetes ID PANCREATIC BETA-CELLS; INDUCED ELECTRICAL-ACTIVITY; BURST MASS; IN-VIVO; METABOLIC OSCILLATIONS; CALCIUM OSCILLATIONS; GLUCAGON-SECRETION; CA2+ OSCILLATIONS; BASAL INSULIN; ION CHANNELS AB Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern, has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Satin, Leslie S.] Univ Michigan, Sch Med, Dept Pharmacol, Brehm Diabet Res Ctr, Ann Arbor, MI 48105 USA. [Butler, Peter C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Ha, Joon; Sherman, Arthur S.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Satin, LS (reprint author), Univ Michigan, Sch Med, Kellogg Eye Ctr, Brehm Tower,Room 5128,1000 Wall St, Ann Arbor, MI 48105 USA. EM lsatin@umich.edu FU National Institutes of Health [RO1 DK46409, RO1 DK059579]; intramural research program of the NIDDK FX The authors gratefully acknowledge research support from the National Institutes of Health as follows: RO1 DK46409 (L. Satin), RO1 DK059579 (P. Butler), and the intramural research program of the NIDDK (A. Sherman, J. Ha). We are also grateful to Mariana R. Ortiz for providing excellent editorial assistance. NR 146 TC 16 Z9 17 U1 6 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0098-2997 EI 1872-9452 J9 MOL ASPECTS MED JI Mol. Asp. Med. PD APR PY 2015 VL 42 SI SI BP 61 EP 77 DI 10.1016/j.mam.2015.01.003 PG 17 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA CH6KE UT WOS:000354144700005 PM 25637831 ER PT J AU Huan, TX Meng, QY Saleh, MA Norlander, AE Joehanes, R Zhu, J Chen, BH Zhang, B Johnson, AD Ying, SX Courchesne, P Raghavachari, N Wang, R Liu, PC O'Donnell, CJ Vasan, R Munson, PJ Madhur, MS Harrison, DG Yang, X Levy, D AF Huan, Tianxiao Meng, Qingying Saleh, Mohamed A. Norlander, Allison E. Joehanes, Roby Zhu, Jun Chen, Brian H. Zhang, Bin Johnson, Andrew D. Ying, Saixia Courchesne, Paul Raghavachari, Nalini Wang, Richard Liu, Poching O'Donnell, Christopher J. Vasan, Ramachandran Munson, Peter J. Madhur, Meena S. Harrison, David G. Yang, Xia Levy, Daniel CA Int Consortium Blood Pressure GWAS TI Integrative network analysis reveals molecular mechanisms of blood pressure regulation SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE blood pressure; coexpression network; gene expression; hypertension; systems biology ID SPONTANEOUSLY HYPERTENSIVE-RATS; II-INDUCED HYPERTENSION; GLYCOGEN-SYNTHASE GENE; CORONARY-HEART-DISEASE; ADAPTER PROTEIN LNK; ANGIOTENSIN-II; CARDIOVASCULAR-DISEASE; SYSTEMS BIOLOGY; GLOBAL BURDEN; UP-REGULATION AB Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3(-/-) mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3(-/-) mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension. C1 [Huan, Tianxiao; Joehanes, Roby; Chen, Brian H.; Johnson, Andrew D.; Courchesne, Paul; O'Donnell, Christopher J.; Vasan, Ramachandran; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA. [Huan, Tianxiao; Joehanes, Roby; Chen, Brian H.; Courchesne, Paul; Levy, Daniel] NHLBI, Populat Sci Branch, Bethesda, MD 20892 USA. [Huan, Tianxiao; Joehanes, Roby; Chen, Brian H.; Courchesne, Paul; Levy, Daniel] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Meng, Qingying; Yang, Xia] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90024 USA. [Saleh, Mohamed A.; Norlander, Allison E.; Madhur, Meena S.; Harrison, David G.] Vanderbilt Univ, Dept Med, Div Clin Pharmacol, Nashville, TN USA. [Saleh, Mohamed A.] Mansoura Univ, Fac Pharm, Dept Pharmacol & Toxicol, Mansoura, Egypt. [Joehanes, Roby; Ying, Saixia; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. [Joehanes, Roby] Harvard Univ, Sch Med, Boston, MA USA. [Joehanes, Roby] Hebrew SeniorLife, Boston, MA USA. [Zhu, Jun; Zhang, Bin] Inst Genom & Multiscale Biol, New York, NY USA. [Zhang, Bin] Mt Sinai Sch Med, Grad Sch Biol Sci, New York, NY USA. [Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Div Intramural Res, Bethesda, MD 20892 USA. [Courchesne, Paul; Raghavachari, Nalini] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Wang, Richard; Liu, Poching] NHLBI, Genom Core facil Genet, Bethesda, MD 20892 USA. [Wang, Richard; Liu, Poching] NHLBI, Ctr Dev Biol, Bethesda, MD 20892 USA. RP Yang, X (reprint author), Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90024 USA. EM xyang123@ucla.edu; levyd@nih.gov RI Johnson, Andrew/G-6520-2013; OI Ramachandran, Vasan/0000-0001-7357-5970; Saleh, Mohamed/0000-0002-6405-6033 FU National Institutes of Health [N01-HC-25195]; Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health; NIH [K08HL121671]; Division of Intramural Research, National Heart, Lung, and Blood Institute; Center for Information Technology, National Institutes of Health, Bethesda, MD; American Heart Association Scientist Development [13SDG17290032] FX 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 (Dr. Daniel Levy), and NIH grant K08HL121671 (Dr. Meena Madhur). The analytical component of this project was funded by the Division of Intramural Research, National Heart, Lung, and Blood Institute, the Center for Information Technology, National Institutes of Health, Bethesda, MD (Dr. Daniel Levy), and the American Heart Association Scientist Development Grant 13SDG17290032 (Dr. Xia Yang). NR 78 TC 1 Z9 1 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD APR PY 2015 VL 11 IS 4 DI 10.15252/msb.20145399 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CH4SD UT WOS:000354022300006 ER PT J AU Balenga, NA Klichinsky, M Xie, ZH Chan, EC Zhao, M Jude, J Laviolette, M Panettieri, RA Druey, KM AF Balenga, Nariman A. Klichinsky, Michael Xie, Zhihui Chan, Eunice C. Zhao, Ming Jude, Joseph Laviolette, Michel Panettieri, Reynold A., Jr. Druey, Kirk M. TI A fungal protease allergen provokes airway hyper-responsiveness in asthma SO NATURE COMMUNICATIONS LA English DT Article ID SMOOTH-MUSCLE-CELLS; EXTRACELLULAR-MATRIX PROTEINS; ASPERGILLUS-FUMIGATUS; EPITHELIAL-CELLS; SERINE PROTEINASE; LUNG-DISEASE; PEN C-13; CONTRACTION; EXPRESSION; MECHANISMS AB Asthma, a common disorder that affects 4250 million people worldwide, is defined by exaggerated bronchoconstriction to inflammatory mediators including acetylcholine (ACh), bradykinin and histamine-also termed airway hyper-responsiveness. Nearly 10% of people with asthma have severe, treatment-resistant disease, which is frequently associated with immunoglobulin-E sensitization to ubiquitous fungi, typically Aspergillus fumigatus (Af). Here we show that a major Af allergen, Asp f13, which is a serine protease, alkaline protease 1 (Alp 1), promotes airway hyper-responsiveness by infiltrating the bronchial submucosa and disrupting airway smooth muscle (ASM) cell-extracellular matrix (ECM) interactions. Alp 1-mediated ECM degradation evokes pathophysiological RhoA-dependent Ca2+ sensitivity and bronchoconstriction. These findings support a pathogenic mechanism in asthma and other lung diseases associated with epithelial barrier impairment, whereby ASM cells respond directly to inhaled environmental allergens to generate airway hyper-responsiveness. C1 [Balenga, Nariman A.; Xie, Zhihui; Chan, Eunice C.; Druey, Kirk M.] NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Klichinsky, Michael; Jude, Joseph; Panettieri, Reynold A., Jr.] Univ Penn, Pulm Allergy & Crit Care Div, Airways Biol Initiat, Philadelphia, PA 19104 USA. [Zhao, Ming] NIAID, Prot Chem, Res Technol Branch, NIH, Rockville, MD 20852 USA. [Laviolette, Michel] Univ Laval, IUCPQ, Inst Univ Cardiol & Pneumol Quebec, Dept Multidisciplinaire Pneumol & Chirurg Thorac, Quebec City, PQ G1V 4G5, Canada. RP Druey, KM (reprint author), NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, 50 South Dr Room 4154, Bethesda, MD 20892 USA. EM kdruey@niaid.nih.gov OI Balenga, Nariman/0000-0002-2741-9595 FU NIH, NIAID; NIH [P01-HL114471, P30-ES013508] FX This research was supported in part by the Intramural Research Program of the NIH, NIAID and by NIH grants P01-HL114471 and P30-ES013508 (to R.A.P.). We thank Lisa R. Olano (Protein Chemistry, Research Technologies Branch, NIAID/NIH) for assistance with mass spectrometry; Sabrina Biardel and Dr Jamila Chakir (IUCPQ) for assistance in obtaining human samples. We thank Sundar Ganesan (Biological Imaging, Research Technologies Branch, NIAID/NIH) for assistance with confocal microscopy. We express our gratitude to Dr Axel A. Brakhage (Leibniz Institute for Natural Product Research and Infection Biology, Germany) for providing reagents. We thank Dr Helene Rosenberg (NIAID/NIH) for critical review of the manuscript and Drs Juraj Kabat and Olena Kamenyeva for assistance with confocal imaging. NR 44 TC 14 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2015 VL 6 AR 6763 DI 10.1038/ncomms7763 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0IH UT WOS:000353702500003 PM 25865874 ER PT J AU Cheng, S Larson, MG McCabe, EL Murabito, JM Rhee, EP Ho, JE Jacques, PF Ghorbani, A Magnusson, M Souza, AL Deik, AA Pierce, KA Bullock, K O'Donnell, CJ Melander, O Clish, CB Vasan, RS Gerszten, RE Wang, TJ AF Cheng, Susan Larson, Martin G. McCabe, Elizabeth L. Murabito, Joanne M. Rhee, Eugene P. Ho, Jennifer E. Jacques, Paul F. Ghorbani, Anahita Magnusson, Martin Souza, Amanda L. Deik, Amy A. Pierce, Kerry A. Bullock, Kevin O'Donnell, Christopher J. Melander, Olle Clish, Clary B. Vasan, Ramachandran S. Gerszten, Robert E. Wang, Thomas J. TI Distinct metabolomic signatures are associated with longevity in humans SO NATURE COMMUNICATIONS LA English DT Article ID MITOCHONDRIAL NADP(+)-ISOCITRATE DEHYDROGENASE; GENOME-WIDE ASSOCIATION; BILE-ACIDS; CARDIOVASCULAR HEALTH; LIFE-SPAN; ISOCITRATE DEHYDROGENASE; HYPERTROPHY DEVELOPMENT; CAENORHABDITIS-ELEGANS; GLUCOSE-HOMEOSTASIS; CARDIAC-HYPERTROPHY AB Alterations in metabolism influence lifespan in experimental models, but data in humans are lacking. Here we use liquid chromatography/mass spectrometry to quantify 217 plasma metabolites and examine their relation to longevity in a large cohort of men and women followed for up to 20 years. We find that, higher concentrations of the citric acid cycle intermediate, isocitrate, and the bile acid, taurocholate, are associated with lower odds of longevity, defined as attaining 80 years of age. Higher concentrations of isocitrate, but not taurocholate, are also associated with worse cardiovascular health at baseline, as well as risk of future cardiovascular disease and death. None of the metabolites identified are associated with cancer risk. Our findings suggest that some, but not all, metabolic pathways related to human longevity are linked to the risk of common causes of death. C1 [Cheng, Susan; Larson, Martin G.; Murabito, Joanne M.; Ho, Jennifer E.; O'Donnell, Christopher J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Cheng, Susan; Larson, Martin G.; Murabito, Joanne M.; Ho, Jennifer E.; O'Donnell, Christopher J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Framingham, MA 01702 USA. [Cheng, Susan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02115 USA. [McCabe, Elizabeth L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Div Gen Internal Med, Boston, MA 02118 USA. [Rhee, Eugene P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Renal, Boston, MA 02116 USA. [Ho, Jennifer E.; Ghorbani, Anahita; O'Donnell, Christopher J.; Gerszten, Robert E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02116 USA. [Ho, Jennifer E.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Div Cardiol, Boston, MA 02118 USA. [Jacques, Paul F.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Magnusson, Martin; Melander, Olle] Lund Univ, Dept Clin Sci, SE-22100 Lund, Sweden. [Souza, Amanda L.; Deik, Amy A.; Pierce, Kerry A.; Bullock, Kevin; Clish, Clary B.; Gerszten, Robert E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Div Prevent Med, Boston, MA 02118 USA. [Gerszten, Robert E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02116 USA. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37232 USA. RP Gerszten, RE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02116 USA. EM rgerszten@partners.org; thomas.j.wang@vanderbilt.edu OI Ho, Jennifer/0000-0002-7987-4768; Magnusson, Martin/0000-0003-1710-5936; Ramachandran, Vasan/0000-0001-7357-5970 FU NIH [N01-HC-25195, R00-HL-107642, R01-DK-HL-081572, R01-HL-098280, U01-HL-107440, R01-AG-29451, K08-DK-090142, K23-HL-116780]; Ellison Foundation; Lerner Award; Leducq Foundation; American Heart Association [12IRG9130006] FX This work was supported by NIH contract N01-HC-25195 and grants R00-HL-107642 (S.C.), R01-DK-HL-081572 (R.E.G. and T.J.W.), R01-HL-098280 (R.E.G.), U01-HL-107440 (R.E.G.), R01-AG-29451 (J.M.M.), K08-DK-090142 (E.P.R.), K23-HL-116780 (J.E.H.), as well as the Ellison Foundation (S.C.), Lerner Award (S.C.), Leducq Foundation (R.E.G.) and American Heart Association grant 12IRG9130006 (R.E.G.). NR 69 TC 10 Z9 10 U1 6 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2015 VL 6 AR 6791 DI 10.1038/ncomms7791 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0IH UT WOS:000353702500031 PM 25864806 ER PT J AU Gu, QH Yu, DN Hu, ZH Liu, X Yang, YQ Luo, Y Zhu, J Li, Z AF Gu, Qin-Hua Yu, Danni Hu, Zhonghua Liu, Xing Yang, Yanqin Luo, Yan Zhu, Jun Li, Zheng TI miR-26a and miR-384-5p are required for LTP maintenance and spine enlargement SO NATURE COMMUNICATIONS LA English DT Article ID LONG-TERM POTENTIATION; SYNAPTIC PLASTICITY; TRANSLATIONAL CONTROL; CA1 REGION; MICRORNA EXPRESSION; DENTATE GYRUS; HIPPOCAMPUS; MEMORY; MECHANISMS; NMDA AB Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength. It is associated with the formation and enlargement of dendritic spines-tiny protrusions accommodating excitatory synapses. Both LTP and spine remodelling are crucial for brain development, cognition and the pathophysiology of neurological disorders. The role of microRNAs (miRNAs) in the maintenance of LTP, however, is not well understood. Using next-generation sequencing to profile miRNA transcriptomes, we demonstrate that miR-26a and miR-384-5p specifically affect the maintenance, but not induction, of LTP and different stages of spine enlargement by regulating the expression of RSK3. Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities. This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate 'LTP miRNAs'. C1 [Gu, Qin-Hua; Hu, Zhonghua; Liu, Xing; Li, Zheng] NIMH, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA. [Yu, Danni] Purdue Univ, Dept Stat, W Lafayette, IN 47907 USA. [Yang, Yanqin; Luo, Yan; Zhu, Jun] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Zhu, J (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM jun.zhu@nih.gov; lizheng2@mail.nih.gov RI Li, Zheng/I-8016-2014; Hu, Zhonghua/J-1169-2016 OI Li, Zheng/0000-0002-2978-2531; Hu, Zhonghua/0000-0002-0117-7081 FU National Institute of Mental Health [1ZIAMH002882] FX We thank Dr Heinz Arnheiter for discussion and critical comments, NIMH editor Dr Elizabeth J. Sherman for close editing of the manuscript and Dr Song Jiao for helping to collect brain tissues for deep sequencing. This research was supported by the Intramural Research Programs of the National Institute of Mental Health, project 1ZIAMH002882. NR 48 TC 13 Z9 13 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2015 VL 6 AR 6789 DI 10.1038/ncomms7789 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0IH UT WOS:000353702500029 PM 25858512 ER PT J AU Wu, IL Narayan, K Castaing, JP Tian, F Subramaniam, S Ramamurthi, KS AF Wu, I-Lin Narayan, Kedar Castaing, Jean-Philippe Tian, Fang Subramaniam, Sriram Ramamurthi, Kumaran S. TI A versatile nano display platform from bacterial spore coat proteins SO NATURE COMMUNICATIONS LA English DT Article ID BACILLUS-SUBTILIS SPORES; MORPHOGENETIC PROTEIN; SPORULATION; LOCALIZATION; GENE; BIOCONJUGATION; INTERMEDIATE; RESISTANCE; DYNAMICS; DELIVERY AB Dormant bacterial spores are encased in a thick protein shell, the 'coat', which contains similar to 70 different proteins. The coat protects the spore from environmental insults, and is among the most durable static structures in biology. Owing to extensive cross-linking among coat proteins, this structure has been recalcitrant to detailed biochemical analysis, so molecular details of how it assembles are largely unknown. Here, we reconstitute the basement layer of the coat atop spherical membranes supported by silica beads to create artificial spore-like particles. We report that these synthetic spore husk-encased lipid bilayers (SSHELs) assemble and polymerize into a static structure, mimicking in vivo basement layer assembly during sporulation in Bacillus subtilis. In addition, we demonstrate that SSHELs may be easily covalently modified with small molecules and proteins. We propose that SSHELs may be versatile display platforms for drugs and vaccines in clinical settings, or for enzymes that neutralize pollutants for environmental remediation. C1 [Wu, I-Lin; Castaing, Jean-Philippe; Ramamurthi, Kumaran S.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Narayan, Kedar; Subramaniam, Sriram] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Tian, Fang] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. RP Ramamurthi, KS (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM ramamurthiks@mail.nih.gov RI Ramamurthi, Kumaran/P-3516-2015 FU NIH [R01GM105963]; Intramural Research Programme of the NIH, National Cancer Institute, Center for Cancer Research FX We thank Vincent Lee and members of our labs for discussion and comments on the manuscript, and Ulrich Baxa, Kunio Nagashima and Adam Harned of the Electron Microscopy Laboratory (Frederick National Laboratory for Cancer Research) for SEM sample preparation. This work was supported by NIH grant R01GM105963 (FT) and by the Intramural Research Programme of the NIH, National Cancer Institute, Center for Cancer Research (SS and KSR). NR 49 TC 3 Z9 3 U1 4 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2015 VL 6 AR 6777 DI 10.1038/ncomms7777 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0IH UT WOS:000353702500017 PM 25854653 ER PT J AU Zoratti, GL Tanabe, LM Varela, FA Murray, AS Bergum, C Colombo, E Lang, JE Molinolo, AA Leduc, R Marsault, E Boerner, J List, K AF Zoratti, Gina L. Tanabe, Lauren M. Varela, Fausto A. Murray, Andrew S. Bergum, Christopher Colombo, Eloic Lang, Julie E. Molinolo, Alfredo A. Leduc, Richard Marsault, Eric Boerner, Julie List, Karin TI Targeting matriptase in breast cancer abrogates tumour progression via impairment of stromal-epithelial growth factor signalling SO NATURE COMMUNICATIONS LA English DT Article ID C-MET RECEPTOR; SERINE-PROTEASE; SCATTER FACTOR; FACTOR/SCATTER FACTOR; MOLECULAR-CLONING; BARRIER FUNCTION; IN-VITRO; EXPRESSION; ACTIVATION; CELLS AB Matriptase is an epithelia-specific membrane-anchored serine protease that has received considerable attention in recent years because of its consistent dysregulation in human epithelial tumours, including breast cancer. Mice with reduced levels of matriptase display a significant delay in oncogene-induced mammary tumour formation and blunted tumour growth. The abated tumour growth is associated with a decrease in cancer cell proliferation. Here we demonstrate by genetic deletion and silencing that the proliferation impairment in matriptase-deficient breast cancer cells is caused by their inability to initiate activation of the c-Met signalling pathway in response to fibroblast-secreted pro-HGF. Similarly, inhibition of matriptase catalytic activity using a selective small-molecule inhibitor abrogates the activation of c-Met, Gab1 and AKT, in response to pro-HGF, which functionally leads to attenuated proliferation in breast carcinoma cells. We conclude that matriptase is critically involved in breast cancer progression and represents a potential therapeutic target in breast cancer. C1 [Zoratti, Gina L.; Tanabe, Lauren M.; Varela, Fausto A.; Murray, Andrew S.; Bergum, Christopher; List, Karin] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. [Zoratti, Gina L.; Tanabe, Lauren M.; Varela, Fausto A.; Murray, Andrew S.; Bergum, Christopher; Boerner, Julie; List, Karin] Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. [Zoratti, Gina L.; Murray, Andrew S.; Boerner, Julie; List, Karin] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI 48201 USA. [Zoratti, Gina L.; Murray, Andrew S.; List, Karin] Wayne State Univ, Sch Med, Canc Biol Grad Program, Detroit, MI 48201 USA. [Colombo, Eloic; Leduc, Richard; Marsault, Eric] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Pharmacol, Sherbrooke, PQ J1H 5N4, Canada. [Lang, Julie E.] Univ So Calif, Norris Comprehens Canc Ctr, Dept Surg, Los Angeles, CA 90033 USA. [Molinolo, Alfredo A.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP List, K (reprint author), Wayne State Univ, Sch Med, Dept Pharmacol, 540 E Canfield,Scott Hall Room 6332, Detroit, MI 48201 USA. EM klist@med.wayne.edu OI Tanabe, Lauren/0000-0003-1760-3468 FU NIH [T32-CA009531]; NIGMS/NIH [R25 GM 058905-15]; NIH/NCI [NCI RCA60565A]; Susan G. Komen For the Cure Career Catalyst Research Grant [KG100598] FX This work was supported by a NIH Ruth L. Kirschstein National Research Service Award T32-CA009531 (G.L.Z. and A.S.M.), a NIGMS/NIH grant R25 GM 058905-15 (F.A.V.), NIH/NCI NCI RCA60565A grant (K.L.) and Susan G. Komen For the Cure Career Catalyst Research Grant KG100598 (K.L.). Dr Judith Abrams from the Biostatistics Core at the Barbara Ann Karmanos Cancer Institute assisted with statistical analysis. The RMF-HGF cell line was a kind gift from Dr Charlotte Kuperwasser, Tufts University. NR 57 TC 7 Z9 7 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD APR PY 2015 VL 6 AR 6776 DI 10.1038/ncomms7776 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0IH UT WOS:000353702500016 PM 25873032 ER PT J AU Mitchell, JF Leopold, DA AF Mitchell, Jude F. Leopold, David A. TI The marmoset monkey as a model for visual neuroscience SO NEUROSCIENCE RESEARCH LA English DT Review DE Primate; Marmoset; Vision; Comparative; Cognition; Behavior ID LATERAL GENICULATE-NUCLEUS; RECEPTIVE-FIELD PROPERTIES; POSTERIOR PARIETAL CORTEX; RETINAL GANGLION-CELLS; NEW-WORLD MONKEYS; OCULAR DOMINANCE COLUMNS; MIDDLE TEMPORAL AREA; PRIMATE COLOR-VISION; PREFRONTAL SEROTONIN DEPLETION; FOXES PTEROPUS-POLIOCEPHALUS AB The common marmoset (Callithrix jacchus) has been valuable as a primate model in biomedical research. Interest in this species has grown recently, in part due to the successful demonstration of transgenic marmosets. Here we examine the prospects of the marmoset model for visual neuroscience research, adopting a comparative framework to place the marmoset within a broader evolutionary context. The marmoset's small brain bears most of the organizational features of other primates, and its smooth surface offers practical advantages over the macaque for areal mapping, laminar electrode penetration, and two-photon and optical imaging. Behaviorally, marmosets are more limited at performing regimented psychophysical tasks, but do readily accept the head restraint that is necessary for accurate eye tracking and neurophysiology, and can perform simple discriminations. Their natural gaze behavior closely resembles that of other primates, with a tendency to focus on objects of social interest including faces. Their immaturity at birth and routine twinning also makes them ideal for the study of postnatal visual development. These experimental factors, together with the theoretical advantages inherent in comparing anatomy, physiology, and behavior across related species, make the marmoset an excellent model for visual neuroscience. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. C1 [Mitchell, Jude F.] Univ Rochester, Brain & Cognit Sci Dept, Rochester, NY 14627 USA. [Leopold, David A.] NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Leopold, David A.] NIMH, Neurophysiol Imaging Facil, NINDS, Natl Eye Inst,NIH, Bethesda, MD 20892 USA. RP Mitchell, JF (reprint author), NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. EM jmitchell@bcs.rochester.edu; leopoldd@mail.nih.gov OI Leopold, David/0000-0002-1345-6360 FU Intramural Research Program of the National Institute of Mental Health; [R21-MH104756] FX We thank Drs. James Bourne, Yogita Chudasama, Greg Field, Rebecca Berman, Lindsey Glickfeld, and Sam Nummela for their comments on an earlier version of this manuscript. This work was supported by R21-MH104756 and the Intramural Research Program of the National Institute of Mental Health. NR 393 TC 19 Z9 19 U1 5 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 EI 1872-8111 J9 NEUROSCI RES JI Neurosci. Res. PD APR PY 2015 VL 93 SI SI BP 20 EP 46 DI 10.1016/j.neures.2015.01.008 PG 27 WC Neurosciences SC Neurosciences & Neurology GA CH9GK UT WOS:000354343800004 PM 25683292 ER PT J AU Weinberger, AH Smith, PH Allen, SS Cosgrove, KP Saladin, ME Gray, KM Mazure, CM Wetherington, CL McKee, SA AF Weinberger, Andrea H. Smith, Philip H. Allen, Sharon S. Cosgrove, Kelly P. Saladin, Michael E. Gray, Kevin M. Mazure, Carolyn M. Wetherington, Cora Lee McKee, Sherry A. TI Systematic and Meta-Analytic Review of Research Examining the Impact of Menstrual Cycle Phase and Ovarian Hormones on Smoking and Cessation SO NICOTINE & TOBACCO RESEARCH LA English DT Review ID AD-LIBITUM SMOKING; TOBACCO WITHDRAWAL; CIGARETTE-SMOKING; DEPRESSIVE SYMPTOMS; NICOTINE ADDICTION; SEX-DIFFERENCES; CUE REACTIVITY; WOMEN SMOKERS; INTRAVENOUS NICOTINE; GENDER-DIFFERENCES AB Introduction: To determine the effect of ovarian hormones on smoking, we conducted a systematic review of menstrual cycle effects on smoking (i.e., ad lib smoking, smoking topography, and subjective effects) and cessation-related behaviors (i.e., cessation, withdrawal, tonic craving, and cue-induced craving). Methods: Thirty-six papers were identified on MEDLINE that included a menstrual-related search term (e.g., menstrual cycle, ovarian hormones), a smoking-related search term (e.g., smoking, nicotine), and met all inclusion criteria. Thirty-two studies examined menstrual phase, 1 study measured hormone levels, and 3 studies administered progesterone. Results: Sufficient data were available to conduct meta-analyses for only 2 of the 7 variables: withdrawal and tonic craving. Women reported greater withdrawal during the luteal phase than during the follicular phase, and there was a nonsignificant trend for greater tonic craving in the luteal phase. Progesterone administration was associated with decreased positive and increased negative subjective effects of nicotine. Studies of menstrual phase effects on the other outcome variables were either small in number or yielded mixed outcomes. Conclusions: The impact of menstrual cycle phase on smoking behavior and cessation is complicated, and insufficient research is available upon which to conduct meta-analyses on most smoking outcomes. Future progress will require collecting ovarian hormone levels to more precisely quantify the impact of dynamic changes in hormone levels through the cycle on smoking behavior. Clarifying the relationship between hormones and smoking-particularly related to quitting, relapse, and medication response-could determine the best type and timing of interventions to improve quit rates for women. C1 [Weinberger, Andrea H.] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY 10461 USA. [Weinberger, Andrea H.; Smith, Philip H.; Saladin, Michael E.; Mazure, Carolyn M.; McKee, Sherry A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Weinberger, Andrea H.; McKee, Sherry A.] Yale Canc Ctr, Canc Prevent & Control Res Program, New Haven, CT USA. [Weinberger, Andrea H.; Allen, Sharon S.; Mazure, Carolyn M.; McKee, Sherry A.] Yale Univ, Sch Med, Womens Hlth Res Yale, New Haven, CT USA. [Cosgrove, Kelly P.] Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, Minneapolis, MN 55455 USA. [Saladin, Michael E.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA. [Saladin, Michael E.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Gray, Kevin M.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Gray, Kevin M.; Wetherington, Cora Lee] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. NIDA, NIH, Bethesda, MD 20892 USA. RP Weinberger, AH (reprint author), Yeshiva Univ, Ferkauf Grad Sch Psychol, 1165 Morris Pk Ave,Room 132, Bronx, NY 10461 USA. EM andrea.weinberger@einstein.yu.edu FU National Institutes of Health [P50-DA033945, P50-DA016511, P50-DA033942, R21-DA034840, R01-DA008075, K02-DA031750]; State of Connecticut, Department of Mental Health and Addiction Services; Merck, Inc FX This work was supported by the National Institutes of Health (P50-DA033945 [ORWH, NIDA, and FDA] to SAM; P50-DA016511 [ORWH, NIDA, and FDA] Component 4 to MES and KMG; P50-DA033942 [ORWH and NIDA] to SSA; R21-DA034840 to SSA; R01-DA008075 to SSA; and K02-DA031750 to KPC); and the State of Connecticut, Department of Mental Health and Addiction Services. KMG has received funding from Merck, Inc, and Supernus Pharmaceuticals for unrelated research. SAM has received investigator-initiated funding from Pfizer for unrelated research. NR 91 TC 13 Z9 13 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD APR PY 2015 VL 17 IS 4 BP 407 EP 421 DI 10.1093/ntr/ntu249 PG 15 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA CH3CC UT WOS:000353903000005 PM 25762750 ER PT J AU Zanella, A Cressoni, M Ferlicca, D Chiurazzi, C Epp, M Rovati, C Chiumello, D Pesenti, A Gattinoni, L Kolobow, T AF Zanella, Alberto Cressoni, Massimo Ferlicca, Daniela Chiurazzi, Chiara Epp, Myra Rovati, Cristina Chiumello, Davide Pesenti, Antonio Gattinoni, Luciano Kolobow, Theodor TI Spatial Orientation and Mechanical Properties of the Human Trachea: A Computed Tomography Study SO RESPIRATORY CARE LA English DT Article DE trachea anatomy; trachea orientation ID RESPIRATORY-DISTRESS-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; TUBE CUFF; PREVENTION AB BACKGROUND: The literature generally describes the trachea as oriented toward the right and back, but there is very little detailed characterization. Therefore, the aim of this study was to precisely determine the spatial orientation and to better characterize the physical properties of the human trachea. METHODS: We analyzed lung computed tomography scans of 68 intubated and mechanically ventilated subjects suffering from acute lung injury/ARDS at airway pressures (P-aw) of 5, 15, and 45 cm H2O. At each P-aw, the inner edge of the trachea from the subglottal space to the carina was captured. Tracheal length and diameter were measured. Tracheal orientation and compliance were estimated from processing barycenter and surface tracheal sections. RESULTS: Tracheal orientation at a P-aw of 5 cm H2O showed a 4.2 +/- 5.3 degrees angle toward the right and a 20.6 +/- 6.9 degrees angle downward toward the back, which decreased significantly while increasing P-aw (19.4 +/- 6.9 degrees at 15 cm H2O and 17.1 +/- 6.8 degrees at 45 cm H2O, P <.001). Tracheal compliance was 0.0113 +/- 0.0131 mL/cm H2O/cm of trachea length from 5 to 15 cm H2O and 0.004 +/- 0.0041 mL/cm H2O/cm of trachea length from 15 to 45 cm H2O (P < .001). Tracheal diameter was 19.6 +/- 3.4 mm on the medial-lateral axis and 21.0 +/- 4.3 mm on the sternal-vertebral axis. CONCLUSIONS: The trachea is oriented downward toward the back at a 20.6 +/- 6.9 degrees angle and slightly toward the right at a 4.2 +/- 5.3 degrees angle. Understanding tracheal orientation may help in enhancing postural drainage and respiratory physiotherapy, and knowing the physical properties of the trachea may aid in endotracheal tube cuff design. C1 [Zanella, Alberto] Univ Milano Bicocca, Osped San Gerardo Nuovo Tintori, Dipartimento Sci Salute, I-20900 Monza, Italy. [Cressoni, Massimo; Chiurazzi, Chiara; Rovati, Cristina; Gattinoni, Luciano] Univ Milan, Dipartimento Fisiopatol Med Chirurg & Trapianti, Milan, Italy. [Chiumello, Davide; Gattinoni, Luciano] Osped Maggiore Policlin, Fdn Ist Ricovero & Cura Carattere Sci Ca Granda, Dipartimento Anestesia Rianimaz Intens & Subinten, Milan, Italy. [Zanella, Alberto; Cressoni, Massimo; Epp, Myra; Kolobow, Theodor] NHLBI, NIH, Bethesda, MD 20892 USA. RP Zanella, A (reprint author), Univ Milano Bicocca, Osped San Gerardo Nuovo Tintori, Dipartimento Sci Salute, Via Donizetti 106, I-20900 Monza, Italy. EM zanella.alb@gmail.com RI Cressoni, Massimo/B-7315-2017; OI Cressoni, Massimo/0000-0002-0089-2905; zanella, Alberto/0000-0002-2967-2527; CHIUMELLO, DAVIDE ALBERTO/0000-0001-9260-3930 FU Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) FX This study was supported by the Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR). The authors have disclosed no conflicts of interest. NR 16 TC 0 Z9 0 U1 5 U2 11 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD APR PY 2015 VL 60 IS 4 BP 561 EP 566 DI 10.4187/respcare.03479 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CH7BQ UT WOS:000354191000021 PM 25492954 ER PT J AU Karzai, FH Madan, RA Figg, WD AF Karzai, Fatima H. Madan, Ravi A. Figg, William D. TI Beyond PSA: Managing Modern Therapeutic Options in Metastatic Castration-Resistant Prostate Cancer SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE prostate-specific antigen; androgen receptor; metastatic castration resistant; PSAWG1; PSAWG2 ID ANTIGEN WORKING GROUP; CLINICAL-TRIALS; BONE-SCINTIGRAPHY; FLARE PHENOMENON; BREAST-CANCER; END-POINTS; GUIDELINES; DOCETAXEL; RECOMMENDATIONS; IMMUNOTHERAPY AB Prostate cancer remains a significant cause of cancer-related deaths in men in the United States. Significant advances in the treatment of metastatic castration-resistant prostate cancer have been made in recent years with the arrival of new therapeutic targets and options. The definition of progression of disease must be thought of in the context of clinical symptoms and radiographic evidence rather than as changes in prostate-specific antigen (PSA). Ultimately, the use of PSA criteria alone should not be used to determine the progression of disease; instead, PSA should be evaluated in combination with other clinical data. C1 [Karzai, Fatima H.; Madan, Ravi A.; Figg, William D.] NCI, Med Oncol Serv, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Oncol Serv, Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wf13e@nih.gov RI Figg Sr, William/M-2411-2016 NR 40 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD APR PY 2015 VL 108 IS 4 BP 224 EP 228 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CH5WW UT WOS:000354107600008 PM 25871992 ER PT J AU Pongpiachan, S Paowa, T AF Pongpiachan, Siwatt Paowa, Tassanee TI Hospital out-and-in-patients as Functions of Trace Gaseous Species and Other Meteorological Parameters in Chiang-Mai, Thailand SO AEROSOL AND AIR QUALITY RESEARCH LA English DT Article DE Trace gaseous species; Hospital admission; Chiang-Mai; FTIR; Incremental lifetime exposure ID POLYCYCLIC AROMATIC-HYDROCARBONS; FINE-PARTICULATE MATTER; COEFFICIENTS K-P; AIR-POLLUTION; VERTICAL-DISTRIBUTION; BIOGENIC EMISSIONS; ADMISSIONS; ISOPRENE; CHINA; IMPACT AB The aims of this study were to investigate the impact of meteorological parameters and trace gas concentrations on daily hospital walk-ins and admissions in Chiang-Mai province, Thailand, during 2007-2013. Advanced statistical models, including t-tests, Analysis of Variance (ANOVA), Multiple Linear Regression Analysis (MLRA) and Incremental Lifetime Particulate Matter Exposure (ILPE), were constructed using meteorological data from the Pollution Control Department (PCD), Ministry of Natural Resources and Environment (MNRE), Thailand, and the Thai Meteorological Department at Chiang-Mai Province Air Quality Observatory Site (TMCS) as well as the number of walk-in and admitted patients at Nakornping Hospital, Chiang-Mai (NHCM). The results showed that all trace gaseous species and PM10 were significantly higher during the "haze episode" than during the "non-haze period." The FTIR spectra highlight the relatively homogeneous organic functional compositions of PM2.5 collected from urban, suburban and rural observatory sites, indicating that agricultural waste burning plays an important role in air quality during the "haze episode." The effect of age on susceptibility to respiratory diseases was investigated by separating the dataset into four groups (i.e., < 15 years, 15-59 years, 60-74 years and >= 75 years). The ANOVA results revealed a significant increase in hospital walk-ins and admissions for both genders in the < 15 years group (p < 0.005). MLRA revealed the significantly highest impacts of CO on hospital walk-ins for both genders. The predicted ILPE of PM10 showed the highest values for both genders during the "haze-episode" in 2007, with average values of 3.338 +/- 0.576 g and 1.838 +/- 0.317 g for male and female outdoor workers, respectively, over an exposure duration of 25 years. C1 [Pongpiachan, Siwatt; Paowa, Tassanee] NIDA, Res Ctr Disaster Prevent Management, Sch Social & Environm Dev, Bangkok 10240, Thailand. RP Pongpiachan, S (reprint author), NIDA, Res Ctr Disaster Prevent Management, Sch Social & Environm Dev, 118 Sereethai, Bangkok 10240, Thailand. EM pongpiajun@gmail.com RI Xiongfei, Zhao/G-7690-2015 NR 61 TC 0 Z9 0 U1 2 U2 11 PU TAIWAN ASSOC AEROSOL RES-TAAR PI TAICHUNG COUNTY PA CHAOYANG UNIV TECH, DEPT ENV ENG & MGMT, PROD CTR AAQR, NO 168, JIFONG E RD, WUFONG TOWNSHIP, TAICHUNG COUNTY, 41349, TAIWAN SN 1680-8584 EI 2071-1409 J9 AEROSOL AIR QUAL RES JI Aerosol Air Qual. Res. PD APR PY 2015 VL 15 IS 2 BP 479 EP 493 DI 10.4209/aaqr.2013.09.0293 PG 15 WC Environmental Sciences SC Environmental Sciences & Ecology GA CG3JE UT WOS:000353175300010 ER PT J AU Lam, TK Chang, CQ Rogers, SD Khoury, MJ Schully, SD AF Lam, Tram Kim Chang, Christine Q. Rogers, Scott D. Khoury, Muin J. Schully, Sheri D. TI Evolution of the "Drivers" of Translational Cancer Epidemiology: Analysis of Funded Grants and the Literature SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cancer; cancer epidemiology; collaboration; consortia; epidemiologic methods; knowledge integration; translation ID KNOWLEDGE INTEGRATION; GENOMIC MEDICINE; 21ST-CENTURY; HEALTH; CONTINUUM; SCIENCE; CARE AB Concurrently with a workshop sponsored by the National Cancer Institute, we identified key "drivers" for accelerating cancer epidemiology across the translational research continuum in the 21st century: emerging technologies, a multilevel approach, knowledge integration, and team science. To map the evolution of these "drivers" and translational phases (T0-T4) in the past decade, we analyzed cancer epidemiology grants funded by the National Cancer Institute and published literature for 2000, 2005, and 2010. For each year, we evaluated the aims of all new/competing grants and abstracts of randomly selected PubMed articles. Compared with grants based on a single institution, consortium-based grants were more likely to incorporate contemporary technologies (P = 0.012), engage in multilevel analyses (P = 0.010), and incorporate elements of knowledge integration (P = 0.036). Approximately 74% of analyzed grants and publications involved discovery (T0) or characterization (T1) research, suggesting a need for more translational (T2-T4) research. Our evaluation indicated limited research in 1) a multilevel approach that incorporates molecular, individual, social, and environmental determinants and 2) knowledge integration that evaluates the robustness of scientific evidence. Cancer epidemiology is at the cusp of a paradigm shift, and the field will need to accelerate the pace of translating scientific discoveries in order to impart population health benefits. While multi-institutional and technology-driven collaboration is happening, concerted efforts to incorporate other key elements are warranted for the discipline to meet future challenges. C1 [Lam, Tram Kim; Chang, Christine Q.; Rogers, Scott D.; Khoury, Muin J.; Schully, Sheri D.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. RP Lam, TK (reprint author), NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E124, Rockville, MD 20850 USA. EM lamt@mail.nih.gov FU Intramural CDC HHS [CC999999] NR 18 TC 3 Z9 3 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2015 VL 181 IS 7 BP 451 EP 458 DI 10.1093/aje/kwu479 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH1XD UT WOS:000353815100001 PM 25767265 ER PT J AU Lam, TK Chang, CQ Rogers, SD Khoury, MJ Schully, SD AF Lam, Tram Kim Chang, Christine Q. Rogers, Scott D. Khoury, Muin J. Schully, Sheri D. TI Lam et al. Respond to "Driving for Further Evolution" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material C1 [Lam, Tram Kim; Chang, Christine Q.; Rogers, Scott D.; Khoury, Muin J.; Schully, Sheri D.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. RP Lam, TK (reprint author), NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E124, Rockville, MD 20850 USA. EM lamt@mail.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2015 VL 181 IS 7 BP 463 EP 463 DI 10.1093/aje/kwu478 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH1XD UT WOS:000353815100003 PM 25767264 ER PT J AU Freedman, LS Commins, JM Moler, JE Willett, W Tinker, LF Subar, AF Spiegelman, D Rhodes, D Potischman, N Neuhouser, ML Moshfegh, AJ Kipnis, V Arab, L Prentice, RL AF Freedman, Laurence S. Commins, John M. Moler, James E. Willett, Walter Tinker, Lesley F. Subar, Amy F. Spiegelman, Donna Rhodes, Donna Potischman, Nancy Neuhouser, Marian L. Moshfegh, Alanna J. Kipnis, Victor Arab, Lenore Prentice, Ross L. TI Pooled Results From 5 Validation Studies of Dietary Self-Report Instruments Using Recovery Biomarkers for Potassium and Sodium Intake SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE attenuation factors; calibration models; dietary measurement error; food frequency questionnaire; 24-hour recall; underreporting ID FOOD FREQUENCY QUESTIONNAIRE; DOUBLY LABELED WATER; ENERGY-EXPENDITURE; MEASUREMENT ERROR; INDIVIDUALS; COLLECTION; BALANCE; PROTEIN; METAANALYSES; NUTRITION AB We pooled data from 5 large validation studies (1999-2009) of dietary self-report instruments that used recovery biomarkers as referents, to assess food frequency questionnaires (FFQs) and 24-hour recalls (24HRs). Here we report on total potassium and sodium intakes, their densities, and their ratio. Results were similar by sex but were heterogeneous across studies. For potassium, potassium density, sodium, sodium density, and sodium: potassium ratio, average correlation coefficients for the correlation of reported intake with true intake on the FFQs were 0.37, 0.47, 0.16, 0.32, and 0.49, respectively. For the same nutrients measured with a single 24HR, they were 0.47, 0.46, 0.32, 0.31, and 0.46, respectively, rising to 0.56, 0.53, 0.41, 0.38, and 0.60 for the average of three 24HRs. Average underreporting was 5%-6% with an FFQ and 0%-4% with a single 24HR for potassium but was 28%-39% and 4%-13%, respectively, for sodium. Higher body mass index was related to underreporting of sodium. Calibration equations for true intake that included personal characteristics provided improved prediction, except for sodium density. In summary, self-reports capture potassium intake quite well but sodium intake less well. Using densities improves the measurement of potassium and sodium on an FFQ. Sodium: potassium ratio is measured much better than sodium itself on both FFQs and 24HRs. C1 [Freedman, Laurence S.; Commins, John M.; Moler, James E.] Informat Management Syst Inc, Rockville, MD USA. [Freedman, Laurence S.] Gertner Inst Epidemiol & Hlth Policy Res, Biostat Unit, Tel Hashomer, Israel. [Arab, Lenore] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. [Rhodes, Donna; Moshfegh, Alanna J.] ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA. [Kipnis, Victor] NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. [Tinker, Lesley F.; Neuhouser, Marian L.; Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Subar, Amy F.; Potischman, Nancy] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Willett, Walter; Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Willett, Walter; Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Willett, Walter] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Willett, Walter] Harvard Univ, Sch Med, Boston, MA USA. RP Freedman, LS (reprint author), Chaim Sheba Med Ctr, Biostat Unit, Gertner Inst Epidemiol & Hlth Policy Res, IL-52621 Tel Hashomer, Israel. EM lsf@actcom.co.il OI Moler, James/0000-0001-8738-6898 FU National Heart, Lung, and Blood Institute [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX The Women's Health Initiative (WHI) was funded by the National Heart, Lung, and Blood Institute through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 42 TC 24 Z9 24 U1 2 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2015 VL 181 IS 7 BP 473 EP 487 DI 10.1093/aje/kwu325 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH1XD UT WOS:000353815100005 PM 25787264 ER PT J AU Freeman, LEB Karagas, MR Baris, D Schwenn, M Johnson, AT Colt, JS Jackson, B Hosain, GMM Cantor, KP Silverman, DT AF Freeman, Laura E. Beane Karagas, Margaret R. Baris, Dalsu Schwenn, Molly Johnson, Alison T. Colt, Joanne S. Jackson, Brian Hosain, G. M. Monawar Cantor, Kenneth P. Silverman, Debra T. TI Is the Inverse Association Between Selenium and Bladder Cancer Due to Confounding by Smoking? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE bladder cancer; case-control study; selenium; smoking ID TOENAIL SELENIUM; SERUM SELENIUM; LIPID-PEROXIDATION; HUMAN HEALTH; VITAMIN-E; RISK; WOMEN; MEN; PREVENTION; SUPPLEMENTATION AB Selenium has been linked to a reduced risk of bladder cancer in some studies. Smoking, a well-established risk factor for bladder cancer, has been associated with lower selenium levels in the body. We investigated the selenium-bladder cancer association in subjects from Maine, New Hampshire, and Vermont in the New England Bladder Cancer Case-Control Study. At interview (2001-2005), participants provided information on a variety of factors, including a comprehensive smoking history, and submitted toenail samples, from which we measured selenium levels. We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271 controls using logistic regression. After controlling for smoking, we saw no evidence of an association between selenium levels and bladder cancer (for fourth quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.77, 1.25). When results were restricted to regular smokers, there appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however, when pack-years of smoking were considered, this association was attenuated (OR = 0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite some reports of an inverse association between selenium and bladder cancer overall, our results, combined with an in-depth evaluation of other studies, suggested that confounding from smoking intensity or duration could explain this association. Our study highlights the need to carefully evaluate the confounding association of smoking in the selenium-bladder cancer association. C1 [Freeman, Laura E. Beane; Baris, Dalsu; Colt, Joanne S.; Cantor, Kenneth P.; Silverman, Debra T.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Karagas, Margaret R.] Dartmouth Coll, Dept Epidemiol, Geisel Sch Med, Hanover, NH 03755 USA. [Schwenn, Molly] Maine Canc Registry, Augusta, ME USA. [Johnson, Alison T.] Vermont Dept Hlth, Burlington, VT 05402 USA. [Jackson, Brian] Dartmouth Coll, Dept Earth Sci, Trace Element Anal Core, Hanover, NH 03755 USA. [Hosain, G. M. Monawar] New Hampshire State Canc Registry, Concord, NH USA. RP Freeman, LEB (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E136,MSC 9771, Bethesda, MD 20892 USA. EM freemala@mail.nih.gov FU Intramural Research Program of the National Cancer Institute, National Institutes of Health; NIEHS [P42 ES007373, P01 ES022832]; EPA [RD83544201] FX This work was funded by the Intramural Research Program of the National Cancer Institute, National Institutes of Health.; The Dartmouth Trace Element Analysis Core is partially supported by NIEHS P42 ES007373, NIEHS P01 ES022832, EPA RD83544201. NR 35 TC 6 Z9 6 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2015 VL 181 IS 7 BP 488 EP 495 DI 10.1093/aje/kwu324 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH1XD UT WOS:000353815100006 ER PT J AU Mitchell, EM Lyles, RH Manatunga, AK Schisterman, EF AF Mitchell, Emily M. Lyles, Robert H. Manatunga, Amita K. Schisterman, Enrique F. TI Semiparametric Regression Models for a Right-Skewed Outcome Subject to Pooling SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE biomarkers; design; pooled specimens; quasi-likelihood; skewness; statistical analysis ID QUASI-LIKELIHOOD FUNCTIONS; EFFICIENT DESIGN; EXPOSURE; BIOSPECIMENS; PREVALENCE; LIMIT; HIV AB Pooling specimens prior to performing laboratory assays has various benefits. Pooling can help to reduce cost, preserve irreplaceable specimens, meet minimal volume requirements for certain lab tests, and even reduce information loss when a limit of detection is present. Regardless of the motivation for pooling, appropriate analytical techniques must be applied in order to obtain valid inference from composite specimens. When biomarkers are treated as the outcome in a regression model, techniques applicable to individually measured specimens may not be valid when measurements are taken from pooled specimens, particularly when the biomarker is positive and right skewed. In this paper, we propose a novel semiparametric estimation method based on an adaptation of the quasi-likelihood approach that can be applied to a right-skewed outcome subject to pooling. We use simulation studies to compare this method with an existing estimation technique that provides valid estimates only when pools are formed from specimens with identical predictor values. Simulation results and analysis of a motivating example demonstrate that, when appropriate estimation techniques are applied to strategically formed pools, valid and efficient estimation of the regression coefficients can be achieved. C1 [Mitchell, Emily M.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20852 USA. [Lyles, Robert H.; Manatunga, Amita K.] Emory Univ, Dept Biostat & Bioinformat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP Mitchell, EM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Bethesda, MD 20852 USA. EM emily.mitchell@nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Long-Range Research Initiative of the American Chemistry Council; National Institute of Nursing Research [1RC4NR012527-01]; National Institute of Environmental Health Sciences [5R01ES012458-07]; National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR000454] FX E.M.M. and E.F.S. were supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and by the Long-Range Research Initiative of the American Chemistry Council; R.H.L. was supported by the National Institute of Nursing Research (grant 1RC4NR012527-01); and R.H.L. and A.K.M. were supported by the National Institute of Environmental Health Sciences (grant 5R01ES012458-07) and by the National Center for Advancing Translational Sciences, National Institutes of Health (award UL1TR000454). NR 23 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2015 VL 181 IS 7 BP 541 EP 548 DI 10.1093/aje/kwu301 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH1XD UT WOS:000353815100012 PM 25737248 ER PT J AU Stevenson, HS Wang, YH Muller, R Edelman, DC AF Stevenson, Holly S. Wang, Yonghong Muller, Rolf Edelman, Daniel C. TI Long-term Stability of Total RNA in RNAstable((R)) as Evaluated by Expression Microarray SO BIOPRESERVATION AND BIOBANKING LA English DT Article ID STORAGE; TISSUE; DEGRADATION; IMPACT; FROZEN AB Storage of labile RNA in laboratories is accomplished through ultra-low freezing of the nucleic acids. This however requires expensive freezers, convenient storage, reliable electrical power, and increased shipping costs, thereby making it a less viable option. Biomatrica (San Diego, CA) has created RNAstable((R)), a stabilization reagent that is used to store RNA in a dehydrated state at room temperature (RT) and protects the RNA from degradation. Our objective was to investigate the sequence integrity and suitability of RNA when stored in RNAstable at extended time periods and at varying temperatures through use of Illumina and Agilent RNA expression microarrays. We observed in Bioanalyzer electropherograms that total RNA extracted from 293 cells stored at RT in RNAstable for 4.5 and 11.5 months is similar in quality to RNA stored at -80 degrees C. Illumina mRNA expression array QC metrics and gene expression patterns from RNAstable-protected RNA, in contrast to RNA stored without RNAstable, correlated well with those of freezer controls. Significantly, when RNA was stored in RNAstable at 45 degrees C for 4.5 months, equivalent to 22 months RT storage, RNA quality, microarray probe signal intensities, probe detection rates, and expression profiles remained similar between RNAstable-protected RNA at RT and the -80 degrees C controls. At 10.5 months, miRNA levels were compared among the storage conditions using miRNA expression arrays. Here too we found strong concordance between miRNA expression patterns when total RNA was stored in RNAstable or at -80 degrees C. Further, Bioanalyzer electrophoresis of RNAstable-protected samples stored at RT for a relative total of 33 months or 50.5 months showed comparable integrity scores to those of -80 degrees C controls. We conclude that use of RNAstable holds promise as an effective stabilization reagent for total RNA and should be useful in situations where shipping and storage options are limited resources. C1 [Stevenson, Holly S.; Wang, Yonghong; Edelman, Daniel C.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Muller, Rolf] Biomatrica Inc, San Diego, CA USA. RP Edelman, DC (reprint author), NCI, NIH, CCR, Genet Branch, 37 Convent Dr,Room 6032a,MSC 426, Bethesda, MD 20892 USA. EM edelmand@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute FX No potential conflicts of interest are reported by NCI personnel. Rolf Muller is the founder, president, and CSO of Biomatrica, Inc. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, and internal resources of Biomatrica, Inc. NR 14 TC 0 Z9 1 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 EI 1947-5543 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PD APR 1 PY 2015 VL 13 IS 2 BP 114 EP 122 DI 10.1089/bio.2014.0068 PG 9 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA CG1DE UT WOS:000353012400008 PM 25826008 ER PT J AU Astry, B Venkatesha, SH Laurence, A Christensen-Quick, A Garzino-demo, A Frieman, MB O'Shea, JJ Moudgil, KD AF Astry, Brian Venkatesha, Shivaprasad H. Laurence, Arian Christensen-Quick, Aaron Garzino-demo, Alfredo Frieman, Matthew B. O'Shea, John J. Moudgil, Kamal D. TI Celastrol, a Chinese herbal compound, controls autoimmune inflammation by altering the balance of pathogenic and regulatory T cells in the target organ SO CLINICAL IMMUNOLOGY LA English DT Article DE Celastrol; Chinese medicine; Experimental arthritis; Rheumatoid arthritis; T helper 17 cells; T regulatory cells; Immune regulation ID ADJUVANT-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; TH17 CELLS; SUPPRESSES; INHIBITION; MECHANISMS; EXPRESSION; GENERATION; INDUCTION; THERAPY AB Inflammation is an integral component of autoimmune arthritis. The balance of pathogenic T helper 17 (Th17) and protective T regulatory (Treg) cells can influence disease severity, and its resetting offers an attractive approach to control autoimmunity. We determined the frequency of Th17 and Treg in the joints of rats with adjuvant arthritis (AA), a model of rheumatoid arthritis (RA). We also investigated the impact of Celastrol, a bioactive compound from the traditional Chinese medicine Celastrus that can suppress AA, on Th17/Treg balance in the joints. Celastrol treatment reduced Th17 cells but increased Treg in the joints, and it inhibited Th17 differentiation but promoted Treg differentiation in vitro by blocking the activation of pSTAT3. Furthermore, Celastrol limited the production of Th17-differentiating cytokines and chemokines (CCL3, CCL5). Thus, Celastrol suppressed arthritis in part by altering Th17/Treg ratio in inflamed joints, and it should be tested as a potential adjunct/alternative for RA therapy. (C) 2015 Elsevier Inc. All rights reserved. C1 [Astry, Brian; Venkatesha, Shivaprasad H.; Frieman, Matthew B.; Moudgil, Kamal D.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Laurence, Arian; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Christensen-Quick, Aaron; Garzino-demo, Alfredo] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. RP Moudgil, KD (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, 685 W Baltimore St,HSF-1,Suite 380, Baltimore, MD 21201 USA. EM kmoudgil@som.umaryland.edu RI Laurence, Arian/A-8770-2009; Venkatesha, Shivaprasad/S-3141-2016 OI Laurence, Arian/0000-0003-0942-8292; FU NIH [R01 AT004321, F31 AT007278] FX This work was supported by NIH grants R01 AT004321 and F31 AT007278. We thank Krystal Matthews for her help with the NF-kappa B reporter assay; Joao Pedra for advice in the testing of mature IL-1 beta; Qing Chen for help with testing of the composition of synovial-infiltrating cells; and Stefanie Vogel for providing the qRT-PCR facility. NR 33 TC 12 Z9 15 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2015 VL 157 IS 2 BP 228 EP 238 DI 10.1016/j.clim.2015.01.011 PG 11 WC Immunology SC Immunology GA CH2FS UT WOS:000353841700014 PM 25660987 ER PT J AU Rosen, LB Pereira, NR Figueiredo, C Fiske, LC Ressner, RA Hong, JC Gregg, KS Henry, TL Pak, KJ Baumgarten, KL Seoane, L Garcia-Diaz, J Olivier, KN Zelazny, AM Holland, SM Browne, SK AF Rosen, Lindsey B. Pereira, Nuno Rocha Figueiredo, Cristovao Fiske, Lauren C. Ressner, Roseanne A. Hong, Julie C. Gregg, Kevin S. Henry, Tracey L. Pak, Kirk J. Baumgarten, Katherine L. Seoane, Leonardo Garcia-Diaz, Julia Olivier, Kenneth N. Zelazny, Adrian M. Holland, Steven M. Browne, Sarah K. TI Nocardia-Induced Granulocyte Macrophage Colony-Stimulating Factor Is Neutralized by Autoantibodies in Disseminated/Extrapulmonary Nocardiosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE adult-onset immunodeficiency; anticytokine autoantibodies; nocardiosis; GM-CSF; opportunistic infection ID PULMONARY ALVEOLAR PROTEINOSIS; GM-CSF AUTOANTIBODIES; CHRONIC MUCOCUTANEOUS CANDIDIASIS; RITUXIMAB THERAPY; INFECTION; IMMUNODEFICIENCY; DISEASE; LUNG; MICE AB Background. Nocardia species cause infections in both immunocompromised and otherwise immunocompetent patients, although the mechanisms defining susceptibility in the latter group are elusive. Anticytokine autoantibodies are an emerging cause of pathogen-specific susceptibility in previously healthy human immunodeficiency virus-uninfected adults, including anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies with cryptococcal meningitis. Methods. Plasma from patients with disseminated/extrapulmonary nocardiosis and healthy controls was screened for anticytokine autoantibodies using a particle-based approach. Autoantibody function was assessed by intranuclear staining for GM-CSF-induced STAT5 phosphorylation in normal cells incubated with either patient or normal plasma. GM-CSF-mediated cellular activation by Nocardia was assessed by staining for intracellular cytokine production and intranuclear STAT5 phosphorylation. Results. We identified neutralizing anti-GM-CSF autoantibodies in 5 of 7 patients studied with central nervous system nocardiosis and in no healthy controls (n = 14). GM-CSF production was induced by Nocardia in vitro, suggesting a causative role for anti-GM-CSF autoantibodies in Nocardia susceptibility and dissemination. Conclusions. In previously healthy adults with otherwise unexplained disseminated/extrapulmonary Nocardia infections, anti-GM-CSF autoantibodies should be considered. Their presence may suggest that these patients may be at risk for later development of pulmonary alveolar proteinosis or other opportunistic infections, and that patients may benefit from therapeutic GM-CSF administration. C1 [Rosen, Lindsey B.; Olivier, Kenneth N.; Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Pereira, Nuno Rocha] Univ Porto, INEB I3S, Nephrol & Infect Dis Res & Dev Grp, P-4100 Oporto, Portugal. [Pereira, Nuno Rocha; Figueiredo, Cristovao] Sao Joao Hosp Ctr, Dept Infect Dis, Oporto, Portugal. [Fiske, Lauren C.; Ressner, Roseanne A.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Ressner, Roseanne A.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Hong, Julie C.] Kaiser Permanente Northwest, Permanente Med Grp, Dept Allergy Immunol, Clackamas, OR USA. [Gregg, Kevin S.] Univ Michigan, Sch Med, Dept Internal Med, Div Infect Dis, Ann Arbor, MI USA. [Henry, Tracey L.; Pak, Kirk J.] Ochsner Clin Fdn, Dept Internal Med, New Orleans, LA USA. [Baumgarten, Katherine L.; Garcia-Diaz, Julia] Ochsner Clin Fdn, Dept Infect Dis, New Orleans, LA USA. [Seoane, Leonardo] Ochsner Clin Fdn, Dept Pulm & Crit Care Med, New Orleans, LA USA. [Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Bethesda, MD 20892 USA. RP Browne, SK (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike,MSC 1684, Bethesda, MD 20892 USA. EM sarah.browne@fda.hhs.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, at the NIH FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, at the NIH. NR 31 TC 6 Z9 6 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2015 VL 60 IS 7 BP 1017 EP 1025 DI 10.1093/cid/ciu968 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CH0MH UT WOS:000353714000006 PM 25472947 ER PT J AU Roychoudhuri, R Eil, RL Restifo, NP AF Roychoudhuri, Rahul Eil, Robert L. Restifo, Nicholas P. TI The interplay of effector and regulatory T cells in cancer SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID GROWTH-FACTOR-BETA; TUMOR-INFILTRATING LYMPHOCYTES; TRANSCRIPTION FACTOR FOXP3; METASTATIC MELANOMA; CTLA-4 BLOCKADE; IFN-GAMMA; THERAPEUTIC VACCINATION; SPONTANEOUS REGRESSION; MEDIATED SUPPRESSION; ANTI-CTLA-4 THERAPY AB Regulatory T (T-reg) cells suppress effector T (T-eff) cells and prevent immune-mediated rejection of cancer. Much less appreciated are mechanisms by which T-eff cells antagonize T-reg cells. Herein, we consider how complex reciprocal interactions between T-eff and Treg cells shape their population dynamics within tumors. Under states of tolerance, including during tumor escape, suppressed T-eff cells support Treg cell populations through antigen-dependent provision of interleukin (IL)-2. During immune activation, T-eff cells can lose this supportive capacity and directly antagonize T-reg cell populations to neutralize their immunosuppressive function. While this latter state is rarely achieved spontaneously within tumors, we propose that therapeutic induction of immune activation has the potential to stably disrupt immunosuppressive population states resulting in durable cancer regression. C1 [Roychoudhuri, Rahul; Eil, Robert L.; Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA. RP Roychoudhuri, R (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM roychoudhuri@mail.nih.gov; restifo@nih.gov RI Roychoudhuri, Rahul/A-7442-2010; OI Roychoudhuri, Rahul/0000-0002-5392-1853; Restifo, Nicholas P./0000-0003-4229-4580 FU Tiens Charitable Foundation; NIH-Center for Regenerative Medicine; Milstein Family Foundation; Intramural Research Program of the National Cancer Institute [ZIA BC010763]; Wellcome Trust; Royal Society [105663/Z/14/Z] FX The authors were supported by a generous gift from Li Jinyuan and the Tiens Charitable Foundation, the NIH-Center for Regenerative Medicine, the Milstein Family Foundation and by the Intramural Research Program of the National Cancer Institute (ZIA BC010763). R.R. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 105663/Z/14/Z). The authors thank Alan Hoofring and Ethan Tyler for their assistance with illustrations, and David Clever, Luca Gattinoni, Christopher Klebanoff, Yun Ji, Madhusudhanan Sukumar, Joseph Crompton and Jenny Pan for insightful comments and discussions. NR 132 TC 24 Z9 30 U1 10 U2 27 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2015 VL 33 BP 101 EP 111 DI 10.1016/j.coi.2015.02.003 PG 11 WC Immunology SC Immunology GA CH1AT UT WOS:000353754200016 PM 25728990 ER PT J AU Bakkum-Gamez, JN Wentzensen, N Maurer, ML Hawthorne, KM Voss, JS Kroneman, TN Famuyide, AO Clayton, AC Hailing, KC Kerr, SE Cliby, WA Dowdy, SC Kipp, BR Mariani, A Oberg, AL Podratz, KC Shridhar, V Sherman, ME AF Bakkum-Gamez, Jamie N. Wentzensen, Nicolas Maurer, Matthew L. Hawthorne, Kieran M. Voss, Jesse S. Kroneman, Trynda N. Famuyide, Abimbola O. Clayton, Amy C. Hailing, Kevin C. Kerr, Sarah E. Cliby, William A. Dowdy, Sean C. Kipp, Benjamin R. Mariani, Andrea Oberg, Ann L. Podratz, Karl C. Shridhar, Viji Sherman, Mark E. TI Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrial cancer; Tampon; Tao brush; Methylation; Early detection ID ATYPICAL HYPERPLASIA; PROMOTER METHYLATION; MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; SEROUS CARCINOMA; OVARIAN-CANCER; TAO BRUSH; HYPERMETHYLATION; WOMEN; GENE AB Objective. We demonstrate the feasibility of detecting EC by combining minimally-invasive specimen collection techniques with sensitive molecular testing. Methods. Prior to hysterectomy for EC or benign indications, women collected vaginal pool samples with intravaginal tampons and underwent endometrial brushing. Specimens underwent pyrosequencing for DNA methylation of genes reported to be hypermethylated in gynecologic cancers and recently identified markers discovered by profiling over 200 ECs. Methylation was evaluated individually across CpGs and averaged across genes. Differences between EC and benign endometrium (BE) were assessed using two-sample t-tests and area under the curve (AUC). Results. Thirty-eight ECs and 28 BEs were included. We evaluated 97 CpGs within 12 genes, including previously reported markers (RASSF1, HSP2A, HOXA9, CDH13, HAAO, and GTF2A1) and those identified in discovery work (ASCL2, HTR1B, NPY, HS3ST2, MME, ADCYAP1, and additional CDH13 CpG sites). Mean methylation was higher in tampon specimens from EC v. BE for 9 of 12 genes (ADCYAP1, ASCL2, CDH13, HS3ST2, HTR1B, MME, HAAO, HOXA9, and RASSF1) (all p < 0.05). Among these genes, relative hypermethylation was observed in EC v. BE across CpGs. Endometrial brush and tampon results were similar. Within tampon specimens, AUC was highest for HTR1B (0.82), RASSF1 (0.75), and HOXA9 (0.74). This is the first report of HOXA9 hypermethylation in EC. Conclusion. DNA hypermethylation in EC tissues can also be identified in vaginal pool DNA collected via intravaginal tampon. Identification of additional EC biomarkers and refined collection methods are needed to develop an early detection tool for EC. (C) 2015 Elsevier Inc. All rights reserved. C1 [Bakkum-Gamez, Jamie N.; Famuyide, Abimbola O.; Cliby, William A.; Dowdy, Sean C.; Mariani, Andrea; Podratz, Karl C.] Mayo Clin, Dept Obstet & Gynecol, Div Gynecol Surg, Rochester, MN 55905 USA. [Wentzensen, Nicolas; Sherman, Mark E.] NCI, Hormonal & Reprod Branch HREB, Div Canc Epidemiol & Genet DCEG, Bethesda, MD 20892 USA. [Maurer, Matthew L.; Hawthorne, Kieran M.; Oberg, Ann L.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Voss, Jesse S.; Kroneman, Trynda N.; Clayton, Amy C.; Kerr, Sarah E.; Kipp, Benjamin R.] Mayo Clin, Dept Lab Med & Pathol, Div Anat Pathol, Rochester, MN 55905 USA. [Hailing, Kevin C.] Mayo Clin, Dept Lab Med & Pathol, Div Lab Genet, Rochester, MN 55905 USA. [Shridhar, Viji] Mayo Clin, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN 55905 USA. RP Bakkum-Gamez, JN (reprint author), Mayo Clin, Eisenberg Lobby 71,200 First St SW, Rochester, MN 55905 USA. EM Bakkum.jamie@mayo.edu FU NCI Cancer Center [P30 CA 15083] FX We thank the staff of the Medical Genome Facility Genotyping Core (GTC) at the Mayo Clinic, particularly Yanhong Wu, PhD for her expert technical help with pyrosequencing, for carrying out the genotyping and/or methylation analyses for this study. The GTC is supported in part by the NCI Cancer Center Support grant P30 CA 15083. NR 50 TC 5 Z9 5 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2015 VL 137 IS 1 BP 14 EP 22 DI 10.1016/j.ygyno.2015.01.552 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CG2BJ UT WOS:000353079600004 PM 25677060 ER EF